Lecture on Hypercoagulable States (Thrombophilia)

Introduction

• Hypercoagulable states are also known as thrombophilia.
• Important in clinical medicine to understand the risks and mechanisms of thrombosis.
• Virchow's Triad: Risk of thrombosis is determined by stasis of blood flow, endothelial injury, and hypercoagulable state.

Pathophysiology

Stasis

• Stasis of blood flow leads to increased platelet binding and thrombus formation.
• Common triggers: immobilization, prolonged travel, surgery-induced bed rest, paralysis.

Endothelial Injury

• Reduction in anti-thrombotic cytokines, e.g., PGI2 and nitric oxide, leads to platelet aggregation.
• Common causes: surgery, trauma, smoking.

Hypercoagulable State

• Increase in pro-coagulants or decrease in anti-coagulants.
• Inherited or acquired.

Inherited Thrombophilia

Types

• Factor V Leiden: Mutation makes Factor V resistant to degradation by Protein C.
• Prothrombin Gene Mutation: Increases prothrombin activity leading to excessive thrombin and fibrin production.
• Protein C and S Deficiency: Reduced ability to degrade Factors V and VIII, increasing clot formation.
• Anti-thrombin III Deficiency: Reduces suppression of thrombin, increasing clot formation.
• Hyperhomocysteinemia: Mutation in enzymes affecting homocysteine levels, influencing clot formation.

Acquired Thrombophilia

Types

• Immune-mediated: Antiphospholipid syndrome, HIT.
• Non-immune-mediated: Pregnancy, oral contraceptives, malignancy.

Antiphospholipid Syndrome

• Recurrent thrombosis and spontaneous abortions.
• Autoantibodies stimulate platelets and inhibit anti-coagulants like Protein C and Antithrombin III.

Heparin-Induced Thrombocytopenia (HIT)

• Formation of heparin-platelet factor 4 complexes leads to thrombosis and platelet consumption.

Paroxysmal Nocturnal Hemoglobinuria (PNH)

• Causes unusual venous thrombosis and hemolysis.

Diagnostic Approach

• Indications for testing: unprovoked clot at a young age, recurrent clots, thrombosis in unusual locations, recurrent spontaneous abortions, strong family history.
• Tests include inherited thrombophilia panel, antiphospholipid antibody panel.

Treatment

Acute Thrombosis

• Anticoagulation is the primary treatment.
• Different anticoagulants: heparin, direct thrombin inhibitors, warfarin.

Long-term Management

• Choice of anticoagulant depends on type of thrombophilia.
• Warfarin for Antiphospholipid syndrome, LMWH for malignancy-related thrombosis.
• Special treatments for PNH (eculizumab) and MPNs (hydroxyurea).

Conclusion

• Hypercoagulable states are a significant risk factor for thrombosis.
• Understanding the pathophysiology, types, and management options is crucial for effective treatment.