From Circulating Biomarkers to Polymorphic Variants: A Narrative Review of Challenges in Thrombophilia Evaluation

Abstract

Thrombophilia is characterized by a hypercoagulable state that predisposes individuals to venous and arterial thrombotic events, posing significant challenges for clinical evaluation and management. This narrative review critically examines the current landscape of thrombophilia testing, focusing on the utility and limitations of both circulating and genetic biomarkers. Circulating biomarkers—such as D-dimer, antithrombin, protein C, and protein S—offer dynamic insights into the coagulation process yet often suffer from low specificity in varied clinical settings. In contrast, genetic biomarkers, notably Factor V Leiden and the prothrombin G20210A mutation, provide stable risk stratification but are limited by their low prevalence in the general population. Emerging markers, including selectins, Factor VIII, Factor XI, neutrophil extracellular traps, and extracellular vesicles, are also discussed for their potential to refine thrombotic risk assessment. By integrating evidence-based guidelines from international health organizations, this review underscores the need for a personalized approach to thrombophilia evaluation that balances comprehensive risk assessment with the avoidance of over-testing. Such an approach is crucial for optimizing patient outcomes and informing the duration and intensity of anticoagulant therapy.