Asymptomatic thrombophilia—a family affair

Abstract

While the identification of heritable thrombophilic conditions in patients with venous thrombosis has important implications for their subsequent management, it also raises a considerable number of questions for the family members of these patients and the physicians who care for them. For example, should asymptomatic family members be screened for the inherited defect previously identified in the patient? Any potential benefit incurred by screening must be weighed against the costs. In addition to the monetary expenses associated with performing these tests, identification of a heritable genetic defect in an asymptomatic person may provoke considerable anxiety, could have insurance and employment ramifications, and may lead to unnecessary therapies. When considering these issues it is important to remember that while available assays have excellent sensitivity and specificity for the identification of the genetic defects in question, the key question is whether such testing adequately predicts which asymptomatic relatives are also at risk for thrombosis and whether these events may be averted by targeted interventions (e.g. counseling against smoking, avoidance of oral contraceptives, and/or use of venous thromboembolism prophylaxis during high-risk situations). While carriage of a thrombophilic defect has clearly been shown to increase the risk of subsequent thrombosis, this risk is greatly affected by other factors (e.g. comorbidities, medications, external stressors). First-degree relatives may share some, but not all, of these additional predisposing factors, thereby altering each subject’s degree of risk. As such, determination of the potential benefits of screening in this population requires carefully designed cohort studies in which asymptomatic subjects with the thrombophilic defect in question are followed for subsequent events. Such studies are infrequent given the relatively limited prevalence of the defects in question and the small number of investigators who are studying