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Uncommon Hereditary Coagulation Disorders

By

Joel L. Moake

, MD, Baylor College of Medicine

Last full review/revision Jan 2020| Content last modified Jan 2020
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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 homozygous people (see table Screening Laboratory Test Results and Treatment of Inherited Blood Coagulation Defects Screening Laboratory Test Results and Treatment of Inherited Blood Coagulation Defects Most hereditary coagulation disorders other than hemophilia are rare autosomal recessive conditions that cause excessive bleeding only in homozygous people (see table Screening Laboratory Test... read more ). 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 homozygous people (see table Screening Laboratory Test... read more is the most common. (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, 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.

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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 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).

Drugs Mentioned In This Article

Drug Name Select Trade
AMICAR
CYKLOKAPRON
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