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Uncommon Hereditary Coagulation Disorders

by Joel L. Moake, MD

Most hereditary coagulation disorders other than hemophilia are rare autosomal recessive conditions that cause disease only in homozygous people ( Screening Laboratory Test Results in Inherited Defects in Blood Coagulation). 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 significant injuries, including trauma or surgery, in people who are homozygotes or compound heterozygotes.

Severe deficiency of α 2 -antiplasmin (levels 1 to 3% of normal), the major physiologic inhibitor of plasmin, can also cause bleeding. Diagnosis is based on a specific α 2 -antiplasmin assay. ε-Aminocaproic acid or tranexamic acid is used to control or prevent acute bleeding. Heterozygous people with α 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).

Screening Laboratory Test Results in Inherited Defects in Blood Coagulation

Screening Test Results*



PTT long

PT normal

Factor XII, high molecular weight kininogen, or prekallikrein

Laboratory test abnormality without clinical bleeding

Specific assays required to distinguish from factor XI deficiency, in which posttraumatic and perioperative bleeding may occur

PTT long

PT normal

Factor XI

Autosomal recessive

Increased frequency in Ashkenazi Jews

Posttraumatic and perioperative bleeding

Diagnosis by specific assay

For bleeding: Fresh frozen plasma 5–20 mL/kg/day to keep factor XI level > 30% of normal

PTT long

PT normal

Factor VIII or IX

Factor VIII deficiency (hemophilia A)

Factor IX deficiency (hemophilia B)

X-linked transmission

Mild or severe bleeding in males, depending on factor VIII or IX level

PTT normal

PT long

Factor VII

Autosomal recessive


If deficiency is severe (< 2% of normal values), serious bleeding

If levels are > 5%, mild or no bleeding

Therapy of choice: Recombinant activated factor VII

PTT long

PT long

Factor X, V, or prothrombin

Autosomal recessive


Mild to severe bleeding

Diagnosed by specific assays

For bleeding episodes due to factor X or prothrombin deficiency: Fresh frozen plasma or prothrombin complex concentrate

For treatment of factor V deficiency: Fresh frozen plasma with or without platelet concentrates (to supply platelet factor V)

In afibrinogenemia (fibrinogen < 10 mg/dL), no clotting in PTT or PT because machine end point is not triggered

In hypofibrinogenemia (fibrinogen 70–100 mg/dL), PTT and PT often prolonged by several seconds and thrombin time long


Severe bleeding in afibrinogenemia (homozygous state)

Posttraumatic and perioperative bleeding in hypofibrinogenemia (heterozygous state)

For treatment: Cryoprecipitate (5–10 bags, with each containing about 250 mg fibrinogen)

PTT and PT long

Thrombin time long


Various manifestations (no, or only mild, posttraumatic and perioperative bleeding, tendency for thrombosis, wound dehiscence)

Fibrinogen low in clotting assay but normal in immunologic assay

PTT normal

PT normal

Thrombin time normal

Clot lysis in 5M urea

Factor XIII

Autosomal recessive


Poor wound healing

Spontaneous abortions in women

Severe bleeding when levels are < 1% of normal

For treatment: Fresh frozen plasma (1–2 units q 4–6 wk is effective because half-life of factor XIII is about 10 days)

PTT and PT normal

Clot lysis times in 5M urea or saline accelerated

α 2 -Antiplasmin deficiency

Severe bleeding in homozygotes

Posttraumatic and perioperative bleeding in heterozygotes

Specific assay required for confirmation of diagnosis

*PT results are typically reported as INR.

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