Treatment of type 3 von Willebrand disease by infusion of von Willebrand factor (VWF) and factor VIII (FVIII) concentrates may lead to the development of anti‐VWF antibodies, challenging haemostasis management. The systematic review of the literature presented here retrieved 15 such cases (surgery n = 11, bleeding n = 4). The heterogeneous patient management mostly involved continuous infusion of FVIII, or recombinant FVIIa together with various other strategies. Off‐label infusion of the bispecific monoclonal antibody emicizumab was prescribed in three cases and in a complex local case, ultimately well‐controlled with emicizumab. This illustrates the fact that emicizumab appears as a therapeutic option in this context of allo‐immunisation.

Heparin, a widely used polysaccharidic anticoagulant of animal origin, is associated with risks of contamination and adverse effects, notably bleeding and thrombocytopenia. These limitations have prompted interest in alternative sulfated polysaccharides with anticoagulant properties and improved safety profiles. This study explored the anticoagulant potential of two marine bacterial exopolysaccharides (EPS), infernan and diabolican. It assessed whether chemical modifications (depolymerization, oversulfation) could enhance their anticoagulant properties compared to unfractionated and low molecular weight heparins. Native EPS were depolymerized to generate different molecular weights and then chemically oversulfated to increase negative charge density. Anticoagulant activities were evaluated using clotting and thrombin generation assays (TGA). Molecular docking was performed to model interactions with antithrombin and heparin cofactor II. Only highly sulfated derivatives significantly prolonged activated partial thromboplastin time while showing negligible effect on thrombin time and anti-factor Xa activity. They present different structures, and their binding to antithrombin is not achieved via the classic pentasaccharide motif. In TGA, these derivatives inhibited thrombin formation at higher doses than heparin but induced a marked delay in clot generation. Docking analyses supported their ability to bind serpins, albeit with lower specificity than heparin. Their limited anti-Xa activity and non-animal origin position them as promising anticoagulant candidates.

Available products for the treatment of von Willebrand disease (VWD) now include a new recombinant von Willebrand factor (rVWF) in addition to plasma-derived concentrates (pdVWF). However, these two therapies have never been compared directly in either preclinical studies or real-world inpatient settings. The Hopscotch Will II study examined the treatment of VWD in hospitals and compared the use of pdVWF and rVWF. Five Rare Bleeding Diseases Centers in Western France retrospectively included patients with VWD over a 48-month period. The data was collected from the BERHLINGO Research Database as well as the French Hospital database, which contains medical information from patient records. Of the 866 patients evaluated in the study, 285 underwent 648 hospitalizations; 126 adult patients (VWD type 3 excluded) were given VWF concentrates during 249 of those hospital stays. rVWF was used in 61% of the cases. The majority of the hospitalizations were motivated by cutaneous-mucosal symptoms in gastroenterology, stomatology, gynecology, and obstetrics. Consumption of rVWF was lower, though the difference in total VWF consumption per stay or per patient per year was not significant: 51 (57)/34 (30) IU/kg/patient/year for pdVWF versus 40 (47)/27 (26) for rVWF (mean [SD]/median [IQR], Wilcoxon rank sum test, p = 0.2025). rVWF was used in similar patient profiles and for identical procedures, but the cost of treatment with rVWF was significantly lower, regardless of whether or not FVIII was added.