The Hemostatic Cascade: Blood Clotting

I. Phases of Hemostasis

1. Vascular Spasm (Vasoconstriction): Immediate constriction of injured blood vessel to reduce blood flow.
2. Primary Hemostasis (Platelet Plug Formation): Platelets adhere, activate, and aggregate to form a loose plug.
3. Secondary Hemostasis (Coagulation Cascade / Fibrin Clot Formation): A series of enzymatic reactions leading to a stable fibrin mesh.

II. Primary Hemostasis: Platelet Plug Formation

• Platelet Adhesion: Platelets stick to exposed collagen and vWF (von Willebrand Factor) at injury site.
• Platelet Activation: Platelets change shape and release granules (ADP, TXA2, Serotonin).
• Platelet Aggregation: Activated platelets bind to fibrinogen via GPIIb/IIIa receptors, forming a plug.

III. Secondary Hemostasis: The Coagulation Cascade

• A series of enzymatic reactions involving plasma proteins (coagulation factors) leading to fibrin formation.
• Key Factors: Fibrinogen (I), Prothrombin (II), Tissue Factor (III), Calcium (IV), Factors V, VII, VIII, IX, X, XI, XII, XIII.
• Traditional Pathways:
  • Extrinsic Pathway: Initiated by Tissue Factor (TF) exposure.
  • Intrinsic Pathway: Initiated by contact with negatively charged surfaces.
  • Common Pathway: Both converge on Factor Xa, leading to thrombin and fibrin formation.

Coagulation Cascade Flowchart (Traditional View)

                                 [VASCULAR INJURY]
                                         │
             ┌───────────────────────────┴───────────────────────────┐
             │                                                       │
             ▼                                                       ▼
      [EXTRINSIC PATHWAY]                                   [INTRINSIC PATHWAY]
             │                                                       │
     Tissue Factor (TF)                                        Factor XII --> XIIa
             │                                                       │
     TF + Factor VIIa                                        Factor XI --> XIa
             │                                                       │
             ▼                                               Factor IX --> IXa
     Activates Factor X                                            │
     (and Factor IX)                                               │
             └───────────────────────────────────────────────────────┘
                                                                     │
                                                                     ▼
                                                               Factor VIIIa
                                                                     │
             ┌───────────────────────────────────────────────────────┘
             │
             ▼
      [COMMON PATHWAY]
             │
     Factor X --> Xa
             │
     Factor Va (Cofactor)
             │
             ▼
     Prothrombin (II) --> Thrombin (IIa)
             │
             ▼
     Fibrinogen (I) --> Fibrin Monomers
             │
     Factor XIIIa (Cross-linking)
             │
             ▼
     [STABLE FIBRIN CLOT]

IV. Regulation of Hemostasis

• Anti-coagulant Mechanisms: Prevent excessive clotting.
  • Tissue Factor Pathway Inhibitor (TFPI): Inhibits TF-VIIa and Xa.
  • Antithrombin (AT): Inactivates thrombin and Xa.
  • Protein C System: Inactivates Factors Va and VIIIa.
  • Fibrinolysis: Breakdown of fibrin clot by Plasmin (activated by t-PA).

V. Clinical Significance

• Bleeding Disorders: Hemophilia A (Factor VIII def.), Hemophilia B (Factor IX def.), Von Willebrand Disease.
• Thrombotic Disorders: Factor V Leiden, Antithrombin deficiency, Protein C/S deficiency.
• Anticoagulant Medications:
  • Antiplatelet Drugs: Aspirin, Clopidogrel.
  • Heparins: Enhance Antithrombin.
  • Vitamin K Antagonists: Warfarin.
  • DOACs: Direct Thrombin/Factor Xa inhibitors.
  • Thrombolytic Drugs: Alteplase (t-PA).