Our November 2021 Quick Question Case attracted 75 responses.
We asked, "A 3-YOA female with normal PT and prolonged PTT and no bleeding. What is the most likely deficiency?" Here are your responses:
- Factor V--3 [4%]
- Factor VIII--18 [20%]
- Factor IX--2 [3%]
- Factor XI--4 [7%]
- Factor XII--44 [59%]
- Factor XIII--4 [7%]
- Congenital factor V deficiency is rare, and since factor V is part of the common pathway, the deficiency would prolong the PT and PTT.
- Congenital factor VIII deficiency [sex-linked Hemophilia A] occurs in 1 in 8000 males and rarely in females except in von Willebrand disease. Factor VIII deficiency is associated with anatomic hemorrhage.
- Congenital factor IX deficiency [sex-linked Hemophilia B, Christmas Disease] occurs in 14% of hemophilic males. Factor IX deficiency is associated with anatomic hemorrhage.
- Congenital factor XI deficiency [autosomal dominant Hemophilia C, Rosenthal Syndrome] occurs in males and females, and bleeding ranges from asymptomatic to moderate.
- Congenital factor XII [Hageman factor] deficiency occurs in 2% of healthy individuals and is not associated with bleeding. Factor XII is part of the contact factor complex and activates the intrinsic pathway. Deficiency is reflected in a prolonged PTT and normal PT.
- Congenital factor XIII deficiency is associated with moderate to severe systemic bleeding and poor wound healing. Factor XIII deficiency does not prolong the PT or the PTT.
Answer 5, factor XII deficiency, was the answer we were looking for, although some would support answer 4, factor XI deficiency, given that many cases of factor XI deficiency are asymptomatic.
Although factor XII deficiency is not associated with bleeding, there is ample evidence that factor XI and XII activation by negatively charged in vivo surfaces such as prostheses can associate with inflammation and thrombosis. Consequently, medical lab science researchers now focus on the development of anticoagulants directed against factors XI or XII, as detailed in Demoulin S, Godfroid E, Hermans C. Dual inhibition of factor XIIa and factor XIa as a therapeutic approach for safe thromboprotection. J Thromb Haemost. 2021;19:323–9. https://doi.org/10.1111/jth.15130, available from the International Society on Thrombosis and Haemostasis. The concept of anticoagulation without bleeding risk is a tempting "free lunch."