Overview
This lecture explains hemostasis, the process of stopping blood loss after vessel injury, including its five key steps and how blood naturally prevents unwanted clotting.
Natural Anticoagulant Mechanisms
- Endothelial cells secrete nitric oxide and prostacyclin (PGI2) to inhibit platelet activation.
- Heparan sulfate on endothelial surfaces activates antithrombin III, which inactivates clotting Factors II, IX, and X.
- Thrombomodulin binds thrombin, which activates protein C; protein C degrades Factors V and VIII to limit coagulation.
Five Steps of Hemostasis
1. Vascular Spasm
- Injury triggers endothelin release, causing smooth muscle contraction (vasoconstriction) and reduced blood loss.
- Myogenic response: direct injury prompts smooth muscle contraction.
- Pain/inflammatory mediators stimulate nociceptors, further enhancing vasoconstriction.
2. Platelet Plug Formation
- Damaged endothelium releases von Willebrand factor, allowing platelets to bind via glycoprotein 1b receptors.
- Activated platelets secrete ADP, thromboxane A2, and serotonin, attracting more platelets (aggregation).
- Platelet-platelet binding uses glycoprotein IIb/IIIa-fibrinogen bridges.
- Thromboxane A2 and serotonin induce vasoconstriction to support vascular spasm.
3. Coagulation Cascade
- Intrinsic pathway: Factors XII → XI → IX (+ VIII, platelet factor 3, Ca2+) → X (common pathway).
- Extrinsic pathway: Tissue factor (III) + Factor VII activates IX & X.
- Common pathway: Factor X (+ V, platelet factor 3, Ca2+) forms prothrombin activator, converting prothrombin (II) to thrombin.
- Thrombin converts fibrinogen (I) to insoluble fibrin; Factor XIII cross-links fibrin, forming a stable mesh.
4. Clot Retraction and Repair
- Platelet actin/myosin contracts, pulling wound edges together.
- Platelet-derived growth factor stimulates smooth muscle/collagen repair.
- Vascular endothelial growth factor (VEGF) promotes endothelial regeneration.
5. Fibrinolysis
- Tissue plasminogen activator (tPA) converts plasminogen to plasmin.
- Plasmin digests fibrin, dissolving the clot and freeing vessel flow.
- D-dimers are released as breakdown products—important for clot diagnostics.
Key Terms & Definitions
- Hemostasis — Process that stops bleeding at injury sites.
- Nitric oxide & Prostacyclin (PGI2) — Molecules that inhibit platelet activation.
- Heparan sulfate — Endothelial surface anticoagulant activating antithrombin III.
- von Willebrand factor — Protein aiding platelet adhesion to collagen.
- Glycoprotein 1b/IIb/IIIa — Platelet surface receptors for binding vWF and fibrinogen.
- Fibrinogen/Fibrin — Plasma proteins forming the clot mesh.
- Plasminogen/Plasmin — Precursors/proteins responsible for clot breakdown.
- tPA — Enzyme that activates plasmin for fibrinolysis.
- D-dimer — Fibrin degradation product used in clot detection tests.
Action Items / Next Steps
- Review coagulation factor numbers and their order in intrinsic, extrinsic, and common pathways.
- Memorize key drug targets in hemostasis (e.g., aspirin, clopidogrel, warfarin).
- Know the five steps of hemostasis and associated key molecules for exams.