Deficiencies of coagulation factors have been recognized for centuries. Patients with genetic deficiencies of plasma coagulation factors exhibit life-long recurrent bleeding episodes into joints, muscles, and closed spaces, either spontaneously or following an injury. The most common inherited factor deficiencies are the hemophilias, X-linked diseases caused by deficiency of factor (F) VIII (hemophilia A) or factor IX (FIX, hemophilia B). Rare congenital bleeding disorders due to deficiencies of other factors, including FII (prothrombin), FV, FVII, FX, FXI, FXIII, and fibrinogen are commonly inherited in an autosomal recessive manner (Table 116–1). Advances in characterization of the molecular bases of clotting factor deficiencies have contributed to better understanding of the disease phenotypes and may eventually allow more targeted therapeutic approaches through the development of small molecules, recombinant proteins, or cell and gene-based therapies.
Table 116–1 Genetic and Laboratory Characteristics of Inherited Coagulation Disorders |Favorite Table|Download (.pdf)
Table 116–1 Genetic and Laboratory Characteristics of Inherited Coagulation Disorders
|Clotting Factor Deficiency||Inheritance||Prevalence in General Population||Laboratory Abnormalitya||Minimum Hemostatic Levels||Treatment||Plasma Half-Life|
|Fibrinogen||AR||1 in 1,000,000||+||+||+||100 mg/dL||Cryoprecipitate||2–4 d|
|Prothrombin||AR||1 in 2,000,000||+||+||−||20–30%||FFP/PCC||3–4 d|
|Factor V||AR||1 in 1,000,000||+/−||+/−||−||15–20%||FFP||36 h|
|Factor VII||AR||1 in 500,000||−||+||−||15–20%||FFP/PCC||4–6 h|
|Factor VIII||X-linked||1 in 5,000||+||−||−||30%||FVIII concentrates||8–12 h|
|Factor IX||X-linked||1 in 30,000||+||−||−||30%||FIX concentrates||18–24 h|
|Factor X||AR||1 in 1,000,000||+/−||+/−||−||15–20%||FFP/PCC||40–60 h|
|Factor XI||AR||1 in 1,000,000||+||−||−||15–20%||FFP||40–70 h|
|Factor XII||AR||ND||+||−||−||b||b||60 h|
|Factor XIII||AR||1 in 2,000,000||−||−||+/−||2–5%||Cryoprecipi-tate||11–14 d|
Commonly used tests of hemostasis provide the initial screening for clotting factor activity (Fig. 116-1), and disease phenotype often correlates with the level of clotting activity. An isolated abnormal prothrombin time (PT) suggests FVII deficiency, whereas a prolonged activated partial thromboplastin time (aPTT) indicates most commonly hemophilia or FXI deficiency (Fig. 116-1). The prolongation of both PT and aPTT suggests deficiency of FV, FX, FII, or fibrinogen abnormalities. The addition of the missing factor at a range of doses to the subject's plasma will correct the abnormal clotting times; the result is expressed as a percentage of the activity observed in normal subjects.