The DOI matches its Crossref record; 69 of the 72 references it cites were found in a registry or an index; 27 of the 77 sources its claims cite were checked for support.
EULAR recommendations for the management of antiphospholipid syndrome in adults
Open accessAbstract
The objective was to develop evidence-based recommendations for the management of antiphospholipid syndrome (APS) in adults. Based on evidence from a systematic literature review and expert opinion, overarching principles and recommendations were formulated and voted. High-risk antiphospholipid antibody (aPL) profile is associated with greater risk for thrombotic and obstetric APS. Risk modification includes screening for and management of cardiovascular and venous thrombosis risk factors, patient education about treatment adherence, and lifestyle counselling. Low-dose aspirin (LDA) is recommended for asymptomatic aPL carriers, patients with systemic lupus erythematosus without prior thrombotic or obstetric APS, and non-pregnant women with a history of obstetric APS only, all with high-risk aPL profiles. Patients with APS and first unprovoked venous thrombosis should receive long-term treatment with vitamin K antagonists (VKA) with a target international normalised ratio (INR) of 2–3. In patients with APS with first arterial thrombosis, treatment with VKA with INR 2–3 or INR 3–4 is recommended, considering the individual’s bleeding/thrombosis risk. Rivaroxaban should not be used in patients with APS with triple aPL positivity. For patients with recurrent arterial or venous thrombosis despite adequate treatment, addition of LDA, increase of INR target to 3–4 or switch to low molecular weight heparin may be considered. In women with prior obstetric APS, combination treatment with LDA and prophylactic dosage heparin during pregnancy is recommended. In patients with recurrent pregnancy complications, increase of heparin to therapeutic dose, addition of hydroxychloroquine or addition of low-dose prednisolone in the first trimester may be considered. These recommendations aim to guide treatment in adults with APS. High-quality evidence is limited, indicating a need for more research.
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Written from the paper’s full text.
TL;DR
This paper presents EULAR evidence-based recommendations for managing antiphospholipid syndrome (APS) in adults, covering risk stratification, thromboprophylaxis, obstetric APS, and catastrophic APS. The recommendations are based on a systematic literature review and expert consensus, with limited high-quality evidence.
Key findings
- High-risk antiphospholipid antibody (aPL) profiles—lupus anticoagulant, double/triple aPL positivity, or persistently high titres—are associated with greater thrombotic and obstetric risk. Low-dose aspirin (LDA) 75–100 mg daily is recommended for asymptomatic aPL carriers, patients with SLE without prior thrombotic or obstetric APS, and non-pregnant women with a history of obstetric APS only, all with high-risk aPL profiles. A meta-analysis of seven observational studies of 460 asymptomatic aPL carriers found first thrombosis risk reduced by half with LDA; in women with obstetric APS without SLE, pooled OR for first thrombosis with LDA was 0.25 (95% CI 0.10 to 0.62).
- For definite APS and first unprovoked venous thrombosis, long-term vitamin K antagonists (VKA) with target INR 2–3 are recommended. For first arterial thrombosis, VKA with INR 2–3 or INR 3–4 is recommended, considering individual bleeding/thrombosis risk. Rivaroxaban should not be used in patients with triple aPL positivity due to excess thromboembolic events in the TRAPS trial. For recurrent arterial or venous thrombosis despite adequate treatment, addition of LDA, increase of INR target to 3–4, or switch to low molecular weight heparin may be considered.
- In obstetric APS, women with prior obstetric APS should receive combination LDA and prophylactic-dose heparin during pregnancy. In recurrent pregnancy complications despite LDA and prophylactic heparin, increasing heparin to therapeutic dose, adding hydroxychloroquine, or adding low-dose prednisolone in the first trimester may be considered. In women with thrombotic APS, LDA plus therapeutic-dose heparin is recommended; observational studies reported live births in 79% of pregnancies on average. For catastrophic APS, combination glucocorticoids, heparin, and plasma exchange or IVIG is recommended first-line; rituximab or eculizumab may be considered for refractory cases.
- The task force developed 3 overarching principles and 12 recommendations. The systematic literature review yielded 7534 articles plus 15 hand-searched articles; after title/abstract review, 670 articles underwent full-text review, 249 underwent data abstraction, 61 were excluded, and 188 were finally considered relevant.
Methods
- The project followed the updated EULAR standardised operating procedure and used the AGREE II tool. The task force included members from 11 European countries: 12 specialists in rheumatology or internal medicine, 2 obstetricians, 2 physicians from vascular medicine/thrombosis centres, 1 healthcare professional, and 2 patient representatives. Thirty-one research questions were formulated using PICO and voted by Delphi method.
- Data sources were PubMed, Embase, and the Cochrane Library, searched for English-language articles from inception through 31 January 2018; one RCT published after this date (TRAPS) was included for safety results. Titles/abstracts were reviewed independently by two literature reviewers; full texts were reviewed independently by three persons. Data abstraction was performed by two reviewers and independently double-checked by the convenor and methodologist.
- Evidence was tabulated with summary of findings tables and pooled estimates where applicable. Draft recommendations were prepared, reviewed, discussed in working groups, and voted at a second task force meeting on 3 September 2018. Levels of evidence and grades of recommendation used Oxford Centre for Evidence-Based Medicine standards; anonymous level of agreement was rated 0–10.
Limitations
- The paper states that the main challenge was low certainty of evidence. Many studies included mixed clinical features and did not provide stratified data for arterial versus venous thrombosis or for different types of obstetric APS, resulting in indirect evidence for many treatment decisions. Meta-analyses also pooled heterogeneous patient groups, and RCTs commonly had high risk of bias and low power due to the rarity of the syndrome.
- The paper states that a significant number of recommendations necessarily relied more, or only, on low-quality evidence or expert opinion. It also notes that cost and availability are not barriers to implementation except for IVIG and plasmapheresis, which were recommended first-line only in catastrophic APS, occurring in less than 1% of patients.
- Evident from the text: several recommendations were based on expert opinion or lacked direct studies, including treatment duration after provoked first venous thrombosis, continuation of prophylactic heparin for 6 weeks postpartum, and management of recurrent pregnancy complications despite LDA and prophylactic heparin. Some supporting evidence came from small observational studies or case series.
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Claims the paper makes
17 Own method · 15 No full text of the sources · 5 Supported · 5 No basis given · 4 Mixed support · 3 Supported so far · 3 Partly supported · 3 Own interpretation · 2 Own result · 1 Not supported · 1 Couldn’t confirm · 1 Sources not found · accuracy not yet measured
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“Studies of women with SLE and prior obstetric APS are scarce, but the protective effect of LDA was supported by three retrospective studies that included a minority of patients with SLE.18–20”
§ EULAR recommendations for the management of antiphospholipid syndrome in adults > RECOMMENDATIONS > Primary thromboprophylaxis in aPL-positive subjects
What the sources say
- Not checked — no full text of the sourcecites [18] Erkan, 2001, High thrombosis rate after fetal loss in antiphospholipid syndrome: effective prophylaxis with aspirin, Arthritis Rheum source
- Not checked — no full text of the sourcecites [19] Forastiero, 2005, A prospective study of antibodies to beta2-glycoprotein I and prothrombin, and risk of thrombosis, J Thromb Haemost source
- Disputedcites [20] Ruffatti, 2011, Risk factors for a first thrombotic event in antiphospholipid antibody carriers: a prospective multicentre follow-up study, Ann Rheum Dis sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 0 partially supported, 2 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Checked by a reasoning model — may be wrong.
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.
Some cited sources support this claim and some don’t — read each source’s verdict below.
In the paper
“Data from an RCT21 reporting exclusively on patients with venous events and pooled data from five studies that included a majority with venous events21–25 showed no additional benefit of a target INR of 3–4 vs INR of 2–3.”
§ EULAR recommendations for the management of antiphospholipid syndrome in adults > RECOMMENDATIONS > Secondary thromboprophylaxis in APS
What the sources say
- Partly supportedcites [21] Crowther, 2003, A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome, N Engl J Med 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 [22] Finazzi, 2005, A randomized clinical trial of high-intensity warfarin vs. conventional antithrombotic therapy for the prevention of recurrent thrombosis in patients with the antiphospholipid syndrome (WAPS), J Thromb Haemost 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.
- Not checked — no full text of the sourcecites [23] Rosove, 1992, Antiphospholipid thrombosis: clinical course after the first thrombotic event in 70 patients, Ann Intern Med source
- Disputedcites [24] Khamashta, 1995, The management of thrombosis in the antiphospholipid-antibody syndrome, N Engl J Med sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 0 partially supported, 2 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Checked by a reasoning model — may be wrong.
- Not checked — no full text of the sourcecites [25] Ames, 2005, Bleeding and re-thrombosis in primary antiphospholipid syndrome on oral anticoagulation: an 8-year longitudinal comparison with mitral valve replacement and inherited thrombophilia, Thromb Haemost 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.
- Partly supported
Some cited sources support this claim and some don’t — read each source’s verdict below.
In the paper
“Pooled data from one RCT including only patients with a history of first trimester losses46 and eight supporting observational studies47–54 that did not exclusively study women with early pregnancy losses indicated a higher likelihood of live births with combination treatment with LDA and heparin at prophylactic dosage versus LDA alone.”
§ EULAR recommendations for the management of antiphospholipid syndrome in adults > RECOMMENDATIONS > Obstetric APS
What the sources say
- Not checked — no full text of the sourcecites [46] Rai, 1997, Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies), BMJ source
- Not checked — no full text of the sourcecites [47] Lima, 1996, A study of sixty pregnancies in patients with the antiphospholipid syndrome, Clin Exp Rheumatol
- Not checked — no full text of the sourcecites [48] Muñoz-Rodriguez, 1999, Clinical study and follow-up of 100 patients with the antiphospholipid syndrome, Semin Arthritis Rheum source
- Disputedcites [49] Naru, 2010, Pregnancy outcome in women with antiphospholipid syndrome on low-dose aspirin and heparin: a retrospective study, East Mediterr Health J sourceExperimental — accuracy not yet measured
This paper is a retrospective observational study, but its Abstract concludes that aspirin alone and aspirin plus heparin were equally efficacious in women with antiphospholipid syndrome and recurrent miscarriage. Its Introduction reports that other randomized trials favored combination treatment; it does not present its own study as supporting a higher likelihood of live birth with heparin. (LLM, conf=0.84)
Checked by a reasoning model — may be wrong.
- Not checked — no full text of the sourcecites [50] Cohn, 2010, Recurrent miscarriage and antiphospholipid antibodies: prognosis of subsequent pregnancy, J Thromb Haemost source
- Supportedcites [51] Mohamed, 2014, Enoxaparin and aspirin therapy for recurrent pregnancy loss due to anti-phospholipid syndrome (APS), Middle East Fertil Soc J source
The Patients and methods section describes a prospective non-randomized comparison and gives the combination group low-dose aspirin plus enoxaparin 40 mg daily. Its pregnancy-morbidity criteria include losses beyond early pregnancy, and the Results report more live births with combination therapy than with aspirin alone (43/47 versus 15/23). The paper supports its role as one observational study in the cited group; it does not itself pool the studies. (LLM, conf=0.90)
- Not checked — no full text of the sourcecites [52] Ruffatti, 2014, Treatment strategies and pregnancy outcomes in antiphospholipid syndrome patients with thrombosis and triple antiphospholipid positivity. a European multicentre retrospective study, Thromb Haemost source
- Not checked — no full text of the sourcecites [53] Franklin, 2002, Antiphospholipid antibodies (APA) and recurrent pregnancy loss: treating a unique APA positive population, Hum Reprod source
- Disputedcites [54] Laskin, 2009, Low molecular weight heparin and aspirin for recurrent pregnancy loss: results from the randomized, controlled HepASA trial, J Rheumatol sourceExperimental — accuracy not yet measured
The Objectives section says the HepASA trial included women with losses before 32 weeks, and Table 1 (Discussion) records participants with histories of losses after 14 weeks. It was therefore not restricted to first-trimester losses. The Abstract reports no live-birth advantage for heparin plus aspirin over aspirin alone in this trial; the eight observational studies are cited separately in the claiming sentence. (LLM, conf=0.92)
Checked by a reasoning model — may be wrong.
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.
Some cited sources support this claim and some don’t — read each source’s verdict below.
In the paper
“Pooled data from two retrospective studies and two RCTs21–24 showed that there was no statistically significant difference in thrombosis recurrences between treatment with VKA with a target INR of 3–4 and treatment with INR of 2–3 (relative risk (RR) 0.46 (0.06–3.52)).”
§ EULAR recommendations for the management of antiphospholipid syndrome in adults > RECOMMENDATIONS > Secondary thromboprophylaxis in APS
What the sources say
- Supportedcites [21] Crowther, 2003, A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome, N Engl J Med source
The citation identifies a constituent RCT, not the source of the pooled estimate on its own. The trial description identifies this as a randomized comparison of target INR 3.1–4.0 versus 2.0–3.0, and the Results report no statistically significant difference in recurrent thrombosis (P=0.15). (LLM, conf=0.88)
- Partly supportedcites [22] Finazzi, 2005, A randomized clinical trial of high-intensity warfarin vs. conventional antithrombotic therapy for the prevention of recurrent thrombosis in patients with the antiphospholipid syndrome (WAPS), J Thromb Haemost sourceExperimental — accuracy not yet measured
The Study design and Results sections (page not specified) establish that WAPS is one of the randomized trials comparing high- and conventional-intensity treatment and found no statistically significant difference in recurrent thrombosis. But its pooled analysis includes only WAPS and the Crowther trial; it does not report a pooled analysis of two retrospective studies and two RCTs or the stated RR of 0.46 (0.06–3.52). (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [23] Rosove, 1992, Antiphospholipid thrombosis: clinical course after the first thrombotic event in 70 patients, Ann Intern Med source
- Disputedcites [24] Khamashta, 1995, The management of thrombosis in the antiphospholipid-antibody syndrome, N Engl J Med sourceExperimental — accuracy not yet measured
Table 3 (p. 995) reports fewer recurrent events during warfarin treatment at INR ≥3 than at INR <3: 0.015 versus 0.23 events per patient-year. The Discussion (p. 996) says INR 2–3 did not prevent thrombotic events and recommends maintaining INR above 3, contrary to the claimed finding of no significant difference. This paper does not report the pooled RR of 0.46; its Table 3 relative risks compare each treatment with no treatment, not the two INR targets with each other. (LLM, conf=0.86)
Checked by a reasoning model — may be wrong.
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
Every source the paper cites for this claim was checked and supports it.
In the paper
“A recent RCT of rivaroxaban versus warfarin in patients with APS with triple aPL positivity was prematurely terminated due to an excess of thromboembolic events (mostly arterial) in the rivaroxaban arm.7”
§ EULAR recommendations for the management of antiphospholipid syndrome in adults > RECOMMENDATIONS > Secondary thromboprophylaxis in APS
What the sources say
- Supportedcites [7] Pengo, 2018, Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome, Blood source
Split into 2 atoms — 2 confirmed, 0 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.
- 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
“In a post-hoc analysis of patients with APS included in three RCTs of dabigatran versus warfarin,26 and in one RCT of rivaroxaban versus warfarin in patients with venous thrombotic APS,27 there were no differences in outcomes between treatment with DOACs and VKA for venous thrombosis”
§ EULAR recommendations for the management of antiphospholipid syndrome in adults > RECOMMENDATIONS > Secondary thromboprophylaxis in APS
What the sources say
- Not checked — no full text of the sourcecites [26] Goldhaber, 2016, Efficacy of dabigatran versus warfarin in patients with acute venous thromboembolism in the presence of thrombophilia: findings from RE-COVER®, RE-COVER™ II, and RE-MEDY™, Vasc Med source
- Supportedcites [27] Cohen, 2016, Rivaroxaban versus warfarin to treat patients with thrombotic antiphospholipid syndrome, with or without systemic lupus erythematosus (RAPS): a randomised, controlled, open-label, phase 2/3, non-inferiority trial, Lancet Haematol source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 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.
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
“Alternatively, treatment with VKA with a target INR of 2–3 plus LDA is used by some experts, supported by limited data from one retrospective cohort study and one small RCT.36 37”
§ EULAR recommendations for the management of antiphospholipid syndrome in adults > RECOMMENDATIONS > Secondary thromboprophylaxis in APS
What the sources say
- Not checked — no full text of the sourcecites [36] Krnic-Barrie, 1997, A retrospective review of 61 patients with antiphospholipid syndrome. Analysis of factors influencing recurrent thrombosis, Arch Intern Med source
- Supportedcites [37] Okuma, 2009, Comparison between single antiplatelet therapy and combination of antiplatelet and anticoagulation therapy for secondary prevention in ischemic stroke patients with antiphospholipid syndrome, Int J Med Sci source
The Materials and Methods section describes a small randomized trial of 20 patients with APS-related ischemic stroke, comparing aspirin alone with aspirin plus anticoagulation targeted to an INR of 2.0–3.0. The Results report fewer recurrent strokes in the combination group, supporting the cited sentence’s description of limited RCT evidence. This paper is not the retrospective cohort study cited alongside it. (LLM, conf=0.90)
hedged- 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 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
“However, these studies included women with histories of both early and mid-pregnancy losses.48–52”
§ EULAR recommendations for the management of antiphospholipid syndrome in adults > RECOMMENDATIONS > Obstetric APS
What the sources say
- Not checked — no full text of the sourcecites [48] Muñoz-Rodriguez, 1999, Clinical study and follow-up of 100 patients with the antiphospholipid syndrome, Semin Arthritis Rheum source
- Supportedcites [49] Naru, 2010, Pregnancy outcome in women with antiphospholipid syndrome on low-dose aspirin and heparin: a retrospective study, East Mediterr Health J source
The Results section reports that the study included 64 women with recurrent miscarriage and compared their numbers of previous first-, second-, and third-trimester pregnancy losses. This supports the claim that the study included histories of both early and mid-pregnancy loss. No page number is available in our copy. (LLM, conf=0.90)
- Not checked — no full text of the sourcecites [50] Cohn, 2010, Recurrent miscarriage and antiphospholipid antibodies: prognosis of subsequent pregnancy, J Thromb Haemost source
- Supportedcites [51] Mohamed, 2014, Enoxaparin and aspirin therapy for recurrent pregnancy loss due to anti-phospholipid syndrome (APS), Middle East Fertil Soc J source
The Pregnancy morbidity criteria (section 2.1.2; page unavailable) include prior abortions before 10 weeks and fetal deaths at or after 10 weeks. Table 1 (section 6, Recommendation; page unavailable) records both prior abortions and prior intrauterine fetal deaths among the study participants, supporting the claim that the study included histories of early and later pregnancy loss. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [52] Ruffatti, 2014, Treatment strategies and pregnancy outcomes in antiphospholipid syndrome patients with thrombosis and triple antiphospholipid positivity. a European multicentre retrospective study, Thromb Haemost 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 cited sources support only part of this claim — read each source’s verdict below.
In the paper
“For women with a history of fetal loss, combination treatment with LDA and heparin was associated with a higher likelihood of live birth compared with treatment with LDA alone.”
§ EULAR recommendations for the management of antiphospholipid syndrome in adults > RECOMMENDATIONS > Obstetric APS
What the sources say
- Not checked — no full text of the sourcecites [48] Muñoz-Rodriguez, 1999, Clinical study and follow-up of 100 patients with the antiphospholipid syndrome, Semin Arthritis Rheum source
- Partly supportedcites [49] Naru, 2010, Pregnancy outcome in women with antiphospholipid syndrome on low-dose aspirin and heparin: a retrospective study, East Mediterr Health J sourceExperimental — accuracy not yet measured
The Introduction and Discussion (pages unavailable in our copy) report two trials in aPL-positive women with recurrent miscarriage that found higher live-birth rates with aspirin plus heparin than with aspirin alone. But the cited paper’s own retrospective study concludes that the treatments were equally efficacious. The claim also omits the APS/aPL and recurrent-loss qualifications on the women studied. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [50] Cohn, 2010, Recurrent miscarriage and antiphospholipid antibodies: prognosis of subsequent pregnancy, J Thromb Haemost source
- Partly supportedcites [51] Mohamed, 2014, Enoxaparin and aspirin therapy for recurrent pregnancy loss due to anti-phospholipid syndrome (APS), Middle East Fertil Soc J sourceExperimental — accuracy not yet measured
The Results (section 3; page not provided) report more live births with low-dose aspirin plus LMWH than with aspirin alone (91% versus 65%; p = 0.02). However, the study included women with antiphospholipid syndrome and recurrent pregnancy loss; it does not establish the comparison for women with a history of fetal loss generally. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [52] Ruffatti, 2014, Treatment strategies and pregnancy outcomes in antiphospholipid syndrome patients with thrombosis and triple antiphospholipid positivity. a European multicentre retrospective study, Thromb Haemost 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.
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Because a history of thrombotic APS is associated with increased risk for future thrombotic or obstetric events,65 treatment with LDA and heparin at therapeutic dosage during pregnancy is recommended.”
§ EULAR recommendations for the management of antiphospholipid syndrome in adults > RECOMMENDATIONS > Obstetric APS
What the sources say
- Could not verifycites [65] de Jesús, 2019, Factors associated with first thrombosis in patients presenting with obstetric antiphospholipid syndrome (APS) in the APS Alliance for clinical trials and international networking clinical database and Repository: a retrospective study, BJOG sourceExperimental — accuracy not yet measured
The Results state that women whose thrombosis preceded obstetric APS were excluded from the analysis. The Discussion (Main Findings) instead examines first thrombosis after pregnancy morbidity; our copy does not assess whether a history of thrombotic APS increases the risk of later thrombotic or obstetric events. (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.
- Could not verify
- It may state two separate claims as one. 15
- Probably not a substantial claim. 8
- The quote only partly states this claim. 2
Some cited sources support this claim and some don’t — read each source’s verdict below.
In the paper
“Use of IVIG was not associated with a higher proportion of live births compared with conventional treatment in three small observational studies58–60 that directly addressed this question, although confounding by indication may have occurred.”
§ EULAR recommendations for the management of antiphospholipid syndrome in adults > RECOMMENDATIONS > Obstetric APS
What the sources say
- Not checked — no full text of the sourcecites [58] Diejomaoh, 2002, A favorable outcome of pregnancies in women with primary and secondary recurrent pregnancy loss associated with antiphospholipid syndrome, Arch Gynecol Obstet source
- Supportedcites [59] Jeremic, 2005, Comparison of two therapeutic protocols in patients with antiphospholipid Antibodies and recurrent miscarriages, Vojnosanit Pregl source
The Methods describe a 40-patient comparison of aspirin and heparin with or without IVIG. The Results report gestational success of 18/20 versus 17/20, with no statistically significant difference in pregnancy outcome (p > 0.05). This supports the cited study’s contribution to the claim; the possible confounding is a caution, not a finding the paper establishes. (LLM, conf=0.87)
- Disputedcites [60] Heilmann, 2008, Pregnancy outcome in women with antiphospholipid antibodies: report on a retrospective study, Semin Thromb Hemost sourceExperimental — accuracy not yet measured
The Abstract reports a higher observed proportion of live births with added IVIG than with standard therapy (83.7% versus 74.3%), contrary to the claim as worded. The Patients section supports the concern about confounding by indication: IVIG was given to women whose standard treatment had failed. The paper does not establish whether the live-birth difference was statistically significant. (LLM, conf=0.78)
Checked by a reasoning model — may be wrong.
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
“Patients with APS with arterial thrombosis have a higher risk of recurrence compared with those with venous thrombosis, and a tendency for recurrences in the same vascular (arterial) bed.34”
§ EULAR recommendations for the management of antiphospholipid syndrome in adults > RECOMMENDATIONS > Secondary thromboprophylaxis in APS
What the sources say
- Partly supportedcites [34] Tektonidou, 2000, Prognostic factors and clustering of serious clinical outcomes in antiphospholipid syndrome, QJM sourceExperimental — accuracy not yet measured
The ‘Clustering of similar clinical events’ section reports a tendency for subsequent thromboses to occur in the same vascular bed as the presenting thrombosis. It does not establish that patients presenting with arterial thrombosis have a higher overall recurrence risk than those presenting with venous thrombosis; its odds ratios measure same-type clustering against other presentations, not arterial-versus-venous recurrence risk. Page numbers were not supplied in our copy. (LLM, conf=0.88)
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
Every source the paper cites for this claim was checked and supports it.
In the paper
“We followed the updated European League Against Rheumatism (EULAR) standardised operating procedure5 and used the Appraisal of Guidelines for Research & Evaluation II tool.6”
§ EULAR recommendations for the management of antiphospholipid syndrome in adults > METHODS
What the sources say
- Supportedcites [5] van der Heijde, 2015, 2014 update of the EULAR standardised operating procedures for EULAR-endorsed recommendations, Ann Rheum Dis source
Citation 5 identifies the updated EULAR standardised operating procedure, which is the cited paper itself. The paper’s “Evaluation of the recommendations” section also describes AGREE II, although the citing sentence assigns that tool its own citation (6). (LLM, conf=0.93)
- Supportedcites [6] Brouwers, 2010, Agree II: advancing Guideline Development, reporting and evaluation in health care, CMAJ source
Citation 6 is attached to the AGREE II tool, not to the EULAR procedure. The Abstract identifies AGREE II as the Appraisal of Guidelines, Research and Evaluation instrument, and “Using AGREE II” describes its use for guideline assessment. Page numbers are not provided in our copy. (LLM, conf=0.94)
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. It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In one trial that provided data specifically on patients with arterial thrombosis, there was no difference in recurrences between those treated to a target INR of 2–3 or INR of 3–4 but without statistical significance (HR 3.1 (0.3–30.0)), although the sample was small and the achievement of a target INR of 3–4 was low.21”
§ EULAR recommendations for the management of antiphospholipid syndrome in adults > RECOMMENDATIONS > Secondary thromboprophylaxis in APS
What the sources say
- Supportedcites [21] Crowther, 2003, A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome, N Engl J Med source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Data from one placebo-controlled RCT of LDA in six women with SLE42 and data from three low-quality studies (two RCTs, one retrospective cohort)43–45 of women without SLE found no difference in the prevalence of live births with use of LDA.”
§ EULAR recommendations for the management of antiphospholipid syndrome in adults > RECOMMENDATIONS > Obstetric APS
What the sources say
- Not checked — no full text of the sourcecites [42] Kaaja, 1993, Production of prostacyclin and thromboxane in lupus pregnancies: effect of Small dose of aspirin, Obstet Gynecol source
- Not checked — no full text of the sourcecites [43] Cowchock, 1997, Do low-risk pregnant women with antiphospholipid antibodies need to be treated? organizing group of the antiphospholipid antibody treatment trial, Am J Obstet Gynecol source
- Not checked — no full text of the sourcecites [44] Kahwa, 2006, Anticardiolipin antibodies in Jamaican primiparae, J Obstet Gynaecol source
- Partly supportedcites [45] Del Ross, 2013, Treatment of 139 pregnancies in antiphospholipid-positive women not fulfilling criteria for antiphospholipid syndrome: a retrospective study, J Rheumatol sourceExperimental — accuracy not yet measured
The Results report no statistically significant difference in pregnancy loss between the LDA and non-LDA groups, supporting the live-birth finding for this retrospective study. But the Results also identify three participants with SLE, so the study was not exclusively of women without SLE; the Discussion says its results cannot be extended to SLE. The RCTs in the citing sentence are attributed to other references, not this paper. (LLM, conf=0.86)
plainn = 6- 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.
Every source the paper cites for this claim was checked and supports it.
In the paper
“An early study in older patients with strokes reported no difference in event recurrences between LDA and warfarin, but aPL was tested only once and was mainly of low titre in this study.33”
§ EULAR recommendations for the management of antiphospholipid syndrome in adults > RECOMMENDATIONS > Secondary thromboprophylaxis in APS
What the sources say
- Supportedcites [33] Levine, 2004, Antiphospholipid Antibodies and subsequent thrombo-occlusive events in patients with ischemic stroke, JAMA source
The COMMENT section reports that warfarin was not associated with fewer subsequent thrombo-occlusive events than aspirin. It also states that aPL positivity was determined from one measurement and that most anticardiolipin immunoreactivity was low-positive. The study used aspirin 325 mg/day; the RESULTS section gives ages averaging about 62–63 years in the aspirin group. (LLM, conf=0.90)
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.
- Supported
In the paper
“Treatment with LDA for patients with SLE and high-risk aPL profile is supported by a subanalysis of eight studies, mostly observational, in a meta-analysis.14 In this analysis, risk of first thrombosis was reduced by almost half among patients treated with LDA versus patients not treated, without major bleeding events.”
§ EULAR recommendations for the management of antiphospholipid syndrome in adults > RECOMMENDATIONS > Primary thromboprophylaxis in aPL-positive subjects
What the sources say
- Not checked — no full text of the sourcecites [14] Arnaud, 2014, Efficacy of aspirin for the primary prevention of thrombosis in patients with antiphospholipid antibodies: an international and collaborative meta-analysis, Autoimmun Rev 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
“An earlier SLR including mainly observational studies reported that recurrent events occurred more often in patients with APS treated with VKA with a target INR of 2–3 compared with an INR of 3–4, but outcomes among patients with first arterial thrombosis were not analysed specifically.35”
§ EULAR recommendations for the management of antiphospholipid syndrome in adults > RECOMMENDATIONS > Secondary thromboprophylaxis in APS
What the sources say
- Not checked — no full text of the sourcecites [35] Ruiz-Irastorza, 2007, A systematic review of secondary thromboprophylaxis in patients with antiphospholipid antibodies, Arthritis Rheum 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“However, evidence is limited by the frequent failure to achieve the target INR in the high-intensity groups in the RCTs.”
§ EULAR recommendations for the management of antiphospholipid syndrome in adults > RECOMMENDATIONS > Secondary thromboprophylaxis in APS
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.
The quote only partly states this claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Data on bleeding were not reported for patients with venous thrombosis specifically.”
§ EULAR recommendations for the management of antiphospholipid syndrome in adults > RECOMMENDATIONS > Secondary thromboprophylaxis in APS
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.
- Rests on an assumption: A higher level of anticoagulation is expected to carry a higher risk of bleeding.
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 presence of aPL in asymptomatic individuals or patients with SLE does not confirm the diagnosis of APS but can be associated with increased risk of thrombosis or pregnancy morbidity, depending on aPL characteristics and coexistence of other risk factors.3 4”
§ EULAR recommendations for the management of antiphospholipid syndrome in adults > INTRODUCTION
What the sources say
- Not checked — no full text of the sourcecites [3] Ruiz-Irastorza, 2011, Evidence-based recommendations for the prevention and long-term management of thrombosis in antiphospholipid antibody-positive patients: report of a task Force at the 13th International Congress on antiphospholipid antibodies, Lupus source
- Not checked — no full text of the sourcecites [4] Garcia, 2018, Diagnosis and management of the antiphospholipid syndrome, N Engl J Med 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“However, these studies included a mixture of patients with either venous or arterial thrombosis, and a minority had arterial events.”
§ EULAR recommendations for the management of antiphospholipid syndrome in adults > RECOMMENDATIONS > Secondary thromboprophylaxis in APS
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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All titles and abstracts of retrieved articles were first reviewed independently by the two literature reviewers. The full-text articles were then reviewed independently by three persons: one literature reviewer, convenor and methodologist.”
§ EULAR recommendations for the management of antiphospholipid syndrome in adults > METHODS
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. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“This review did not compare the target INR 2–3 and INR 3–4 arms within the same study, but disaggregated the arms.”
§ EULAR recommendations for the management of antiphospholipid syndrome in adults > RECOMMENDATIONS > Secondary thromboprophylaxis in APS
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.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Each included article was graded for its methodological quality and assigned to the relevant PICO question by the convenor and methodologist.”
§ EULAR recommendations for the management of antiphospholipid syndrome in adults > METHODS
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.
Probably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Because studies combined several types of pregnancy losses without specifying on the proportion of ‘non-criteria’ APS and due to very limited evidence, this recommendation is mainly based on expert opinion.”
§ EULAR recommendations for the management of antiphospholipid syndrome in adults > RECOMMENDATIONS > Obstetric APS
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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“was sent by the convenor to all task force members, who voted anonymously on the level of agreement (LoA). A rating scale of 0–10 (0: do not agree; 10: fully agree) was used for each recommendation.”
§ EULAR recommendations for the management of antiphospholipid syndrome in adults > METHODS
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.
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
“Data from two studies (one RCT, one retrospective cohort)48 55 showed that the likelihood of live births did not differ between women treated with LDA plus heparin and those treated with LDA alone.”
§ EULAR recommendations for the management of antiphospholipid syndrome in adults > RECOMMENDATIONS > Obstetric APS
What the sources say
- Not checked — no full text of the sourcecites [48] Muñoz-Rodriguez, 1999, Clinical study and follow-up of 100 patients with the antiphospholipid syndrome, Semin Arthritis Rheum source
- Not checked — no full text of the sourcecites [55] van Hoorn, 2016, Low-molecular-weight heparin and aspirin in the prevention of recurrent early-onset pre-eclampsia in women with antiphospholipid antibodies: the FRUIT-RCT, Eur J Obstet Gynecol Reprod Biol 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.
The quote only partly states this claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The data abstraction was performed by the two literature reviewers according to a written protocol and supervised by the methodologist. Data abstraction was then independently double-checked by the convenor and methodologist.”
§ EULAR recommendations for the management of antiphospholipid syndrome in adults > METHODS
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. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The task force included members from several professional groups covering different perspectives and also involved two patients who participated actively in both meetings.”
§ EULAR recommendations for the management of antiphospholipid syndrome in adults > DISCUSSION
plainn = 2- 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. It may state two separate claims as one.
The paper relies on this without support.
A higher level of anticoagulation is expected to carry a higher risk of bleeding.
“However, although not based on data from these studies, higher level of anticoagulation would be anticipated to also have a higher risk of bleeding.”
The paper relies on this without support.
For antiphospholipid syndrome patients with provoked first venous thrombosis, the anticoagulation duration recommended for patients without antiphospholipid syndrome is appropriate.
“The panel recommended a duration of anticoagulation according to international guidelines for patients without APS30 because the benefit of long-term anticoagulation in this population is unclear.”
The paper relies on this without support.
Low-dose aspirin has a low risk of adverse events in asymptomatic antiphospholipid antibody carriers.
“given the likelihood of benefit and low risk of adverse events of this intervention.”
The paper relies on this without support.
High-risk aPL profile is associated with risk of obstetric and thrombotic complications during pregnancy.
“The panel agreed that use of LDA should be considered in pregnant women with high-risk aPL profile due to the risk of obstetric and thrombotic complications during pregnancy associated with high-risk aPL profile.”
The paper relies on this without support.
Women with a history of clinical non-criteria obstetric APS have a potential higher risk for obstetric and/or thrombotic complications during pregnancy.
“Because of a potential higher risk for obstetric and/or thrombotic complications during pregnancy in women with a history of clinical ‘non-criteria’ obstetric APS, the panel agreed that treatment with LDA alone or in combination with heparin might be considered, based on an individual’s risk profile (aPL profile, concomitant SLE, prior live births, and additional risk factors for pregnancy loss or”
The paper relies on this without support.
There is an increased risk of thrombosis at puerperium.
“The panel suggested that in women receiving prophylactic dose heparin during pregnancy, the same dosage of heparin should be continued for 6 weeks after delivery due to an increased risk of thrombosis at puerperium.”
The paper relies on this without support.
The most common practice when LDA plus prophylactic heparin fails is to increase heparin dose to therapeutic dose.
“The most common practice if the combination of LDA and prophylactic dose heparin fails is to increase the dose of heparin to therapeutic dose, although no supporting evidence exists.”
The paper relies on this without support.
Cost and availability of suggested treatments are not a barrier to implementation, except IVIG and plasmapheresis.
“The cost and availability of suggested treatments are not a barrier to implementation of these recommendations, with the exception of IVIG and plasmapheresis.”
The paper relies on this without support.
CAPS occurs in less than 1% of patients.
“However, both treatments were recommended as first-line treatment only in CAPS which occurs in less than 1% of patients, while B cell depletion and complement inhibitors may be considered in refractory cases of CAPS.”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ EULAR recommendations for the management of antiphospholipid syndrome in adults > RECOMMENDATIONS > Obstetric APS
“Pooled data from one RCT including only patients with a history of first trimester losses46 and eight supporting observational studies47–54”
§ EULAR recommendations for the management of antiphospholipid syndrome in adults > References
“54. Laskin CA, Spitzer KA, Clark CA, Low molecular weight heparin and aspirin for recurrent pregnancy loss: results from the randomized, controlled HepASA trial.”
Citations
Cites
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Avascular necrosis in antiphospholipid syndrome: pathophysiology, risk factors, and management
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“However, LDA + W was associated with a higher risk of bleeding [35].”
Alvarez, E. J. D., Balladares, M. A. M., & Rodriguez, M. S. (2025) · Cureus · doi:10.7759/cureus.97497
“This approach aligns with current EULAR recommendations for APS management [11].”
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“Vitamin K Antagonists (VKAs) are prescribed for anticoagulant treatment in selected patients with atrial (cid:976)ibrillation, mechanical heart valves and antiphospholipid syndrome [5,6].”
Cruz, P. P., Digiacomo, D., Varghese, M., & Spencer, C. T. (2025) · Cureus · doi:10.7759/cureus.98743
“Warfarin (INR 2-3) is preferred, as direct oral anticoagulants (DOACs) are associated with higher recurrence rates, particularly in triple-positive APS [16,17].”
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“Altogether, anticoagulants and ASA can markedly reduce pregnancy-related complications in women with OAPS, but this therapy is less effective in patients with the highest risk, mainly triple positive cases [41].”
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“7 In contrast, patients with oAPS require antiplatelet treatment and heparin at prophylactic dosage only during pregnancy and post-partum It has been suggested however that oAPS patients without previous thromboses may bene fi t from long-term antith-rombotic treatment.”
Self-citationJiménez-Soto, R., Espinosa-León, M., Said-Diego, J. E., et al. (2026) · Lupus · doi:10.1177/09612033261422651
Jiao, S., Yan, S., Zhang, Y., Teng, Y., Liu, G., Li, Z., Zhou, Z., & Ji, B. (2026) · Seminars in Thrombosis and Hemostasis · doi:10.1055/a-2799-0619
Neurologic Complications of Hematologic Disorders
Patrick, L. M., & Terrelonge, M. (2026) · CONTINUUM Lifelong Learning in Neurology · doi:10.1212/cont.0000000000001660
Adams, C. G., Rudnicki, J., Petersen, B. F., et al. (2026) · Frontiers in Lupus · doi:10.3389/flupu.2026.1747204
Venous Thromboembolism in Pregnancy
Kozak, M., & Cosmi, B. (2026) · Springer eBooks · doi:10.1007/978-3-031-82232-2_70
Ischemic duodenal injury due to systemic lupus erythematosus: A case report
Kim, Y. K., Jung, H. I., Kim, H., et al. (2026) · World Journal of Gastroenterology · doi:10.3748/wjg.v32.i8.115654
Vascular events in autoantibody-defined clusters of SLE: a 12-year prospective cohort study
Ferrigno, S., Arkema, E. V., Gunnarsson, I., et al. (2026) · Lara D. Veeken · doi:10.1093/rheumatology/keag065
Self-citationIndications for PEX: Rheumatology
Filipov, J. J. (2026) · In clinical practice · doi:10.1007/978-3-032-17275-4_5
Miscarriages: Epidemiology, diagnosis, and management
MEKINIAN, A., & Abisror, N. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-13825-6.00357-5
Geertsema-Hoeve, B. C., Stam‐Slob, M. C., Bijl, M., Eikenboom, D. J., Frijns, C. J. M., Goekoop, R. J., van den Hoogen, L. L., Huisman, A., Jansen, A., Kooiman, J., et al. (2026) · The American Journal of Medicine · doi:10.1016/j.amjmed.2026.02.012
Self-citationAntiphospholipid syndrome and pregnancy—a hematologic perspective
Doyle, A. J., Cox, C., & Breen, K. A. (2026) · Research and Practice in Thrombosis and Haemostasis · doi:10.1016/j.rpth.2026.103396
“These include steroids, hydroxychloroquine, statins, IVIg, and newer options, such as TNF-1 inhibitors, which have shown some potential benefit in previous studies [37,73,88–92].”
InfluentialCai, Y., Song, M., Lv, Q., Liu, H., Wang, Y. L., Qi, W., Jing, D., Xia, Y., & Wang, X. (2026) · Antioxidants and Redox Signaling · doi:10.1177/15230864261424203
“Ongoing debates about HCQ timing (pre-vs. post-conception) underscore the need for large-scale randomized trials and rigorous mechanistic studies to optimize clinical protocols (Ambati et al., 2023; Tektonidou et al., 2019).”
Multifactorial thrombotic risk in Evans syndrome: a case report and review of the literature
Erölmez, H. N., Eker, S., Siddiqui, F., et al. (2026) · Thrombosis Journal · doi:10.1186/s12959-026-00846-9
“The European Alliance of Associations for Rheumatology (EULAR) guidelines recommend long-term treatment with vitamin K antagonists targeting an international normalized ratio (INR) of 2–3 for patients with APS and first unprovoked VTE [47].”
George, S. S., Adam, B., & Senaratne, J. M. (2026) · BMJ Case Reports · doi:10.1136/bcr-2025-269302
“24 Low- molecular-weight heparin or unfractionated heparin may be used in specific situations, such as during pregnancy, those with recurrent arterial or venous thrombosis despite adequate oral anticoagulation or in the perioperative setting.”
Treatment of infertility in a patient with recurrent implantation failure
Ozhogina, E. V., Fedorova, E. V., Minashkina, E. V., et al. (2026) · Russian Journal of Human Reproduction · doi:10.17116/repro20263201164
de Hoek, L. J. O., Camilleri, E., Eikenboom, J. C. J., et al. (2026) · Journal of Thrombosis and Haemostasis · doi:10.1016/j.jtha.2026.02.021
Rojas-Romero, P., González-Quijano, M., Abril-Molina, A., et al. (2026) · Cardiovascular Revascularization Medicine Interesting Cases · doi:10.1016/j.crmic.2026.100150
Persistent thrombotic events in a seronegative patient with antiphospholipid syndrome
Saeed, S. M., Fine, R. L., Baker, H., et al. (2026) · JAAD Case Reports · doi:10.1016/j.jdcr.2026.02.048
“6 Our case further confirms that DOACs are insufficient for patients with multiple thrombotic risk factors such as severe atherosclerotic disease, under-scoring the necessity for more robust anticoagulation in high-risk patients.”
Sharma, P., Sharma, Y., Kumar, A., et al. (2026) · IHJ Cardiovascular Reports · doi:10.1016/j.ihjcvr.2026.03.001
Ye, S., Xu, X., Zhang, Y., et al. (2026) · Clinical Rheumatology · doi:10.1007/s10067-026-08025-x
Paquette, M. L., MIRANDA, S., Xu, Y., Skeith, L., Miron-Celis, M., Booth, R. A., Buyukdere, H., Siegal, D. M., Gal, G. L., Carrier, M., et al. (2026) · Blood Advances · doi:10.1182/bloodadvances.2026019610 · Cited by 1
“11,18 However, these recommendations are based mainly on expert opinion and extrapolation from non-APS populations.”
Mesenteric steal syndrome as an unusual manifestation of catastrophic antiphospholipid syndrome
Torres‐Machorro, A., Madrid-Fraga, I., Flores-Espino, O., et al. (2026) · Journal of Vascular Surgery Cases and Innovative Techniques · doi:10.1016/j.jvscit.2026.102236
Zitouni, S. (2026) · Kidney International Case Reports · doi:10.1016/j.kintcr.2026.100015
Yan, J., Chen, M., Kang, X., et al. (2026) · Clinica Chimica Acta · doi:10.1016/j.cca.2026.120988
de Chambrun, M. P. (2022) · theses.fr (ABES) · doi:10.70675/1e049e27ze37dz429dzae52z8127f9f6117d
Diallo, B. M., Fall, K. A. M., Sow, A., et al. (2026) · American Journal of Internal Medicine · doi:10.11648/j.ajim.20261401.12
Hassan, A., Elkasaby, M. H., Elshahat, M. S., et al. (2026) · ASIDE Case Reports · doi:10.71079/aside.cr.041026465
“In this case, the patient exhibited both significant anatomical obstruction on CTPA and functional impairment of the RV, fulfilling the criteria for intermediate-high-risk PE [12].”
InfluentialCase report of a fatal probable catastrophic antiphospholipid syndrome
Hou, S.-J., Xie, M.-X., Feng, X., et al. (2026) · Frontiers in Medicine · doi:10.3389/fmed.2026.1752865
“Long-term glucocorticoids are not standard therapy for APS (20); in CAPS, they are used acutely as part of combined treatment.”
Management von Notfällen in der Rheumatologie
Ritter, P., & Weiner, S. M. (2026) · Medizinische Klinik - Intensivmedizin und Notfallmedizin · doi:10.1007/s00063-026-01439-0
“Infekte, Trauma oderStress können auslösende Fakto-rendarstellen[27].”
Recurrent pregnancy loss and thyroid autoimmunity: A review of mechanisms and clinical management
Liang, Y., Wang, Z., Mai, Z., Chen, X., Lin, H., Cao, C., 祝丽琼, Ren, M., & Chen, H. (2026) · Journal of Reproductive Immunology · doi:10.1016/j.jri.2026.104896
ARAUJO, A. D. Q., Júnior, E. A., Rufino, I. S., et al. (2026) · Cardiology in the Young · doi:10.1017/s1047951126112189
Koike, T., Yaginuma, K., & Isoda, K. (2026) · Journal of Cardiology Cases · doi:10.1016/j.jccase.2026.04.004
“In the chronic phase, European Alliance of Associations for Rheumatology recommendations support vitamin K antagonist – based anticoagulation (with or without low-dose aspirin) forarterial events,w ithindividualizedbalancingofbleedingandthrom-bosis risks [9].”
Androulakis, N. E. M., Striligka, O., Nioti, E., Dilintas, A., Darivianaki, A., Papadopoulou, A., Nistikaki, F., Iatridi, T., Kampa, M., & Kalpadakis, C. H. (2026) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2025-1709
Rastogi, N., & Rastogi, S. (2026) · Sri Ramachandra Journal of Health Sciences · doi:10.25259/srjhs_27_2025
Sugraliyev, A., & Cirillo, P. L. (2026) · Angiology · doi:10.1177/00033197261443810
Sun, B., Lu, Y., Liu, W., & Wang, C. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.04.28.721277
Thrombosis and Bleeding in Pregnancy
Middeldorp, S. (2026) · Springer eBooks · doi:10.1007/978-3-032-13858-3_63
Antiphospholipid Antibodies and Syndrome
Doyle, A. J., Breen, K. A., & Hunt, B. J. (2026) · Springer eBooks · doi:10.1007/978-3-032-13858-3_32
Systemic lupus erythematosus and acute cerebral circulatory disorders
Пизова, Н. В., & Pizov, A. V. (2026) · Rheumatology Science and Practice · doi:10.47360/1995-4484-2026-141-148
Bor, B., Schreiber, K. I., Deleuran, B. W., & Bor, M. V. (2026) · Seminars in Thrombosis and Hemostasis · doi:10.1055/a-2866-2950
Dramatically changing intracranial arteriopathy due to antiphospholipid syndrome: A case report
Nakajima, H., Sato, Y., Yago, T., et al. (2026) · Radiology Case Reports · doi:10.1016/j.radcr.2026.03.071
“…immunosuppressive therapies, including corticosteroids, rituximab, and plasma exchange, may be considered in APS with systemic inflammation or catastrophic presentations, the vascular manifestations in our patient were purely thrombotic without evidence of systemic autoimmune activity [ 22 ].”
InfluentialJansen, V. L. B. I., Wiegers, H. M. G., Salet, D. M., van Mens, T. E., & Middeldorp, S. (2026) · Research and Practice in Thrombosis and Haemostasis · doi:10.1016/j.rpth.2026.106634 · Cited by 1
Metabolic-immune axis in pregnancy: Implications for women with autoimmune diseases
Ding, X., Liu, L., & Zhou, Y. (2026) · Journal of Reproductive Immunology · doi:10.1016/j.jri.2026.104914
Pérez, S. F., Sosa, F. A., & Chong, R. W. (2026) · Cureus · doi:10.7759/cureus.109221
“Despite the increasing use of direct oral anticoagulants, warfarin remains an important and appropriate therapeutic option for select patient populations, including those with cost limitations or specific indications such as mechanical heart valves or antiphospholipid syndrome [3,4].”
Zhang, Z., Li, F., Li, Y., Xie, Z., Du, J., Mao, N., Li, S., Liu, Y., Ge, Y., Wang, J., et al. (2026) · Lupus Science & Medicine · doi:10.1136/lupus-2026-001981
Liu, D., Chen, Y., & Liu, F. (2026) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-026-04083-x
“…of HCQ on the critical pregnancy outcomes of SLE is not only helpful to optimize clinical decision-making, but also provides evidence-based guidance for individualized treat-ment in high-risk individuals, such as those with antiphospholipid syndrome [18] or pre-pregnancy hypertension [ 3].”
Yoshida, Y., Iriyama, T., Ariyoshi, Y., et al. (2026) · BMC Pregnancy and Childbirth · doi:10.1186/s12884-026-09306-8
“Second, the predominant dosage in our cohort was 10,000 IU/day, a standard prophylactic dose recommended for pregnant women with APS or a history of venous thromboembolism [17, 26, 27].”
InfluentialSystemic Lupus Erythematosus: What Every Clinician Needs to Know
Duarte‐García, A., Ardekani, A., Jackson, S. W., & Jorge, A. (2026) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2026.05.009
Tanglay, O., Cordato, D., Ng, S., et al. (2026) · BMJ Case Reports · doi:10.1136/bcr-2025-271302
“27 34 Some guidelines suggest DOACs may be considered in non- triple-positive patients without a history of arterial thrombosis based on shared decision-making.”
Avčin, T., & Monagle, P. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-11980-4.00029-5
Novel mechanisms linking platelet activation to antiphospholipid syndrome
Camera, M., Tremoli, E., Lonati, P. A., & Meroni, P. L. (2026) · Current Opinion in Immunology · doi:10.1016/j.coi.2026.102791
Self-citationGaspar, P., Ribeiro, F., Fonseca, V. R., Romão, V. C., Fonseca, J. P. A., & Graça, L. (2026) · Autoimmunity Reviews · doi:10.1016/j.autrev.2026.104112
Abdelwahab, M. A., Kamal, K., El-Ramly, M., et al. (2026) · Cor et Vasa · doi:10.33678/cor.2025.094
Zeng, H., Ding, C., Dong, W., et al. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1783244
“A necessary factor for the onset of these clinical events is the persistent detection of antiphospholipid antibodies (APL) (7).”
Bravo, S. G., Martínez-Taboada, V. M., Barrio-Longarela, S. D., Merino, A., Comins‐Boo, A., López‐Hoyos, M., & Hernández, J. L. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1818605
Fang, Y., Kang, X., He, A., et al. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1847320
Khan, A., Tahir, O., Batool, A., et al. (2026) · Journal of Cardiothoracic Surgery · doi:10.1186/s13019-026-04410-4
“According to the literature [20], the presence of involvement of at least three different organ systems at the same time or within a week period with evidence of histopathological features of microangiopathy is needed to define CAPS.”
Jiang, M., Zhang, F., Ren, M., Li, Z., Xie, Z., & Sun, J. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1841513
“Their underlying conditions could further amplify the safety concerns associated with JAK inhibitors (116).”
Xourgia, E., & Tektonidou, M. G. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-33957-8.00059-7
Self-citationTam, V., Schaff, H. V., Greason, K. L., Daly, R. C., Lee, A. M., Todd, A. L., Holst, K. A., & Crestanello, J. A. (2026) · JTCVS Open · doi:10.1016/j.xjon.2026.101927
The nervous system in systemic lupus erythematosus
Bridson, J. D., & Hunt, D. P. J. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-33957-8.00050-0
Sole, F. D., Bucci, T., Menichelli, D., Antonucci, E., Poli, D., Pengo, V., Ames, P. R. J., Barcellona, D., Sivera, P., Pizzini, A. M., et al. (2026) · Internal and Emergency Medicine · doi:10.1007/s11739-026-04416-9
Self-citationSystemic Lupus Erythematosus and Antiphospholipid Syndrome
Gensous, N., Morel, N., Skopinski, S., et al. (2026) · Contemporary rheumatology · doi:10.1007/978-3-032-22966-3_7
Longitudinal observation of thrombotic events in patients with obstetric antiphospholipid syndrome
Inoue, Y., Nakamura, H., Fujieda, Y., Yasuda, M., Karino, K., Hisada, R., Kono, M., Amengual, O., & Atsumi, T. (2026) · Lupus · doi:10.1177/09612033261464227
Survival After Catastrophic Antiphospholipid Syndrome With Diffuse Alveolar Hemorrhage
Quizhpe, E., Uguña, F., Velastegui, J., et al. (2026) · Journal of Investigative Medicine High Impact Case Reports · doi:10.1177/23247096261455115
“8 “Triple therapy” has been associated with improved survival compared to incomplete regimens.”
Pazoki, M., Faranoush, M., Nojoomizadeh, L., et al. (2026) · Sonography · doi:10.1002/sono.70069
Maladies systémiques et grossesse
Raimond, É., Orquevaux, P., & Gabriel, R. (2026) · EMC - Obstétrique · doi:10.1016/s0246-0335(26)44889-9
Khudhair, H. A. A., & Lafta, S. F. (2026) · European Journal of Clinical and Experimental Medicine · doi:10.15584/ejcem.2026.2.1
“31 These findings reinforce the idea that ANA and APL-Abs may have similar immunopathogenesis linked to endothelial injury and subsequent throm-bo-inflammatory events.”
Kawtharany, H., Azzam, M., Khawandi, J., et al. (2026) · Blood Advances · doi:10.1182/bloodadvances.2026020321
Immuno-regulatory effects of hydroxychloroquine in experimental autoimmune thyroiditis
Cheng, C., Fang, W.-F., Yang, Y.-M., et al. (2026) · Immunopharmacology and Immunotoxicology · doi:10.1080/08923973.2026.2692421
“…(iBD), antiphospholipid syndrome (aPs), and sjögren’s disease, among others, and has demonstrated beneficial outcomes in these conditions [12–15]. however, information regarding the use of hcQ in the management of aitD, including both GD and ht, remains limited. the potential role of hcQ in…”
Mikołajczyk, M. M., Bal, W., Mastej-Witek, G., et al. (2026) · European Journal of Clinical and Experimental Medicine · doi:10.15584/ejcem.2026.2.19
Metadata
- Authors
- Tektonidou, M. G., Andreoli, L., Limper, M., Amoura, Z., Cervera, R., Costedoat-Chalumeau, N., Cuadrado, M. J., Dörner, T., Ferrer-Oliveras, R., Hambly, K., Khamashta, M. A., King, J., Marchiori, F., Meroni, P. L., Mosca, M., Pengo, V., Raio, L., Ruiz-Irastorza, G., Shoenfeld, Y., Stojanovich, L., Svenungsson, E., Wahl, D., Tincani, A., & Ward, M. M.
- Affiliations
- National and Kapodistrian University of Athens (GR)
- University Medical Center Utrecht (NL)
- Sorbonne Université (FR)
- Hospital Clínic de Barcelona (ES)
- Inserm (FR)
- Charité – Universitätsmedizin Berlin (DE)
- University of Kent (GB)
- Dubai Hospital (AE)
- European League Against Rheumatism (CH)
- IRCCS Istituto Auxologico Italiano (IT)
- University of Pisa (IT)
- University of Padua (IT)
- University Hospital of Bern (CH)
- Tel Aviv University (IL)
- University of Belgrade (RS)
- Karolinska University Hospital (SE)
- National Institutes of Health (US)
- ORCID
- Tektonidou, Maria G
- Andreoli, Laura
- Amoura, Zahir
- Cervera, Ricard
- Costedoat-Chalumeau, Nathalie
- Dörner, Thomas
- Hambly, Karen
- Khamashta, Munther A
- Marchiori, Francesca
- Meroni, Pier Luigi
- Mosca, Marta
- Pengo, Vittorio
- Raio, Luigi
- Ruiz-Irastorza, Guillermo
- Shoenfeld, Yehuda
- Stojanovich, Ljudmila
- Svenungsson, Elisabet
- Wahl, Denis
- Ward, Michael M
- Venue
- Annals of the Rheumatic Diseases
- Publisher
- Elsevier BV
- Published
- 2019-10
- Volume
- 78
- Issue
- 10
- Pages
- 1296-1304
- ISSN
- 0003-4967 (ISSN-L)
- PMC
- PMC11034817
- OpenAlex
- W2946160313
- Semantic Scholar
- cca4d07183616eebc75996c57f7d029bd63e5bf2
- Cited by
- 1,318
- References
- 72
- Citations by year
- 2026: 200 · 2025: 188 · 2024: 221 · 2023: 191 · 2022: 171 · 2021: 140 · 2020: 163 · 2019: 42
- FWCI
- 87.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Annals of the Rheumatic Diseases (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion, cc-by-nc)
- BORIS (University Library Bern) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
- Kent Academic Repository (University of Kent) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- European League Against Rheumatism
- Topics
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
- Keywords
- antiphospholipid syndrome, antiphospholipid antibodies, thrombosis, obstetric antiphospholipid syndrome, low-dose aspirin, vitamin K antagonists, rivaroxaban, low molecular weight heparin, recurrent thrombosis, pregnancy, systemic lupus erythematosus, hydroxychloroquine, prednisolone, thromboprophylaxis, cardiovascular risk
- MeSH terms
- Adult, Anticoagulants, Female, Humans, Male, Pregnancy, Pregnancy Complications, Rheumatology, Risk Factors, Antiphospholipid Syndrome, Antibodies, Antiphospholipid, Practice Guidelines as Topic, Venous Thrombosis
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