Hypercoagulability States in Genetics

Hypercoagulability States

• Primary States (Genetic):

  • Involve inherited mutations or deficiencies in coagulation factors.
  • Common (>1% population):
    • Factor V Leiden mutation: Most common inherited thrombophilia, causes resistance to inactivation by protein C.
    • Prothrombin mutation: Leads to increased prothrombin levels, increasing thrombin generation.
    • Elevated Factor VII, IX, XI, or fibrinogen: Increase risk of thrombosis.
  • Rare: Deficiencies in natural anticoagulants:
    • Antithrombin III deficiency: Reduces ability to inactivate thrombin and other coagulation factors.
    • Protein C deficiency: Affects activation of protein C which degrades factors Va and VIIIa.
    • Protein S deficiency: Co-factor for protein C, reducing its effectiveness.
  • Very Rare:
    • Fibrinolysis defects: Impaired breakdown of blood clots.
    • Homozygous homocystinuria: A deficiency of cystathione β synthase enzyme, leading to elevated homocysteine levels, increasing risk of thrombosis.

• Secondary States (Acquired):

  • Result from conditions or exposures that alter coagulation pathways.
  • High Risk For Thrombosis:
    • Prolonged bed rest: Reduced blood flow leading to increased clotting risk.
    • Myocardial infarction (MI): Damage to the heart can activate coagulation.
    • Atrial fibrillation (A-fib): Stasis of blood in the atrium increases clot formation.
    • Tissue injury (fracture, surgery, burn): Release of tissue factor increases coagulation.
    • Cancer: Tumors may release pro-coagulant substances.
    • Prosthetic cardiac valves: Artificial surfaces stimulate coagulation.
    • Disseminated intravascular coagulation (DIC): Widespread activation of coagulation, often triggered by sepsis or trauma.
    • Heparin-induced thrombocytopenia (HIT): Antibodies against heparin-platelet complexes, leading to platelet aggregation and thrombosis.
    • Antiphospholipid antibody syndrome: Autoantibodies against phospholipids, increasing clotting risk.
  • Lower Risk for Thrombosis:
    • Cardiomyopathy: Abnormal heart function may lead to stasis of blood.
    • Nephrotic syndrome: Increased loss of coagulation inhibitors in urine.
    • Hyperestrogenic states: Pregnancy and postpartum periods are associated with increased coagulation.
    • Sickle cell anemia: Increased red blood cell fragility can lead to microvascular occlusion and thrombosis.
    • Smoking: Increased platelet aggregation and adherence, as well as damage to blood vessel lining.

This quiz explores the various genetic factors contributing to hypercoagulability states. It covers common mutations like Factor V Leiden and Prothrombin mutation, as well as rarer deficiencies affecting anticoagulation. Test your knowledge on these conditions and their implications for thrombosis risk.