Coagulation factor concentrates and pharmacologic therapies for acquired bleeding disorders

Acquired bleeding disorders are much more common than congenital bleeding disorders and may occur in association with specific clinical conditions or may arise spontaneously in otherwise healthy patients. Prothrombin complex concentrates (PCCs) contain vitamin-K dependent coagulation factors (VKDFs) and are available as activated and nonactivated concentrates. Recombinant activated factor VII (rFVIIa) is a vitamin-K-dependent glycoprotein that initiates the tissue factor pathway of the coagulation cascade. At physiologic concentration, rFVIIa complexes with tissue factor (TF) at the site of vascular injury, forming the TF-FVIIa complex. Protamine sulfate is a strongly basic, arginine-rich protein that binds to the negatively charged heparin molecules forming an inactive salt, neutralizing heparin's anticoagulant effect within minutes. Idarucizumab is a humanized monoclonal Fab antibody fragment that binds dabigatran with a 350-fold higher affinity than thrombin, neutralizing its activity and reversing the anticoagulant effect within minutes.