Pathophysiology
Clinical meaning
Anticoagulation therapy targets specific components of the coagulation cascade to prevent pathologic thrombus formation. The coagulation cascade operates through intrinsic (contact activation), extrinsic (tissue factor), and common pathways, all converging on the conversion of prothrombin (Factor II) to thrombin, which then converts fibrinogen to fibrin. Unfractionated heparin (UFH) binds to antithrombin III (AT-III), dramatically accelerating its inhibition of thrombin (Factor IIa), Factor Xa, and other serine proteases (IXa, XIa, XIIa). UFH has a short half-life (60-90 minutes IV), is monitored by activated partial thromboplastin time (aPTT), and is fully reversible with protamine sulfate. Low-molecular-weight heparins (LMWH, e.g., enoxaparin) preferentially inhibit Factor Xa over thrombin, have more predictable pharmacokinetics, longer half-lives (4-6 hours), are given subcutaneously, and are monitored by anti-Xa levels when needed. Warfarin is a vitamin K antagonist that inhibits hepatic synthesis of vitamin K-dependent clotting factors (II, VII, IX, X) and natural anticoagulants (protein C and protein S). Warfarin has a delayed onset (3-5 days for full effect) and is monitored by the International Normalized Ratio (INR). Direct oral anticoagulants (DOACs) include direct thrombin inhibitors (dabigatran) and direct...