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Medical Review - Articles by Medical Review Staff

November 12, 2004

Hereditary Thrombophilias

Prepared October 14, 2004

By Howell Johnson, M.D., Associate Medical Director

Venous thrombosis may result from inherited or acquired causes.



  • Major surgery
  • Trauma
  • Previous thrombosis
  • Immobilization
  • Obesity
  • Pregnancy
  • Estrogen administration
  • Nephrotic syndrome
  • Cancer
  • Antiphospholid antibody syndrome
  • Myeloproliferative disorders
  • Inflammatory bowel disease
  • Paroxysmal nocturnal hemoglobinuria
  • Heparin induced thrombocytopenia
  • Older age


  • Factor V Leiden
  • Prothrombin (factor II) gene mutation
  • Mutation in the methylenetetrahydrofolate reductase gene


  • Antithrombin deficiency
  • Protein C deficiency
  • Protein S deficiency

A hereditary thrombophilia should be suspected with the following:

  1. Age less than 45 years.
  2. Recurrent venous thrombotic event.
  3. Family history of venous thrombosis.
  4. Cerebral or viseral-vein thrombosis.
  5. Stillbirth.
  6. Three or more unexplained spontaneous abortions.
  7. First unprovoked thrombotic event.
  8. Thrombotic event provoked by pregnancy or the puerperium or the use of oral contraceptives or hormone replacement therapy.
  9. Proximal-vein thrombosis or pulmonary embolism.

If a hereditary thrombophilia is likely, an initial series of diagnostic tests should be performed based on prevalence:
Factor V Leiden
Prothrombin mutation
Fasting plasma homocysteine

If these tests are negative, testing for less common hereditary thrombophilia disorders should be performed:
Protein C
Protein S

Other issues to consider:

  1. Factor V Leiden and prothrombin mutation are common among healthy whites but rare among Asians and Africans.
  2. Women who intend to become pregnant should be screened for inherited thrombophilias if they have a personal or family history of venous thrombosis or if they have three unexplained miscarriages, or a stillbirth.
  3. Women with inherited thrombophilia should avoid using oral contraceptives. Screening should be confined to women with a personal or family history of thrombosis. Screening of healthy women is not recommended.
  4. The optimal time for performing tests is six months after the thrombotic event. Results may be misleading if performed before this time. Warfarin should be discontinued at least 2 weeks before testing (however Factor V Leiden’s prothrombin mutation tests are DNA assays and not affected by anticoagulant therapy). Low molecular weight heparin may be substituted for 2 weeks if anticoagulation must be maintained.
  5. Asymptomatic first degree relatives with abnormal test results should receive primary prophylaxis which includes:
    1. Low molecular weight heparin in high-risk conditions such as during surgery, trauma, immobilization, and the six-week postpartum period.
    2. Maintenance of normal weight and homocysteine levels.
    3. Avoidance of contraceptives and hormone replacement therapy.
  6. For unprovoked venous thrombosis after age 50 with no positive family history, test for factor V Leiden, prothrombin mutation, antiphopholid antibody syndrome, and plasma homocysteine.
  7. It is not recommended to test for methylenetetrahydrofolate reduction mutation but instead to measure fasting plasma homocysteine.
  8. Routine screening for hereditary thrombophilia is not recommended. Most asymptomatic individuals with a hereditary thrombophilia will never experience a thrombotic event.
  9. Hereditary thrombophilia predisposes to venous, not arterial thrombosis (with the exception of hyperhomocysteinemia). Testing for these hereditary disorders is therefore not indicated in the evaluation of myocardial infarction, stroke, or related conditions except stroke in patients less than 50 years of age.
  10. Screening for hyperhomocysteinemia is not recommended. B vitamins and folate can lower homocysteine levels but it is not yet known whether this intervention reduces the risk of thrombosis.

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