Hemostasis (Stopping of Bleeding)
Hemostasis occurs in three major stages: vascular spasm, platelet plug formation, and coagulation.
1. Vascular Spasm (Vasoconstriction)
- Immediate response to blood vessel injury.
- Mechanism:
- Damage to endothelium → exposure of subendothelial collagen → local vasoconstriction.
- Endothelial cells release endothelin → powerful vasoconstrictor.
- Nervous reflex via sympathetic fibers also contributes.
- Purpose: Reduces blood flow and limits blood loss.
- Duration: seconds to minutes, temporary until platelet plug and coagulation occur.
2. Platelet Plug Formation (Primary Hemostasis)
- Platelets (thrombocytes) adhere to exposed collagen at injury site.
- Steps:
- Adhesion:
- Platelets bind to exposed collagen via von Willebrand factor (vWF).
- Glycoprotein Ib (GpIb) receptor on platelets mediates attachment.
- Activation:
- Platelets change shape → pseudopodia formation.
- Release granule contents: ADP, serotonin, thromboxane A₂ (TXA₂), Ca²⁺.
- Recruitment/Aggregation:
- ADP and TXA₂ recruit more platelets.
- Platelets stick together via fibrinogen bridges binding GpIIb/IIIa receptors.
- Result: Formation of a temporary platelet plug at the injury site.
- Purpose: Quickly reduces blood loss; not very stable.
3. Coagulation (Secondary Hemostasis)
- Definition: Conversion of soluble fibrinogen into insoluble fibrin → stabilizes platelet plug.
- Steps/Phases:
A. Initiation Phase
- Triggered by tissue injury and exposure of tissue factor (TF, factor III).
- Extrinsic pathway:
- TF + factor VII → TF–VIIa complex → activates factor X.
- Produces small amounts of thrombin, enough to initiate amplification.
B. Amplification Phase
- Thrombin activates:
- Platelets → more aggregation.
- Factor V → forms prothrombinase complex.
- Factor VIII → participates in intrinsic pathway.
- Factor XI → intrinsic pathway activation.
C. Propagation Phase (Formation of Fibrin Mesh)
- Intrinsic pathway:
- Factors XII → XI → IX → VIII → X.
- Activated factor X combines with V (prothrombinase complex).
- Conversion of prothrombin (II) to thrombin (IIa).
- Thrombin converts fibrinogen (I) → fibrin (Ia).
- Fibrin fibers cross-link by factor XIIIa → stable fibrin clot.
4. Clot Retraction and Stabilization
- Platelets contract via actin–myosin → pull fibrin strands → clot shrinks.
- Reduces blood vessel diameter → aids healing.
- Serum (plasma without fibrinogen) squeezed out.
5. Fibrinolysis (Clot Removal)
- Purpose: Removes clot after tissue repair.
- Mechanism:
- Endothelial cells release tissue plasminogen activator (tPA).
- tPA converts plasminogen → plasmin.
- Plasmin digests fibrin → clot dissolves.
- Regulated by plasmin inhibitors to prevent excessive bleeding.
6. Regulatory Mechanisms
- Prevent excessive coagulation:
- Antithrombin III → inhibits thrombin and factors IX, X, XI, XII.
- Protein C & Protein S system → inactivates factors Va and VIIIa.
- Tissue factor pathway inhibitor (TFPI) → inhibits TF–VIIa complex.