The DOI matches its Crossref record; 86 of the 88 references it cites were found in a registry or an index; 45 of the 85 sources its claims cite were checked for support.
Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis
Open accessAbstract
This guidance focuses on methodological aspects of lupus anticoagulant (LA) testing, as well as interpretation of results for clinicians. The main changes in how to test for LA compared with the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee 2009 guidelines, in the preanalytical phase are more detailed recommendations on how to handle testing in anticoagulated patients, and the timing of testing. Also, routine coagulation tests are advised to obtain more information on the coagulation background of the patient, and when necessary, anti-Xa activity measurement for heparins or specific assays for direct oral anticoagulants should be performed. The three-step procedure with two test systems (diluted Russell's viper venom time and activated partial thromboplastin time [aPTT]) is essentially not changed. Silica remains the preferable activator in the aPTT assays, but ellagic acid is not excluded. We advise simultaneous performance of the mixing and confirmatory step, in each sample with a prolonged screening test. The confirmatory step can also be performed on a mixture of patient plasma and normal pooled plasma. Cutoff values should be established in-house on at least 120 normals, with transference of the manufacturer's cutoffs as an alternative. Reporting of results has not been changed, although more attention is focused on what clinicians should know. Patient selection for LA testing has been expanded.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
This ISTH-SSC guidance updates recommendations for lupus anticoagulant (LA) testing and interpretation, focusing on preanalytical factors, assay choice, cutoff values, result calculation, and timing. It retains the three-step screen-mix-confirm procedure with dRVVT and aPTT while adding detailed advice for anticoagulated patients, pregnancy, and persistent positivity.
Key findings
- The three-step procedure with two test systems (dRVVT and aPTT) is essentially unchanged; silica remains the preferable aPTT activator, but ellagic acid is not excluded. The guidance advises simultaneous mixing and confirmatory steps in each sample with a prolonged screening test.
- Cutoff values should be established in-house on at least 120 normals, with transference of manufacturer’s cutoffs as an alternative; the 99th centile is maintained. In the ISTH-SSC survey, 79% calculated in-house cutoffs but only 12% used >120 normals, and 50% applied the 99th centile.
- Anticoagulant interference remains a major issue: DOACs give false-positive APTT and dRVVT results even at low concentrations; if DOACs are briefly interrupted, testing can be done at least 48 hours after the last dose, longer in renal impairment, with DOAC levels checked. For LMWH, samples should be taken at least 12 hours after the last dose and anti-Xa activity checked.
- Repeat testing after an initial positive LA result is still recommended after at least 12 weeks to confirm persistent positivity; triple-positive patients may have predictable persistence, but the guidance concludes retesting after 12 weeks is still recommended.
Methods
- This is consensus guidance from the ISTH-SSC for lupus anticoagulant/antiphospholipid antibodies, developed after a 2018 ISTH-SSC survey and panel discussion, with invited authors from the 2009 guidelines and other experts.
- It reviews current literature and focuses on methodology, choice of assays, cutoff values, calculation and interpretation of results, and timing of testing in relation to thrombosis and pregnancy; laboratory aspects in anticoagulated patients are addressed in separate ISTH-SSC guidance.
- Recommendations are presented in comparison with the ISTH-SSC 2009 guidelines, with a research agenda for unresolved issues.
Limitations
- The paper states that some points need more evidence before being recommended and provides a research agenda, including optimal timing of initial and subsequent aPL testing, use of lower cutoffs in pregnancy, annual retesting, timing in stroke/TIA, multicenter validation of TSVT/ET, universal cutoff values, and biochemical basis of LA.
- Evident from the text: this is expert consensus guidance rather than a systematic review or primary validation study, and several recommendations rely on survey practice and literature with acknowledged uncertainty or lack of agreement.
- Evident from the text: cutoff values determined elsewhere cannot be transferred irrefutably between laboratories because of variables such as sample collection, tubes, normal population demographics, PNP variation, and reagent lots; interlaboratory variability remains a challenge.
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Claims the paper makes
21 Partly supported · 14 No full text of the sources · 9 Supported · 4 Supported so far · 4 Own interpretation · 3 Sources not found · 2 Not checked yet · 2 Own result · 1 Couldn’t confirm · accuracy not yet measured
Every source the paper cites for this claim was checked and supports it.
In the paper
“Lupus anticoagulant (LA) is one of the three laboratory criteria for the identification of the antiphospholipid syndrome (APS).1,2”
§ Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis Update of the guidelines for lupus anticoagulant detection and interpretation > 1 | INTRODUC TI ON
What the sources say
- Supportedcites [1] source
The paper’s Laboratory criteria list names lupus anticoagulant as criterion 1 of 3, alongside anticardiolipin and anti-β2-glycoprotein-I antibodies. This supports the claim that it is one of three laboratory criteria for APS. (LLM, conf=0.94)
- Supportedcites [2] source
The Introduction identifies lupus anticoagulant, anticardiolipin antibodies, and beta2-glycoprotein I antibodies as the three laboratory criteria for APS. The section on anticardiolipin and beta2-glycoprotein I antibodies also recommends all three tests for APS diagnosis. (LLM, conf=0.95)
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 cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The last update of the guidelines for LA detection by the International Society on Thrombosis and Haemostasis Scientific and Standardization Subcommittee (ISTH-SSC) in 2009 12 has proven useful in achieving greater uniformity in performance and interpretation of LA testing.”
§ Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis Update of the guidelines for lupus anticoagulant detection and interpretation > 1 | INTRODUC TI ON
What the sources say
- Partly supportedcites [12] sourceExperimental — accuracy not yet measured
The Abstract identifies this as the 2009 update and specifies procedures for LA testing and interpretation. Its statement that guidelines had been useful over the preceding 13 years refers to the earlier criteria, not demonstrated effects of the 2009 update. The paper does not establish that the update had already increased uniformity. (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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“LA is the best-established risk factor for APS-related clinical manifestations.[5][6][7][8][9]”
§ Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis Update of the guidelines for lupus anticoagulant detection and interpretation > 1 | INTRODUC TI ON
What the sources say
- Supportedcites [5] source
The Introduction reports that LA had the strongest association with thrombotic complications in a systematic review and was most strongly associated with late recurrent fetal loss in a meta-analysis. The paper’s Results and Discussion also associate LA positivity with high-risk APS in its cohort. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [6] source
- Partly supportedcites [7] sourceExperimental — accuracy not yet measured
The Discussion identifies lupus anticoagulant (LAC) as the primary predictor of adverse pregnancy outcome among patients with antiphospholipid antibodies. The study addresses pregnancy outcomes, not APS-related clinical manifestations generally, so it does not establish LA as the best-established risk factor for the broader claim. Page numbers were not provided in our copy. (LLM, conf=0.86)
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.
- 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
“One of the main confounding factors in LA testing is anticoagulant therapy, prolonging the clotting times in the PL-dependent assays used for LA detection.”
§ Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis Update of the guidelines for lupus anticoagulant detection and interpretation > 3.2 | Interferences
What the sources say
- Supportedcites [3] source
In the ‘LUPU S A NTICOAGULANT’ section (page unavailable), the paper calls sensitivity to anticoagulant therapy a major drawback of LA tests because they are coagulation-based. It identifies dRVVT and aPTT as phospholipid-dependent assays and describes elevated clotting times in LA testing, supporting the citing sentence’s paraphrase. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [32] 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.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“LA results returned to baseline status by 3 months postdelivery in one study.23”
§ Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis Update of the guidelines for lupus anticoagulant detection and interpretation > K E Y W O R D S
What the sources say
- Supportedcites [23] source
The Results section (“Variation in aPL levels through pregnancy”) states that LAC test results returned to baseline levels at three months postpartum. This directly supports the cited sentence’s timing and finding. (LLM, conf=0.94)
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
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
“External quality assessment exercises still show high rates of false-positive or false-negative results.10,11”
§ Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis Update of the guidelines for lupus anticoagulant detection and interpretation > 1 | INTRODUC TI ON
What the sources say
- Supportedcites [10] source
The Results report false-negative rates of 24–28% for three weaker lupus anticoagulant samples in proficiency-testing challenges. The Discussion reports an approximately 11% false-positive rate for a normal sample when borderline results were counted as positive. The rates therefore depend on sample strength and how borderline results are classified. (LLM, conf=0.94)
- Not checked — no full text of the sourcecites [11] 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 cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Hemolysis, icterus, and lipemia mainly affects the APTT, resulting in a falsely normal APTT in hemolyzed samples.[29][30][31]”
§ Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis Update of the guidelines for lupus anticoagulant detection and interpretation > 3.1 | Sample preparation and quality
What the sources say
- Partly supportedcites [29] sourceExperimental — accuracy not yet measured
The Abstract and Conclusion report that some haemolysed samples had falsely normal APTTs, while PT and fibrinogen were not clinically significantly affected by HIL. But the Discussion says icterus and lipaemia did not produce clinically relevant APTT bias with this analyser, so the claim overstates their effect on APTT. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [30] source
- Not matchedcites [31]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
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 99th centile, chosen to avoid false positives, was applied by 50% of survey participants.15”
§ Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis Update of the guidelines for lupus anticoagulant detection and interpretation > 3.7 | Cutoff values
What the sources say
- Partly supportedcites [15] sourceExperimental — accuracy not yet measured
The cut-offs results (Figure 4A; page not provided) report that 50% of respondents said the cut-off for screen, mixing, and confirmatory tests should be above the 99th centile. That supports the percentage, but the question asked what the cut-off should be, not whether participants applied it; the paper also does not give avoiding false positives as their reason for choosing it. (LLM, conf=0.86)
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
“Normalized ratios calculated by dividing the clotting time of the patient by the clotting time of the PNP measured in the same run, as advised in the 2009 guidelines, is applied by the majority of laboratories.15”
§ Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis Update of the guidelines for lupus anticoagulant detection and interpretation > 3.6 | Normalization of results
What the sources say
- Partly supportedcites [15] sourceExperimental — accuracy not yet measured
In the section on normalized-ratio calculations (page not available), 65.7% of survey respondents said the denominator should be pooled normal plasma analyzed in the same run. That supports the majority and same-run aspects, but the passage reports what respondents said should be done, not that most laboratories actually use this calculation. (LLM, conf=0.82)
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
Every source the paper cites for this claim was checked and supports it.
In the paper
“In contrast, enoxaparin caused false-positive aPTT-based LA detection only at supra-therapeutic anti-Xa activity levels.”
§ Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis Update of the guidelines for lupus anticoagulant detection and interpretation > 3.2 | Interferences
What the sources say
- Supportedcites [33] source
The Results and Discussion section states that false-positive APTT-based lupus anticoagulant conclusions occurred with enoxaparin only at supratherapeutic levels, starting at 2.5 anti-Xa IU/mL. Table 1 likewise lists the enoxaparin APTT conclusion threshold as ≥2.5 anti-Xa IU/mL. (LLM, conf=0.95)
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
- Probably not a substantial claim. 6
- It may state two separate claims as one. 16
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Sample collection and processing as described in the ISTH-SSC 2009 guidelines is widely applied.15”
§ Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis Update of the guidelines for lupus anticoagulant detection and interpretation > 3.1 | Sample preparation and quality
What the sources say
- Partly supportedcites [15] sourceExperimental — accuracy not yet measured
The Essentials section reports that 86.8% of respondents agreed samples should be collected and processed in line with the 2009 guidelines. That supports broad acceptance of the procedures, but the survey response does not establish that they are widely applied in practice. (LLM, conf=0.82)
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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“LA detection is based on phospholipid (PL)-dependent coagulation tests, which complicate the methodology and hamper its interpretation because of interference, for instance by anticoagulant therapy and some acute phase response proteins.3,4”
§ Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis Update of the guidelines for lupus anticoagulant detection and interpretation > 1 | INTRODUC TI ON
What the sources say
- Supportedcites [3] source
The LUPUS ANTICOAGULANT section describes LAC detection using coagulation assays whose performance depends on their phospholipid composition. It identifies anticoagulant therapy as a major source of interference and says elevated FVIII or C-reactive protein during the acute phase can cause false-negative or false-positive results. The Conclusion's Table 2 likewise identifies these as pitfalls of PL-dependent LAC testing. (LLM, conf=0.94)
- Partly supportedcites [4] sourceExperimental — accuracy not yet measured
The “Lupus anticoagulant testing” section says LAC detection uses phospholipid-dependent coagulation assays and describes the methodology as complicated. The paper also says anticoagulant therapy can prolong these assays and produce false-positive results. The passages do not establish the claimed interference from acute-phase response proteins. (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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Equally, the British Society for Haematology 13 and the Clinical and Laboratory Standards Institute (CLSI) guidelines 14 have contributed to increased uniformity.”
§ Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis Update of the guidelines for lupus anticoagulant detection and interpretation > 1 | INTRODUC TI ON
What the sources say
- Supportedcites [13] source
The Introduction identifies this as a British haematology guideline, and the Lupus anticoagulant testing section gives common procedures for reporting results and quality control. It therefore supports the citation’s use of this guideline as an example of guidance promoting uniformity. The separate CLSI guideline is attributed to citation 14, not this source. (LLM, conf=0.84)
- Not matchedcites [14]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
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 cited sources support only part of this claim — read each source’s verdict below.
In the paper
“LA positivity may fluctuate over time with or without the presence of systemic lupus erythematosus 22,23 and during pregnancy, either decreasing or increasing.22,24,25”
§ Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis Update of the guidelines for lupus anticoagulant detection and interpretation > K E Y W O R D S
What the sources say
- Partly supportedcites [22] sourceExperimental — accuracy not yet measured
The Introduction (page not provided), under “Limitations to current classification criteria for APS,” says antiphospholipid antibodies can fluctuate in patients with or without SLE, supporting the general fluctuation claim. It does not say that lupus anticoagulant specifically decreases or increases during pregnancy; its pregnancy discussion concerns adverse outcomes, not changes in positivity. (LLM, conf=0.85)
- Partly supportedcites [23] sourceExperimental — accuracy not yet measured
The Results section (page unavailable) reports that LAC positivity declined during pregnancy among women positive at screening, while 18% of those negative at screening became positive by the second trimester. The study included women with and without SLE, but reports these changes for the group overall; it does not establish that LAC positivity fluctuates in each SLE subgroup or outside pregnancy. (LLM, conf=0.82)
- Partly supportedcites [24] sourceExperimental — accuracy not yet measured
The Results and Discussion report changing anti-cardiolipin and anti-β2-glycoprotein antibody levels during healthy pregnancy, including increases in IgG and a transient decrease in IgM. They do not establish that lupus anticoagulant (LA) positivity fluctuates, either during pregnancy or in people with or without systemic lupus erythematosus. (LLM, conf=0.84)
- Not checked — no full text of the sourcecites [25] 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.
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
“However, on other points, including testing in patients on anticoagulation, cutoff values, and calculation and interpretation of results, there was uncertainty or lack of agreement.12,15”
§ Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis Update of the guidelines for lupus anticoagulant detection and interpretation > 1 | INTRODUC TI ON
What the sources say
- Partly supportedcites [12] sourceExperimental — accuracy not yet measured
The Patient selection section (page unavailable) reports variability in laboratory performance and says cut-off values and expression of results affect LA testing. The Integrated tests section (page unavailable) says interpreting results in patients taking vitamin K antagonists is difficult. These passages support difficulties with the named testing issues, but the paper does not report survey responses showing uncertainty or lack of agreement on them. (LLM, conf=0.77)
- Supportedcites [15] source
The Discussion states that survey results showed less agreement on testing patients on anticoagulation, cutoff values, and calculation and interpretation of results. The conclusion repeats this finding, and the reported responses on cutoff values and anticoagulant testing illustrate the variation. (LLM, conf=0.95)
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
“a recent study 33 showed unfractionated heparin (UFH) and enoxaparin affect the dRVVT at supra-therapeutic anti-Xa levels but did not lead to false-positive LA in the three step procedure.”
§ Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis Update of the guidelines for lupus anticoagulant detection and interpretation > 3.2 | Interferences
What the sources say
- Supportedcites [33] source
The Results and Discussion report that UFH and enoxaparin affected dRVVT screening at higher anti-Xa levels, but neither produced a false-positive dRVVT-based lupus anticoagulant conclusion after the three-step procedure. The paper distinguishes this dRVVT finding from its APTT-based results. (LLM, conf=0.90)
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
Every source the paper cites for this claim was checked and supports it.
In the paper
“A recent study showed that clotting times or ratios in LA testing were not normally distributed, which confirms that cutoff values should be determined by a nonparametric method based on centiles.73”
§ Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis Update of the guidelines for lupus anticoagulant detection and interpretation > 3.7 | Cutoff values
What the sources say
- Supportedcites [73] source
The LA-negative plasma conclusion states that clotting times or ratios for healthy subjects were not normally distributed in the majority of cases and recommends determining cutoffs preferably by a nonparametric centile method. The Cut-off values section makes the same connection between the observed distributions and the recommended method. (LLM, conf=0.93)
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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“a restriction in the choice of assays reduces the interlaboratory and interassay variability, as well as the number of false positives.2”
§ Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis Update of the guidelines for lupus anticoagulant detection and interpretation > 3.3 | Choice of assays
What the sources say
- Partly supportedcites [2] sourceExperimental — accuracy not yet measured
The ‘Anticardiolipin and beta2-glycoprotein I antibodies’ section (page unavailable) says harmonized protocols on automated platforms may reduce interlaboratory variation. The ‘Antibody profiles’ section (page unavailable) also notes interassay variability, but the paper does not say that restricting assay choice reduces either form of variability or the number of false positives. (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 ISTH-SSC survey showed a considerable lack of agreement on calculation of cutoff values, although 79% stated that they calculate their in-house cutoff values, but only 12% indicated use of >120 normals.15”
§ Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis Update of the guidelines for lupus anticoagulant detection and interpretation > 3.7 | Cutoff values
What the sources say
- Partly supportedcites [15] sourceExperimental — accuracy not yet measured
The 'Number of healthy adult donors for the preparation of in-house' section reports that 78.9% of laboratories calculated in-house cutoffs, and the discussion reports considerable disagreement about cutoffs. The 12% figure applies only to respondents who indicated use of the 99th centile, not to respondents overall; Figure 4B shows 4% selecting >120 donors in its broader question. (LLM, conf=0.89)
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
“Several studies indicated that pretreatment with adsorbents may affect clotting times resulting in false-positive or false-negative LA results, or incomplete removal of DOACs.33,[41][42][43]”
§ Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis Update of the guidelines for lupus anticoagulant detection and interpretation > 3.2 | Interferences
What the sources say
- Partly supportedcites [33] sourceExperimental — accuracy not yet measured
The Results and Discussion report that activated-carbon pretreatment prolonged APTT screening clotting times, and the Conclusions warn that three-step testing is needed to avoid potential misdiagnosis. But the study found that pretreatment did not alter its final LA interpretations; it does not report false-negative LA results or incomplete DOAC removal. Its false-positive LA findings concerned high levels of enoxaparin and danaparoid, not adsorbent pretreatment. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [41] source
- Partly supportedcites [42] sourceExperimental — accuracy not yet measured
The DOAC-Stop® Treatment section (page unavailable) says the adsorbent minimally affected aPTT and PT in samples without DOACs. It does not show adsorbent-induced false-positive or false-negative LA results: the Results report that false-positive LA results fell to zero after treatment and residual DOAC levels were below assay quantification limits. The Discussion notes that LA-positive patients were not included, limiting what the study can say about false negatives. (LLM, conf=0.84)
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.
- Partly supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“The majority of survey participants indicated that the number should be at least 40, which seems reasonable to guarantee an overall normal clotting factor activity. 12”
§ Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis Update of the guidelines for lupus anticoagulant detection and interpretation > 3.4 | Three step procedure
What the sources say
- Could not verifycites [12] sourceExperimental — accuracy not yet measured
The Mixing test section says pooled normal plasma should have approximately 100% activity for all clotting factors, but gives no donor count or survey response. The Integrated tests section specifies at least 40 healthy donors for establishing local test cut-offs, not for constituting pooled normal plasma. A search for the survey majority and the proposed PNP donor count found no passage addressing either point; page numbers were unavailable in our copy. (LLM, conf=0.76)
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.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Differences were observed between platforms for clotting times as well as results expressed as ratio, but also between participants using the same platform.These differences were observed even after detection and exclusion of outliers before cutoff calculation.74”
§ Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis Update of the guidelines for lupus anticoagulant detection and interpretation > 3.7 | Cutoff values
What the sources say
- Partly supportedcites [73] sourceExperimental — accuracy not yet measured
The Results and Cut-off values sections describe three commercial platforms and differences in cut-off values between platforms and between laboratories using the same platform, for both clotting times and ratios. But the LA-negative plasma section explicitly says the authors analyzed all results without detecting or rejecting outliers. The claim that the differences persisted after outlier exclusion is therefore not supported by this study. (LLM, conf=0.92)
- Not checked — no full text of the sourcecites [74] source
plaincorrelationaln = 120- 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 interval of 12 weeks, defined in the Sydney criteria (previously 6 weeks in the Sapporo criteria), was based on expert opinion and little is known on persistence of aPL beyond 3 months.1”
§ Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis Update of the guidelines for lupus anticoagulant detection and interpretation > 4 | CONFIRMATI ON OF PER S IS TENT L A P OS ITIVIT Y
What the sources say
- Partly supportedcites [1] sourceExperimental — accuracy not yet measured
The Update of the classification criteria section says the Sapporo interval was 6 weeks, proposes 12 weeks, and explicitly states that the proposed time intervals are based on expert opinion. It calls for studies validating those intervals and describes relevant data as poor, but does not specifically say that little is known about aPL persistence beyond 3 months. (LLM, conf=0.83)
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.
- Partly supported
In the paper
“A total of 51% of the participants of the survey indicated plasma should ideally be frozen within 4 hours, in accordance with general guidelines for coagulation assays.27”
§ Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis Update of the guidelines for lupus anticoagulant detection and interpretation > 3.1 | Sample preparation and quality
What the sources say
- Not matchedcites [27]
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: 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
In the paper
“The effect of freeze-thawing on diluted Russell's viper venom time (dRVVT) ratios leading to false-negative results was confirmed in a more recent study.28”
§ Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis Update of the guidelines for lupus anticoagulant detection and interpretation > 3.1 | Sample preparation and quality
What the sources say
- Not checked — no full text of the sourcecites [28] 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.
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
“negative or positive LA (or anticardiolipin [aCL]/ anti-β2glycoprotein I [aβ2GPI]) during pregnancy does not exclude or confirm a diagnosis of APS.”
§ Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis Update of the guidelines for lupus anticoagulant detection and interpretation > K E Y W O R D S
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.
In the paper
“This notwithstanding, the authors recommended the identification of outliers before cutoff calculation by using one of the current available algorithms.74”
§ Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis Update of the guidelines for lupus anticoagulant detection and interpretation > 3.7 | Cutoff values
What the sources say
- Not checked — no full text of the sourcecites [74] 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.
Probably not a substantial claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Based on the same data of this multicenter study, it was illustrated that variable numbers of outliers were identified depending on the algorithm used for identification and that their elimination showed no appreciable effects on the inter-laboratory variability of cutoff values, indicating that outliers are not the main cause of the inter-laboratory variability of cutoffs for LA detection.”
§ Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis Update of the guidelines for lupus anticoagulant detection and interpretation > 3.7 | Cutoff values
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.
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
“Confirmation of triple-positive patients (same isotype 81 or independent of isotype of aCL and aβ2GPI 80 ) seems to be predictable without the need to retest after 12 weeks because triplepositivity persists in the majority of patients.80,81”
§ Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis Update of the guidelines for lupus anticoagulant detection and interpretation > 4 | CONFIRMATI ON OF PER S IS TENT L A P OS ITIVIT Y
What the sources say
hedgeddirect- 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
“These results support the choice of extending the retest interval beyond 12 weeks, which would identify patients who remain persistently positive even beyond this period.80”
§ Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis Update of the guidelines for lupus anticoagulant detection and interpretation > 4 | CONFIRMATI ON OF PER S IS TENT L A P OS ITIVIT Y
What the sources say
- Not checked — no full text of the sourcecites [80] source
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.
Probably not a substantial claim.
In the paper
“A retrospective study evaluated extended persistence and demonstrated persistence in 96% in a median follow-up of 56 weeks, with no significant lower persistence in the single positive patients compared with the double and triple positives.80”
§ Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis Update of the guidelines for lupus anticoagulant detection and interpretation > 4 | CONFIRMATI ON OF PER S IS TENT L A P OS ITIVIT Y
What the sources say
- Not checked — no full text of the sourcecites [80] source
boosted- 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
“Probably, they might be explained by the variation in reagent lots, as confirmed in another multicenter study with the same reagent lot used by all participating centers.77”
§ Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis Update of the guidelines for lupus anticoagulant detection and interpretation > 3.7 | Cutoff values
What the sources say
- Not checked — no full text of the sourcecites [77] 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.
It may state two separate claims as one.
The paper relies on this without support.
The survey respondents are representative of the spectrum of clinical and laboratory practice in LA detection.
“The responses forced the formulation of further ISTH-SSC recommendations.”
The authors state this as an assumption.
Manufacturers' cutoffs are established by appropriate statistical models using a sufficiently large donor population.
“However, this assumes that manufacturers' cutoffs are established by appropriate statistical models using a sufficiently large donor population.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In contrast, the ISTH SSC 2020 guideline recommends performing the mixing and confirmatory tests simultaneously if the screening test shows the presence of LA [20].”
From Comparison of different algorithms for lupus anticoagulant detection: a single-center experience (2024) · cites this paper as [20]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“PNP is very important for the standardization of the mixing test; it should be platelet-free, its content of each coagulation factor should be close to 100%, and it should be obtained from at least 20–40 healthy donors (males and females) [9,48].”
From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [9]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Current guidelines recommend avoiding LA testing during an acute thrombotic event or an acute episode (e.g., an infection) [9]”
From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [9]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Clotting times of screening, mixing, and confirmatory procedures are prone to inter- (between same-principle tests offered by different manufacturers) and intra-assay (between batches of the same reagent) variability [25]; for this reason, it is recommended to normalize a screening, mixing, and confirmatory clotting time, generating a ratio between test clotting time and NPP clotting time [9,36,48”
From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [9]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“ISTH guidelines expressly recommend not using cut-off values established elsewhere, but using “in house” cut-off values deriving from a sufficiently large population of healthy individuals (at least 120): the value of cut-off is determined to be the 99th percentile [9].”
From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [9]
Experimental — accuracy not yet measured
The cited source says what the claim attributes to it.
In the citing paper
“Although it is known that persistence, defined currently by 12 weeks, is associated with thrombotic risk, little is known about the stability of these antibodies beyond this time, predictors of persistence, and whether subsequent fluctuations in antibody status affect future risk of thrombosis.6”
From Lupus anticoagulant test persistence over time and its associations with future thrombotic events (2022) · cites this paper as [6]
The cited source says what the claim attributes to it.
In the citing paper
“Interestingly, when the ISTH SSC 2020 guideline [20] was employed, a maximum of an additional 8 patients who were classified LA-negative by the reference algorithm were considered LA-positive with a “negative mixing but positive confirmatory tests” pattern.”
From Comparison of different algorithms for lupus anticoagulant detection: a single-center experience (2024) · cites this paper as [20]
The cited source says what the claim attributes to it.
In the citing paper
“It was revealed that the PPA was clearly improved by applying algorithms following the updated ISTH SSC 2020 guideline compared with the previous guideline in 2009 (median PPA, 93.6% vs 100.0%) (Table 1).”
From Comparison of different algorithms for lupus anticoagulant detection: a single-center experience (2024) · cites this paper as [20]
The cited source says what the claim attributes to it.
In the citing paper
“Each laboratory employed guideline compliant plasma preparation and storage procedures, and dRVVT and APTT assay performance and interpretation [17][18][19].”
From Triple-positive antiphospholipid syndrome does not guarantee positivity in each lupus anticoagulant assay (2023) · cites this paper as [19]
The cited source says what the claim attributes to it.
In the citing paper
“ISTH guidelines recommend that confirmatory test(s) must be performed by increasing the concentration of phospholipids used in the screening test(s) [9].”
From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [9]
The cited source says what the claim attributes to it.
In the citing paper
“The most recent ISTH guidelines [9] recommend using at least two tests as screening, based on different principles:A LA-sensitive test derived from aPTT (such as SCT, silica clotting time);The dRVVT (dilute Russell viper venom time).”
From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [9]
The cited source says what the claim attributes to it.
In the citing paper
“It is recommended to select an aPTT that uses silica as activator [9].”
From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [9]
The cited source says what the claim attributes to it.
In the citing paper
“dRVVT is recommended for its specificity and robustness [9].”
From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [9]
The cited source says what the claim attributes to it.
In the citing paper
“Testing for LA is appropriate only in those patients in which there is a reasonable suspicion of APS [9]”
From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [9]
The cited source says what the claim attributes to it.
In the citing paper
“Therefore, ISTH guidelines recommend a mixing-test-specific cut-off over ICA [9].”
From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [9]
The cited source says what the claim attributes to it.
In the citing paper
“ISTH guidelines affirm that this approach is possible “if manufacturers provide cut off values established in accordance with guidelines and by appropriate statistical models using a sufficiently large donor population” [9].”
From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [9]
The cited source says what the claim attributes to it.
In the citing paper
“For this reason, current ISTH guidelines [9] consider the mixing procedure to be unreliable for VKA-treated patients.”
From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [9]
The cited source says what the claim attributes to it.
In the citing paper
“and LAC was performed according to the ISTH guidelines. 1,34”
From Clinical Relevance of Isolated Lupus Anticoagulant Positivity in Patients with Thrombotic Antiphospholipid Syndrome (2021) · cites this paper as [34]
Citations
Cites
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Self-citationUpdate of the guidelines for lupus anticoagulant detection
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Self-citation
Metadata
- Authors
- Devreese, K. M. J., de Groot, P. G., de Laat, B., Erkan, D., Favaloro, E. J., Mackie, I., Martinuzzo, M., Ortel, T. L., Pengo, V., Rand, J. H., Tripodi, A., Wahl, D., & Cohen, H.
- Affiliations
- Ghent University Hospital (BE)
- Maastricht University Medical Centre (NL)
- Hospital for Special Surgery (US)
- Westmead Hospital (AU)
- University College London (GB)
- Hospital Italiano de Buenos Aires (AR)
- Duke Medical Center (US)
- University of Padua (IT)
- Cornell University (US)
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
- Inserm (FR)
- University College Hospital (GB)
- Corresponding author
- Devreese, Katrien M.J.
- ORCID
- Venue
- Journal of Thrombosis and Haemostasis
- Publisher
- Elsevier BV
- Published
- 2020-11
- Volume
- 18
- Issue
- 11
- Pages
- 2828-2839
- ISSN
- 1538-7836 (ISSN-L)
- OpenAlex
- W3096784218
- Cited by
- 467
- References
- 88
- Citations by year
- 2026: 85 · 2025: 80 · 2024: 103 · 2023: 94 · 2022: 57 · 2021: 43 · 2020: 4
- FWCI
- 31.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Thrombosis and Haemostasis (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, other-oa)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Hematology › Heparin-Induced Thrombocytopenia and Thrombosis
- Keywords
- lupus anticoagulant, antiphospholipid antibodies, pre-analytical phase, anticoagulated patients, coagulation tests, anti-Xa activity, direct oral anticoagulants, activated partial thromboplastin time, ellagic acid, cut-off values, patient selection, thrombosis
- MeSH terms
- Blood Coagulation Tests, Humans, Partial Thromboplastin Time, Prothrombin Time, Reference Standards, Thrombosis, Lupus Coagulation Inhibitor, Antiphospholipid Syndrome
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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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