Thrombin generation test as a useful tool for improving disease severity stratification in antiphospholipid syndrome

Background Patients with antiphospholipid syndrome (APS) display a wide range of clinical manifestations with similar immunological profile with the presence of lupus anticoagulant in around 70% of them. Although antiphospholipid antibodies (aPL) profile influences the risk of thrombosis in APS, APS...

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Main Authors: Eric Hachulla, Julien Labreuche, David Launay, Marc Lambert, Cecile Yelnik, Marie Frimat, Sylvain Dubucquoi, Anne Bauters, Maximilien Desvages, Steve Lancel
Format: Article
Language:English
Published: BMJ Publishing Group 2025-07-01
Series:RMD Open
Online Access:https://rmdopen.bmj.com/content/11/3/e005489.full
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author Eric Hachulla
Julien Labreuche
David Launay
Marc Lambert
Cecile Yelnik
Marie Frimat
Sylvain Dubucquoi
Anne Bauters
Maximilien Desvages
Steve Lancel
author_facet Eric Hachulla
Julien Labreuche
David Launay
Marc Lambert
Cecile Yelnik
Marie Frimat
Sylvain Dubucquoi
Anne Bauters
Maximilien Desvages
Steve Lancel
author_sort Eric Hachulla
collection DOAJ
description Background Patients with antiphospholipid syndrome (APS) display a wide range of clinical manifestations with similar immunological profile with the presence of lupus anticoagulant in around 70% of them. Although antiphospholipid antibodies (aPL) profile influences the risk of thrombosis in APS, APS risk stratification remains to be improved.Objectives Our study aimed to evaluate thrombin generation test (TGT) interest to improve disease severity stratification in APS patients.Patients/methods In this monocentric, transversal study, we included unselected primary thrombotic APS patients, fulfilling APS classification criteria and treated by vitamin K antagonist (VKA). 28 non-APS patients under VKA followed in our hospital were included as controls. TGT was performed on plasma samples with the calibrated automated thrombogram in our core laboratory.Results Between January 2020 and March 2023, 114 thrombotic APS patients (without systemic lupus erythematosus) were included (female 71 (62.3%), mean age 50±14 years old, median duration since the last APS event of 51 months (IQR 23–129 months)). APS patients had prolonged lag time (LT) and time to peak (TTP) compared with anticoagulated controls. History of relapse, catastrophic APS (CAPS), all aPL positivities and elevated Bb fragments were strongly associated with a prolonged LT and TTP.Conclusions Our findings suggest that APS patients under VKA had significantly prolonged TGT times compared with anticoagulated controls, with the greatest prolongations in patients with history of relapse or CAPS. Thus, TGT might be a useful tool to improve APS disease severity stratification without temporary cessation of VKA.
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spelling doaj-art-bf79151492594748a1e5528ede9b24612025-08-20T03:31:06ZengBMJ Publishing GroupRMD Open2056-59332025-07-0111310.1136/rmdopen-2025-005489Thrombin generation test as a useful tool for improving disease severity stratification in antiphospholipid syndromeEric Hachulla0Julien Labreuche1David Launay2Marc Lambert3Cecile Yelnik4Marie Frimat5Sylvain Dubucquoi6Anne Bauters7Maximilien Desvages8Steve Lancel9Département de Médecine Interne et d’Immunologie Clinique, Centre de référence des Maladies Auto-Immunes et Auto-inflammatoires Systémiques rares de l’Adulte du Nord, Nord-Ouest, Méditerranée et Guadeloupe (CeRAINOM), European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNECT), University Hospital of Lille, CHU Lille, Lille, FranceULR 2694 - METRICS: Évaluation des technologies de santé et des pratiques médicales, Lille University Hospital, CHU Lille, Lille, FranceDépartement de Médecine Interne et d’Immunologie Clinique, Centre de référence des Maladies Auto-Immunes et Auto-inflammatoires Systémiques rares de l’Adulte du Nord, Nord-Ouest, Méditerranée et Guadeloupe (CeRAINOM), European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNECT), University Hospital of Lille, CHU Lille, Lille, FranceDépartement de Médecine Interne et d’Immunologie Clinique, Centre de référence des Maladies Auto-Immunes et Auto-inflammatoires Systémiques rares de l’Adulte du Nord, Nord-Ouest, Méditerranée et Guadeloupe (CeRAINOM), European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNECT), University Hospital of Lille, CHU Lille, Lille, FranceDépartement de Médecine Interne et d’Immunologie Clinique, Centre de référence des Maladies Auto-Immunes et Auto-inflammatoires Systémiques rares de l’Adulte du Nord, Nord-Ouest, Méditerranée et Guadeloupe (CeRAINOM), European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNECT), University Hospital of Lille, CHU Lille, Lille, FranceRID-AGE - Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement, INSERM U1167, Lille, FranceImmunologie, Centre de biologie Pathologie, Lille University Hospital, CHU Lille, Lille, FranceInstitut d’Hématologie-Transfusion, Centre de biologie Pathologie, Lille University Hospital, CHU Lille, Lille, FranceInstitut d’Hématologie-Transfusion, Centre de biologie Pathologie, Lille University Hospital, CHU Lille, Lille, FranceRID-AGE - Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement, INSERM U1167, Lille, FranceBackground Patients with antiphospholipid syndrome (APS) display a wide range of clinical manifestations with similar immunological profile with the presence of lupus anticoagulant in around 70% of them. Although antiphospholipid antibodies (aPL) profile influences the risk of thrombosis in APS, APS risk stratification remains to be improved.Objectives Our study aimed to evaluate thrombin generation test (TGT) interest to improve disease severity stratification in APS patients.Patients/methods In this monocentric, transversal study, we included unselected primary thrombotic APS patients, fulfilling APS classification criteria and treated by vitamin K antagonist (VKA). 28 non-APS patients under VKA followed in our hospital were included as controls. TGT was performed on plasma samples with the calibrated automated thrombogram in our core laboratory.Results Between January 2020 and March 2023, 114 thrombotic APS patients (without systemic lupus erythematosus) were included (female 71 (62.3%), mean age 50±14 years old, median duration since the last APS event of 51 months (IQR 23–129 months)). APS patients had prolonged lag time (LT) and time to peak (TTP) compared with anticoagulated controls. History of relapse, catastrophic APS (CAPS), all aPL positivities and elevated Bb fragments were strongly associated with a prolonged LT and TTP.Conclusions Our findings suggest that APS patients under VKA had significantly prolonged TGT times compared with anticoagulated controls, with the greatest prolongations in patients with history of relapse or CAPS. Thus, TGT might be a useful tool to improve APS disease severity stratification without temporary cessation of VKA.https://rmdopen.bmj.com/content/11/3/e005489.full
spellingShingle Eric Hachulla
Julien Labreuche
David Launay
Marc Lambert
Cecile Yelnik
Marie Frimat
Sylvain Dubucquoi
Anne Bauters
Maximilien Desvages
Steve Lancel
Thrombin generation test as a useful tool for improving disease severity stratification in antiphospholipid syndrome
RMD Open
title Thrombin generation test as a useful tool for improving disease severity stratification in antiphospholipid syndrome
title_full Thrombin generation test as a useful tool for improving disease severity stratification in antiphospholipid syndrome
title_fullStr Thrombin generation test as a useful tool for improving disease severity stratification in antiphospholipid syndrome
title_full_unstemmed Thrombin generation test as a useful tool for improving disease severity stratification in antiphospholipid syndrome
title_short Thrombin generation test as a useful tool for improving disease severity stratification in antiphospholipid syndrome
title_sort thrombin generation test as a useful tool for improving disease severity stratification in antiphospholipid syndrome
url https://rmdopen.bmj.com/content/11/3/e005489.full
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