Thrombin (factor IIa)
Thrombin · Central enzyme PAR-1 Thrombin time
Thrombin is the central enzyme of haemostasis. It cleaves fibrinopeptides A and B from fibrinogen to make fibrin monomer, activates factors V, VIII, XI and XIII, and activates platelets through PAR-1 — and then, once bound to endothelial thrombomodulin, reverses role entirely and activates protein C. Almost every loop on this map exists to make thrombin faster or to switch it off.
Traced from the start
- Tissue factor and the extrinsic triggerVitamin K cycle and gamma-carboxylation
- Contact activation system (factor XII, prekallikrein, high-molecular-weight kininogen)
- Subendothelial collagen and von Willebrand factor
- Tissue factor-factor VIIa complex (extrinsic tenase)Factor IXaFactor VIIIa and its von Willebrand factor carrierActivated platelet phospholipid surface
- Factor XaFactor VaProthrombin (factor II)
- Thrombin (factor IIa)
Detail
- Generated by
- Prothrombinase: Xa + Va + Ca2+ + phospholipid on the activated platelet surface
- Procoagulant actions
- Fibrinogen to fibrin; activates factors V, VIII, XI and XIII; activates platelets via PAR-1 and PAR-4; releases factor VIII from vWF
- Anticoagulant actions
- Bound to thrombomodulin it loses fibrinogen specificity and activates protein C over 1000-fold faster; it also activates TAFI, which restrains fibrinolysis
- Inhibited by
- Antithrombin (accelerated by endothelial heparan sulfate and by heparin), heparin cofactor II, and the direct inhibitors dabigatran, bivalirudin and argatroban
- Measured by
- Thrombin time; thrombin generation assays and viscoelastic tests such as TEG and ROTEM
When it goes wrong
Unopposed systemic thrombin generation in sepsis, obstetric catastrophe, major trauma or acute promyelocytic leukaemia
Disseminated intravascular coagulation: platelets and fibrinogen are consumed while fibrin occludes the microvasculature, so the patient thromboses and bleeds at the same time
Heparin-induced thrombocytopenia — IgG against the heparin-platelet factor 4 complex cross-linking platelet FcgammaRIIa
Platelet count falls by more than 50% at day 5-10 with thrombosis rather than bleeding; stop all heparin including flushes and anticoagulate with argatroban, bivalirudin or fondaparinux — never platelets, never warfarin alone
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