Abstract
Orthopedic surgeons frequently manage patients taking clopidogrel who require low-molecular-weight heparin (LMWH) for venous thromboprophylaxis. This review examines the differences between arterial and venous thrombosis and explains why both medications are often necessary despite the increased bleeding risk. We conducted a comprehensive literature search of PubMed, Cochrane Library, Embase, and Google Scholar from January 2000 to August 2025, screening 1,184 records and ultimately including 57 studies comprising eight randomized controlled trials, 32 cohort studies, and 17 systematic reviews. Quality assessment was performed using the Cochrane Risk of Bias tool and Newcastle-Ottawa Scale. Due to substantial heterogeneity in study populations, interventions, and outcome definitions, we conducted structured narrative synthesis rather than meta-analysis. We provide clear guidance on when to stop or continue clopidogrel therapy in elective versus trauma surgery and how to safely combine it with LMWH when needed. Key recommendations include that clopidogrel alone does not prevent venous thromboembolism, LMWH remains necessary in immobilized patients, elective surgery usually requires the temporary cessation of clopidogrel, and trauma surgery should not be delayed despite ongoing therapy.