Lupus anticoagulant identifies two distinct groups of patients with different antibody patterns

Pengo, Vittorio; Ross, Teresa Del; Ruffatti, Amelia; Bison, Elisa; Cattini, Maria Grazia; Pontara, Elena; Testa, Sophie; Legnani, Cristina; Pozzi, Nicola; Peterle, Daniele; Acquasaliente, Laura; Filippis, Vincenzo De; Denas, Gentian

doi:10.1016/j.thromres.2018.11.003

Cited by 49 publications

(70 citation statements)

References 25 publications

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“…This suggests a novel mechanism by which aPS/PT antibodies could increase the risk of thromboembolism in APS. The present study expanded data reported by Pengo et al by showing that the coexistence of LA, aβ2GPI, and IgG aPS/PT antibodies is associated with reduced clot porosity and slower D ‐dimer release. Even if the differences were below 10%, this observation warrants further investigations to explore fibrin‐related harmful effects of such a combination of antibodies in APS.…”

Section: Discussionsupporting

confidence: 87%

“…Both LA‐positive and aβ2GPI‐positive patients were characterized by higher titers of IgG aPS/PT antibodies compared to LA‐positive but aβ2GPI‐negative patients . In that study, titers of IgM aPS/PT antibodies did not differ between the groups, while a coexistence of LA, aβ2GPI, and IgG aPS/PT antibodies was related to high risk of thrombosis …”

Section: Introductionmentioning

confidence: 69%

“…IgM aPS/PT antibodies had only weak or no associations with IgM aCL or aβ2GPI antibodies . Recently, Pengo et al have shown that assessment of aPS/PT, along with aβ2GPI antibodies, in patients with present LA activity can identify two subgroups of patients with different risk of thromboembolism. Both LA‐positive and aβ2GPI‐positive patients were characterized by higher titers of IgG aPS/PT antibodies compared to LA‐positive but aβ2GPI‐negative patients .…”

Section: Introductionmentioning

confidence: 99%

“…Recently, Pengo et al have shown that assessment of aPS/PT, along with aβ2GPI antibodies, in patients with present LA activity can identify two subgroups of patients with different risk of thromboembolism. Both LA‐positive and aβ2GPI‐positive patients were characterized by higher titers of IgG aPS/PT antibodies compared to LA‐positive but aβ2GPI‐negative patients . In that study, titers of IgM aPS/PT antibodies did not differ between the groups, while a coexistence of LA, aβ2GPI, and IgG aPS/PT antibodies was related to high risk of thrombosis …”

Section: Introductionmentioning

confidence: 99%

“…15 IgM aPS/PT antibodies had only weak or no associations with IgM aCL or aβ2GPI antibodies. 16 Recently, Pengo et al 17 have shown that assessment of aPS/PT, along with aβ2GPI antibodies, in patients with present LA activity can identify two subgroups of patients with different risk of thromboembolism.…”

Section: Introductionmentioning

confidence: 99%

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Antiphosphatidylserine/prothrombin complex antibodies as a determinant of prothrombotic plasma fibrin clot properties in patients with antiphospholipid syndrome

Ząbczyk

Celińska-Löwenhoff

Plens

et al. 2019

Journal of Thrombosis and Haemostasis

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Background Antiphosphatidylserine/prothrombin complex (aPS/PT) antibodies are recognized as a marker for antiphospholipid syndrome (APS). Dense and poorly lysable fibrin clots occur in thrombotic APS. Compact clots predict thromboembolism, but determinants of the unfavorable clot phenotype remain unknown in APS. We hypothesized that elevated aPS/PT antibodies determine unfavorable clot features. Methods In a cohort study involving 124 consecutive patients with thrombotic APS, we measured at baseline plasma fibrin clot permeability (Ks), efficiency of fibrinolysis (clot lysis time, CLT), and turbidity (off anticoagulation) along with immunoglobulin (Ig)G/IgM aPS/PT. During follow‐up, symptomatic thromboembolic events were recorded. Results Elevated IgG and IgM aPS/PT antibodies >30 international enzyme units (UI) were detected in 54.8% and 42.7% of APS patients, including 76.2% and 54% of lupus anticoagulant‐ (LA, n = 63) positive patients, respectively. Elevated IgG and IgM aPS/PT antibodies predicted low Ks (lower quartile, <6 × 10−9 cm2; odds ratio [OR] = 5.93, 95% confidence interval [CI] 2.09‐16.82 and OR = 11.79, 95% CI 4.10‐33.92) and prolonged CLT (top quartile, ≥116 min; OR = 4.85, 95% CI 2.42‐25.07 and OR = 6.04, 95% CI 2.42‐15.07). No such associations were observed for anticardiolipin or β2‐glycoprotein I antibodies or LA presence. During follow‐up (median 72.5, range 66‐83 months), thromboembolic events observed in 32 (26.7%, 4.6%/year) patients were independently predicted by IgG aPS/PT antibodies >30 UI (hazard ratio [HR] = 3.04, 95% CI 1.20‐8.88) and low Ks (HR = 3.00, 95% CI 1.41‐6.50). Conclusions We identified aPS/PT antibodies as a determinant of denser and poorly lysable plasma fibrin clot formation in APS patients. The association of elevated aPS/PT antibodies with thromboembolism in APS could be at least in part mediated by prothrombotic clot properties.

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Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 69%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Antiphosphatidylserine/prothrombin complex antibodies as a determinant of prothrombotic plasma fibrin clot properties in patients with antiphospholipid syndrome

Ząbczyk

Celińska-Löwenhoff

Plens

et al. 2019

Journal of Thrombosis and Haemostasis

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Lupus anticoagulant testing during anticoagulation, including direct oral anticoagulants

Favaloro

Pasalic

2022

Research and Practice in Thrombosis and Haemostasis

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Background Lupus anticoagulants (LA) are one laboratory criterion for classification of antiphospholipid syndrome, with presence of vascular thrombosis and/or pregnancy/fetal morbidity being clinical criteria. The presence of LA is detected (or excluded) by laboratory testing, with the activated partial thromboplastin time and dilute Russell's viper venom time the most commonly used tests. Given the association of thrombosis with LA, it is no surprise that anticoagulants are used to treat or manage such patients. Objectives To review and discuss interferences from anticoagulants on LA testing, and strategies to mitigate these. Methods This narrative review assessed interference from commonly used anticoagulants, focusing on LA testing while on direct oral anticoagulants (DOACs), including use of DOAC neutralizers. Results The classical anticoagulants comprise vitamin K antagonists such as warfarin, and heparins, predominantly unfractionated heparin and low molecular weight heparin (LMWH). DOACs have emerged with favorable efficacy and safety. These comprise two classes: direct anti‐thrombin (anti‐IIa; dabigatran) or direct anti‐Xa (rivaroxaban, apixaban, edoxaban) agents. All anticoagulants affect clotting assays, although there are differences in effects according to anticoagulant and assay. Nevertheless, because of such interferences, anticoagulants can lead to false‐negative or false‐positive LA findings. Several strategies can mitigate such interferences, including avoidance of testing while patients are on such anticoagulants, temporarily switching to an anticoagulant (i.e., LMWH) with less assay interference, testing for LA at nadir levels of anticoagulants, and/or use of anticoagulant neutralizers. Conclusion Whilst the best approach is to avoid LA testing on patients taking anticoagulants; if unavoidable, testing may be facilitated by various mitigating strategies.

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Laboratory Testing for Non-criteria Antiphospholipid Antibodies: Anti-phosphatidylserine/Prothrombin Antibodies (aPS/PT)

Devreese

2023

Methods in Molecular Biology

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Lupus anticoagulant identifies two distinct groups of patients with different antibody patterns

Cited by 49 publications

References 25 publications

Antiphosphatidylserine/prothrombin complex antibodies as a determinant of prothrombotic plasma fibrin clot properties in patients with antiphospholipid syndrome

Antiphosphatidylserine/prothrombin complex antibodies as a determinant of prothrombotic plasma fibrin clot properties in patients with antiphospholipid syndrome

Lupus anticoagulant testing during anticoagulation, including direct oral anticoagulants

Laboratory Testing for Non-criteria Antiphospholipid Antibodies: Anti-phosphatidylserine/Prothrombin Antibodies (aPS/PT)

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