Inherited thrombophilias: Genetics and testing considerations

ABSTRACT: Inherited thrombophilias are genetic conditions that increase the lifetime risk of venous thromboembolism (VTE), specifically deep vein thromboembolism and pulmonary embolism. However, most people with thrombophilia never develop a VTE. The five classic inherited thrombophilias, such as Factor V Leiden, prothrombin G20210A mutation, protein C deficiency, protein S deficiency, and antithrombin deficiency, differ in prevalence and VTE risk, influenced by factors such as zygosity and coinheritance. Current clinical guidelines discourage universal thrombophilia testing, recommending it only when a positive result would alter patient-management decisions or where family members might benefit. These recommendations are based on low-certainty evidence due to the lack of high-quality outcome data. Conflicting guidance is common, and questions remain about some clinical scenarios clinicians encounter in practice. Two national guidelines from the American Hematology Association and the American College of Obstetricians and Gynecologists illustrate thrombophilia testing considerations. Advanced practice nurses play a central role in providing individualized risk assessment, working collaboratively with others to guide testing decisions and interpretation of results, and coordinating care. When used selectively, thrombophilia testing can enhance VTE prevention while avoiding unnecessary and expensive screening.