Thrombophilia: How To Test? How To Manage?

By Julie Hambleton, MD

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Clinical Presentation

The clinical manifestations of patients with PC, PS, and AT deficiencies and the factor V Leiden and prothrombin mutations are all very similar. Upwards of 90% of patients will present with venous thrombosis of the lower extremity, with or without accompanying PE. A minority of patients (generally 5%) will present with venous thrombosis in an unusual location, such as cerebral veins or the mesenteric venous system. Rarely, these disorders are associated with arterial thrombosis.

Venous thromboembolism develops in 60 to 80% of individuals heterozygous for AT, PC, or PS deficiency, typically before the age of 40 to 45 years. Approximately 50% of patients suffer from recurrent disease.² Individuals with the factor V Leiden and prothrombin mutations have a less marked tendency for thrombosis, and often the first episode of thrombosis occurs at a more advanced age. However, the combined presence of factor V Leiden mutation together with AT, PC, or PS deficiency greatly enhances an individual's risk of thrombosis beyond a purely additive effect.

Approximately 50% of patients with AT, PS, PC, factor V Leiden, or prothrombin mutations will have no inciting event as the cause of their DVT. In the remaining patients, thrombosis may be associated with minor trauma, pregnancy, oral contraceptive use, or recent surgery or immobilization.^2,5,6 The frequency of thrombosis during pregnancy and the peripartum period is 31 and 44%, respectively, for AT deficiency; 10 and 19% for PC + PS deficiency; and 28% for the factor V Leiden mutation. The frequency of postoperative thrombosis has been shown to be high in patients with AT, PC, or PS deficiencies: 21% of patients after abdominal surgery and 37% of patients following high-risk orthopedic or cancer surgery. The incidence of postoperative thrombosis attributable to the presence of the factor V Leiden and prothrombin mutations is unknown. Patients with factor V Leiden mutation, if treated with pharmacologic prophylaxis during high-risk surgeries such as joint replacements, do not appear to have an increased risk of thrombosis compared with patients who do not have the factor V Leiden mutation.⁷

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