Overview on Rare Congenital Bleeding Disorders and Epidemiological Data from the German Haemophilia Registry (DHR) and a Survey in Germany, Austria, and Switzerland.

Abstract

Rare bleeding disorders (RBDs), defined as hereditary coagulation factor deficits other than haemophilia, are characterized by a heterogenous clinical phenotype ranging from life-threatening bleeding to thrombosis. There are uncertainties concerning treatment intensity and levels needed to achieve haemostasis, and epidemiological data from Germany, Austria, and Switzerland (GTH region) are scarce.We performed a narrative literature review, focusing on bleeding phenotype and thrombotic risk. Epidemiologic data, including adults and children, and general treatment approaches have been collected via an online survey among GTH haemophilia centres (all categories) and the general information service of the German national registry (Deutsches Hämophilieregister, DHR).We provided an overview on RBDs, revealing that especially in FV, FVII, and FXI deficiencies, the correlation between factor levels and bleeding phenotype is poor. A thrombotic risk needs to be considered in FVII deficiency and afibrinogenaemia or dysfibrinogenaemia. The survey was completed by 34 centres from Germany, Austria, and Switzerland, and compared with 137 centres reporting data to the DHR. FVII deficiency was confirmed to be the most frequent, and FII deficiency was the rarest RBD in this region. For treatment, single factor concentrates were preferred over multifactor concentrates or plasma, and tranexamic acid was often part of the treatment. Approximately 30, 40, and <10% of patients with severe FV, FVII, and FXI deficiency (defined as factor level <10%), respectively, were receiving prophylactic treatment, suggesting an overall milder bleeding phenotype.More detailed registry data could give insights into the treatment landscape of RBDs, considering the challenge of clinical trials in rare diseases.