Coagulation
Hereditary bleeding disorders
Factor XII deficiency

Authors: Kendall Crookston, M.D., Ph.D., Lizabeth Rosenbaum, M.D. and Julie Gober-Wilcox, M.D. (see Authors page)

Revised: 28 April 2016, last major update October 2010

Copyright: (c) 2002-2016, PathologyOutlines.com, Inc.

PubMed Search: Factor XII deficiency

Definition / General
  • Factor XII deficiency is a congenital disorder that is most commonly inherited as an autosomal recessive trait and is not associated with a bleeding diathesis
  • It is typically discovered in individuals with an isolated prolonged PTT
  • Homozygous individuals have undetectable factor XII levels
  • Heterozygous individuals have factor XII levels between 20 - 60%
Epidemiology
  • Actual prevalence difficult to determine since individuals are asymptomatic
  • One study of 300 healthy blood donors reported a prevalence of 2.3% (Thromb Haemost 1994;71:68)
Pathophysiology
  • Factor XII is a coagulation protein which is either autoactivated by contact with a number of artificial or biologic negatively charged surfaces (contact activation) or by proteolytic activation on the surface of endothelial cells by prekallikrein/kallikrein and high molecular weight kininogen
  • Activated factor XII converts prekallikrein to kallikrein (which activates more factor XII, liberates bradykinin from high molecular weight kininogen, and activates complement components C3 and C5), activates factor XI which eventually leads to thrombin generation via the intrinsic pathway, and also activates C1 esterase, thereby activating the complement system

Images hosted on other servers:

Coagulation cascade



Mechanisms of factor XII activation

Etiology
  • Most commonly inherited in an autosomal recessive pattern
  • Autosomal dominant inheritance has been described in one family (Blood 1972;40:412)
Clinical Features
  • Not associated with bleeding episodes, even after major surgical procedures or trauma
  • Most patients are detected by routine preoperative coagulation studies (isolated prolonged PTT)
  • Very rarely may manifest with epistaxis or easy bruising
  • There is some debate about the association of factor XII deficiency and an increased risk of arterial and venous thrombosis, myocardial infarction and pulmonary embolism
Laboratory
  • Prolonged PTT that corrects with mixing study
  • Normal PT, thrombin time and bleeding time
  • Specific factor XII assay is diagnostic
Case Reports
Differential Diagnosis