Factor XI deficiency in humans.

Area of Science:

• Genetics
• Hematology
• Epidemiology

Background:

• Factor XI (FXI) deficiency is an autosomal recessive bleeding disorder.
• Specific mutations, like Glu117stop in Ashkenazi Jews, show founder effects.
• FXI deficiency's prevalence is notable in certain populations, particularly of Ashkenazi Jewish origin.

Purpose of the Study:

• To review the genetic basis and clinical implications of Factor XI deficiency.
• To discuss the epidemiology and specific population-based mutations.
• To outline current therapeutic strategies for managing Factor XI deficiency and associated complications.

Main Methods:

• Literature review of reported Factor XI gene mutations.
• Analysis of clinical associations, including cardiovascular and cerebrovascular events.
• Summary of treatment modalities for bleeding prevention and inhibitor management.

Main Results:

• Over 150 mutations in the FXI gene have been identified.
• Four mutations exhibit founder effects in specific ethnic groups.
• Severe FXI deficiency is associated with a lower incidence of ischemic stroke.
• Inhibitors to FXI develop in a third of patients with very severe deficiency.

Conclusions:

• Factor XI deficiency has a significant genetic component with population-specific mutations.
• While not protective against myocardial infarction, it reduces ischemic stroke risk.
• Management requires tailored approaches, including factor concentrates and recombinant factor VIIa for inhibitor cases.