Our August 2021 Quick Question, which asks, “Which factor deficiency causes the smallest risk of bleeding?” drew a respectable 48 votes. Answers:
- VWF deficiency: 9% 
- Factor X deficiency: 4% 
- Factor XI deficiency: 7% 
- Factor XII deficiency: 52% 
- Prekallikrein deficiency: 28% 
Both 4 and 5 are correct, deficiencies of contact factors XII and prekallikrein do not associate with bleeding disorders, though current clinical research results illustrate that their in vivo activation may contribute to venous thromboembolic disease. Some have shown that the activated form of prekallikrein, kallikrein, may activate factor IX.
Von Willebrand factor deficiency, the basis for von Willebrand disease, is a congenital deficiency detectable in 1% of an unselected population that associates with systemic [mucocutaneous] bleeding with varying penetration, leading to a range of absent to moderate bleeding. Variation may occur within a kindred or even an individual over time.
Factor X deficiency, the result of one of several mutations, has been identified in just over 100 kindred worldwide and appears as mild to severe bleeding, depending on the mutation. Factor XI deficiency, with a gene frequency of 4.3% in Ashkenazi Jews, is also called hemophilia C or Rosenthal syndrome. Bleeding ranges from absent to moderate.
Current efforts at developing oral anticoagulants target factors XI or XII on the principle that suppression may reduce thrombosis risk without raising the risk of bleeding, the key safety concern that moderates the application of current anticoagulants.