The History of Rare Bleeding Disorders

Abstract

Deficiencies in coagulation factors I (FI), FII, FV, combined FV and FVIII (CF5F8) and vitamin K-dependent coagulation factors FVII, FX, FXI, and FXIII have been referred to as rare bleeding disorders (RBDs), rare coagulation factor deficiencies (RCFDs), or recessively inherited coagulation disorders. Fibrinogen was most likely the first member of this group to be identified, with reports of its discovery spanning from 1859 to 1966. If not, then the first coagulation factor to be identified was prothrombin in 1894, and the last coagulation factor to be found was FX in 1956, about 60 years later. The first patient to be diagnosed with an RBD was a 9-year-old boy with afibrinogenemia in 1920 and the vitamin K-dependent coagulation factors deficiency was the most recent RBD in this group to be identified in a 3-month-old child in 1966. The initial therapeutic option for nearly all patients with RBDs was whole blood transfusion; this was replaced in 1941 by fresh frozen plasma (FFP), and then in later years by cryoprecipitate and coagulation factor concentrates. Fibrinogen concentrate was the first coagulation factor concentrate produced in 1956. Coagulation factor concentrate is now available for FI, FVII, FX, FXI, and FXIII; however, FFP and/or platelet transfusion are the only treatments available for FV deficiency. The only recombinant concentrates available for RBDs are for FVII and FXIII, which date from 1988 and the 2000s, respectively. Even though the clinical presentations, diagnosis, and management of lesser-known bleeding disorders have improved significantly in recent decades, more studies are needed to reveal the hidden aspects of these disorders in order to overcome diagnostic and therapeutic challenges and ultimately improve the quality of life for those who are affected.