D-dimer testing has long been established as a cornerstone in the diagnostic evaluation of suspected venous thromboembolism (VTE), offering a high negative predictive value when combined with clinical probability assessment. However, its performance and interpretation remain challenging in real-world practice, particularly among patients with high baseline thrombotic risk or a history of previous deep vein thrombosis (DVT). This review summarizes recent advances and practice patterns concerning Ddimer-based diagnostic algorithms, with an emphasis on their application in complex clinical settings. Recent evidence demonstrates that D-dimer retains diagnostic value in low- and intermediate-probability patients but loses specificity in the presence of active malignancy, postoperative inflammation, or chronic vascular disease. In individuals with prior DVT, baseline elevation and residual thrombus often lead to false-positive results, underscoring the need for integrated diagnostic strategies combining D-dimer testing with compression ultrasonography and validated clinical scores. Despite the availability of refined approaches, such as age-adjusted or pretest-probability-adjusted thresholds, their implementation in routine care remains limited. Real-world data reveal frequent test overuse, variable assay interpretation, and inconsistent adherence to guidelinerecommended diagnostic pathways. Understanding these limitations and contextual factors is essential to enhance diagnostic precision and resource utilization. Future directions include improved algorithm adherence through electronic decision-support systems, harmonization of assay reporting standards, and further validation of D-dimer– based models in diverse patient populations.

Venous thromboembolism (VTE), encompassing deep vein thrombosis and pulmonary embolism, remains a major cause of morbidity and mortality. In carefully selected patients, evaluation for inherited or acquired thrombophilia can offer valuable insights for individualized management and recurrence prevention. Current international guidelines recommend targeted thrombophilia testing only in cases of unprovoked or recurrent VTE, early-onset disease, strong family history, or thrombosis at unusual sites.Clinically relevant tests include Factor V Leiden, Prothrombin G20210A, and deficiencies of antithrombin, protein C, and protein S, as well as antiphospholipid antibodies. The prevalence and clinical impact of inherited thrombophilias differ across populations;mutations such as Factor V Leiden and Prothrombin G20210A are rare in East Asians, whereas natural anticoagulant deficiencies and antiphospholipid syndrome are more significant. Thrombophilia testing should therefore be individualized and guided by clinical context, ensuring that results meaningfully influence management decisions.Recognition of ethnic variation and adherence to evidence-based diagnostic strategies can enhance precision in the prevention and treatment of VTE.