What are examples of thrombophilic conditions?

Examples of Thrombophilic Conditions

Thrombophilia refers to inherited or acquired conditions that are associated with an increased risk of developing venous thrombosis, characterized by a hypercoagulable state. 1

Inherited Thrombophilias

Common Inherited Thrombophilias

• Factor V Leiden (R506Q) mutation: Most common inherited risk factor (population prevalence ~5%; relative risk 5-7 for first venous thrombosis) 1
• Prothrombin gene (G20210A) mutation: Second most common inherited risk factor (population prevalence ~2%; relative risk 2-3) 1
• Antithrombin deficiency: Rare (population prevalence 0.04%; relative risk 15-20) 1
• Protein C deficiency: Uncommon (population prevalence 0.3%; relative risk 15-20) 1
• Protein S deficiency: Uncommon (population prevalence 0.3%; relative risk 15-20) 1

Other Inherited Thrombophilic Factors

• Elevated fibrinogen levels 1
• Factor VIII elevation 1
• Factor XIII Val34 Leu mutation 1
• Von Willebrand factor small polymorphism in intron 2 1
• Tissue-type plasminogen activator -7351 C/T 1
• Dysfibrinogenemia 2

Acquired Thrombophilias

Common Acquired Thrombophilias

• Antiphospholipid antibody syndrome (APS): Population prevalence 1-5.6%; relative risk 3-10 1, 3
  • Lupus anticoagulants
  • Anticardiolipin antibodies
  • Anti-beta-2-glycoprotein-I antibodies

Other Acquired Thrombophilic Conditions

• Hyperhomocysteinemia 4
• Malignancy 1, 2
• Pregnancy and postpartum state 1, 5
• Oral contraceptive use 1, 5
• Hormone replacement therapy 2
• Surgery 2
• Trauma 2
• Prolonged immobilization 2
• Obesity 2
• Advanced age 1
• Inflammatory conditions 1

Clinical Significance of Thrombophilias

Risk Stratification

• The absolute annual incidence of venous thromboembolism (VTE) in asymptomatic persons with thrombophilia who are relatives of probands with VTE ranges from 0.1% per year for carriers of factor V Leiden to 1.7% per year for those with antithrombin deficiency or mixed thrombophilic defects 1

Compound Risk

• Multiple thrombophilic factors often coexist, significantly increasing thrombosis risk 4
• For example, hyperhomocysteinemia interacts synergistically with Factor V Leiden, increasing the relative risk of venous thrombosis 20-fold compared to individuals without either risk factor 4

Special Considerations

• Thrombophilias are particularly important risk factors in:
  • Patients with thrombosis at unusual sites 4
  • Individuals with strong family history of thrombotic disease 4
  • Cases of recurrent venous thrombosis 4
  • Cerebral venous thrombosis 1
  • Long-distance travelers 1

Testing Considerations

• Testing for a single thrombophilic factor is insufficient, as venous thrombosis is often multifactorial 4
• For patients with positive Factor V Leiden, testing for other common thrombophilias (particularly prothrombin 20210A variant) is recommended 4
• Plasma homocysteine measurement is more informative than molecular testing for MTHFR mutations 4
• Sample handling requires proper processing (double-centrifugation to ensure residual platelet count <10.0 × 10^9/L) 4

Important Caveats

• The presence of thrombophilia does not always lead to thrombosis - additional risk factors or triggers are often required 5
• Inappropriate or excessive thrombophilia testing may be detrimental rather than beneficial 2
• Factor deficiencies, pregnancy, oral contraceptive use, and lupus anticoagulant can affect test results 4
• Repetitive testing when the patient is not on anticoagulant therapy is often necessary to confirm diagnoses, particularly for natural anticoagulant deficiencies 3