Fitusiran, a subcutaneous investigational small interfering RNA therapeutic, lowers antithrombin (AT) to increase thrombin generation and rebalance hemostasis in people with hemophilia. This phase 3 open-label extension study (ATLAS-OLE) evaluated safety and efficacy of an AT-based dose regimen (AT-DR) in males aged ≥12 years with severe hemophilia A/B, with/without inhibitors. The original dose regimen (ODR) of 80 mg monthly was optimized to AT-DR targeting AT activity levels 15% to 35% to mitigate thrombotic risk (starting dose of 50 mg once every 2 months, individually adjusted to 20 mg once every 2 months, or 20/50/80 mg monthly as needed). Primary and secondary end points were safety and efficacy, respectively. Integrated safety analyses assessed safety of AT-DR and ODR across all fitusiran studies and integrated efficacy analyses compared efficacy of AT-DR in ATLAS-OLE with phase 3 parent study control groups. At interim data cutoff, 213 participants were enrolled on AT-DR (78% on regimens of once every 2 months). Integrated safety analyses of participants receiving AT-DR (n = 286) demonstrated that AT-DR was well tolerated. In ATLAS-OLE, median observed annualized bleeding rate (ABR) with AT-DR was 3.7 (interquartile range, 0.0-7.5). Integrated efficacy analyses demonstrated superiority of AT-DR over on-demand clotting factor concentrates (CFCs; 71% mean ABR reduction; P < .0001), and on-demand bypassing agents (BPAs; 73% mean ABR reduction; P = .0006); improvement over BPA prophylaxis (70% mean ABR reduction); and ABR comparable with that observed with CFC prophylaxis. Fitusiran AT-DR was well tolerated and maintained bleed protection with as few as 6 injections per year. This trial was registered at www.ClinicalTrials.gov as #NCT03754790.

Inferior vena cava thrombosis (IVCT) is rare and can be under-recognized. However, the associated complications and mortality may be severe. We report the first case series of IVCT observed in Taiwan with a brief literature review. Eight Taiwanese patients with IVCT between May 2012 and December 2019 were enrolled in this study. Deep venous thrombosis (DVT, 8/8) and pulmonary embolism (5/8) were reported. Various risk factors were identified, including an unretrieved inferior vena cava (IVC) filter, pregnancy, surgery, presence of lupus of anticoagulants, essential thrombocythemia, antithrombin deficiency, and hemoglobin H disease. Of note, four of our patients experienced complete IVC thrombosis with bilateral lower extremity swelling (due to DVT) and abdominal wall superficial venous dilatation, while four other patients presented with partial IVCT and unilateral DVT. The etiology, clinical characteristics, presentations, diagnosis, and treatment of IVCT were reviewed.

Heritable thrombophilias are assumed important etiologies for recurrent pregnancy loss. Unlike in the Caucasian populations, protein S and protein C deficiencies, instead of Factor V Lieden and Prothrombin mutations, are relatively common in the Han Chinese population. In this study we aimed to investigate the therapeutic effect of low molecular weight heparin upon women with recurrent pregnancy loss and documented protein S deficiency. During 2011–2016, 68 women with recurrent pregnancy loss (RPL) and protein S deficiency (both the free antigen and function of protein S were reduced) were initially enrolled. All the women must have experienced at least three recurrent miscarriages. After excluding those carrying balanced translocation, medical condition such as diabetes mellitus, chronic hypertension, and autoimmune disorders (including systemic lupus erythematosus and anti-phospholipid syndrome), coexisting thrombophilias other than persistent protein S deficiency (including transient low protein S level, protein C deficiency, and antithrombin III), only 51 women with RPL and sole protein S deficiency were enrolled. Initially they were prescribed low dose Aspirin (ASA: 100 mg/day) and unfortunately there were still 39 women ended up again with early pregnancy loss (12 livebirths were achieved though). Low-molecular-weight-heparin (LMWH) was given for the 39 women in a dose of 1 mg/Kg every 12 h from the day when the next clinical pregnancy was confirmed to the timing at least 24 h before delivery. The perinatal outcomes were assessed. Of 50 treatment subjects performed for the 39 women (i.e. 11 women enrolled twice for two pregnancies), 46 singletons and one twin achieved livebirths. The successful live-birth rate in the whole series was 94 % (47/50). Nineteen livebirths delivered vaginally whereas 28 delivered by cesarean section. The cesarean delivery rate is thus 59.57 %. Emergent deliveries occurred in 3 but no postpartum hemorrhage had been noted. Our pilot study in Taiwan, an East Asian population, indicated anti-coagulation therapy is of benefit to women with recurrent pregnancy loss who had documented sole protein S deficiency. ISRCTN64574169 . Retrospectively registered 29 Jun 2016.

Introduction: Liver health is essential for persons with hemophilia (PWH) in order to maintain access to new therapies, such as gene therapy. Non-alcoholic fatty liver disease (NAFLD) is seldom reported in the hemophilia population. The study aimed to investigate the prevalence of NAFLD and associated factors in PWH. Methods: Data of this cross-sectional study were obtained from a multicenter collaborative registry database. Results: A total of 163 moderate or severe PWH with a complete data of liver examination were analyzed. There were 77 (47.2%) PWH diagnosed with NAFLD. The multivariate analysis showed that overweight/obesity was associated with NAFLD (OR, 4.31, P < .001). In comparison with hemophilia B patients, hemophilia A patients showed a weaker correlation with NAFLD, (OR, 0.30, P = .009). A total of 17 (25.8%) PWH with NAFLD had an elevated level of alanine transaminase (ALT). Both overweight/obesity and presence of inhibitor to clotting factor were independently associated with elevated ALT in PWH with NAFLD. Conclusions: The study indicated that a high prevalence of NAFLD existed in the hemophilia population. Overweight/obesity was an independent factor for NAFLD and elevated ALT.