Hemophilia management: Huge impact of a tiny difference

Abstract

Hemophilia A and B are inherited X‐linked disorders of hemostasis, associated with an increased bleeding tendency. Patients with severe hemophilia have undetectable clotting factor levels and experience spontaneous bleeds. In patients with nonsevere hemophilia, the clotting factor levels are 2% to 40% of normal and bleeds predominantly occur after provocative events such as trauma and surgery. Despite this milder phenotype, patients with nonsevere hemophilia may suffer from considerable morbidity and have an increased mortality risk. However, many aspects of the course of disease and treatment remain unclear. Information on the factors influencing interindividual differences in bleeding phenotype is lacking, and misdiagnosis may occur due to assay discrepancies in the diagnostic workup. Desmopressin is the preferred treatment modality, but some patients and indications require treatment with clotting factor concentrates. This may elicit inhibitor formation, which is associated with an increased burden of disease and a higher mortality rate. It has been found that patients with nonsevere hemophilia A carry a lifelong risk for this serious complication. In this review, we provide an overview of the current knowledge of the diagnosis and management of nonsevere hemophilia. A report of science presented at the International Society on Thrombosis and Haemostasis 2019 Annual Congress is also provided.

Nonsevere Hemophilia: The Need for a Renewed Focus and Improved Outcomes

“…55 Mild hemophilia B appears to confer very low inhibitor risk. 56 Evidence relating to inhibitors has largely been obtained from patients with severe hemophilia A, in whom the majority of inhibitors develop during the first 50 exposure days, after which the risk of inhibitor development decreases to <1%. 57 In contrast, for patients with nonsevere disease, inhibitor risk has been calculated as 6.7% and 13.3% at 50 and 100 exposure days, respectively.…”

Preoperative diagnosis and management of inherited bleeding disorders in female adolescents and adults

“…Prophylaxis with FVIII replacement remains the standard of care for male hemophilia A, as nonreplacement products such as prophylactic emicizumab, given subcutaneously every 4 weeks, are not suitable for acute bleeding episodes or management in major surgery. 80 , 81 , 102 …”

Preference of treatment characteristics among people with haemophilia or their caregivers, and physicians in the Japanese healthcare environment

“…1 Haemophilia treatments are used to prevent and manage bleeding episodes, which may result in long-term musculoskeletal damage if left untreated. 2,3 Given the differences in bleeding prevention, haemostatic efficacy, safety, and other characteristics of available products, as well as variation among people with haemophilia (PWH), such as severity of disease, bleeding and treatment history, bleeding phenotype, inhibitor status, etc. individualised treatment is often preferred to optimally address patients' needs.…”