Prevalence and Significance of Non-conventional Antiphospholipid Antibodies in Patients With Clinical APS Criteria

Background: The biological diagnostics of antiphospholipid syndrome (APS) takes into account the persistent positivity for anticardiolipin and/or anti-β2GP1 antibodies and/or presence of lupus anticoagulant (LA). However, some non-conventional antiphospholipid antibodies have emerged that could help in the diagnosis of APS.Objectives: To study the potential usefulness of non-conventional antiphospholipid antibodies in clinical practice.Methods: Eighty-seven patients, aged from 15 to 92 years were included and classified in following groups: 41 patients positive for the conventional antibodies with clinical criterion of APS (31 with primary APS and 10 secondary), 17 seronegative APS (SNAPS) patients (i.e., persistent negativity for the conventional antibodies with a strong clinical suspicion of APS), 11 asymptomatic antiphospholipid antibodies carriers (i.e., persistent positivity for the conventional antibodies without clinical evidence of APS), and 18 patients presenting with a first thrombotic or obstetrical event. IgG and IgM were detected to the following antigens: phosphatidylserine/prothrombin (PS/PT) by ELISA, and phosphatidic acid, phosphatidyl-ethanolamine, phosphatidyl-glycerol, phosphatidyl-inositol, phosphatidylserine, annexin V, prothrombin by immunodot. Anti-β2GP1 IgA, and anti-β2GP1 domain 1 IgG were detected by chemiluminescence.Results: Positivity for the non-conventional antibodies was correlated with APS severity; patients with catastrophic APS (CAPS) being positive for 10.7 (Median, Range: 5–14) non-conventional antibodies. 9/17 seronegative patients were positive for at least one of non-conventional antibodies. A study of non-supervised hierarchical clustering of all markers revealed that anti-PS/PT antibodies showed high correlation with the presence of LA. All patients with APS triple positivity (highest risk profile) exhibited also persistent positivity for anti-PS/PT antibodies.Conclusions: Our data obtained from a prospective cohort constituted mainly by patients with primary APS, suggest that non-conventional APS antibodies may be useful for patients classified as SNAPS. They demonstrate the potential value of aPS/PT antibodies as a strong marker of APS. We propose that anti-PS/PT antibodies could be a surrogate APS biological marker of LA to classify in high-risk profile patients treated by direct oral anticoagulants (DOACs), in whom LA detection cannot be achieved

Br J Haematol

International audienc

Etiologies et traitements de la carence en vitamine B12 chez l'adulte

PARIS-BIUP (751062107) / SudocSudocFranceF

Intérêts et surveillance du traitement par hydroxychloroquine du lupus érythémateux systémique

PARIS-BIUP (751062107) / SudocSudocFranceF

Etude des microparticules plaquettaires et des anticorps antiphospholipides dans la maladie de Buerger

PARIS-BIUP (751062107) / SudocSudocFranceF

Amylose AL et activité anti-Xa circulante spontanée (à propos d'un cas)

CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Recherche de la mutation V617F de JAK2 (évaluation des pratiques à l'hôpital Georges Pompidou)

Une grande avancée dans la compréhension de la physiopathologie des syndromes myéloprolifératifs BCR-ABL1 négatifs (la polyglobulie de Vaquez, la thrombocytémie essentielle et la myélofibrose primitive) a été réalisée avec la découverte en 2005 d'une mutation du gène codant la protéine à activité tyrosine kinase JAK2, au niveau de l'exon 14 en position 617 (Val617Phe), commune à ces 3 pathologies. En 2006 puis 2007, des mutations sur le récepteur de la thrombopoïétine (MPL) ont été mises en évidence chez des patients avec une TE et une MFP négatifs pour la mutation V617F de JAK2 ; ainsi que d'autres mutations du gène JAK2 situées dans l'exon 12 dans de rares cas de PV négatives pour la mutation V617F de JAK2. Les indications reconnues de recherche de la mutation V617F de JAK2 sont l'existence d'une polyglobulie, thrombocytose, fibrose médullaire, hyperleucocytose BCR-ABL1 négative, monocytose et splénomégalie inexpliquées, prurit à l'eau chaude, thrombose veineuse en territoire splanchnique. Il était donc intéressant d'évaluer les pratiques de recherche de la mutation V617F de JAK2 à l'HEGP. Cette dernière a été recherchée chez 347 patients et était positive chez 64 d'entre eux (18,4%). Une mutation de l'exon 12 de JAK2 était positive chez un patient. La mutation V617F est retrouvée chez 19% des patients présentant une polyglobulie, 40% des patients présentant une thrombocytose et 7% des patients avec un contexte de thrombose veineuse en territoire splanchnique. Si on se réfère aux indications reconnues, la mutation V617F de JAK2 à l'HEGP est recherchée de manière trop importante dans les thromboses artérielles et/ou veineuses des sites habituels (environ 32%) et pas de manière assez ciblée en présence d'un polyglobulie (environ 15% de fausse polyglobulie et 28% de polyglobulie secondaire). C'est pour cette raison qu'une feuille de renseignements clinico-biologiques à remplir par le médecin doit accompagner la prescription dans le but d'éviter les prescriptions excessives.CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Recent Advances in Anticoagulant Treatment of Immune Thrombosis: A Focus on Direct Oral Anticoagulants in Heparin-Induced Thrombocytopenia and Anti-Phospholipid Syndrome

For more than 10 years, direct oral anticoagulants (DOACs) have been increasingly prescribed for the prevention and treatment of thrombotic events. However, their use in immunothrombotic disorders, namely heparin-induced thrombocytopenia (HIT) and antiphospholipid syndrome (APS), is still under investigation. The prothrombotic state resulting from the autoimmune mechanism, multicellular activation, and platelet count decrease, constitutes similarities between HIT and APS. Moreover, they both share the complexity of the biological diagnosis. Current treatment of HIT firstly relies on parenteral non-heparin therapies, but DOACs have been included in American and French guidelines for a few years, providing the advantage of limiting the need for treatment monitoring. In APS, vitamin K antagonists are conversely the main treatment (+/− anti-platelet agents), and the use of DOACs is either subject to precautionary recommendations or is not recommended in severe APS. While some randomized controlled trials have been conducted regarding the use of DOACs in APS, only retrospective studies have examined HIT. In addition, vaccine-induced immune thrombotic thrombocytopenia (VITT) is now a part of immunothrombotic disorders, and guidelines have been created concerning an anticoagulant strategy in this case. This literature review aims to summarize available data on HIT, APS, and VITT treatments and define the use of DOACs in therapeutic strategies