The DOI matches its Crossref record; 237 of the 239 references it cites were found in a registry or an index; 80 of the 157 sources its claims cite were checked for support.
Pathophysiology of Sickle Cell Disease
Open accessAbstract
Since the discovery of sickle cell disease (SCD) in 1910, enormous strides have been made in the elucidation of the pathogenesis of its protean complications, which has inspired recent advances in targeted molecular therapies. In SCD, a single amino acid substitution in the β-globin chain leads to polymerization of mutant hemoglobin S, impairing erythrocyte rheology and survival. Clinically, erythrocyte abnormalities in SCD manifest in hemolytic anemia and cycles of microvascular vaso-occlusion leading to end-organ ischemia-reperfusion injury and infarction. Vaso-occlusive events and intravascular hemolysis promote inflammation and redox instability that lead to progressive small- and large-vessel vasculopathy. Based on current evidence, the pathobiology of SCD is considered to be a vicious cycle of four major processes, all the subject of active study and novel therapeutic targeting: ( a) hemoglobin S polymerization, ( b) impaired biorheology and increased adhesion-mediated vaso-occlusion, ( c) hemolysis-mediated endothelial dysfunction, and ( d) concerted activation of sterile inflammation (Toll-like receptor 4- and inflammasome-dependent innate immune pathways). These molecular, cellular, and biophysical processes synergize to promote acute and chronic pain and end-organ injury and failure in SCD. This review provides an exhaustive overview of the current understanding of the molecular pathophysiology of SCD, how this pathophysiology contributes to complications of the central nervous and cardiopulmonary systems, and how this knowledge is being harnessed to develop current and potential therapies.
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Claims the paper makes
39 Partly supported · 32 No full text of the sources · 16 Own interpretation · 15 Supported · 12 No basis given · 9 Supported so far · 5 Not checked yet · 1 Mixed support · 1 Sources not found · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Intravital imaging studies done in transgenic humanized SCD mice and in vitro flow chamber studies done with SCD human blood over the past decade have contributed to the current understanding of vaso-occlusion as the interplay among impaired blood rheology, increased adhesiveness of erythrocytes with inflammatory cells and vascular endothelium, and hemostatic activation (14).”
§ Pathophysiology of Sickle Cell Disease > VASO-OCCLUSION
What the sources say
- Partly supportedcites [14] sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) describes sickle red cells adhering to neutrophils, endothelial activation, and a cycle of obstructed blood flow and further sickling. It also describes a hypercoagulable state, but explicitly says direct evidence that coagulation contributes to vaso-occlusion is lacking. The claimed role of hemostatic activation in vaso-occlusion is therefore stronger than the source supports; impaired blood rheology is not explicitly identified as a component of that model. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Findings from transgenic SCD mice, non-SCD mice with adoptively transferred sickle erythrocytes, and in vitro flow chamber systems are representative of human SCD pathophysiology.
- Partly supported
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In the paper
“Importantly, sickling-dependent damage of erythrocyte membranes also promotes exposure of adhesion molecules and binding motifs not normally expressed on erythrocytes, such as phosphatidyl serine (PS), basal cell adhesion molecule-1/Lutheran (B-CAM-1/Lu), integrin-associated protein (IAP), and intercellular-adhesion-molecule-4 (ICAM-4) (7, 9, 15).”
§ Pathophysiology of Sickle Cell Disease > VASO-OCCLUSION
What the sources say
- Not checked — no full text of the sourcecites [7] source
- Not checked — no full text of the sourcecites [9] source
- Partly supportedcites [15] sourceExperimental — accuracy not yet measured
The ADHESION MOLECULES section (page not supplied) identifies exposed PS and lists B-CAM-1/Lu, IAP, and ICAM-4 as molecules involved in sickle red-cell adhesion. It says the latter three require activation via signal transduction, not that sickling-dependent membrane damage exposes them. It also describes ICAM-4 as expressed on erythroid cells, so the claim that these molecules are not normally expressed on erythrocytes is not supported. (LLM, conf=0.89)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“therapy with hydroxyurea, which induces HbF and reduces white blood cell count, reticulocyte count, and hemolysis, is effective in the primary prevention of stroke (152).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Large-Vessel Vasculopathy in the Central Nervous System
What the sources say
- Partly supportedcites [152] sourceExperimental — accuracy not yet measured
The Interpretation (page not provided) says hydroxyurea can replace chronic transfusions to maintain TCD velocities and help prevent primary stroke in selected high-risk children with sickle cell anaemia, after years of transfusions and without severe vasculopathy. The claim omits those limits and states stroke-prevention effectiveness more broadly than this trial established; its primary finding concerned TCD velocities, and no strokes occurred in either arm. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“the oxygen extraction fraction is also increased at baseline (139, 140).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Large-Vessel Vasculopathy in the Central Nervous System
What the sources say
- Supportedcites [139] source
The SCD results report significantly higher whole-brain oxygen extraction fraction in children with sickle cell disease than in healthy controls. Table 2 gives 42.7 versus 28.8 (p < 0.001). No page number is provided in our copy. (LLM, conf=0.94)
- Supportedcites [140] source
The Results report significantly higher oxygen extraction fraction in adults with sickle cell anaemia than in controls in this observational study (adjusted P = 0.0012 for participants not receiving transfusions). This supports the claim about baseline oxygen extraction fraction in the adults studied. (LLM, conf=0.92)
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“a worrisome finding that suggests accelerated brain aging in SCD (145).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Large-Vessel Vasculopathy in the Central Nervous System
What the sources say
- Partly supportedcites [145] sourceExperimental — accuracy not yet measured
The paper’s Abstract reports that brain atrophy in children with sickle cell anaemia and silent cerebral infarction was greater than reported in healthy children and adults, and comparable to that seen in adults with small-vessel disease. This supports the suggestion of accelerated brain aging, but the measured rate was for whole-brain volume change, not cortical atrophy specifically; the study population was also narrower than children with sickle cell disease generally. Page numbers were not supplied in our copy. (LLM, conf=0.85)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“There is recent evidence that cortical atrophy progresses in children with SCD at a rate similar to that of adults without SCD but with small-vessel disease (0.6–1% per year)—a worrisome finding that suggests accelerated brain aging in SCD (145).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Large-Vessel Vasculopathy in the Central Nervous System
What the sources say
- Partly supportedcites [145] sourceExperimental — accuracy not yet measured
The reported results (labelled Abstract in our copy) give annual brain-volume losses of 0.62% and 0.96%, and the summary says cerebral atrophy was comparable to that in adults with small-vessel disease. The study measured global brain-volume change, not specifically cortical atrophy, and its children with sickle cell disease all had existing silent cerebral infarction. (LLM, conf=0.87)
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“degeneration of the internal elastic lamina”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Large-Vessel Vasculopathy in the Central Nervous System
What the sources say
- Not checked — no full text of the sourcecites [134] source
- Supportedcites [135] source
The Neuropathologic Findings describe focal splitting of the internal elastic lamina in the cerebral arteries of a child with sickle cell anemia and strokes. The Discussion identifies splitting as a sign of degeneration of that lamina. (LLM, conf=0.93)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Young sickle mice do not commonly develop large-vessel vasculopathy and stroke (153, 154)”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Large-Vessel Vasculopathy in the Central Nervous System
What the sources say
- Supportedcites [153] source
The Discussion reports no large-vessel vasculopathy, thrombotic or embolic infarcts, or hemorrhagic strokes in the relatively young Berkeley sickle mice studied. The paper identifies these mice as 1 to 6 months old (Histopathology; page numbers not supplied). (LLM, conf=0.93)
- Not checked — no full text of the sourcecites [154] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“the cerebral autoregulatory capacity, i.e., the capacity to adjust vessel volume in response to carbon monoxide challenge or systemic blood pressure changes, is impaired in SCD (137, 138).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Large-Vessel Vasculopathy in the Central Nervous System
What the sources say
- Supportedcites [137] source
The Discussion reports impaired dynamic cerebral autoregulation in patients with sickle cell disease. It specifically describes a reduced capacity to buffer blood-pressure surges, supporting the claim about autoregulatory capacity. (LLM, conf=0.93)
- Not checked — no full text of the sourcecites [138] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“These studies have shown that the large and medium-sized branches of the internal carotid artery are affected.”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Large-Vessel Vasculopathy in the Central Nervous System
What the sources say
- Not checked — no full text of the sourcecites [134] source
- Supportedcites [135] source
The Abstract describes a child with sickle cell anemia who died of strokes and had severe occlusive disease at the major bifurcations of both internal carotid arteries. The figure descriptions also identify thrombi in the anterior and middle cerebral arteries, supporting the paraphrase that larger carotid branches were affected. (LLM, conf=0.88)
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“chronic prophylactic transfusions prevent stroke in 90% of children with high cerebral blood velocities as measured by transcranial Doppler (148).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Large-Vessel Vasculopathy in the Central Nervous System
What the sources say
- Partly supportedcites [148] sourceExperimental — accuracy not yet measured
The Results report that transfusions lowered the risk of a first stroke by 92% compared with standard care—close to the claimed 90%. But the study was limited to children with sickle cell anemia and confirmed high Doppler velocities; it did not establish that transfusions prevent stroke in 90% of children with high velocities generally. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Lesions include intimal hyperplasia leading to obliteration of the lumen”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Large-Vessel Vasculopathy in the Central Nervous System
What the sources say
- Not checked — no full text of the sourcecites [134] source
- Supportedcites [135] source
The Abstract identifies the patient as a child with sickle cell anemia who died of strokes. In II. Neuropathologic Findings, the paper reports total occlusion of large cerebral arteries in some areas due to exuberant intimal hyperplasia; the Discussion’s Figure 7 caption says the lumen was entirely filled by proliferated intima. Page numbers are not available in the supplied copy. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“and intraluminal thrombosis (134, 135).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Large-Vessel Vasculopathy in the Central Nervous System
What the sources say
- Not checked — no full text of the sourcecites [134] source
- Supportedcites [135] source
The Abstract describes a child with sickle cell anemia who died of strokes and identifies old and recent thrombi among the causes of arterial occlusion. The Neuropathologic Findings section also reports a thrombus occluding the lumen of the left middle cerebral artery. (LLM, conf=0.94)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“normalization of transcranial Doppler velocity with transfusion in children was not associated with a reduction in markers of hemolysis in the Optimizing Primary Stroke Prevention in Sickle Cell Anemia (STOP 2) trial (161).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Large-Vessel Vasculopathy in the Central Nervous System
What the sources say
- Partly supportedcites [161] sourceExperimental — accuracy not yet measured
The Results section (page unavailable) reports that LDH levels were not significantly different between children whose TCD velocities normalized on transfusion and those whose did not. The Discussion likewise says LDH levels were not associated with the probability of normalization. But the paper does not report whether normalization was associated with a *reduction* in hemolysis markers over time; it separately states that transfusion reduces hemolysis. (LLM, conf=0.86)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“multivariate analysis of hemodynamic variables identified systolic pulmonary artery pressure, pulmonary pulse pressure, transpulmonary gradient, and PVR as predictors of mortality (66).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Development of Pulmonary Hypertension and Left Ventricular Diastolic Heart Dysfunction in Adults with Sickle Cell Disease
What the sources say
- Supportedcites [66] source
The Discussion states that systolic pulmonary artery pressure, pulmonary pulse pressure, transpulmonary gradient, and pulmonary vascular resistance were independently associated with mortality in models that included specified serum biomarkers. The Results also report significant multivariate associations for transpulmonary gradient and pulmonary vascular resistance, although systolic pulmonary artery pressure was only borderline significant in the main adjusted analysis. (LLM, conf=0.91)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“However, there was no association between lacunae and cognitive function (178).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Small-Vessel Vasculopathy in the Central Nervous System
What the sources say
- Partly supportedcites [178] sourceExperimental — accuracy not yet measured
The Results (Correlates of WAIS-III PIQ Score) report lower cognitive scores in patients with lacunae, a difference that was no longer statistically significant after adjustment for age. The claim omits that qualification and presents the finding as no association at all. (LLM, conf=0.88)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“more recent MRI evidence shows potential involvement of deep medullary veins (175, 176).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Small-Vessel Vasculopathy in the Central Nervous System
What the sources say
- Supportedcites [175] source
The Methods describe 7T MRI measurement of small intraparenchymal venules between the frontal and occipital cornu. The Results report significantly fewer long venules in patients with sickle cell anaemia than in controls, supporting potential involvement of deep cerebral veins. The copy provides no page numbers for these sections. (LLM, conf=0.85)
- Supportedcites [176] source
The Results report lower visible venous contrast in children with sickle cell disease than in controls, including in the deep medullary veins. This supports the citing sentence’s cautious description of potential involvement. (LLM, conf=0.91)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Pulmonary arterial hypertension is caused by progressive smooth muscle and intimal proliferation and in situ thrombosis, ultimately obliterating the pulmonary arterioles and increasing pulmonary vascular resistance (PVR) (184).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Development of Pulmonary Hypertension and Left Ventricular Diastolic Heart Dysfunction in Adults with Sickle Cell Disease
What the sources say
- Supportedcites [184] source
The Abstract says that endothelial and smooth-muscle proliferation, vascular remodeling, and in situ thrombosis progressively narrow small pulmonary vessels and increase resistance to blood flow. The Cellular changes section describes smooth-muscle migration into the intima, lumen-obliterating lesions, and in situ thrombi that further occlude vessels. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Alternatively, decreased autoregulation may allow the detrimental effects of elevated cerebral blood flow, pulse pressure (67), and velocity to be transmitted to the microcirculation and cause damage, as occurs in older individuals with atherosclerosis.”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Small-Vessel Vasculopathy in the Central Nervous System
What the sources say
- Supportedcites [67] source
The citation is attached specifically to “pulse pressure.” The Discussion states that elevated pulse pressure could damage small vessels and lead to microvascular rarefaction, supporting the attributed microcirculatory-damage mechanism. The paper presents this as a possible mechanism, consistent with the citing sentence’s “may.” (LLM, conf=0.90)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Both hemodynamic forms of pulmonary hypertension are independent predictors of death in the adult SCD patient population (66).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Development of Pulmonary Hypertension and Left Ventricular Diastolic Heart Dysfunction in Adults with Sickle Cell Disease
What the sources say
- Partly supportedcites [66] sourceExperimental — accuracy not yet measured
The Discussion identifies precapillary hemodynamic measures, including transpulmonary gradient and pulmonary vascular resistance, as independent risk factors for death. It says the postcapillary subgroup also had high mortality, but pulmonary capillary wedge pressure was not a significant predictor; it does not establish postcapillary PH as an independent predictor. (LLM, conf=0.90)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
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In the paper
“Autopsy review of patients with Moyamoya syndrome revealed that all three layers of the large intracerebral arteries were affected, with intimal hyperplasia, medial atrophy with fibrosis, and adventitial fibrosis (135).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Vasculopathy as a Risk Factor for Intracerebral Hemorrhage
What the sources say
- Partly supportedcites [135] sourceExperimental — accuracy not yet measured
The Discussion (page not provided) reviews postmortem reports of Moyamoya disease and lists the claimed changes in all three arterial layers. It says those layers “may be involved,” however, rather than establishing that all three were affected in every patient reviewed. (LLM, conf=0.84)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Studies in adults with SCD lend further support to the role of hemolysis by showing a link between the hyperhemolysis phenotype of SCD and stroke risk (17).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Large-Vessel Vasculopathy in the Central Nervous System
What the sources say
- Partly supportedcites [17] sourceExperimental — accuracy not yet measured
Table 1 (The hemolysis hypothesis; page unavailable) lists increased risk of stroke or elevated transcranial Doppler velocity with the hyperhemolytic subphenotype, and the Hyperhemolysis-associated SCD subphenotypes section includes cerebrovascular disease. The table combines stroke with Doppler findings and does not establish that the reported stroke-risk association specifically came from studies in adults. (LLM, conf=0.78)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Measures of diastolic dysfunction obtained by cardiac echocardiography are associated with excess mortality, even after adjustment for tricuspid regurgitant jet velocity, with a risk ratio of 3.5 (82).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Development of Pulmonary Hypertension and Left Ventricular Diastolic Heart Dysfunction in Adults with Sickle Cell Disease
What the sources say
- Supportedcites [82] source
The Abstract reports that a low E/A ratio, an echocardiographic measure of diastolic dysfunction, was associated with mortality in patients with sickle cell disease after adjustment for TR jet velocity, with a risk ratio of 3.5. This matches the attributed claim. (LLM, conf=0.92)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
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In the paper
“A meta-analysis of 45 screening studies from 15 countries of more than 6,000 patients indicates that the prevalence of elevated tricuspid regurgitant jet velocity ≥2.5 m/s is 30% (range 26–35%) in adults.”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Development of Pulmonary Hypertension and Left Ventricular Diastolic Heart Dysfunction in Adults with Sickle Cell Disease
What the sources say
- Partly supportedcites [191] sourceExperimental — accuracy not yet measured
The Results report 45 studies from 15 countries involving 6,109 people and an estimated 30% prevalence of elevated estimated pulmonary artery systolic pressure among adults with sickle cell disease. However, the studies used varying definitions of elevation: the reported 30% (26–35%) is not specifically the prevalence of TRV ≥2.5 m/s, although the Results say restricting analyses to that threshold did not substantially change the estimates. The 26–35% figures are a 95% confidence interval, not a range of observed prevalence. (LLM, conf=0.88)
hedgedn = 6,000- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“the presence of both diastolic dysfunction and an elevated tricuspid regurgitant jet velocity is associated with a risk ratio for death of 12.0 (82).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Development of Pulmonary Hypertension and Left Ventricular Diastolic Heart Dysfunction in Adults with Sickle Cell Disease
What the sources say
- Supportedcites [82] source
The Proportional Hazards (Cox) Regression Analysis of Mortality section reports an observed risk ratio for death of 12.0 when a high TR jet velocity and low E/A ratio were present together. Table 4 gives the same value, with a 95% confidence interval of 3.8–38.1, in patients with sickle cell disease. (LLM, conf=0.95)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“the Silent Infarct Transfusion (SIT) trial has shown that, without transfusion, SCI burden at baseline predicts further accrual of ischemic lesions and stroke (172)”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Small-Vessel Vasculopathy in the Central Nervous System
What the sources say
- Partly supportedcites [172] sourceExperimental — accuracy not yet measured
The Results (Neurologic Outcomes; page unavailable) report new or enlarged infarcts and strokes in the observation group, supporting recurrence without transfusion. But the reported baseline factors associated with recurrence are younger age, recurring headaches, and higher reticulocyte count; the paper does not report that baseline silent cerebral infarct burden predicts those outcomes. (LLM, conf=0.87)
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“even mild increases of >2.5–2.7 m/s are associated with increased risk of death (58, 77, 110, 188–190).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Development of Pulmonary Hypertension and Left Ventricular Diastolic Heart Dysfunction in Adults with Sickle Cell Disease
What the sources say
- Not checked — no full text of the sourcecites [58] source
- Partly supportedcites [77] sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) states that increased tricuspid regurgitant velocity is a marker of increased mortality in adults with sickle cell disease. The Methods and Results use a 2.7 m/s cutoff, but the paper does not link the specific >2.5–2.7 m/s range to mortality; its own outcome analysis concerns six-minute walk distance. (LLM, conf=0.85)
- Not checked — no full text of the sourcecites [110] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Every source the paper cites for this claim was checked and supports it.
In the paper
“The diagnosis of both forms of pulmonary hypertension was associated with a high risk of death”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Development of Pulmonary Hypertension and Left Ventricular Diastolic Heart Dysfunction in Adults with Sickle Cell Disease
What the sources say
- Supportedcites [66] source
The Discussion reports that precapillary pulmonary hypertension is a risk factor for early mortality in adults with sickle cell disease and that the postcapillary subgroup also had a high mortality rate. It distinguishes that shared mortality finding from the weaker prognostic significance of postcapillary hemodynamic markers. (LLM, conf=0.91)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“animal models showing that heme is directly responsible for acute lung injury in SCD mouse models (89).”
§ Pathophysiology of Sickle Cell Disease > CONVERGENCE OF MULTIPLE PATHOGENIC PATHWAYS: ACUTE CHEST SYNDROME
What the sources say
- Supportedcites [89] source
The Results section (‘EHC is a prodrome to lethal acute lung injury in SS mice’; page unavailable) reports that hemin-treated sickle mice developed severe hypoxemia and other hallmarks of acute lung injury, while control mice did not. The Discussion also describes the hemin bolus as causing lung injury in sickle mice. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“The kidneys are among the most commonly affected organs in patients with SCD (70, 201)”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Development of Pulmonary Hypertension and Left Ventricular Diastolic Heart Dysfunction in Adults with Sickle Cell Disease
What the sources say
- Supportedcites [70] source
The Introduction states that the kidneys are frequently involved in sickle cell anaemia, with injury affecting several kidney structures. This supports the citing sentence’s broad point that kidney involvement is common in sickle cell disease. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [201] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Recent autopsy findings have revealed platelet thrombi and increased endothelial von Willebrand factor deposition in the lung microvasculature of patients who died from ACS (218).”
§ Pathophysiology of Sickle Cell Disease > CONVERGENCE OF MULTIPLE PATHOGENIC PATHWAYS: ACUTE CHEST SYNDROME
What the sources say
- Supportedcites [218] source
The Results section reports pulmonary platelet thrombi in 3 of 10 patients who died from acute chest syndrome, including in arterioles and part of the capillary system. It also reports increased endothelial von Willebrand factor deposition in cases with platelet-rich thrombi compared with cases without them. The claim does not say these findings occurred in every patient. (LLM, conf=0.93)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Elevated initial platelet count and dramatic drops during VOC have been found to portend a poor prognosis in ACS (29, 208, 219).”
§ Pathophysiology of Sickle Cell Disease > CONVERGENCE OF MULTIPLE PATHOGENIC PATHWAYS: ACUTE CHEST SYNDROME
What the sources say
- Partly supportedcites [29] sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) associates thrombocytopenia with poor ACS outcomes, and the results identify a decrease in platelet count at presentation as a predictor of rapidly progressive ACS. The paper does not establish that an elevated initial platelet count predicts poor prognosis; its platelet-drop finding concerns presentation with ACS, not specifically drops during vaso-occlusive crisis. (LLM, conf=0.87)
- Could not verifycites [208] sourceExperimental — accuracy not yet measured
The Laboratory findings passage compares hemoglobin and white blood cell counts with baseline values, but does not report platelet counts. The Hospital course says there were no clinical predictors of which patients would die, but it does not assess elevated initial platelet counts or platelet drops during vaso-occlusive crisis. Searches for platelet and platelet-count changes found no passage addressing the claimed prognostic association. (LLM, conf=0.73)
- Not checked — no full text of the sourcecites [219] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“studies have found that elevated baseline levels of circulating fibrocytes, a type of mesenchymal, bone marrow–derived cell, are responsible for lung fibrogenesis in SCD mouse models (223).”
§ Pathophysiology of Sickle Cell Disease > CONVERGENCE OF MULTIPLE PATHOGENIC PATHWAYS: ACUTE CHEST SYNDROME
What the sources say
- Partly supportedcites [223] sourceExperimental — accuracy not yet measured
The Results report elevated baseline fibrocytes in the circulation and lungs of NY1DD sickle cell mice. The Discussion says circulating fibrocytes contribute to lung fibroproliferation, and reports that neutralizing CXCL12 reduced both their movement into the lungs and lung collagen deposition. Calling the fibrocytes responsible for fibrogenesis is stronger than the paper's conclusion that they contribute to it. (LLM, conf=0.84)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The role of hemolysis in ACS is underscored by clinical observations linking severe hemolysis to increased risk (216, 217)”
§ Pathophysiology of Sickle Cell Disease > CONVERGENCE OF MULTIPLE PATHOGENIC PATHWAYS: ACUTE CHEST SYNDROME
What the sources say
- Partly supportedcites [216] sourceExperimental — accuracy not yet measured
The Abstract reports that higher plasma free haem was associated with increased odds of acute chest syndrome in children with sickle cell disease. Results and Discussion also links higher bilirubin, a marker of haemolysis, to ACS, but cautions that haemolysis itself may not be a major discriminator. The evidence supports an association with specific markers, not the broader claim that severe haemolysis increases risk. (LLM, conf=0.85)
- Not checked — no full text of the sourcecites [217] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“inhibition of HbS polymerization with hydroxyurea reduces the incidence of ACS (205).”
§ Pathophysiology of Sickle Cell Disease > CONVERGENCE OF MULTIPLE PATHOGENIC PATHWAYS: ACUTE CHEST SYNDROME
What the sources say
- Partly supportedcites [205] sourceExperimental — accuracy not yet measured
The Results in the Abstract report fewer cases of chest syndrome with hydroxyurea than with placebo (25 vs. 51). The Abstract explains that fetal hemoglobin interferes with HbS polymerization, but the Discussion says hydroxyurea’s clinical mechanism is unclear; the paper does not establish polymerization inhibition as the cause of the reduction in chest syndrome. Page numbers are unavailable in our copy. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“the presence of chronic kidney disease is an independent predictor of pulmonary vascular disease and early mortality in adults with SCD (68, 202).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Development of Pulmonary Hypertension and Left Ventricular Diastolic Heart Dysfunction in Adults with Sickle Cell Disease
What the sources say
- Partly supportedcites [68] sourceExperimental — accuracy not yet measured
Table 5 (p. 6) identifies renal failure as a risk factor for early death in a multivariate model of adults with sickle cell anemia. It does not assess whether chronic kidney disease independently predicts pulmonary vascular disease; the Circumstances of Death section (p. 3) says the study had no working definition of chronic pulmonary failure. (LLM, conf=0.90)
- Not checked — no full text of the sourcecites [202] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“fat and marrow emboli lodge in the pulmonary microcirculation, resulting in infarction (212).”
§ Pathophysiology of Sickle Cell Disease > CONVERGENCE OF MULTIPLE PATHOGENIC PATHWAYS: ACUTE CHEST SYNDROME
What the sources say
- Partly supportedcites [212] sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) describes fat emboli in the lungs and vascular obstruction with injury to the pulmonary microvasculature. It does not say that fat and marrow emboli cause pulmonary infarction; the infarction it describes occurs in bone before fat embolization. (LLM, conf=0.84)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Epidemiologically, ACS is a complication of VOC, based on its typical development 2–3 days after the onset of vaso-occlusive pain (111)”
§ Pathophysiology of Sickle Cell Disease > CONVERGENCE OF MULTIPLE PATHOGENIC PATHWAYS: ACUTE CHEST SYNDROME
What the sources say
- Partly supportedcites [111] sourceExperimental — accuracy not yet measured
In “Diagnosis and Symptoms of the Acute Chest Syndrome at Admission” (page unavailable), the paper reports that 72% of patients admitted for a reason other than ACS had a vaso-occlusive crisis, and ACS findings appeared a mean of 2.5 days after admission in that group. The Discussion calls pain a prodrome of ACS. These passages support the association, but the measured interval starts at admission, not at the onset of pain, and applies to a subset rather than establishing a typical interval for all ACS cases. (LLM, conf=0.87)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“patients with evidence of platelet thrombi in lung arterioles post mortem had a higher platelet count at the onset of ACS (218).”
§ Pathophysiology of Sickle Cell Disease > CONVERGENCE OF MULTIPLE PATHOGENIC PATHWAYS: ACUTE CHEST SYNDROME
What the sources say
- Supportedcites [218] source
The Results section (‘Clinical variables associated with pulmonary platelet thrombi in ACS’) reports higher initial platelet counts during the fatal ACS episode in patients whose lung autopsies showed platelet thrombi than in those without thrombi (median 581 versus 324 × 10³ cells/ml; P = 0.023). The autopsy Results section confirms that the thrombi occurred in pulmonary vessels, including arterioles. (LLM, conf=0.94)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Importantly, these in vivo studies suggest that the cellular and molecular mechanisms of vaso-occlusion are also dictated by the type of organ or vascular bed.”
§ Pathophysiology of Sickle Cell Disease > VASO-OCCLUSION
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Findings from transgenic SCD mice, non-SCD mice with adoptively transferred sickle erythrocytes, and in vitro flow chamber systems are representative of human SCD pathophysiology.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, heme seems to promote sterile inflammation in SCD by stimulating TLR4-dependent innate immune signaling in endothelial and mononuclear cells.”
§ Pathophysiology of Sickle Cell Disease > STERILE INFLAMMATION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Findings from transgenic SCD mice, non-SCD mice with adoptively transferred sickle erythrocytes, and in vitro flow chamber systems are representative of human SCD pathophysiology.
In the paper
“Vaso-occlusion, or blood vessel occlusion, leading to ischemia is the predominant pathophysiology responsible for acute systemic painful vaso-occlusive crisis (VOC) and the requirement for emergency medical care by SCD patients (13).”
§ Pathophysiology of Sickle Cell Disease > VASO-OCCLUSION
What the sources say
- Not checked — no full text of the sourcecites [13] source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In addition to antipolymerization or antisickling therapies, several antiadhesion therapies are approved or being tested that seek to inhibit the multicellular adhesion cascade of vaso-occlusion (Figure 2b).”
§ Pathophysiology of Sickle Cell Disease > CURRENT AND FUTURE THERAPIES TARGETING SICKLE CELL DISEASE PATHOBIOLOGY
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This knowledge gap is partly due to the lack of adequate animal models of stroke in SCD.”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Large-Vessel Vasculopathy in the Central Nervous System
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In addition, elevations of hypoxia inducible factor-1α (HIF-1α) expression have confirmed the presence of tissue-level hypoxia (157).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Large-Vessel Vasculopathy in the Central Nervous System
What the sources say
- Not checked — no full text of the sourcecites [157] source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The finding of a similar pattern of lesions in the pulmonary arteries (described below) and large internal carotid branches in SCD (159) is intriguing”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Large-Vessel Vasculopathy in the Central Nervous System
What the sources say
- Not checked — no full text of the sourcecites [159] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The main mechanism underlying the high susceptibility to stroke of children with SCD involves the phenomenon known as decreased cerebrovascular reserve.”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Large-Vessel Vasculopathy in the Central Nervous System
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The complex pathways described above converge to cause large- and small-vessel vasculopathy in SCD.”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“and 70% of children with SCD will experience a stroke recurrence (81).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Large-Vessel Vasculopathy in the Central Nervous System
What the sources say
- Not matchedcites [81] Ohene-Frempong K, 1998, Blood
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“very little progress has been made in the elucidation of the mechanisms leading to the primary vascular lesions, particularly large-vessel stenosis.”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Large-Vessel Vasculopathy in the Central Nervous System
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As a result of maximized compensatory mechanisms at steady state, when events characterized by acute or chronic anemia, such as aplastic crises from parvovirus B19, occur, children with SCD may have no residual reserve to meet the acutely increased oxygen demand.”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Large-Vessel Vasculopathy in the Central Nervous System
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Children with sickle cell anemia have a 100-fold risk of developing stroke as compared to children without SCD (146)”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Large-Vessel Vasculopathy in the Central Nervous System
What the sources say
- Not checked — no full text of the sourcecites [146] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Cerebral blood flow is increased at baseline in children with SCD (136) to compensate for anemia and hemodynamically significant stenosis.”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Large-Vessel Vasculopathy in the Central Nervous System
What the sources say
- Not checked — no full text of the sourcecites [136] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Platelet recruitment and hemostatic activation then further contribute to obliteration of the lumen (158).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Large-Vessel Vasculopathy in the Central Nervous System
What the sources say
- Not checked — no full text of the sourcecites [158] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“the prevalence of aneurysms may be as high as 15% in women with SCD aged 30–39 (181)”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Vasculopathy as a Risk Factor for Intracerebral Hemorrhage
What the sources say
- Not checked — no full text of the sourcecites [181] source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“the approximately 22% of children who did not achieve normalization of transcranial Doppler velocity in spite of optimal transfusion in the trial were also protected from stroke (162).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Large-Vessel Vasculopathy in the Central Nervous System
What the sources say
- Not checked — no full text of the sourcecites [162] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“elevated lactate dehydrogenase is independently associated with increased risk of transcranial Doppler ≥2 m/sec (OR per IU/L = 1.001, 95% CI 1.000–1.002; P = 0.047) (160).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Large-Vessel Vasculopathy in the Central Nervous System
What the sources say
- Not checked — no full text of the sourcecites [160] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Regardless of the effect of anemia, the cerebral arterial and venous microcirculation may be directly involved by the processes of vaso-occlusion, ischemia-reperfusion injury, and endothelial dysfunction.”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Small-Vessel Vasculopathy in the Central Nervous System
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“the prevalence of Moyamoya syndrome may be as high as 43% in patients who have experienced a pediatric stroke (180).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Vasculopathy as a Risk Factor for Intracerebral Hemorrhage
What the sources say
- Not checked — no full text of the sourcecites [180] source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“A value of ≥160 pg/ml identifies SCD patients at higher risk of having pulmonary hypertension and death.”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Development of Pulmonary Hypertension and Left Ventricular Diastolic Heart Dysfunction in Adults with Sickle Cell Disease
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“there is evidence that children without MRI evidence of small-vessel disease also develop cognitive impairment (177).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Small-Vessel Vasculopathy in the Central Nervous System
What the sources say
- Not checked — no full text of the sourcecites [177] source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Old autopsy studies did show diffuse thickening and sclerosis of intracerebral arterioles (174)”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Small-Vessel Vasculopathy in the Central Nervous System
What the sources say
- Not checked — no full text of the sourcecites [174] Koshy M, 1990, J. Assoc. Acad. Minor. Phys.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“One particularly subtle cerebral manifestation of SCD is cognitive impairment.”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Small-Vessel Vasculopathy in the Central Nervous System
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“confirming the Cooperative Study of Sickle Cell Disease (CSSCD) report of a higher risk of stroke in children with SCI (173).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Small-Vessel Vasculopathy in the Central Nervous System
What the sources say
- Not checked — no full text of the sourcecites [173] source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In these children, the beneficial effect of transfusion may have been mitigation of hemolysis-induced endothelial dysfunction rather than reduction of hyperperfusion.”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Large-Vessel Vasculopathy in the Central Nervous System
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“While ACS may accelerate restrictive lung disease (222)”
§ Pathophysiology of Sickle Cell Disease > CONVERGENCE OF MULTIPLE PATHOGENIC PATHWAYS: ACUTE CHEST SYNDROME
What the sources say
- Not checked — no full text of the sourcecites [222] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Unlike pneumonia, ACS is the result of intrinsic SCD pathology.”
§ Pathophysiology of Sickle Cell Disease > CONVERGENCE OF MULTIPLE PATHOGENIC PATHWAYS: ACUTE CHEST SYNDROME
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Many lines of evidence point to thrombosis as a significant ACS trigger.”
§ Pathophysiology of Sickle Cell Disease > CONVERGENCE OF MULTIPLE PATHOGENIC PATHWAYS: ACUTE CHEST SYNDROME
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“in situ pulmonary thrombosis has been found to complicate approximately 17% of ACS cases (219).”
§ Pathophysiology of Sickle Cell Disease > CONVERGENCE OF MULTIPLE PATHOGENIC PATHWAYS: ACUTE CHEST SYNDROME
What the sources say
- Not checked — no full text of the sourcecites [219] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Fat emboli syndrome is often fatal, even with aggressive transfusion and supportive care (215).”
§ Pathophysiology of Sickle Cell Disease > CONVERGENCE OF MULTIPLE PATHOGENIC PATHWAYS: ACUTE CHEST SYNDROME
What the sources say
- Not checked — no full text of the sourcecites [215] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“ACS is an acute lung injury syndrome that affects children and adults with any of the major SCD subtypes.”
§ Pathophysiology of Sickle Cell Disease > CONVERGENCE OF MULTIPLE PATHOGENIC PATHWAYS: ACUTE CHEST SYNDROME
What the sources say
- Not checked — no full text of the sourcecites [204] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“the lung, in general, is more vulnerable to infection in children with SCD.”
§ Pathophysiology of Sickle Cell Disease > CONVERGENCE OF MULTIPLE PATHOGENIC PATHWAYS: ACUTE CHEST SYNDROME
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“recent findings showing a potential role for innate immune pathways in promoting sterile inflammation in SCD suggest that our current understanding of the SCD pathophysiology is still incomplete”
§ Pathophysiology of Sickle Cell Disease > CONCLUSION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“there is evidence that other pathologic insults are necessary for the development of lung fibrosis.”
§ Pathophysiology of Sickle Cell Disease > CONVERGENCE OF MULTIPLE PATHOGENIC PATHWAYS: ACUTE CHEST SYNDROME
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Five major pathologic mechanisms leading to ACS have been identified”
§ Pathophysiology of Sickle Cell Disease > CONVERGENCE OF MULTIPLE PATHOGENIC PATHWAYS: ACUTE CHEST SYNDROME
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Taken together and in the context of the well-described hemostatic activation at baseline and its increase during VOC in SCD (91), these findings suggest that the prothrombotic environment of VOC and ACS is conducive to pulmonary thrombosis.”
§ Pathophysiology of Sickle Cell Disease > CONVERGENCE OF MULTIPLE PATHOGENIC PATHWAYS: ACUTE CHEST SYNDROME
What the sources say
- Not checked — no full text of the sourcecites [91] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“fat emboli may activate alveolar phospholipase A2 and other proinflammatory and pro-oxidant lung enzymes, leading to injury (213).”
§ Pathophysiology of Sickle Cell Disease > CONVERGENCE OF MULTIPLE PATHOGENIC PATHWAYS: ACUTE CHEST SYNDROME
What the sources say
- Not checked — no full text of the sourcecites [213] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These observations suggest that the contribution of chronic pathology may compound the role of recurrent ACS in the development of restrictive lung disease in SCD.”
§ Pathophysiology of Sickle Cell Disease > CONVERGENCE OF MULTIPLE PATHOGENIC PATHWAYS: ACUTE CHEST SYNDROME
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Acute bouts of bone ischemia during VOC lead, in severe cases, to necrosis of the bone marrow.”
§ Pathophysiology of Sickle Cell Disease > CONVERGENCE OF MULTIPLE PATHOGENIC PATHWAYS: ACUTE CHEST SYNDROME
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 45
- Borderline: one of the tests for a substantial claim is unclear. 1
- Probably not a substantial claim. 5
- The quote only partly states this claim. 1
Some cited sources support this claim and some don’t — read each source’s verdict below.
In the paper
“The largest study with the longest follow-up is the NIH-PH cohort study, which screened 531 patients and followed them for a median of 4.4 years (66, 194).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Development of Pulmonary Hypertension and Left Ventricular Diastolic Heart Dysfunction in Adults with Sickle Cell Disease
What the sources say
- Disputedcites [66] sourceExperimental — accuracy not yet measured
The Methods report 529 subjects screened, not 531. Survival and Risk Factors for Mortality reports a median follow-up of 4.7 years, not 4.4 years. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
- Supportedcites [194] source
The Results state that 531 patients were screened by echocardiography and that median follow-up since enrollment was 4.4 years. The Comment also describes this as, to the authors’ knowledge, the largest cohort of its kind. (LLM, conf=0.94)
plainn = 531- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Disputed
Every source the paper cites for this claim was checked and supports it.
In the paper
“Recently (96), cell-free heme was shown to promote NLRP3 inflammasome activation in LPS-primed macrophages, leading to IL-1β release.”
§ Pathophysiology of Sickle Cell Disease > STERILE INFLAMMATION
What the sources say
- Supportedcites [96] source
The Results passage beginning “To examine the ability of heme to act as a second signal” reports that LPS-pretreated bone-marrow–derived macrophages secreted processed IL-1β after heme stimulation. The Results passage headed “Heme Causes Activation of NLRP3 Inflammasome” shows that NLRP3-deficient macrophages could not process or secrete IL-1β in response to heme. (LLM, conf=0.94)
direct- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Borderline substantial claim. It is unclear whether the paper’s conclusions depend on it.
- Rests on an assumption: Findings from transgenic SCD mice, non-SCD mice with adoptively transferred sickle erythrocytes, and in vitro flow chamber systems are representative of human SCD pathophysiology.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Sickle cell anemia is caused by homozygosity of the beta-S (βS) allele (located on chromosome 11p15.5), which differs from the wild-type β-allele by a single nucleotide polymorphism dbSNP Rs334(T;T) in which GTG is substituted for GAG in the sixth codon of the β-globin gene (1, 3, 5, 6).”
§ Pathophysiology of Sickle Cell Disease > INTRODUCTION
What the sources say
- Not checked — no full text of the sourcecites [1] source
- Partly supportedcites [3] sourceExperimental — accuracy not yet measured
The paper’s Abstract (page not provided) states that HbS has a β-globin Glu→Val substitution at position 6 and that a child inheriting HbS from both parents suffers from sickle cell anaemia. Our copy does not specify the single-nucleotide change, rs334 identifier, GTG/GAG codons, or chromosome location given in the citing sentence. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [5] source
- Not checked — no full text of the sourcecites [6] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Indeed, SCD patients are known to have elevated levels of neutrophils, monocytes and platelets at baseline, and elevated levels of circulating neutrophil-platelet and monocyte-platelet aggregates in SCD human blood correlate with disease severity (19–28).”
§ Pathophysiology of Sickle Cell Disease > VASO-OCCLUSION
What the sources say
- Not checked — no full text of the sourcecites [19] source
- Not checked — no full text of the sourcecites [20] source
- Not checked — no full text of the sourcecites [21] Westwick J, 1983, J. Med.
- Partly supportedcites [22] sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) reports higher steady-state white blood cell and platelet counts among adults with sickle cell anemia who used the emergency department more frequently. The Methods (page unavailable) list total white blood cell and platelet counts, but not neutrophil or monocyte counts or platelet aggregates. The paper therefore supports the platelet and general white-blood-cell association, not the claim about specific cell types or aggregates correlating with disease severity. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [23] source
- Partly supportedcites [24] sourceExperimental — accuracy not yet measured
The introduction (p. 1) says high leukocyte counts are often observed in sickle cell anemia and associated with clinical severity; it also describes circulating neutrophil-platelet aggregates as well documented in the condition. It does not establish elevated baseline counts for each named cell type, report monocyte-platelet aggregates, or link either platelet-aggregate type to disease severity. The correlation reported on p. 3 is between platelet counts and neutrophil-reticulocyte aggregates, not disease severity. (LLM, conf=0.85)
- Partly supportedcites [25] sourceExperimental — accuracy not yet measured
The Results section, “Increased platelet-leukocyte aggregation in SCD” (page unavailable), reports higher percentages of both neutrophils and monocytes aggregated with platelets in blood from SCD patients than in controls. It does not establish elevated baseline counts of neutrophils, monocytes, or platelets in patients, or a correlation between aggregate levels and disease severity. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [26] source
- Not checked — no full text of the sourcecites [27] source
- Not checked — no full text of the sourcecites [28] source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Interestingly, IL-1RA-blocking Ab (anakinra) and IL-1β-blocking Ab (canakinumab) are already FDA approved as anti-inflammatory biologics for the treatment of rheumatoid arthritis (130) and NLRP3-inflammasome-mediated cryopyrin-associated periodic syndrome (CAPS) (131), respectively.”
§ Pathophysiology of Sickle Cell Disease > CURRENT AND FUTURE THERAPIES TARGETING SICKLE CELL DISEASE PATHOBIOLOGY
What the sources say
- Partly supportedcites [130] sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) says anakinra was approved to treat rheumatoid arthritis in adults, supporting the part of the sentence attached to this citation. The paper does not specify FDA approval, and the Conclusion (page unavailable) identifies anakinra as a recombinant IL-1 receptor antagonist, not an antibody. The canakinumab/CAPS statement is attached to a different citation and is not judged here. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [131] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Once released, IL-1β binds to IL-1 receptor (IL-1R) on leukocytes and vascular cells, promoting a cascade of downstream events that lead to activation of neutrophils and platelets and upregulation of E-selectin, P-selectin, VCAM-1, ICAM-1, and chemokines such as IL-8 in endothelial cells, all of which promote vaso-occlusion (14, 17) (Figure 1).”
§ Pathophysiology of Sickle Cell Disease > STERILE INFLAMMATION
What the sources say
- Partly supportedcites [14] sourceExperimental — accuracy not yet measured
The Introduction (page not provided) says monocyte-derived IL-1β activates endothelial cells through NF-κB and links endothelial adhesion molecules, including E-selectin, P-selectin, VCAM-1, and ICAM-1, to vaso-occlusive events. It does not establish the specified IL-1R-to-neutrophil-and-platelet activation cascade or IL-1β-induced endothelial IL-8 production. It also says direct evidence that platelets participate in sickle-cell vaso-occlusion is lacking. (LLM, conf=0.88)
- Partly supportedcites [17] sourceExperimental — accuracy not yet measured
The Abstract describes an inflammatory, proadhesive endothelial state that promotes sickle vaso-occlusion, and “Evidence linking cell-free hemoglobin to SCD complications” reports platelet activation. Neither passage attributes those effects to IL-1β binding IL-1R or describes the claimed neutrophil activation and endothelial upregulation of E-selectin, P-selectin, VCAM-1, ICAM-1, and IL-8. Page numbers were not provided in our copy. (LLM, conf=0.84)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Findings from transgenic SCD mice, non-SCD mice with adoptively transferred sickle erythrocytes, and in vitro flow chamber systems are representative of human SCD pathophysiology.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Vaso-occlusion contributes to ischemia-reperfusion injury, which, along with release of eDAMPs, promotes the progression of sterile inflammation (Figure 1d) in SCD (14, 17, 18).”
§ Pathophysiology of Sickle Cell Disease > STERILE INFLAMMATION
What the sources say
- Partly supportedcites [14] sourceExperimental — accuracy not yet measured
The Introduction says that obstructed blood flow produces ischemia and that hemolysis releases hemoglobin and heme, which promote inflammation in SCD. It does not establish the more specific claim that vaso-occlusion causes ischemia-reperfusion injury that, together with erythrocyte damage-associated molecular patterns, drives the progression of sterile inflammation. (LLM, conf=0.85)
- Partly supportedcites [17] sourceExperimental — accuracy not yet measured
The section ‘Evidence linking cell-free hemoglobin to SCD complications’ says eDAMPs promote sterile inflammation and may be central to the inflammation of sickle vaso-occlusion. The cited paper also links vaso-occlusive episodes to enhanced eDAMP release, but the passages do not establish the claimed ischemia-reperfusion injury step; a search for that term found no supporting passage. (LLM, conf=0.85)
- Partly supportedcites [18] sourceExperimental — accuracy not yet measured
The paper’s Abstract (pp. 3689–3690) says that hemolysis releases erythrocyte products that can act as DAMPs and drive sterile inflammation in SCD. It discusses vaso-occlusion, but does not state the claimed link from vaso-occlusion through ischemia-reperfusion injury to sterile inflammation. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Findings from transgenic SCD mice, non-SCD mice with adoptively transferred sickle erythrocytes, and in vitro flow chamber systems are representative of human SCD pathophysiology.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Observational studies have shown that reticulocytosis (149), low HbF levels, leukocytosis (150, 151), and complications such as ACS (81) are associated with an increased risk of stroke.”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Large-Vessel Vasculopathy in the Central Nervous System
What the sources say
- Partly supportedcites [149] sourceExperimental — accuracy not yet measured
The Results and Discussion report that reticulocytosis in early infancy was associated with increased risk of the combined outcome of stroke or death during childhood. They do not establish an increased risk of stroke alone. Citation 149 is attached to reticulocytosis; the other listed factors are not attributed to this source by that citation. (LLM, conf=0.85)
- Not checked — no full text of the sourcecites [150] source
- Not checked — no full text of the sourcecites [151] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“cortical brain areas and cortical and white matter watershed (border zone) areas (134, 141, 142), which are particularly vulnerable to ischemia, may undergo acute infarction.”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Large-Vessel Vasculopathy in the Central Nervous System
What the sources say
- Not checked — no full text of the sourcecites [134] source
- Not checked — no full text of the sourcecites [141] source
- Supportedcites [142] source
The Results section reports infarcts in the deep white-matter internal borderzone and cortical borderzone regions in children with sickle cell disease. The Discussion describes the borderzone as highly vulnerable to ischemia and says restricted blood flow may lead to acute ischemic events. Page numbers were not provided in our copy. (LLM, conf=0.87)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Patients with higher rates of hemolysis have lower steady-state Hb levels and are more likely to develop vascular injury and organ dysfunction as they age, manifesting as pulmonary hypertension, diastolic left heart disease, and renal dysfunction (proteinuria, albuminuria, and chronic kidney dysfunction) (62, 64, 65, 70, 79).”
§ Pathophysiology of Sickle Cell Disease > ENDOTHELIAL DYSFUNCTION
What the sources say
- Partly supportedcites [62] sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) links hemolysis and anemia to organ injury as patients with sickle cell disease age, and identifies pulmonary vascular disease and renal failure as complications. The copy does not establish that higher hemolysis rates predict lower steady-state hemoglobin or the full specified set of outcomes, particularly left-heart diastolic disease, proteinuria, and albuminuria. (LLM, conf=0.84)
- Not checked — no full text of the sourcecites [64] source
- Partly supportedcites [65] sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [70] sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Not checked — no full text of the sourcecites [79] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“NT-proBNP, a prepro hormone released from cardiac myocytes of the left and right ventricles in response to pressure overload and wall stress, also identifies patients at higher risk of having pulmonary hypertension, with lower exercise capacity and increased mortality risk.”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Development of Pulmonary Hypertension and Left Ventricular Diastolic Heart Dysfunction in Adults with Sickle Cell Disease
What the sources say
- Not checked — no full text of the sourcecites [193] source
- Partly supportedcites [62] sourceExperimental — accuracy not yet measured
The Results sections on cohort characteristics and univariate mortality describe NT-proBNP as a marker associated with pulmonary hypertension and report higher mortality among patients with elevated levels. The cohort characteristics report six-minute walk distances separately, but do not link elevated NT-proBNP to lower exercise capacity. These findings concern patients with sickle cell disease, rather than patients generally. (LLM, conf=0.87)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“There is a surprising similarity between the arteriopathy of the CNS and pulmonary arterial vasculature in SCD, and both are epidemiologically and mechanistically related to the severity of the hemolytic anemia (183).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Development of Pulmonary Hypertension and Left Ventricular Diastolic Heart Dysfunction in Adults with Sickle Cell Disease
What the sources say
- Partly supportedcites [183] sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In children with SCD, the SIT trial has shown that transfusion may reduce incident SCI, although SCIs were part of a composite endpoint that also included stroke, thus hampering the analysis of the effect of transfusion on SCI alone (172).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Small-Vessel Vasculopathy in the Central Nervous System
What the sources say
- Supportedcites [172] source
The Methods define the primary endpoint as stroke or a new or enlarged silent cerebral infarct. The Abstract Results report fewer new or enlarged silent infarcts with transfusion (5 versus 7), but the reported effect estimate and significance test are for the combined endpoint, not silent infarcts alone. The trial enrolled children with sickle cell anemia who already had a silent cerebral infarct. (LLM, conf=0.88)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Among the group with pulmonary hypertension, 56.4% had precapillary pulmonary arterial hypertension, with a pulmonary artery occlusion pressure ≤15 mm Hg, and the remainder had pulmonary venous hypertension, with elevated pulmonary artery occlusion pressures >15 mm Hg.”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Development of Pulmonary Hypertension and Left Ventricular Diastolic Heart Dysfunction in Adults with Sickle Cell Disease
What the sources say
- Partly supportedcites [66] sourceExperimental — accuracy not yet measured
Hemodynamic Parameters reports that 31 of 55 subjects with pulmonary hypertension (56.4%) had precapillary PH and the remaining 24 (43.6%) had postcapillary PH. Methods defines postcapillary PH by PCWP >15 mm Hg, but defines precapillary PH by PCWP <15 mm Hg, not the claimed ≤15 mm Hg; our copy therefore does not support the boundary at exactly 15 mm Hg. The paper uses PCWP (pulmonary capillary wedge pressure) rather than the claim’s term pulmonary artery occlusion pressure. (LLM, conf=0.86)
- Could not verifycites [194] sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 2 unverifiable. Expand the claim to see per-atom verdicts.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Patients with elevated tricuspid regurgitant jet velocity walked an estimated 30.4 (6.9–53.9) meters less than those without elevated tricuspid regurgitant jet velocity, with an associated hazard ratio for death of 4.9 (2.4–9.7) (191).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Development of Pulmonary Hypertension and Left Ventricular Diastolic Heart Dysfunction in Adults with Sickle Cell Disease
What the sources say
- Supportedcites [191] source
The Results (page unavailable) report that sickle cell disease patients with elevated estimated pulmonary artery systolic pressure walked 30.4 (6.9–53.9) metres less and had a pooled mortality hazard ratio of 4.9 (2.4–9.7). The Abstract (page unavailable) states that elevated pressure was defined by tricuspid regurgitant velocity in most studies. (LLM, conf=0.94)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Of these patients, 84 received right heart catheterizations due to suspected pulmonary hypertension, and 55 (10.4%) were diagnosed with pulmonary hypertension based on a mean pulmonary artery pressure >25 mm Hg.”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Development of Pulmonary Hypertension and Left Ventricular Diastolic Heart Dysfunction in Adults with Sickle Cell Disease
What the sources say
- Supportedcites [66] source
The Methods state that 84 of 529 screened adults with sickle cell disease underwent right heart catheterization because of elevated echocardiographic readings and clinical suspicion of pulmonary hypertension. Hemodynamic Parameters reports that 55 of the 529 (10.4%) were diagnosed with pulmonary hypertension; the paper defines it as mean pulmonary artery pressure >25 mm Hg. (LLM, conf=0.94)
- Partly supportedcites [194] sourceExperimental — accuracy not yet measured
The Results report that 84 of 531 patients underwent right heart catheterization and 55 had pulmonary hypertension, representing 10.4% of the total population. The Methods link catheterization to clinical suspicion but define pulmonary hypertension as mean pulmonary artery pressure of 25 mm Hg or greater, not greater than 25 mm Hg. (LLM, conf=0.90)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The largest study to date of cognitive function in adults with SCD has shown that 33% of a cohort of patients with homozygous SCD and without severe complications performed 1 standard deviation worse than the population mean in cognitive tests and had a much higher prevalence of lacunar infarcts (13% versus 2%).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Small-Vessel Vasculopathy in the Central Nervous System
What the sources say
- Partly supportedcites [178] sourceExperimental — accuracy not yet measured
Split into 3 atoms — 2 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“While the development of pulmonary hypertension is related to pulmonary vascular disease in the setting of intravascular hemolysis and thrombotic events, it can also occur secondary to diastolic left heart disease (77, 82).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Development of Pulmonary Hypertension and Left Ventricular Diastolic Heart Dysfunction in Adults with Sickle Cell Disease
What the sources say
- Partly supportedcites [77] sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) reports that confirmed pulmonary hypertension can reflect either increased pulmonary vascular resistance or pulmonary venous hypertension attributed to left ventricular diastolic dysfunction. It also links hemolytic severity to elevated estimated pulmonary pressure. The paper does not link thrombotic events to the development of pulmonary hypertension, so that part of the claim is unsupported. (LLM, conf=0.86)
- Partly supportedcites [82] sourceExperimental — accuracy not yet measured
The introductory passage (page not provided) links pulmonary hypertension in sickle cell disease to vasculopathy arising in the setting of hemolytic anemia and recurrent vaso-occlusion. The Conclusions (page not provided) say diastolic dysfunction directly contributes to elevated pulmonary pressures in a small fraction of patients. The paper does not specifically identify thrombotic events as a cause, and it limits the diastolic contribution rather than presenting it as a general mechanism. (LLM, conf=0.84)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The fundamental lesion of ACS is a hyperinflammatory event leading to classic acute lung injury (Figure 4), defined by alveolar-capillary leak and neutrophilic inflammation, most commonly in two or more dependent lobes, which may be radiographically and clinically indistinguishable from multilobar pneumonia (206).”
§ Pathophysiology of Sickle Cell Disease > CONVERGENCE OF MULTIPLE PATHOGENIC PATHWAYS: ACUTE CHEST SYNDROME
What the sources say
- Partly supportedcites [206] sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Recent studies in SCD mice further highlight the importance of diastolic dysfunction in SCD, and myocardial fibrosis is reported to occur both in these mice and in patients (the latter measured by extracellular volume using cardiac MRI imaging) (197–199).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Development of Pulmonary Hypertension and Left Ventricular Diastolic Heart Dysfunction in Adults with Sickle Cell Disease
What the sources say
- Not checked — no full text of the sourcecites [197] source
- Partly supportedcites [198] sourceExperimental — accuracy not yet measured
The Results section (page unavailable) reports diastolic dysfunction in patients with sickle cell disease, and the Discussion says prior cardiac MRI studies found small degrees of focal myocardial fibrosis in patients. This paper does not report findings in sickle cell disease mice or say that patient fibrosis was measured by MRI-derived extracellular volume; it also notes that MRI studies have been inconsistent about the extent of fibrosis. (LLM, conf=0.88)
- Supportedcites [199] source
The Introduction reports that diastolic dysfunction in sickle cell anemia mice was associated with microscopic myocardial fibrosis. The Abstract and Discussion report diffuse myocardial fibrosis in patients, assessed using cardiac MRI measurements of extracellular volume, and its association with diastolic dysfunction. (LLM, conf=0.92)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Bronchial hyper-reactivity, asthma, and chronic airway inflammation (209) are highly prevalent in children with SCD and may result in a proinflammatory milieu that amplifies cellular and humoral immunity to airway pathogens, thus leading to a paroxysmal, detrimental response (210, 211).”
§ Pathophysiology of Sickle Cell Disease > CONVERGENCE OF MULTIPLE PATHOGENIC PATHWAYS: ACUTE CHEST SYNDROME
What the sources say
- Not checked — no full text of the sourcecites [209] source
- Partly supportedcites [210] sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [211] sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“it is more common in children and, if untreated, has a high mortality [9% in adults (111)].”
§ Pathophysiology of Sickle Cell Disease > CONVERGENCE OF MULTIPLE PATHOGENIC PATHWAYS: ACUTE CHEST SYNDROME
What the sources say
- Partly supportedcites [111] sourceExperimental — accuracy not yet measured
Table 1 lists more children than adults among the patients studied, and Table 2 reports 9% mortality in patients aged 20 or older. But the Hospital Course and Treatment section says patients received treatment, so the 9% figure is not an untreated mortality rate. The study's age-group counts also do not establish that acute chest syndrome is more common in children in the wider sickle cell population. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“high levels of hemopexin, the enzyme that scavenges heme, can rescue acute lung injury (89), while HO-1 deficiency potentiates it (57).”
§ Pathophysiology of Sickle Cell Disease > CONVERGENCE OF MULTIPLE PATHOGENIC PATHWAYS: ACUTE CHEST SYNDROME
What the sources say
- Supportedcites [89] source
The Results section reports that sickle mice treated with recombinant human hemopexin after a hemin challenge did not develop respiratory symptoms and all survived. The HO-1-deficiency statement has a separate citation in the citing sentence, so it is not assessed against this source. (LLM, conf=0.92)
- Not checked — no full text of the sourcecites [57] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Infection is the most common ACS trigger in children; common isolates include atypical microorganisms and Streptococcus pneumoniae (208).”
§ Pathophysiology of Sickle Cell Disease > CONVERGENCE OF MULTIPLE PATHOGENIC PATHWAYS: ACUTE CHEST SYNDROME
What the sources say
- Partly supportedcites [208] sourceExperimental — accuracy not yet measured
The Hospital course section says childhood ACS most likely results from infectious causes, but describes this as an inference rather than a confirmed ranking of triggers. The Results section identifies Streptococcus pneumoniae as a common isolate; it does not identify atypical microorganisms as common isolates. Page numbers are unavailable in our copy. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In its most extreme manifestation (207), acute lung injury presents with or evolves into acute respiratory distress syndrome.”
§ Pathophysiology of Sickle Cell Disease > CONVERGENCE OF MULTIPLE PATHOGENIC PATHWAYS: ACUTE CHEST SYNDROME
What the sources say
- Supportedcites [207] source
The Definitions section (p. 1) defines ARDS using a more severe hypoxemia threshold than acute lung injury, supporting the description of ARDS as its more extreme manifestation. Figure 1 (p. 2) also describes early lung injury progressing to respiratory failure. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“As a result, βS-globin chains on different deoxygenated HbS tetramers bind to each other to hide the hydrophobic motifs, thus initiating the nucleation of an HbS polymer.”
§ Pathophysiology of Sickle Cell Disease > HEMOGLOBIN S POLYMERIZATION
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“The rate of polymerization is proportional to the intraerythrocytic concentration of HbS (to the 34th power) and inversely proportional to the concentration of fetal Hb (HbF), which both replaces HbS and interferes with HbS polymerization (7, 10, 11).”
§ Pathophysiology of Sickle Cell Disease > HEMOGLOBIN S POLYMERIZATION
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“stroke affected up to 10% of children prior to the implementation of screening programs (81, 133).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Large-Vessel Vasculopathy in the Central Nervous System
What the sources say
- Not matchedcites [81] Ohene-Frempong K, 1998, Blood
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not checked — no full text of the sourcecites [133] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Because oxy-Hb reacts with nitric oxide (NO) in an extremely fast and essentially irreversible reaction to form inert nitrate, the release of intraerythrocytic Hb into plasma during intravascular hemolysis promotes NO scavenging reactions and impairs NO-dependent basal vasodilation.”
§ Pathophysiology of Sickle Cell Disease > ENDOTHELIAL DYSFUNCTION
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Stenosis of the large branches of the internal carotid artery predisposes children to devastating strokes.”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Large-Vessel Vasculopathy in the Central Nervous System
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
In the paper
“red blood cell transfusion rapidly improves stroke symptoms and cerebral tissue oxygen saturation in children (147)”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Large-Vessel Vasculopathy in the Central Nervous System
What the sources say
- Not checked — no full text of the sourcecites [147] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“both hypoperfusion of the microcirculation (due to microvascular occlusion or altered vasoregulation) and hyperperfusion of the systemic macrocirculation and major organ systems (due to anemia and fixed stenosis) coexist, a phenomenon that has been referred to as the perfusion paradox of SCD (132).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS
What the sources say
- Not checked — no full text of the sourcecites [132] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Cell-free Hb also promotes ROS formation, critically altering the vascular redox balance of steady-state NO production to ROS production (decreasing NO–ROS balance).”
§ Pathophysiology of Sickle Cell Disease > ENDOTHELIAL DYSFUNCTION
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Other proposed or FDA-approved therapies may prevent endothelial dysfunction by scavenging cell-free Hb (haptoglobin), promoting NO production (hydroxyurea, oral or IV nitrite, inhaled NO, and oral arginine), or reducing oxidative stress (l-glutamine and antioxidants).”
§ Pathophysiology of Sickle Cell Disease > CURRENT AND FUTURE THERAPIES TARGETING SICKLE CELL DISEASE PATHOBIOLOGY
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“SCD mouse models do, however, exhibit certain specific aspects of the cerebral pathology seen with sickle cell anemia, including decreased brain oxygen tension, increased cerebral blood flow (155), decreased blood flow regulation, and microinfarcts (156, 157).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Large-Vessel Vasculopathy in the Central Nervous System
What the sources say
- Not checked — no full text of the sourcecites [155] source
- Not checked — no full text of the sourcecites [156] 156. Hyacinth HI, Sugihara CL, Spencer TL, Archer DR, Shih AY. 2017. Higher prevalence of spontaneous cerebral vasculopathy and cerebral infarcts in a mouse model of sickle cell disease. J. Cereb. Blood Flow Metab. https://doi.org/10.1177/0271678X17732275 source
- Not checked — no full text of the sourcecites [157] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Aneurysms are typically saccular and <5 mm in size and may coexist with vasculopathy and a Moyamoya pattern of cerebral vascularization (182).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Vasculopathy as a Risk Factor for Intracerebral Hemorrhage
What the sources say
- Not checked — no full text of the sourcecites [182] source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“small-vessel lesions are the most common cerebrovascular lesions in SCD, with a prevalence of 13% at 14 months of age (163) that progressively rises throughout childhood (164) such that, by adulthood, it is approximately 50% (165, 166).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Small-Vessel Vasculopathy in the Central Nervous System
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Over time, the right heart begins to fail as afterload increases, leading to progressive dyspnea, reduced exercise capacity, and increased risk of acute cor pulmonale and sudden cardiac death.”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Development of Pulmonary Hypertension and Left Ventricular Diastolic Heart Dysfunction in Adults with Sickle Cell Disease
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Intracerebral hemorrhage preferentially affects young adults with SCD and is particularly common in those suffering from aneurysms and Moyamoya syndrome (180).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Vasculopathy as a Risk Factor for Intracerebral Hemorrhage
What the sources say
- Not checked — no full text of the sourcecites [180] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Anemia clearly also plays a role in the development of SCI, as demonstrated by studies in children without SCD, where an acute, severe drop in hemoglobin has been associated with the development of new white matter hyperintensities.”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Small-Vessel Vasculopathy in the Central Nervous System
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Another large population screening study confirmed that a tricuspid regurgitant jet velocity ≥2.5 m/s was associated with a hazard ratio of 6.81 in multivariate analysis and rose linearly above this value (50% of death at tricuspid regurgitant jet velocity of 3.2 m/s) (192).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Development of Pulmonary Hypertension and Left Ventricular Diastolic Heart Dysfunction in Adults with Sickle Cell Disease
What the sources say
- Not checked — no full text of the sourcecites [192] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Basic science and clinical studies over past decade have led to the understanding of the cellular, molecular, and biophysical mechanisms that promote these pathophysiological events and inspired the development of several prophylactic therapies that are either FDA approved or currently in clinical trials.”
§ Pathophysiology of Sickle Cell Disease > CONCLUSION
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“the development of chronic kidney disease is a risk factor for the development of pulmonary hypertension and appears to occur as a consequence of chronic hemolysis and the injurious effects of filtered cell-free hemoglobin.”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Development of Pulmonary Hypertension and Left Ventricular Diastolic Heart Dysfunction in Adults with Sickle Cell Disease
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“any initial lung insult is bound to result in lung ventilation–perfusion mismatch, hypoxemia, and a potentiation of the initial pathogenic triggers, a phenomenon that has been described as “the vicious cycle of ACS” (110).”
§ Pathophysiology of Sickle Cell Disease > CONVERGENCE OF MULTIPLE PATHOGENIC PATHWAYS: ACUTE CHEST SYNDROME
What the sources say
- Not checked — no full text of the sourcecites [110] source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is also likely that ACS triggers or insults that activate neutrophils and platelets, in the setting of intensifying hemolytic anemia with release of eDAMPs, will propagate sterile inflammatory pathways through TLR4 and inflammasome signaling (discussed in Figure 1).”
§ Pathophysiology of Sickle Cell Disease > CONVERGENCE OF MULTIPLE PATHOGENIC PATHWAYS: ACUTE CHEST SYNDROME
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“Proposed mechanisms for SCD nephropathy include hemoglobinuria, ischemia-reperfusion injury, hyperfiltration, and hypertension (203).”
§ Pathophysiology of Sickle Cell Disease > THE PERFUSION PARADOX OF SICKLE CELL DISEASE: PATHOLOGY IN THE CENTRAL NERVOUS AND CARDIOPULMONARY SYSTEMS > Development of Pulmonary Hypertension and Left Ventricular Diastolic Heart Dysfunction in Adults with Sickle Cell Disease
What the sources say
- Not checked — no full text of the sourcecites [203] source
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The five mechanisms described above may coexist or independently cause ACS”
§ Pathophysiology of Sickle Cell Disease > CONVERGENCE OF MULTIPLE PATHOGENIC PATHWAYS: ACUTE CHEST SYNDROME
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Fat embolism is suspected when abundant lipid-laden macrophages are detected in the bronchoalveolar lavage, a sensitive but nonspecific test (214).”
§ Pathophysiology of Sickle Cell Disease > CONVERGENCE OF MULTIPLE PATHOGENIC PATHWAYS: ACUTE CHEST SYNDROME
What the sources say
- Not checked — no full text of the sourcecites [214] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The interplay among genetics, HbS polymerization–dependent hemolysis and sickling, vaso-occlusion-dependent ischemia-reperfusion injury, endothelial dysfunction–dependent vasculopathy, and sterile inflammation contributes to the pathophysiology of SCD, which promotes acute and chronic complications of the CNS, heart, lung, kidney, liver, and other organs.”
§ Pathophysiology of Sickle Cell Disease > CONCLUSION
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In humans, circulating fibrocytes are present in high numbers; are activated in SCD, particularly in VOC; and are associated with restrictive pulmonary function test patterns (224).”
§ Pathophysiology of Sickle Cell Disease > CONVERGENCE OF MULTIPLE PATHOGENIC PATHWAYS: ACUTE CHEST SYNDROME
What the sources say
- Not checked — no full text of the sourcecites [224] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Hypoventilation, as a result of pain with inspiration deriving from rib infarction (220) or oversedation from opiate analgesia, may lead to atelectasis, which is a known risk factor for pneumonia and lung injury (221).”
§ Pathophysiology of Sickle Cell Disease > CONVERGENCE OF MULTIPLE PATHOGENIC PATHWAYS: ACUTE CHEST SYNDROME
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
Findings from transgenic SCD mice, non-SCD mice with adoptively transferred sickle erythrocytes, and in vitro flow chamber systems are representative of human SCD pathophysiology.
“Intravital imaging studies done in transgenic humanized SCD mice and in vitro flow chamber studies done with SCD human blood over the past decade have contributed to the current understanding of vaso-occlusion as the interplay among impaired blood rheology, increased adhesiveness of erythrocytes with inflammatory cells and vascular endothelium, and hemostatic activation (14).”
Citations
Cites
Chen, Y., Wang, L., Kang, Q., Zhang, X., Yu, G., Wan, X., Wang, J., & Zhu, K. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000477308 · Cited by 10,730
Mizgerd, J. P., Kubo, H., Kutkoski, G. J., Bhagwan, S. D., Scharffetter-Kochanek, K., Beaudet, A. L., & Doerschuk, C. M. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.186.8.1357 · Cited by 7,332
Ischemia and reperfusion—from mechanism to translation
Eltzschig, H. K., & Eckle, T. D. L. G. (2011) · Nature Medicine · doi:10.1038/nm.2507 · Cited by 3,468
Mortality in sickle cell disease. Life expectancy and risk factors for early death
Platt, O. S., Brambilla, D. J., Rosse, W. F., Milner, P. F., Castro, O., Steinberg, M. H., & Klug, P. P. (1994) · New England Journal of Medicine · doi:10.1056/nejm199406093302303 · Cited by 3,320
Sterile inflammation: sensing and reacting to damage
Chen, G. Y., & Nuñez, G. (2010) · Nature Reviews Immunology · doi:10.1038/nri2873 · Cited by 3,051
Rees, D. C., Williams, T. N., & Gladwin, M. T. (2010) · The Lancet · doi:10.1016/s0140-6736(10)61029-x · Cited by 2,504
Self-citationEffect of hydroxyurea on the frequency of painful crises in sickle cell anemia
Charache, S., Terrin, M. L., Moore, R. D., Dover, G. J., Barton, F. B., Eckert, S. V., McMahon, R. P., & Bonds, D. R. (1995) · New England Journal of Medicine · doi:10.1056/nejm199505183322001 · Cited by 2,340
Sickle Cell Anemia, a Molecular Disease
Pauling, L., Itano, H. A., Singer, S. J., & Wells, I. C. (1949) · Science · doi:10.1126/science.110.2865.543 · Cited by 2,319
Adams, R. J., McKie, V. C., Hsu, L., Files, B., Vichinsky, E., Pegelow, C., Abboud, M., Gallagher, D., Kutlar, A., Nichols, F. T., et al. (1998) · New England Journal of Medicine · doi:10.1056/nejm199807023390102 · Cited by 1,866
Research works printed but not linked: 4
- Westwick J, 1983, J. Med., 14, 17
- Ohene-Frempong K, 1998, Blood, 91, 288
- Malik Z, 1983, Cytobios, 38, 33
- Koshy M, 1990, J. Assoc. Acad. Minor. Phys., 1, 71
Cited by
Sorted by citations
Exagamglogene Autotemcel for Severe Sickle Cell Disease
Frangoul, H., Locatelli, F., Sharma, A., Bhatia, M., Mapara, M., Molinari, L., Wall, D., Liem, R. I., Telfer, P., Shah, A. J., et al. (2024) · New England Journal of Medicine · doi:10.1056/nejmoa2309676 · Cited by 493
Biologic and Clinical Efficacy of LentiGlobin for Sickle Cell Disease
Kanter, J., Walters, M. C., Krishnamurti, L., Mapara, M. Y., Kwiatkowski, J. L., Rifkin-Zenenberg, S., Aygun, B., Kasow, K. A., Pierciey, F. J., Bonner, M., et al. (2022) · New England Journal of Medicine · doi:10.1056/nejmoa2117175 · Cited by 442
Gene therapy using haematopoietic stem and progenitor cells
Ferrari, G., Thrasher, A. J., & Aiuti, A. (2020) · Nature Reviews Genetics · doi:10.1038/s41576-020-00298-5 · Cited by 263
Acute Myeloid Leukemia Case after Gene Therapy for Sickle Cell Disease
Goyal, S., Tisdale, J., Schmidt, M., Kanter, J., Jaroscak, J., Whitney, D., Bitter, H., Gregory, P. D., Parsons, G., Foos, M., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2109167 · Cited by 215
Recent Advances in the Treatment of Sickle Cell Disease
Cisneros, G. S., & Thein, S. L. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00435 · Cited by 210
Metadata
- Authors
- Sundd, P., Gladwin, M. T., & Novelli, E. M.
- Affiliations
- University of Pittsburgh (US)
- Venue
- Annual Review of Pathology Mechanisms of Disease
- Publisher
- Annual Reviews
- Published
- 2019-01-24
- Volume
- 14
- Issue
- 1
- Pages
- 263-292
- ISSN
- 1553-4006 (ISSN-L)
- 1553-4014
- PMC
- PMC7053558
- OpenAlex
- W2898014977
- Cited by
- 813
- References
- 239
- Citations by year
- 2026: 121 · 2025: 155 · 2024: 132 · 2023: 133 · 2022: 114 · 2021: 75 · 2020: 53 · 2019: 22
- FWCI
- 5.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Annual Review of Pathology Mechanisms of Disease (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Heart Association (18TPA34170588)
- National Heart, Lung, and Blood Institute (R01HL127107, K23HL112848, P01HL103455, HL110849, R01HL141080, R01HL128297, R01HL125886, R01HL098032, T32HL110849)
- Topics
- Health Sciences › Medicine › Genetics (clinical) › Hemoglobinopathies and Related Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
- Health Sciences › Medicine › Hematology › Blood properties and coagulation
- Keywords
- sickle cell disease, hemoglobin S polymerization, erythrocyte rheology, vascular occlusion, hemolysis, endothelial dysfunction, sterile inflammation, TLR4, inflammasome, redox imbalance, vasculopathy, pain, end-organ failure, beta-globin gene mutations, targeted therapy
- MeSH terms
- Anemia, Sickle Cell, Hemolysis, Humans, Inflammation, Reperfusion Injury, Oxidative Stress, Toll-Like Receptor 4
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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