Most hereditary coagulation disorders other than hemophilia are rare autosomal recessive conditions that cause excessive bleeding only in people homozygous for the recessive gene mutation. The rare inherited coagulation disorders can involve factors II, V, VII, X, XI, and XIII. Of these, factor XI deficiency is the most common (1). (See also Overview of Coagulation Disorders.)
In patients with a deficiency of factor XI, there is no clear association between factor XI plasma levels and the severity of bleeding, indicating 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 (see table Screening Laboratory Test Results and Treatment of Inherited Blood Coagulation Defects).
Результати скринінгових лабораторних аналізів і лікування спадкових порушень згортання крові
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 No treatment required |
PTT long PT normal | Factor XI | Autosomal recessive Increased frequency in patients of Ashkenazi Jewish ancestry Posttraumatic and perioperative bleeding Diagnosis by specific factor assay For treatment of bleeding: plasma-derived factor XI concentrate or fresh frozen plasma, plus inhibition of fibrinolysis by aminocaproic acid or tranexamic acid Plasma factor XI half-life = 50 hours |
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 factor IX level For treatment of bleeding: factor replacement Plasma factor VIII half-life = 8–12 hours Plasma factor IX half-life = 18 hours |
PTT normal PT long | Factor VII | Autosomal recessive, rare Diagnosed by specific factor assay For treatment of bleeding: Recombinant activated factor VII or plasma-derived factor VII concentrate Plasma factor VII half-life = 4–6 hours |
PTT long PT long | Factor X, V, or prothrombin | Autosomal recessive, rare Mild to severe bleeding Diagnosed by specific assays For treatment of bleeding due to factor X or prothrombin deficiency:
For treatment of bleeding due to factor V deficiency: Fresh frozen plasma with or without platelet concentrates (to supply platelet factor V) Plasma half-life of factor X = 40–60 hours Plasma half-life of prothrombin = 60–72 hours Plasma half-life of factor V = 36 hours |
In afibrinogenemia (fibrinogen < 10 mg/dL [< 0.1 g/L]), no clotting in PTT or PT because machine end point is not triggered In hypofibrinogenemia (fibrinogen 70–100 mg/dL [0.7–1 g/L]), 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 of bleeding:
Plasma half-life of fibrinogen = 2–4 days |
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 For treatment of bleeding:
Plasma half-life of factor XIII = 9–12 days |
PTT and PT normal Clot lysis times in 5M urea or saline accelerated | Alpha 2-antiplasmin deficiency | Severe bleeding in homozygotes Posttraumatic and perioperative bleeding in heterozygotes Specific assay required for confirmation of diagnosis For treatment of bleeding: Inhibition of excessive fibrinolysis using aminocaproic acid or tranexamic acid |
* PT results are typically reported as INR. | ||
PT = prothrombin time; PTT = partial thromboplastin time. | ||
дефіцит фактора XI
Factor XI deficiency is uncommon in the general population but common among patients of Ashkenazi Jewish ancestry (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 the plasma factor XI level and severity of bleeding.
Дефіцит альфа-2-антиплазміну
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).
Довідковий матеріал загального характеру
1. Menegatti M, Peyvandi F. Treatment of rare factor deficiencies other than hemophilia. Blood 2019;133(5):415-424. doi:10.1182/blood-2018-06-820738
