3. Hemostasis

Hemostasis Overview

  • Definition: Hemostasis is the process of stopping bleeding (heima = blood, stasis = halt).

  • Purpose: Halts blood loss through damaged vessel walls and establishes a framework for tissue repair.

  • Phases of Hemostasis:

    • Vascular Phase

    • Platelet Phase

    • Coagulation Phase

  • Nature: A complex cascade where various processes occur simultaneously and interact with one another.

1. Vascular Phase

  • Trigger: Cutting of a blood vessel wall initiates a contraction in the smooth muscle of the vessel (vascular spasm).

  • Effect: Decreases vessel diameter, slowing or stopping blood loss, lasting about 30 minutes.

  • Changes in Endothelium:

    • Endothelial cells contract, exposing basal lamina.

    • Release of chemical factors and hormones:

      • ADP

      • Tissue factor

      • Prostacyclin and endothelins

    • Functions of released factors:

      1. Stimulate smooth muscle contraction and vascular spasm.

      2. Promote division of endothelial cells and smooth muscle cells for repair.

  • Stickiness of Endothelial Cells:

    • Facilitates adhesion of platelets to the site of injury.

2. Platelet Phase

  • Initiation: Platelets adhere to sticky surfaces created by damaged endothelium and exposed collagen fibers.

  • Platelet Adhesion: Initial attachment of platelets to exposed surfaces.

  • Platelet Aggregation:

    • As more platelets arrive, they adhere to each other to form a platelet plug, potentially sealing small vessel breaches within 15 seconds of injury.

  • Activation of Platelets:

    • Shape changes to spherical with extending cytoplasmic processes.

    • Release of compounds:

      • ADP: Stimulates platelet aggregation.

      • Thromboxane A2 and serotonin: Stimulate vascular spasms.

      • Clotting factors: Essential for blood clotting.

      • Platelet-derived growth factor (PDGF): Promotes vessel repair.

      • Calcium ions: Required for clotting processes.

  • Control of Platelet Aggregation:

    1. Prostacyclin: Inhibits platelet aggregation, released by endothelial cells.

    2. Inhibitory compounds from white blood cells.

    3. Circulating plasma enzymes degrade ADP.

    4. Other substances that inhibit aggregation at high concentrations.

    5. Formation of stable blood clots, reinforcing platelet plugs.

3. Coagulation Phase

  • Timing: Begins 30 seconds or more post-injury.

  • Process: Complex sequence that converts fibrinogen into insoluble fibrin strands which traps blood cells, forming a stable clot.

  • Pathways:

    • Extrinsic Pathway: Initiated by the release of tissue factor (Factor III) from damaged cells, interacting with Ca2+ and Factor VII to activate Factor X.

    • Intrinsic Pathway: Initiates from circulating proenzymes (like Factor XII) exposed to collagen; proceeds with help from PF-3 released by activated platelets.

    • Common Pathway: Activated by either pathway, triggering prothrombinase formation, which convert prothrombin to thrombin. Thrombin converts fibrinogen to fibrin.

4. Interactions Among Pathways

  • Response: Both pathways are activated upon vessel damage.

  • Efficiency: Extrinsic is faster, producing thrombin quickly, while intrinsic reinforces clotting later.

5. Regulatory Mechanisms of Clotting

  • Negative Feedback: Normal plasma contains anticoagulants (e.g., antithrombin III) to inhibit clotting.

  • Key Factors:

    • Thrombomodulin: Converts thrombin to an enzyme activating protein C, which inactivates clotting factors.

    • Heparin: Released by basophils; accelerates antithrombin III.

    • Plasma proteins: Other anticoagulants like alpha-2-macroglobulin and C1 inactivator.

6. Calcium and Vitamin K in Clotting

  • Role of Calcium Ions: Essential for all pathways of the clotting process.

  • Vitamin K: Necessary for synthesizing four clotting factors in the liver; derived from diet and intestinal bacteria.

7. Clot Retraction and Fibrinolysis

  • Clot Retraction: Post-clot formation, platelets contract to reduce break size (30-60 mins), stabilizing injury and enhancing repair.

  • Fibrinolysis: Gradual clot dissolution, initiated by plasminogen activated by thrombin and t-PA, which digests fibrin strands.

8. Platelet Functions and Production

  • Functions:

    1. Release chemicals essential for clotting.

    2. Form temporary patches at injury sites.

    3. Contain actin and myosin filaments that contract the clot post-formation.

  • Production: Occurs through thrombocytopoiesis in the bone marrow, stimulated by factors like thrombopoietin.

9. Disorders of Hemostasis

  • Thrombocytopenia: Low platelet count, possibly due to bone marrow impairment.

  • Thrombus and Embolus: Clots can form in unbroken vessels (thrombus) or travel in the bloodstream (embolus), risking serious outcomes like heart attack.

  • Hemophilia: Genetic clotting disorder; minor trauma can lead to excessive bleeding, particularly dangerous if affecting major vessels.