Physiologic coagulation cascade

The physiologic coagulation cascade is a highly regulated sequence of enzymatic reactions designed to maintain vascular integrity by forming a stable fibrin clot at sites of injury [7, 11]. It involves the sequential activation of various proenzymes (zymogens) into active serine proteases, traditionally categorized into the extrinsic (tissue factor) and intrinsic (contact activation) pathways [9, 11]. These pathways converge at the common pathway, where Factor Xa converts prothrombin into thrombin, the central enzyme that transforms fibrinogen into fibrin [1, 11]. Pathological activation of this system leads to thrombotic disorders such as myocardial infarction and stroke, while deficiencies in cascade components result in bleeding disorders like hemophilia [11, 12]. Therapeutic strategies focus on modulating specific factors within the cascade to prevent or treat thrombosis while minimizing the risk of excessive bleeding [5, 6]. Beyond hemostasis, the cascade also plays a significant role in inflammation and innate immunity through signaling via protease-activated receptors [8, 13].

Other names

Blood coagulation pathwayClotting cascadeHemostatic cascadeCoagulation system

Drugs targeting the coagulation cascade act by inhibiting specific serine proteases such as Factor Xa or Thrombin, antagonizing the synthesis of vitamin K-dependent clotting factors (II, VII, IX, and X), or enhancing the activity of natural anticoagulants like antithrombin III [5, 6, 9]. Additionally, thrombolytic agents promote the dissolution of clots by activating plasminogen to plasmin [3, 4].