coagulation factor
Summary
Coagulation factors are plasma proteins (mostly serine proteases and cofactors) that act in a sequential cascade to convert soluble fibrinogen into insoluble fibrin, stabilizing platelet plugs and forming a definitive clot. Most are synthesized in the liver, and factors II, VII, IX, and X require vitamin K for activity. Deficiencies or dysfunctions cause bleeding disorders (e.g., hemophilia), while excess activity promotes thrombosis.
Detail
Coagulation factors are numbered I–XIII (with some overlap, e.g., factor VI is not used) and participate in the intrinsic, extrinsic, and common pathways of the coagulation cascade, ultimately converging on the activation of factor X, which converts prothrombin (II) to thrombin (IIa). Thrombin then cleaves fibrinogen (I) to fibrin and activates factor XIII, which cross-links fibrin strands to stabilize the clot.
Key pathways: - Intrinsic pathway: activated by subendothelial collagen exposure; involves factors XII, XI, IX, VIII (measured by PTT). - Extrinsic pathway: activated by tissue factor (III) released from damaged endothelium; involves factor VII (measured by PT/INR). - Common pathway: factors X, V, II (prothrombin), I (fibrinogen), and XIII.
Vitamin K–dependent factors (II, VII, IX, X, plus proteins C and S) require gamma-carboxylation in the liver for calcium-binding activity; this step is inhibited by warfarin. Factor VIII and von Willebrand factor circulate as a complex; factor VIII deficiency causes Hemophilia A, and factor IX deficiency causes Hemophilia B, both X-linked recessive disorders with prolonged PTT. Factor XI deficiency (Hemophilia C) is less common and less severe.
Liver disease and vitamin K deficiency can cause deficiencies of multiple factors, prolonging both PT and PTT. Disseminated intravascular coagulation (DIC) consumes factors and platelets, leading to simultaneous bleeding and clotting.
Clinically, coagulation factor assays and PT/PTT/INR are used to evaluate bleeding disorders, monitor anticoagulation (e.g., warfarin via INR), and diagnose factor deficiencies or inhibitors (e.g., lupus anticoagulant, factor VIII inhibitors in acquired hemophilia). Recombinant factor concentrates (e.g., factor VIII, IX) are used therapeutically in hemophilia, and fresh frozen plasma or prothrombin complex concentrates can reverse deficiencies or anticoagulant effects.
Sources
- First Aid for the USMLE Step 1
- Robbins and Cotran Pathologic Basis of Disease
- Harrison's Principles of Internal Medicine
- Goldman-Cecil Medicine
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