Triple-positive antiphospholipid syndrome does not guarantee positivity in each lupus anticoagulant assay

Probably not a substantial claim: may not pass S3 (load-bearing).

aPL profiling also involves consideration of antibody titers since higher titers are associated with higher risk.

“aPL profiling also involves consideration of antibody titers since higher titers are associated with higher risk [7,8,30,31].”

• cites [7] Pengo, 2010, Clinical course of high-risk patients diagnosed with antiphospholipid syndrome, J Thromb Haemost sourcePartly supported

  The Discussion (page not provided) says a previous study found a strong correlation between anticardiolipin (aCL) titer and thrombosis, and uses an aCL titer cutoff to select patients at risk. That supports considering aCL titers, but it does not establish the same higher-titer association for aPL antibodies generally. (LLM, conf=0.83)

  Experimental — accuracy not yet measured
• cites [8] Pengo, 2011, Incidence of a first thromboembolic event in asymptomatic carriers of high-risk antiphospholipid antibody profile: a multicenter prospective study, Blood sourceDisputed

  Table 3 (Discussion; page unavailable) compares anticardiolipin antibody titres in participants with and without thrombosis and reports a univariate hazard ratio of 1.0 (95% CI, 0.99–1.01). In this cohort, the paper does not find the claimed association between higher titres and higher thromboembolic risk; it identifies male sex and venous risk factors as independent predictors instead. (LLM, conf=0.84)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured
• cites [30] Bertin, 2021, Single or triple positivity for antiphospholipid antibodies in “carriers” or symptomatic patients: untangling the knot, J Thromb Haemost sourceDisputed

  The Discussion (p. 12) concludes that thrombotic risk does not necessarily increase with an elevated aPL titer, contrary to the claim's general association between higher titers and higher risk. The Results (p. 9) found only a trend, not a statistically significant association, for aCL IgG at a higher threshold. (LLM, conf=0.88)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured
• cites [31] da Silva Saraiva, 2017, The impact of antibody profile in thrombosis associated with primary antiphospholipid syndrome, Am J Hematol sourcePartly supported

  The Methods define persistent aPL positivity partly by moderate-to-high antibody titers, so the paper supports considering titers when assessing aPL status. The Results report higher IgG aCL titers in the triple-positive group, but the Discussion says new thrombotic events were not related to triple positivity and that the clinical significance of the higher antibody levels remains undetermined. It does not establish that higher titers confer higher risk. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

May combine two claims.

Most triple-positivity studies report LA testing as positive without distinguishing between dRVVT and APTT and single-assay positivity or only perform dRVVT.

“Of note is that many studies on triple positivity merely report patients as being positive for LA without assessing dRVVT and APTT results separately [10,[23][24][25][26][27][28][29], or even use only 1 assay [7,8,12].”

• cites [10,[23][24][25][26][27][28][29]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [7] Pengo, 2010, Clinical course of high-risk patients diagnosed with antiphospholipid syndrome, J Thromb Haemost sourceSupported
• cites [8] Pengo, 2011, Incidence of a first thromboembolic event in asymptomatic carriers of high-risk antiphospholipid antibody profile: a multicenter prospective study, Blood sourceSupported
• cites [12] Qi, 2022, Clinical characteristics and prognosis of patients with antiphospholipid antibodies based on cluster analysis: an 8-year cohort study, Arthritis Res Ther sourceSupported

Probably not a substantial claim: may not pass S4 (based).

Positivity with both assays may identify higher risk.

“Positivity with both assays may identify higher risk.”

• cites [30] Bertin, 2021, Single or triple positivity for antiphospholipid antibodies in “carriers” or symptomatic patients: untangling the knot, J Thromb Haemost sourcePartly supported

  The Laboratory tests section (p. 3) identifies two assays for lupus anticoagulant, APTT and dRVVT. The Discussion (pp. 11–12) proposes positivity on both tests as part of a profile for identifying higher-risk carriers, but that profile also requires positive IgG aCL and IgG aB2GPI. The source does not establish that positivity on the two assays alone identifies higher risk. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Bertin et al. found that LA positivity with both dRVVT and APTT combined with elevated IgG aCL and aβ2GPI represented a high risk of thrombotic events in asymptomatic carriers.

“Bertin et al. found that LA positivity with both dRVVT and APTT combined with elevated IgG aCL and aβ2GPI represented a high risk of thrombotic events in asymptomatic carriers [30].”

• cites [30] Bertin, 2021, Single or triple positivity for antiphospholipid antibodies in “carriers” or symptomatic patients: untangling the knot, J Thromb Haemost sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

Bertin et al. found LA positivity in dRVVT and APTT accompanied by elevated IgG aCL and aβ2GPI to be the most common aPL pattern in patients with APS.

“Bertin et al. found LA positivity in dRVVT and APTT accompanied by elevated IgG aCL and aβ2GPI to be the most common aPL pattern in patients with APS [30].”

• cites [30] Bertin, 2021, Single or triple positivity for antiphospholipid antibodies in “carriers” or symptomatic patients: untangling the knot, J Thromb Haemost sourcePartly supported

  Section 3.2 (p. 9) identifies positivity on both LA tests with IgG aCL and IgG aB2GPI as the most prevalent profile among the triple-aPL-positive patients studied (27/88, 30.7%). The paper says this profile was associated with symptomatic triple-positive patients, but does not establish that it is the most common pattern among APS patients generally; the group studied also included asymptomatic carriers. Section 2.3 (p. 3) identifies the two LA tests as APTT and dRVVT. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Each laboratory employed guideline compliant plasma preparation and storage procedures, and dRVVT and APTT assay performance and interpretation.

“Each laboratory employed guideline compliant plasma preparation and storage procedures, and dRVVT and APTT assay performance and interpretation [17][18][19].”

• cites [17] Keeling, 2012, Guidelines on the investigation and management of antiphospholipid syndrome, Br J Haematol sourceSupported
• cites [18] 2014Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [19] Devreese, 2020, 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, J Thromb Haemost sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

Double LA assay positivity may contribute to risk stratification.

“Additionally, double LA assay positivity may contribute to risk stratification [30].”

• cites [30] Bertin, 2021, Single or triple positivity for antiphospholipid antibodies in “carriers” or symptomatic patients: untangling the knot, J Thromb Haemost sourceSupported

May combine two claims.

Single LA assay repertoires are still in use and risk missing not only single-positive APS where isolated persistent LA is a risk factor, but also identification of triple-positive patients who require different management.

“Single LA assay repertoires are still in use and risk missing not only single-positive APS where isolated persistent LA is a risk factor [11,30], but also identification of triple-positive patients who require different management.”

• cites [11] Yin, 2021, Clinical relevance of isolated lupus anticoagulant positivity in patients with thrombotic antiphospholipid syndrome, Thromb Haemost sourceSupported
• cites [30] Bertin, 2021, Single or triple positivity for antiphospholipid antibodies in “carriers” or symptomatic patients: untangling the knot, J Thromb Haemost sourcePartly supported

  The Introduction (p. 2) says isolated LA positivity is highly associated with thrombosis, supporting the risk-factor point to which the citation is attached. The Discussion (p. 12) says the study did not investigate single-LA-positive patients, so its own findings do not establish the risk specifically for persistent isolated LA. (LLM, conf=0.82)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The value of IgM aCL and aβ2GPI measurement in APS is debated as there is a weaker correlation with thrombosis than with IgG isotypes and LA, although they may be valuable in the diagnosis of obstetric APS and contribute to risk stratification in the detection of triple positivity.

“The value of IgM aCL and aβ2GPI measurement in APS is debated as there is a weaker correlation with thrombosis than with IgG isotypes and LA, although they may be valuable in the diagnosis of obstetric APS and contribute to risk stratification in the detection of triple positivity [41].”

• cites [41] Chayoua, 2020, The (non-)sense of detecting anti-cardiolipin and anti-β2glycoprotein I IgM antibodies in the antiphospholipid syndrome, J Thromb Haemost sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

A recent internationally circulated ISTH SSC questionnaire revealed that 98.9% of respondents used dRVVT and 79.7% used an LA-sensitive APTT for routine LA detection.

“A recent internationally circulated ISTH SSC questionnaire revealed that 98.9% of respondents used dRVVT and 79.7% used an LA-sensitive APTT for routine LA detection [34].”

• cites [34] Cohen, 2019, J Thromb Haemost sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

Solid-phase assays for IgG and IgM aCL and aβ2GPI were performed according to international guidelines.

“Solid-phase assays for immunoglobulin (Ig) G and IgM aCL and aβ2GPI were performed according to international guidelines [36].”

• cites [36] Devreese, 2014, Subcommittee on Lupus Anticoagulant/Phospholipid/Dependent Antibodies. Testing for antiphospholipid antibodies with solid phase assays: guidance from the SSC of the ISTH, J Thromb Haemost sourceSupported

May combine two claims.

IgM aCL levels were comparable in the nonclinical criteria cohort, while mean IgM aβ2GPI levels were lower in patients LA-positive by APTT only than in the other 2 groups.

“IgM aCL levels were comparable in the nonclinical criteria cohort, while mean IgM aβ2GPI levels were lower in patients LA-positive by APTT only than in the other 2 groups.”

May combine two claims.

In the present study, 76/342 (22.2%) LA were positive by dRVVT only and 49/342 (14.3%) by APTT only.

“In the present study, 76/342 (22.2%)LA were positive by dRVVT only and 49/342 (14.3%) by APTT only”

May combine two claims.

In patients with APS, mean IgM aCL and aβ2GPI levels were higher when LA testing was positive by dRVVT only and levels were higher when dRVVT and APTT were positive than when only APTT was positive.

“In patients with APS, mean IgM aCL and aβ2GPI levels were higher when LA testing was positive by dRVVT only and levels were higher when dRVVT and APTT were positive than when only APTT was positive.”

May combine two claims.

For patients with SLE, elevated levels in all 4 solid-phase assays or in IgG aCL and aβ2GPI were equally prevalent when dRVVT and APTT were positive, comprising most of the profiles, while elevated IgG aCL and aβ2GPI predominated in single LA assay positivity.

“For patients with SLE, elevated levels in all 4 solid-phase assays or in IgG aCL and aβ2GPI were equally prevalent when dRVVT and APTT were positive, comprising most of the profiles, while elevated IgG aCL and aβ2GPI predominated in single LA assay positivity.”

May combine two claims.

Up to 55.0% of triple-positive samples were positive in 1 LA assay, representing significant potential for misdiagnosis and inappropriate management via single LA assay repertoires.

“Up to 55.0% of triple-positive samples were positive in 1 LA assay, representing significant potential for misdiagnosis and inappropriate management via single LA assay repertoires.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Triple positivity for all 3 criteria antiphospholipid antibodies confers high risk of symptom development in carriers, and recurrence in antiphospholipid syndrome (APS).

“Positivity for persistence of >1 criterion antibody has a stronger association with thrombotic and obstetric APS, and patients with APS and its carriers with the triple-positive profile (LA, and aCL and aβ2GPI of the same isotype) are at a high risk of recurrence of thrombosis or development of a first thrombosis, respectively [2,[7][8][9]”

• cites [2,[7][8][9]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Single LA assay repertoires remain in use in some centers, which risks missing some triple positives.

“Single LA assay repertoires remain in use in some centers, which risks missing some triple positives.”

• cites [7,8,12,[32][33][34]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Over a third of the samples were LA-positive by only one assay, representing significant potential for misdiagnosis in single-assay repertoires.

“representing over a third of the samples and significant potential for misdiagnosis in single-assay repertoires.”

May combine two claims.

A recent external quality assurance (EQA) exercise distributed internationally by the UK NEQAS Blood Coagulation scheme reported that 5/233 (2.2%) of centers employed APTT without dRVVT and 13/233 (5.6%) performed dRVVT without APTT or silica clotting time.

“A recent external quality assurance (EQA) exercise distributed internationally by the UK NEQAS Blood Coagulation scheme reported that 5/233 (2.2%) of centers employed APTT without dRVVT and 13/233 (5.6%) performed dRVVT without APTT or silica clotting time [42].”

• cites [42] UK NEQAS Blood Coagulation overall summary report on Lupus Anticoagulant Exercise LA20. January 2023.Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

A strength of the present study is that it represented routine daily laboratory data and involved the use of multiple aPL assay reagents, reducing analytical bias.

“A strength of the present study is that it represented routine daily laboratory data and involved the use of multiple aPL assay reagents, reducing analytical bias.”

May combine two claims.

Ten of 109 (9.2%) used only APTT-based assays and 99/109 (90.8%) used only dRVVT.

“Ten of 109 (9.2%) used only APTTbased assays and 99/109 (90.8%) used only dRVVT.”

Probably not a substantial claim: may not pass S3 (load-bearing).

A recent EQA exercise distributed internationally by the ECAT scheme in 2023 noted that 109/567 (19.2%) of centers employed single-assay repertoires.

“A recent EQA exercise distributed internationally by the ECAT (External quality Control of diagnostic Assays and Tests) scheme in 2023 noted that 109/ 567 (19.2%) of centers employed single-assay repertoires (Dr Piet Meijer, personal communication).”

May combine two claims.

LA positivity in both dRVVT and APTT was more common than single LA assay positivity in patients with APS and SLE, but had a similar frequency to LA positivity with dRVVT only in patients not fulfilling APS clinical criteria.

“LA positivity in both dRVVT and APTT was more common than single LA assay positivity in patients with APS and SLE, but had a similar frequency to LA positivity with dRVVT only in patients not fulfilling APS clinical criteria.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

A triple-positive aPL profile indicates a high risk of developing thrombosis or obstetric complications and noncriteria events in carriers, a high risk of recurrence in patients with established APS, and is common in catastrophic APS.

“A triple-positive aPL profile indicates a high risk of developing thrombosis or obstetric complications and noncriteria events in carriers, a high risk of recurrence in patients with established APS, and is common in catastrophic APS [2,[7][8][9][38][39][40].”

• cites [2,[7][8][9][38][39][40]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.