Treatment of rare factor deficiencies in 2016

Hematology Am Soc Hematol Educ Program. 2016 Dec 2;2016(1):663-669. doi: 10.1182/asheducation-2016.1.663.


Rare bleeding disorders (RBDs) are a heterogeneous group of coagulation disorders characterized by fibrinogen, prothrombin, factors V, VII, X, XI, or XIII (FV, FVII, FX, FXI, or FXIII, respectively), and the combined factor V + VIII and vitamin K-dependent proteins deficiencies, representing roughly 5% of all bleeding disorders. They are usually transmitted as autosomal, recessive disorders, and the prevalence of the severe forms could range from 1 case in 500 000 for FVII up to 1 in 2-3 million for FXIII in the general population. Patients affected with RBDs may present a wide range of clinical symptoms, varying from mucocutaneous bleeding, common to all types of RBDs to the most life-threatening symptoms such as central nervous system and gastrointestinal bleeding. Treatment of these disorders is mainly based on the replacement of the deficient factor, using specific plasma-derived or recombinant products. In countries where these facilities are not available, bleedings could be managed using cryoprecipitate, fresh frozen plasma (FFP), or virus-inactivated plasma. Minor bleedings could be managed using antifibrinolytic agents. Recently, 2 novel drugs, recombinant FXIIIA and a plasma-derived FX, have been added to the list of available specific hemostatic factors; only prothrombin and FV deficiencies still remain without a specific product. Novel no-replacement therapies, such as monoclonal antibody anti-tissue factor pathway inhibitor, RNA interference, and a bispecific antibody that is an FVIIIa mimetic, enhancing thrombin generation through different mechanisms, were developed for patients with hemophilia and may in the future be a good therapeutic option also in RBDs.

Publication types

  • Review

MeSH terms

  • Blood Coagulation Factors / therapeutic use*
  • Blood Component Transfusion*
  • Coagulation Protein Disorders / diagnosis
  • Coagulation Protein Disorders / drug therapy*
  • Factor VIII / therapeutic use*
  • Fibrinogen / therapeutic use*
  • Humans
  • Plasma*
  • Rare Diseases


  • Blood Coagulation Factors
  • cryoprecipitate coagulum
  • Factor VIII
  • Fibrinogen