Navigating the Hemostatic Balance: Anticoagulation and Antiplatelet Therapy in Patients with Thrombocytopenia

Background: Thrombocytopenia is traditionally perceived as a bleeding-predominant condition; however, growing evidence indicates that many thrombocytopenic states are paradoxically associated with an increased risk of venous and arterial thrombosis. This dual hemostatic derangement poses major therapeutic challenges when anticoagulant or antiplatelet therapy is indicated, particularly in complex settings such as cancer-associated thrombosis, immune thrombocytopenia, and advanced liver disease. Methods: We conducted a narrative review of the literature published between January 2021 and May 2025 using PubMed and guideline repositories. Search terms included thrombocytopenia, anticoagulation, antiplatelet therapy, cancer-associated thrombosis, immune thrombocytopenia, and cirrhosis. International guidelines from ASH, ISTH, ASCO, EHA, ESC, and AHA were prioritized. Evidence was synthesized to define platelet-based safety thresholds and disease-specific management strategies. Results/Discussion: Thrombocytopenia does not uniformly confer protection against thrombosis. Platelet activation, endothelial dysfunction, inflammatory signaling, impaired fibrinolysis, and procoagulant microparticles contribute to a prothrombotic milieu despite reduced platelet counts. Most guidelines support full-dose anticoagulation at platelet counts ≥ 50 × 10⁹/L, with dose modification between 25 and 50 × 10⁹/L and treatment interruption below 25 × 10⁹/L, depending on thrombotic risk. Antiplatelet therapy requires stricter individualization, particularly regarding dual antiplatelet therapy. Conclusions: Management of antithrombotic therapy in thrombocytopenic patients requires a dynamic, individualized approach balancing ischemic and bleeding risks. Pragmatic algorithms may guide clinical decision-making while prospective data remain limited.