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Most hereditary coagulation disorders other than hemophilia are rare autosomal recessive conditions that cause disease only in homozygous people (see Table 1: Coagulation Disorders: Screening Laboratory Test Results in Inherited Defects in Blood Coagulation). Factor XI deficiency is uncommon in the general population but common in 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 α₂-antiplasmin (1 to 3% of normal), the major physiologic inhibitor of plasmin, can also cause bleeding. Diagnosis is based on a specific α₂-antiplasmin assay. ε- Aminocaproic acid Some Trade Names
AMICAR
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or tranexamic acid Some Trade Names
CYKLOKAPRON
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is used to control or prevent acute bleeding. Heterozygous people with α₂-antiplasmin levels of 40 to 60% of normal can occasionally experience excessive surgical bleeding if secondary fibrinolysis is extensive (eg, in patients who have had open prostatectomy).

Table 1
Screening Laboratory Test Results in Inherited Defects in Blood Coagulation Screening Test Results* Defect Comments PTT long PT normal Factor XII, high mol wt kininogen, or prekallikrein Laboratory test abnormality without clinical bleeding Must be distinguished by specific assays 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% 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 Rare If deficiency is severe (< 2%), serious bleeding If levels are > 5%, mild or no bleeding Therapy of choice: Recombinant factor VIIa PTT long PT long Factor X, V, or prothrombin Autosomal recessive Rare 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 endpoint is not triggered In hypofibrinogenemia (fibrinogen 70–100 mg/dL), PTT and PT often prolonged by several seconds and thrombin time long Fibrinogen 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 Dysfibrinogenemia 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 Rare 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 α2-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.

Last full review/revision June 2009 by Joel L. Moake, MD

Content last modified June 2009