Most hereditary coagulation disorders other than hemophilia Hemophilia Hemophilias are common hereditary bleeding disorders caused by deficiencies of either clotting factor VIII or IX. The extent of factor deficiency determines the probability and severity of bleeding... read more are rare autosomal recessive conditions that cause excessive bleeding Excessive Bleeding Unusual or excessive bleeding may be indicated by several different signs and symptoms. Patients may present with unexplained nosebleeds (epistaxis), excessive or prolonged menstrual blood flow... read more 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 Factor XI deficiency 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... read more is the most common (1 General reference 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... read more ). (See also Overview of Coagulation Disorders Overview of Coagulation Disorders Abnormal bleeding can result from disorders of the coagulation system, of platelets, or of blood vessels. Disorders of coagulation can be acquired or hereditary. The major causes of acquired... read more .)
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 ).
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
Severe deficiency of alpha 2-antiplasmin (levels 1 to 3% of normal), the major physiologic inhibitor of plasmin, can also cause bleeding as a result of poor control of plasmin-mediated proteolysis of fibrin polymers. Diagnosis is based on a specific alpha 2-antiplasmin assay. Aminocaproic acid or tranexamic acid is used to control or prevent acute bleeding by blocking 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
Drugs Mentioned In This Article
| Drug Name | Select Trade |
|---|---|
aminocaproic acid |
Amicar |
tranexamic acid |
Cyklokapron, Lysteda |
