Hemostasis - Chapter 19 Notes

Hemostasis - Chapter 19

Introduction to Hemostasis

Hemostasis is a critical physiological process that prevents excessive bleeding when blood vessels are injured. This process consists of a series of five distinct events that work together to form a gelatinous blood clot that plugs broken vessels. The primary function of hemostasis is to limit significant blood loss. The five main parts of hemostasis include:

  1. Vascular Spasm

  2. Platelet Plug Formation

  3. Coagulation (Intrinsically and Extrinsically)

  4. Clot Retraction

  5. Thrombolysis

Key Definitions

  • Hemostasis: The cessation of bleeding by various mechanisms in response to blood vessel injury.

  • Vascular Spasm: Immediate constriction of a damaged blood vessel, reducing blood flow.

  • Platelet Plug Formation: The accumulation and adhesion of platelets to the site of injury to form a temporary seal.

  • Coagulation: The process turning blood into a gel-like consistency to further stabilize the plug, involving complex biochemical pathways.

  • Thrombolysis: The breakdown and removal of a clot after the vessel has healed.

Events of Hemostasis

Part 1: Vascular Spasm

  • Occurs immediately after a blood vessel injury.

  • Triggers include:

    • Direct injury to the vascular smooth muscle.

    • Chemicals released by endothelial cells and platelets.

    • Pain reflexes.

  • Most effective in smaller blood vessels, leading to:

    • Increased tissue pressure.

    • Decreased blood vessel diameter, consequently reducing local blood flow and pressure.

Part 2: Platelet Plug Formation

  • Involves a positive feedback cycle where more platelets adhere to the site of injury and release additional chemicals that attract even more platelets.

  • Damaged endothelium exposes collagen fibers:

    • Platelets stick to collagen via the von Willebrand factor (vWF), a plasma protein released by injured endothelial cells.

    • Platelets become spiked and sticky, releasing chemical messengers that include:

    • ADP: Attracts more platelets to the site.

    • Serotonin and Thromboxane A2: Enhance vascular spasm and promote further platelet aggregation.

  • Aggregation of activated platelets leads to the formation of a platelet plug.

Part 3: Coagulation

  • Reinforcement of the platelet plug through the coagulation cascade, which transforms blood from a liquid to a gel.

  • Coagulation involves three primary phases:

    1. Intrinsic Pathway: Triggered by damage to the blood vessel.

    2. Extrinsic Pathway: Triggered by tissue damage outside the blood vessel.

    3. Common Pathway: Both pathways converge to activate the final clotting agents.

  • Clotting factors (procoagulants) are involved, numbered I through XIII—most are proteins produced by the liver, circulating in an inactive state.

  • Vitamin K is essential for the synthesis of four of these coagulation factors.

Coagulation Cascade
Extrinsic Pathway

  1. Triggered by the release of thromboplastin from outside the vessel (injured tissue).

  2. Initiates a cascade of reactions that lead to prothrombin conversion to thrombin.

Intrinsic Pathway

  1. Initiated when inactive factor XII in plasma contacts damaged surface (blood vessel).

  2. This pathway also activates factor X and leads to thrombin production.

Steps in the Coagulation Process

  1. Tissue Damage: Activation of factor X, leading to the formation of prothrombinase with factor V, phospholipids, and Ca2+.

  2. Prothrombin Activation: Prothrombin is converted into thrombin by prothrombinase.

  3. Fibrin Formation: Thrombin converts soluble fibrinogen into insoluble fibrin, forming a mesh that stabilizes the platelet plug.

  4. Fibrin Stabilization: Factor XIII (fibrin-stabilizing factor) cross-links fibrin strands for a stronger clot.

Part 4: Clot Retraction

  • Begins within 30 to 60 minutes post-injury and continues for several days.

  • Actin and myosin in platelets contract, pulling on the fibrin strands, which squeezes serum out of the clot and draws the edges of the ruptured blood vessel together to aid healing.

Part 5: Thrombolysis

  • As the blood vessel heals, chemicals such as tissue plasminogen activator (tPA) are released.

  • tPA converts plasminogen to plasmin, which actively degrades fibrin, removing the clot while promoting tissue repair through:

    • Platelet-derived growth factor (PDGF): Stimulates division of smooth muscle cells and fibroblasts for vessel wall rebuilding.

    • Vascular endothelial growth factor (VEGF): Stimulates endothelial cell proliferation to restore the endothelial lining.

Regulation of Coagulation

  • Anticoagulants and thrombolytics prevent excessive clotting. - Mechanisms include the swift removal and dilution of clotting factors, and inhibition of activated factors.

  • Factors regulating clotting:

    • Antithrombin III: Inactivates unbound thrombin in circulation.

    • Heparin: Enhances the effect of antithrombin III.

    • Endothelial cells: Secrete substances like nitric oxide for vasodilation and prostacyclin to inhibit platelet aggregation.

    • Vitamin E quinone: A potent anticoagulant formed when vitamin E reacts with oxygen.

    • Protein C: Activated by protein S to degrade factors Va and VIIIa, limiting clot formation.

Disorders of Hemostasis

Thromboembolic Disorders

  • Result in undesirable clot formations (thrombi) in unbroken blood vessels, potentially leading to tissue death.

  • Thrombus: A clot persisting in an unbroken vessel, often found in veins due to lower blood flow.

    • Example: Deep vein thrombosis (DVT).

  • Embolus: A thrombus that detaches and travels throughout the bloodstream, potentially blocking smaller vessels.

    • Example: Pulmonary embolism or cerebral embolism.

  • Risk factors include atherosclerosis, inflammation, and blood stasis from immobility.

Anticoagulant Drugs

  • Aspirin: Reduces platelet stickiness.

  • Heparin: Administered clinically in cardiac care.

  • Warfarin: Used in patients with atrial fibrillation.

  • Dabigatran: Direct thrombin inhibitor.

Bleeding Disorders

  • Thrombocytopenia: Deficient levels of circulating platelets leading to spontaneous bleeding.

    • Treatment includes platelet transfusions.

  • Impaired Liver Function: Affects the synthesis of clotting factors, often resulting from vitamin K deficiency or liver disease.

  • Hemophilia: Genetic disorders leading to deficiencies in specific clotting factors.

    • Hemophilia A: Due to factor VIII deficiency.

    • Hemophilia B: Factor IX deficiency.

    • Hemophilia C: Factor XI deficiency.

    • Symptoms include prolonged bleeding, especially into joints.

    • Treatment involves genetically engineered factor replacements to prevent the need for plasma transfusions.

Disseminated Intravascular Coagulation (DIC)

  • Characterized by widespread clotting and severe bleeding.

  • Occurs due to an overstimulation of the clotting cascade, resulting in depleted clotting factors, leading to severe bleeding even when blood vessels remain intact.

  • Can be triggered by conditions like septicemia or complications during pregnancy.