Genetics – Group 1 conditions

 

Antithrombin deficiency

  1. Antithrombin is a naturally occurring inhibitor of the coagulation cascade. It binds to and inactivates
    thrombin and factors Xa, IXa, XIa and XIIa.
  2. Antithrombin deficiency occurs in approximately 1 in 500 in the healthy population and in 4 to 5% of individuals with venous thromboembolism (VTE).
  3. Antithrombin deficiency is a strong thrombophilic condition, with approximately 60% of heterozygous carriers developing VTE by age 60 years.
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Protein C deficiency

  1. Protein C is a natural anticoagulant that inactivates factors Va and VIIIa in a reaction requiring its cofactor, protein S.
  2. Protein C deficiency occurs in approximately 1 in 500 in the healthy population and in 2 to 4% of individuals with VTE.
  3. Heterozygous protein C deficiency is a moderate to strong thrombophilic condition, with up to 50% of people developing VTE by age 60 years.
  4. Individuals with heterozygous protein C deficiency commenced on warfarin without heparin cover may develop skin necrosis.
  5. Homozygous protein C deficiency is a severe thrombophilic condition characterised by the development of neonatal purpura fulminans and disseminated intravascular coagulation.
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Protein S deficiency

  1. Protein S is an essential cofactor in the inactivation of factors Va and VIIIa by protein C.
  2. Protein S deficiency occurs in 3 to 13 in 1000 in the healthy population and in 2 to 4% of patients
    with VTE.
  3. Heterozygous protein S deficiency is a moderate thrombophilic condition, with approximately one third of carriers developing thrombosis by age 60 years.
  4. Like protein C deficiency, skin necrosis may occur in heterozygous carriers commenced on warfarin,
    while homozygous deficiency results in neonatal purpura fulminans.
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