Most hereditary coagulation disorders other than hemophilia are rare autosomal recessive conditions that cause excessive bleeding only in people homozygous for the recessive gene mutation. The rare inherited coagulation disorders can involve factors II, V, VII, X, XI, and XIII. Of these, factor XI deficiency is the most common (1). (See also Overview of Coagulation Disorders.)
In patients with a deficiency of factor XI, there is no clear association between factor XI plasma levels and the severity of bleeding, indicating that the molecular action of factor XI in normal hemostasis is not precisely understood.
In the other rare coagulation disorders (excluding hemophilia A and B), normal hemostasis usually requires a plasma level of the deficient factor in excess of about 20% of normal (see table Screening Laboratory Test Results and Treatment of Inherited Blood Coagulation Defects).
Factor XI deficiency
Factor XI deficiency is uncommon in the general population but common among patients of Ashkenazi Jewish ancestry (gene frequency about 5 to 9%). Bleeding typically occurs after trauma or surgery in people who are homozygotes or compound heterozygotes for factor XI gene abnormalities. There is no precise relationship between the plasma factor XI level and severity of bleeding.
Deficiency of alpha 2-antiplasmin
plasminogen binding to fibrin polymers.
Heterozygous people with alpha 2-antiplasmin levels of 40 to 60% of normal can occasionally experience excessive surgical bleeding if secondary fibrinolysis is extensive (eg, in patients who have released excessive amounts of urokinase-type plasminogen activator during open prostatectomy).
General reference
1. Menegatti M, Peyvandi F. Treatment of rare factor deficiencies other than hemophilia. Blood 2019;133(5):415-424. doi:10.1182/blood-2018-06-820738
