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Uncommon Hereditary Coagulation Disorders


Joel L. Moake

, MD, Baylor College of Medicine

Last full review/revision Sep 2021| Content last modified Sep 2021
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In patients with a deficiency of factor XI, there is no clear association between factor XI plasma levels and the severity of bleeding, suggesting 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.

The drugs fitusiran and concizumab may be useful treatments for several of the rare congenital coagulation disorders, but clinical trials will be needed.


Factor XI deficiency

Factor XI deficiency is uncommon in the general population but common among descendants of European Jews (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 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).

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