Pediatric antiphospholipid syndrome: clinical features and therapeutic interventions in a single center retrospective case series.

BACKGROUND/PURPOSE: Pediatric antiphospholipid syndrome (APS) is a thromboinflammatory disease characterized by the presence of circulating antiphospholipid antibodies and either thrombotic events or pregnancy morbidity. The objective of this study was to review a large institution's experience to better understand the characteristics of children with APS. METHODS: We conducted a retrospective review of pediatric APS at a tertiary referral center. The electronic medical record system was queried from 2000 through 2019, and 21 cases were included based on meeting the revised Sapporo Classification criteria by age 18 or younger. Comparisons between primary and secondary APS patients were made with two-tailed t-tests. RESULTS: Twenty-one patients were included with a median age at diagnosis of 16 years and median follow-up of 5.8 years. Secondary APS was slightly more common than primary APS (11 vs. 10 cases) and was primarily diagnosed in the context of systemic lupus erythematosus. Two thirds of patients (67%) also had "non-criteria" manifestations of APS including thrombocytopenia, autoimmune hemolytic anemia, and livedo reticularis/racemosa. Almost half of patients (43%) had recurrent thrombosis, typically when patients were subtherapeutic or non-adherent with anticoagulation. Damage Index in Patients with Thrombotic APS (DIAPS) scores indicated a chronic burden of disease in both primary and secondary APS patients. CONCLUSION: This case series of pediatric APS provides important context regarding disease phenotypes displayed by children with APS. High prevalence of non-criteria clinical manifestations highlights the need to consider these characteristics when developing pediatric-specific classification criteria and when considering this relatively rare diagnosis in pediatric practice.

[Prospective assessment of a multidisciplinary meeting dedicated to inflammatory and vascular diseases during pregnancy]. / Évaluation prospective d'une réunion de concertation pluridisciplinaire dédiée aux pathologies inflammatoires et vasculaires lors de la grossesse : la RCP « PREGNANT ¼ au CHU de Bordeaux.

OBJECTIVES: The pluridisciplinary meeting "PREGNANT - Pregnancy and Auto-immunity, Nephropathy, Thrombophilic Disorders" at the university hospital of Bordeaux is dedicated to inflammatory and thrombophilic disorders during pregnancy. The objective of our study was to evaluate the quality of this meeting in terms of: compliance with the mandatory criteria, adequacy with standard care, homogeneity of care, becoming of proposals issued. METHODS: We conducted a prospective observational study including patients whose files were submitted to the meeting from January 2018 to June 2019. RESULTS: In all, 16 meeting were conducted with 152 cases presented. Sixty-two patients were pregnant and 90 were in preconception. The most common reasons for presentation were vasculo-placentary diseases (22.3%), systemic lupus (16.4%), venous thromboembolic diseases (15.1%) and chronic intervillositis of unknown etiology (9.8%). Other reasons were antiphospholipid antibody syndrome and repeated spontaneous miscarriages. The mandatory criteria for multidisciplinary meeting were met. For 89 cases (58.5%), the problem was dictated by recommendations. Decisions made were consistent with recommendations in 89.8% of cases. Among the 63 cases without any published recommendations (41.5%), there was some homogeneity of the proposals. In all, 92.8% of the proposals issued by the meeting were implemented. CONCLUSIONS: Multidisciplinary meeting "PREGNANT" has a prominent locoregional role in the management of patients with autoimmune, inflammatory or thrombophilic disorders in a pregnancy context.

Risk assessment in patients with antiphospholipid antibodies.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the association of antiphospholipid antibodies (aPL) with thrombosis and/or pregnancy loss: classification criteria were defined in the updated international consensus held in Sidney in 2005. Vascular and obstetric manifestations display partially different pathogenetic mechanisms. Thrombosis develop as a result of local procoagulative changes upon triggers influence (second-hit theory). Pregnancy morbidity is thought to be dependent on placental thrombosis and complement activation. The laboratory tests include Lupus Anticoagulant (LA), a functional assay, and anticardiolipin (aCL) and anti-ß2-glycoprotein I antibodies detected by solid phase enzyme-linked immunosorbent assay (ELISA). The LA testing is relatively standardized while there's still significant interlaboratory discrepancy in ELISA tests. Current APS criteria are under discussion: since for vascular and obstetric APS, different pathogenetic mechanisms have been shown, some criteria variation could also be contemplated. What is the weight of aPL antibodies in provoking thrombosis and which contribution could be expected from aPL per se is debated. As thrombosis is generally considered to be multi-factorial, each case needs a risk-stratified approach. Any primary prophylaxis, intensity and duration of secondary prophylaxis should take into account aPL profile, other cardiovascular risk factors and systemic autoimmune diseases associated. We look forward to the publication of recommendations of the leading experts in the field, developed during the recent 14th International Congress in Rio de Janeiro, Brazil.

Thrombin generation assay as a possible tool for assessment of reduced activity of clotting factors induced by antiphospholipid antibodies and in-vitro evaluation of treatment options.

Bleeding is a rare manifestation of antiphospholipid syndrome, unless associated with reduced clotting factors or severe thrombocytopenia. Accurate assessment of the autoantibodies in plasma is very important since the autoantibodies can lead to bleeding or thrombosis. The objective of the present study was to define the inhibitors causing reduced clotting activity in a patient with antiphospholipids antibodies and to assess the potential of thrombin generation assay to assist in establishment of optimal treatment in case of major bleeding. Levels of clotting factors as well as inhibitors to factors II, V, VII, VIII, IX, X and XI were defined. For detection of inhibitors to prothrombin crossed immunoelectrophoresis was used. IgG was purified by commercial protein A column. Thrombin generation was measured using a fluorometric assay in platelet-poor and platelet-rich plasma. Inhibitors toward the activity of factors V, VII, VIII, IX, X and XI were defined and also an inhibitor to prothrombin antigen. No thrombin generation was induced in the patient's plasma by recalcification even in the presence of recombinant factor VIIa or factor VIII inhibitor bypassing activity. In contrast, addition of platelets from either donor or patient or synthetic phospholipids normalized the thrombin generation. The thrombin generation model showed that the addition of platelets and no recombinant factor VIIa or factor VIII inhibitor bypassing activity would correct thrombin generation in vitro. On this basis, platelet concentrates were administered to a patient with bleeding caused by lupus anticoagulant and low clotting factors activity.