Thrombophilia testing: when is it appropriate and when is it not?

Abstract

Thrombophilia testing (TT) is often misused in clinical practice, with limited diagnostic value in many thromboembolic events, which frequently arise from multifactorial causes not detectable by laboratory assays. While some biomarkers - such as factor V Leiden, prothrombin G20210A, natural anticoagulant deficiencies, anti-phospholipid antibodies, and elevated homocysteine - are recognized as legitimate risk factors, other genetic markers, including MTHFR polymorphisms, lack clinical relevance and contribute to over-testing, anxiety, and unnecessary treatment. Thrombophilia testing should be reserved for specific scenarios, such as unprovoked venous thromboembolism in young patients, recurrent pregnancy loss, and splanchnic vein thrombosis, in which it may influence management. In contrast, thrombophilia testing is not indicated in cases such as provoked venous thromboembolism or retinal vein occlusion. In a recent study of healthy hematopoietic stem cell donors there were no thrombotic events despite the findings of thrombophilia testing, suggesting that systematic screening in this population - currently mandated by the Italian Bone Marrow Donor Registry - lacks international support and may reflect a form of defensive medicine. A revision of current protocols is recommended to align practice with evidence-based guidelines.