IBMS Congress

www.ibms.org

Thrombophilia guidelines

Session 2

Haematology

Prof Mike Greaves

Learning outcomes

• Indications for testing for heritable thrombophilia
• Impact of testing on clinical management
• Consequences of thrombophilia testing

'Heritable thrombophilia' describes an inherited tendency to venous thromboembolism (VTE). It includes deficiencies of physiological anticoagulants (antithrombin, protein C, protein S) and two quite prevalent gene mutations (factor V Leiden-FVR506Q, and a mutation in the prothrombin gene- F2G20210A). Some other associations have been reported but the thrombosis risk associated with them is less well established.

Although testing for these heritable thrombophilias is superficially attractive in order to ‘explain’ an episode of VTE, in fact the condition is multifactorial in pathogenesis and no identifiable heritable thrombophilia is detected in many affected individuals, even when VTE appears to have been unprovoked. Furthermore, detection of heritable thrombophilia adds little to assessment of risk of recurrent VTE after discontinuation of anticoagulant therapy and testing does not reduce the risk of recurrence. In addition, testing for predisposition to a generally late-onset, usually non-fatal disorder can lead to unwarranted patient anxiety and medical overtreatment.

In view of these considerations the indications for thrombophilia testing are few. Routine testing in newly presenting patients with VTE is not of clinical value- it does not impact on treatment decisions. Some clinicians favour testing when there is an exceptionally strong family history of VTE but it is unclear how such families should be selected, and if that route is followed careful genetic counselling is essential before testing asymptomatic relatives. In pregnancy the risk of VTE is increased but the individual assessment of risk is primarily clinical, for example by consideration of body mass index and the need for interventions such as delivery by Caesarian section. In a small minority of women, perhaps those with a family history of pregnancy-related VTE, testing for heritable thrombophilia may contribute to risk assessment. Finally, testing for protein C and S deficiency is indicated in the rare conditions of purpura fulminans in neonates and children, and warfarin-induced skin necrosis.