Hereditary thrombophilias

Differential Diagnosis

• Antithrombin III deficiency
• Protein C deficiency
• Protein S deficiency
• PTGM 20210A
• FV Leiden (heterozygous/homozygous)
• Hyperhomocysteinemia, maybe
• Elevated Factor VII

Risk of recurrence

• RR 2.5 for ATIII/Protein C/Protein S deficiencies
• RR 1.3-1.4 for Factor V Leiden

Investigations

• Not very predictive of recurrence with most testable thrombophilias
• Diagnosis does not (or at least should not) change management
• Do not test in
  • First unprovoked
  • Provoked
  • Upper extremity DVT
  • On anticoagulation regardless
  • After first cerebral vein thrombosis or intra-abdominal thrombus
  • Retinal venous or arterial thrombus
• Only test if it will change management
  • In a patient with unprovoked clots who are less than 40 years old and more than two first-degree relatives
  • If skin necrosis on warfarin, test for protein C and S deficiency
  • Test for APLA if there's a plan to stop anticoagulation
• Do not test while acute VTE
• APLA need at least two tests


Further Reading

• Smith TW, Pi D, Hudoba M, Lee AY. Reducing inpatient heritable thrombophilia testing using a clinical decision-making tool.. J Clin Pathol. 2014;67(4):345-9.