Thrombosis and Its Risk Factors

  • Thrombosis Overview

  • Thrombosis: Pathologic formation of intravascular blood clots.

    • Unlike normal coagulation, which serves to repair vessel injury, thrombosis occurs abnormally, sealing off blood vessels when not required.
    • Can occur in arteries (e.g., coronary artery) or veins (most commonly in deep veins of the leg, known as deep vein thrombosis (DVT)).

  • Characteristics of a Thrombus

  • Lines of Zahn: Unique pattern found in thrombus that helps indicate the timing of the thrombus formation.

    • Composed of alternating layers of red blood cells and fibrin (part of the clotting process).
    • Attachment: Thrombus is attached to the blood vessel wall, contrasting post-mortem clots that are not.

  • Virchow's Triad: Risk Factors for Thrombosis

  • Disruption in Normal Blood Flow

    • Laminar vs. Turbulent Flow: Normal blood flow is laminar (smooth). Turbulence or stasis increases thrombus risk.
    • Examples:
    • Immobilization: Leads to stasis, increasing DVT risk.
    • Atrial Fibrillation (Afib): Irregular heart rhythm can cause blood pooling in the atria.
    • Myocardial Infarction: Reduced blood flow in heart muscles can lead to thrombus formation.
    • Aneurysms: Irregular blood flow allows for thrombus formation within dilated areas.

  • Endothelial Damage

    • The endothelium generally protects against thrombosis.
    • Mechanisms of protection include:
    • Barrier Function: Prevents exposure of sub-endothelial collagen and tissue factor.
    • Molecular Secretion:
      • Prostaglandin I2: Inhibits platelet aggregation.
      • Nitric Oxide: Promotes vasodilation and inhibits coagulation.
      • Heparin-like Molecules: Activate antithrombin III, inhibiting thrombin.
      • Tissue Plasminogen Activator (TPA): Converts plasminogen to plasmin, dissolving fibrin clots.
      • Thrombomodulin: Modulates thrombin to activate Protein C, which inactivates Factors V and VIII.
    • Examples of Endothelial Damage:
    • Atherosclerosis: Leads to endothelial injury.
    • Vasculitis: Inflammatory damage to blood vessels.
    • High Homocysteine: Linked to vitamin B12 or folate deficiency, causing endothelial damage.

  • Hypercoagulable States

    • Imbalance in coagulation factors leading to increased thrombus risk.
    • May be inherited or acquired.
    • Common Presentations: Recurrent DVTs, often in younger individuals.
    • Two primary causes: excess procoagulants or deficiency of anticoagulants.
    • Examples of Hypercoagulable States:
    • Protein C or S Deficiency: Inability to inactivate Factors V and VIII leads to hypercoagulability.
    • Factor V Leiden: Mutation prevents protein C and S from shutting down Factor V activity.
    • Prothrombin G20210A Mutation: Increases prothrombin production, promoting thrombus formation.
    • Antithrombin III Deficiency: Results in ineffective anticoagulation. High-dose heparin may be required in treatment.
    • Oral Contraceptives: Estrogen increases coagulation factor production, raising thrombus risk.