Sequential serine-protease activations producing thrombin (factor IIa) and ultimately fibrin clot. Extrinsic pathway: TF (factor III) + VIIa → activates X. Intrinsic pathway: XII → XI → IX (+ VIII cofactor) → X. Common pathway: X (+ V cofactor) → thrombin → fibrin. Vitamin-K-dependent factors (II, VII, IX, X + proteins C, S) require γ-carboxylation — warfarin target via VKORC1 (see vitamin_k_cycle). Heparin enhances antithrombin's inhibition of IIa + Xa. LMWHs (enoxaparin) selectively boost Xa inhibition. DOACs directly inhibit factor IIa (dabigatran) or factor Xa (apixaban, rivaroxaban, edoxaban) — bypassing antithrombin.
Organ Systems
immune-hematologic
cardiovascular
Pathway Steps
tissue-factor → factor-viia — via extrinsic pathway initiation. The extrinsic pathway is the physiologic trigger: injury exposes tissue factor, which binds and activates factor VII. The TF/VIIa complex is the dominant in-vivo initiator and is reflected by the prothrombin time (PT/INR) — the warfarin monitoring test.
factor-viia → factor-xa — via common pathway entry (TF/VIIa activates X). TF/VIIa activates factor X, starting the common pathway. Factor Xa is the convergence point and the target of the direct oral “-xaban” anticoagulants (apixaban, rivaroxaban); fondaparinux/heparin–antithrombin act largely here too.
factor-xii → factor-xa — via intrinsic pathway: XII → XI → IX (+ VIIIa cofactor) → X. The intrinsic (contact) pathway (XII→XI→IX with VIIIa) amplifies thrombin and is measured by the aPTT (heparin monitoring). Hemophilia A (VIII) and B (IX) are intrinsic deficiencies; factor XII deficiency prolongs aPTT but doesn’t cause bleeding.
factor-xa → thrombin — via prothrombinase complex (Xa + Va on platelet phospholipid surface). The prothrombinase complex (Xa + Va on a Ca²⁺-dependent platelet phospholipid surface) converts prothrombin to thrombin — a massive amplification. Factors II/VII/IX/X (and proteins C/S) need vitamin-K-dependent γ-carboxylation, the warfarin target.
thrombin → fibrin — via cleaves fibrinogen → fibrin monomers; also activates V, VIII, XI, XIII (positive feedback). Thrombin cleaves fibrinogen to fibrin and activates factor XIII (cross-linking) plus cofactors V/VIII/XI (feed-forward), while via thrombomodulin it activates protein C (an anticoagulant brake). Thrombin is the direct target of dabigatran and of heparin-potentiated antithrombin.