Uncommon Hereditary Coagulation Disorders

By Joel L. Moake, MD, Rice University;Baylor College of Medicine

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Coagulation Disorders
Overview of Coagulation Disorders
Disseminated Intravascular Coagulation (DIC)
Hemophilia
Coagulation Disorders Caused by Circulating Anticoagulants
Uncommon Hereditary Coagulation Disorders

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 Results in Inherited Defects in Blood Coagulation). The rare inherited coagulation disorders can involve factors II, V, VII, X, XI, and XIII. Of these, factor XI deficiency is the most common.

Screening Laboratory Test Results in Inherited Defects in Blood Coagulation

Screening Test Results*	Defect	Comments
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 Rare 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 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 end point 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	Alpha2-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.

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).

Last full review/revision September 2016 by Joel L. Moake, MD