Clinical meaning
The cell-based model of coagulation has replaced the traditional cascade model. Initiation occurs on tissue factor-bearing cells where TF-VIIa generates small amounts of thrombin. Amplification occurs on activated platelet surfaces where thrombin activates factors V, VIII, XI, and platelets. Propagation involves tenase (IXa-VIIIa) and prothrombinase (Xa-Va) complexes on platelet surfaces generating a thrombin burst sufficient for stable fibrin clot formation. Natural anticoagulants include: antithrombin III (heparin cofactor; inhibits IIa, Xa, IXa), protein C pathway (thrombomodulin-thrombin activates protein C, which with protein S inactivates Va/VIIIa), and TFPI (limits TF-VIIa). Fibrinolysis: plasminogen is converted to plasmin by tPA, degrading fibrin into D-dimers and fibrin degradation products.
Diagnosis & workup
Diagnostics & workup: - Coagulation panel: PT/INR (extrinsic + common), aPTT (intrinsic + common), thrombin time, fibrinogen - Mixing study: distinguishes factor deficiency (corrects) from inhibitor (does not correct); if inhibitor suspected, incubate at 37°C for 2 hours (Factor VIII inhibitor is time-dependent) - Specific factor assays: quantify individual factors; von Willebrand panel (vWF antigen, ristocetin cofactor activity, Factor VIII level, multimer analysis) - Thrombophilia workup: Factor V Leiden (APC resistance screen then genetic test), prothrombin gene mutation, protein C/S levels, antithrombin level, lupus anticoagulant, anticardiolipin/anti-beta2GP1 antibodies - Thromboelastography (TEG/ROTEM): point-of-care viscoelastic testing of whole blood clot formation and lysis; guides blood product replacement in massive hemorrhage - Platelet function testing: PFA-100 (screen for vWD and platelet dysfunction), platelet aggregation studies - Anti-Xa assay: monitors LMWH and can monitor DOACs when needed