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Objectives: Thrombocytopenia is frequently observed in antiphospholipid antibody (aPL) carriers. Due to the paradoxical risks of thrombosis and hemorrhage, the management of aPL-associated thrombocytopenia (APAT) is often deductive. We aimed to investigate the efficacy and safety of therapeutic approaches for APAT through a systematic review. Methods: Four therapeutic approaches for APAT, including antiplatelet agents, glucocorticoids, splenectomy and thrombopoietin receptor agonists, were selected. Clinical trials evaluating therapeutic outcomes including the remission, complications, mortality and relapse, were searched in MEDLINE, EMBASE and CENTRAL from the inception dates to 28 November 2016. A meta-analysis was performed to calculate risk ratios (RRs) and 95% confidence intervals (CIs) using random-effects models. Results: Out of 1407 papers, eight controlled clinical trials were included. In patients with APAT, the remission rates were higher in patients on glucocorticoids (RR 8.33 [95% CI 3.07-22.6]) or splenectomy (RR 8.37 [95% CI 1.61-43.7]) than in patients without those treatments. There was no significant association between glucocorticoids and thrombosis (RR 1.57 [95% CI, 0.17-14.9]) or between splenectomy and hemorrhage (RR 0.17 [95% CI 0.02-1.28]). The extracted data of mortality and relapse rate were not available for synthesis. Conclusion: Glucocorticoids or splenectomy seemed suitable therapeutic approaches for APAT.

Objective: The objective of this study was to clarify the efficacy and safety of factor Xa inhibitors for antiphospholipid syndrome patients in real world utilization., Methods: This is a retrospective cohort study comprised of all consecutive patients with antiphospholipid syndrome in our department over a period of 28 years. Patients treated with factor Xa inhibitors were extracted from the cohort. As a control group, patients treated with warfarin were selected from the same cohort with matched age, gender, coexistence of systemic lupus erythematosus, and the presence of antiplatelet therapy, after which we used a propensity score for each of the risk factors as an additional covariate in multivariate Cox proportional hazard regression. The primary endpoint was set as thrombotic and hemorrhagic event-free survival for five years., Results: Among 206 patients with antiphospholipid syndrome, 18 had a history of anti-Xa therapy (five rivaroxaban, 12 edoxaban, one apixaban). Fourteen out of 18 patients on anti-Xa therapy had switched to factor Xa inhibitors from warfarin. Event-free survival was significantly shorter during anti-Xa therapy than that during warfarin therapy (hazard ratio: 12.1, 95% confidence interval: 1.73-248, p  = 0.01) ( Figure 1(a) ). Similarly, event-free survival in patients treated with factor Xa inhibitors was significantly shorter compared with controls (hazard ratio: 4.62, 95% confidence interval: 1.54-13.6, p  = 0.0075). In the multivariate Cox proportional hazard model, event-free survival in patients with anti-Xa therapy remained significantly shorter (hazard ratio: 11.9, 95% confidence interval: 2.93-56.0, p  = 0.0005)., Conclusions: Factor Xa inhibitors may not be recommended for antiphospholipid syndrome.

Objective: Warfarin is regarded as the standard treatment for preventing thrombotic events in APS, but the recurrence rate is still high. Dual antiplatelet therapy (DAPT) has been shown to be effective for the prevention of acute coronary syndrome or stroke. The objective of this study was to evaluate the efficacy of DAPT for the prevention of thrombosis recurrence in APS patients with history of arterial thrombosis., Methods: This retrospective cohort study of APS patients was conducted at Hokkaido University Hospital between 1990 and 2016. The secondary prophylactic effects and safety of warfarin monotherapy (Wf), antiplatelet monotherapy (AP), warfarin and antiplatelet combination therapy (Wf + AP) and DAPT were evaluated. The primary endpoints were set as thrombosis-free and adverse events-free survival period. Adverse events were defined as severe bleeding and death., Results: A total of 90 APS patients were enrolled. Thrombotic recurrence was found in 40 patients (35 arterial and 5 venous thromboses) and serious adverse events in 20 patients (9 severe bleeding events and 14 deaths). Kaplan-Meier analysis demonstrated a 10-year recurrence-free survival rate of 62%. The recurrence rate per 100 patient-years was as follows: Wf: 11.6, AP: 5.5, Wf: + AP: 3.7, DAPT: 1.8. We demonstrated that DAPT significantly reduced the rate of recurrence compared with Wf (log-rank P = 0.001). There were no significant differences in the rate of serious adverse events among the groups., Conclusion: DAPT might be considered as an effective and safe option for the prophylaxis of recurrent arterial thrombosis in APS., (© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Essentials Thrombotic risk stratification is an unmet need in antiphospholipid antibody carriers. Platelet count and antiphospholipid score (aPL-S) were combined to predict thrombotic events. Patients with high aPL-S are at high thrombotic risk regardless of platelet count. If platelet count is low, patients with low aPL-S are also on high thrombotic risk., Summary: Background Thrombocytopenia is a non-criteria clinical manifestation of antiphospholipid syndrome. However, it remains to be elucidated whether thrombocytopenia increases thrombotic risk in antiphospholipid antibody (aPL) carriers. Objectives To investigate the impact of platelet count in terms of predicting thrombotic events in aPL carriers, and to stratify the thrombotic risk by combining platelet count and antiphospholipid score (aPL-S), which represents a quantification of aPL varieties and titers. Patients/methods A single-center, retrospective, longitudinal study comprising 953 consecutive patients who were suspected of having autoimmune disease between January 2002 and December 2006 was performed. Low platelet count was defined as a count of < 150 × 10 3 μL -1 at the time of aPL testing. Results A negative correlation was observed between aPL-S and platelet count (r = - 0.2477). Among aPL-positive patients, those with a low platelet count developed thrombosis more frequently than those without (hazard ratio [HR] 2.95, 95% confidence interval [CI] 1.11-7.88). Among aPL-negative patients, no difference was found in the predictive value of thrombosis regardless of platelet count. Patients with aPLs were further divided into two subgroups according to aPL-S. Among low-aPL-S patients, those with low platelet counts developed thrombosis more frequently than those without (HR 3.44, 95% CI 1.05-11.2). In contrast, high-aPL-S patients developed thrombosis frequently regardless of platelet count. Conclusions aPL carriers with low platelet counts are at high risk of developing thrombosis. In particular, 'low-aPL-S carriers' may be stratified by platelet count in terms of predicting future thrombotic events., (© 2017 International Society on Thrombosis and Haemostasis.)

Background: CD36, known as a scavenger receptor, is a transmembrane glycoprotein expressed on monocytes, platelets and endothelial cells, recognizes multiple ligands, including phosphatidylserine, and regulates atherogenesis and thrombosis. The objective of this study is to investigate the possible involvement of CD36 in the pathophysiology of thrombosis in patients with antiphospholipid syndrome (APS)., Methods: First, rs3765187, a missense mutation linked to CD36 deficiency, was investigated by TaqMan polymerase chain reaction (PCR) genotyping method in 819 Japanese, including 132 patients with APS, 265 with systemic lupus erythematosus (SLE) in the absence of APS, and 422 healthy subjects. Then, the involvement of CD36 in antiphospholipid antibody (aPL)-induced tissue factor (TF) expression was examined using CD36-null mice or anti-CD36. Purified IgG from patients with APS and a monoclonal phosphatidylserine-dependent antiprothrombin antibody were used in these experiments. TF expression was tested by real-time PCR and flow cytometry., Results: Minor allele carrier of rs3765187 was less frequent in patients with APS (3.8% p=0.032), but not in patients with SLE in the absence of APS (7.9% p=0.32), compared with healthy subjects (10.2%). The aPL-induced TF expression was significantly suppressed on peritoneal macrophages from CD36-null mice compared to wild type and significantly inhibited by anti-CD36 on human monocytes., Conclusions: The gene mutation linked to CD36 deficiency was less frequent in patients with APS. The deficient or suppressed CD36 function significantly reduced aPL-induced TF expression in vitro. Taken together, in a susceptible background CD36 scavenger receptor function may be involved in the thrombotic pathophysiology in patients with APS.

Objective: To study the clinical and immunological manifestations of antiphospholipid syndrome (APS) in the Japanese population by a single-centre registration., Methods: In this retrospective cohort study, 141 consecutive patients with APS, fulfilling the Sydney revised Sapporo criteria for definite APS, who visited our autoimmune clinic from 1988 to 2010, were recruited and followed up. All the patients were interviewed and underwent a general physical examination by qualified rheumatologists on the day of blood sampling., Results: The population comprised 119 woman and 22 men with a mean age at diagnosis of 44 years (range 9-79 years). Seventy patients (49.6%) had primary APS, and 71 (50.4%) had systemic lupus erythematosus. The prevalence of thrombosis was 85.8 per cent, arterial thrombosis was found in 93 patients (66.0%) and venous thrombosis was found in 46 patients (32.6%). The most common thrombosis was cerebral infarction [86/141 (61.0%)] followed by deep vein thrombosis [33/141 (23.4%)]. Among 70 pregnant women, 45 (64.3%) had obstetric complications. Lupus anticoagulant was detected in 116 patients (82.3%), anticardiolipin antibodies in 83 (58.9%), anti-β2 glycoprotein I antibodies in 73 (51.8%) and phosphatidylserine-dependent antiprothrombin antibodies in 98 (69.5%)., Conclusion: High prevalence of arterial thrombosis was noted in Japanese patients with APS. The profile of heterogeneous and complex clinical manifestations was substantiated in Japanese patients with APS.

Objective: To define the antiphospholipid score (aPL-S) by testing multiple antiphospholipid antibodies (aPL) and to evaluate its efficacy for the diagnosis of antiphospholipid syndrome (APS) and predictive value for thrombosis., Methods: This study comprised 2 independent sets of patients with autoimmune diseases. In the first set of patients (n = 233), the aPL profiles were analyzed. Five clotting assays for testing lupus anticoagulant and 6 enzyme-linked immunosorbent assays (IgG/IgM anticardiolipin antibodies, IgG/IgM anti-β(2)-glycoprotein I, and IgG/IgM phosphatidylserine-dependent antiprothrombin antibodies) were included. The association of the aPL-S with a history of thrombosis/pregnancy morbidity was assessed. In the second set of patients (n = 411), the predictive value of the aPL-S for thrombosis was evaluated retrospectively. Two hundred ninety-six of these patients were followed up for >2 years. The relationship between the aPL-S and the risk of developing thrombosis was analyzed., Results: In the first set of patients, the aPL-S was higher in those with thrombosis/pregnancy morbidity than in those without manifestations of APS (P < 0.00001). For the aPL-S, the area under the receiver operating characteristic curve value was 0.752. In the second set of patients, new thromboses developed in 32 patients. The odds ratio (OR) for thrombosis in patients with an aPL-S of ≥30 was 5.27 (95% confidence interval [95% CI] 2.32-11.95, P < 0.0001). By multivariate analysis, an aPL-S of ≥30 appeared to be an independent risk factor for thrombosis (hazard ratio 3.144 [95% CI 1.383-7.150], P = 0.006)., Conclusion: The aPL-S is a useful quantitative index for diagnosing APS and may be a predictive marker for thrombosis in autoimmune diseases., (Copyright © 2012 by the American College of Rheumatology.)