Recent advances in therapeutic options for rare hemostatic disorders: selected poster extracts of recent research in hemophilia A, congenital hemophilia with inhibitors, von Willebrand disease, and thrombotic thrombocytopenic purpura presented at the 29th congress of the International Society on Thrombosis and Haemostasis (ISTH 2021, Jul 17-21; virtual congress).

Hemophilia, von Willebrand disease (VWD), and thrombotic thrombocytopenic purpura (TTP) are rare diseases affecting normal hemostasis. Although they differ in their pathogenesis and clinical manifestation, if left undiagnosed and untreated, all these conditions can result in severe long-term consequences and can be potentially life-threatening. This article summarizes a poster series funded by Takeda and presented virtually at the 29th annual congress of the International Society on Thrombosis and Haemostasis (ISTH) in 2021: Data from real-world evidence highlight the importance of joint health and personalized prophylaxis to prevent bleeding for patients with hemophilia, the need to further raise disease awareness in support of timely diagnosis and access to treatment in general practice settings for patients with VWD, and describe the clinical burden for patients with TTP and the importance to advance treatment options for these patients.

Thrombotic events with recombinant activated factor VII (rFVIIa) in approved indications are rare and associated with older age, cardiovascular disease, and concomitant use of activated prothrombin complex concentrates (aPCC).

PURPOSE: Recombinant activated factor VII (rFVIIa; NovoSeven® RT; Novo Nordisk A/S, Bagsvaerd, Denmark) is approved in the United States for the treatment of bleeding and perioperative management in congenital hemophilia with inhibitors (CHwI), acquired hemophilia (AH), congenital factor VII (FVII) deficiency, and Glanzmann's thrombasthenia (GT) with refractoriness to platelets. The aim of the current analysis was to review clinical trials and registries pre- and post-licensure for each indication to establish the estimated rate of thrombosis and then to establish the association of all reported thrombotic events (TEs) with certain risk factors listed for many years in the prescribing information (PI). PATIENTS AND METHODS: A retrospective safety assessment of both clinical trials and registries used to support licensure and postmarketing surveillance was performed. The rate of thrombosis was calculated in the 4 indicated disorders and an assessment of TE risk factors was conducted through a review of all narratives within those indications in the safety database. RESULTS: In clinical trials and registries used to support licensure and in postmarketing surveillance, the overall rate of thrombosis was 0.17% of 12,288 bleeding and surgical episodes. The specific risk by indication was 0.11% for CHwI, 0.82% for FVII deficiency, 0.19% for GT, and 1.77% for AH. The most common associated risk factor-"elderly" (29%), defined in the PI as age ≥65 years-was particularly prevalent in patients with AH. TE was also frequently reported with concomitant cardiac or vascular disease (18%) and use of activated prothrombin complex concentrates (18%). CONCLUSION: Data show that the rate of TEs within the 4 licensed indications is low, as was originally described in the US PI from 1999 to 2009. It has remained stable over time during postapproval surveillance in multiple US and global registries with active surveillance for safety information across the 4 approved indications.

Eptacog Alfa (Activated) Is Physically and Chemically Stable over 24 Hours when Administered as Bolus Injections in an Automated Infusion Pump.

Introduction Eptacog alfa (activated) is a recombinant activated factor VII (rFVIIa) used for the treatment and prevention of bleeding episodes in patients with congenital hemophilia with inhibitors. Frequent dosing requirements make the use of an automated bolus infusion pump a promising alternative to manual administration. Aims The objective of this in vitro study was to evaluate the physical and chemical stability of room temperature-stable rFVIIa at 25°C over 24 hours in an automated bolus infusion pump. Methods An automated bolus infusion pump with preset bolus injection intervals of 2 to 6 hours was used. Samples of rFVIIa were analyzed for critical quality parameters, presence of leachables, and microbiological growth. The infusion system was evaluated visually. Results rFVIIa is physically and chemically stable when used in an automated bolus infusion pump system for up to 24 hours at 25°C. All critical quality parameter results were within the shelf-life limits and complied with the acceptance criteria. Leachables were observed at concentrations within their respective acceptance criteria. No visual changes in the syringe or infusion tube were observed; inherent particles in the reconstituted rFVIIa similar in size and description to those previously found in rFVIIa were seen. No microbiological growth was detected. Conclusions rFVIIa is stable in a bolus infusion pump system for up to 24 hours at 25°C. Bolus injection intervals of 2 to 6 hours can be used without physical or chemical changes to rFVIIa. This study supports the use of an automated bolus infusion pump in the hospital setting, across all indications for rFVIIa.