Congenital Bleeding Disorders

Abstract

Deficiencies of coagulation factors VIII and IX and von Willebrand factor constitute the majority of inherited bleeding disorders, while deficiencies of fibrinogen; prothrombin; factors V, VII, X, XI, and XIII; and PAI-1 constitute rare bleeding disorders (RBDs). Inherited deficiencies of inhibitors of fibrinolysis are extremely rare bleeding disorders and are included under the “miscellaneous” category. The clinical spectrum of bleeding symptoms in these disorders ranges from mucocutaneous bleeding to musculoskeletal bleeding. Rarely, these disorders are asymptomatic and present only after hemostatic challenge such as surgical procedures or trauma. Availability of clotting factor concentrates and adjuvant therapies, such as desmopressin (DDAVP) and antifibrinolytics, as well as comprehensive care within specialized hemophilia treatment centers (HTCs), has transformed patient outcomes and quality of life. Modifications to the recombinant factor proteins have prolonged the half-life of these factors, hence reducing the number of doses and increasing the residual trough levels in patients on prophylaxis. Newer therapies for patients with hemophilia A and B include alternative substitution and hemostatic rebalancing therapies and gene therapy. This chapter provides an overview of the clinical presentation, diagnostic testing, and principles of management for patients with inherited bleeding disorders.