The evolving landscape of platelet therapy: risks, innovations, and clinical judgment.

Platelet transfusion is a cornerstone of modern supportive care, yet its application is characterized by significant practice variation and uncertainty regarding optimal strategies. This comprehensive review synthesizes current evidence to delineate a more nuanced, physiologically informed approach to platelet therapy. A paradigm shift is underway, moving from uniform count-based triggers toward more restrictive, evidence-based practices; this includes prophylactic thresholds of < 10 × 10⁹/L in stable hematology-oncology patients and therapeutic-only strategies in select populations. In massive hemorrhage, fixed-ratio resuscitation protocols incorporating early platelet administration are critical for improving hemostasis. Conversely, high-quality evidence now defines populations where transfusion may be harmful, including in thrombotic microangiopathies like TTP, heparin-induced thrombocytopenia, and spontaneous intracerebral hemorrhage in patients on antiplatelet agents. The utility of viscoelastic assays in guiding goal-directed therapy and the potential of novel products such as pathogen-reduced, cold-stored, and cryopreserved platelets to mitigate the limitations of conventional storage are also critically examined. This review provides clinicians with a framework to navigate these complexities, emphasizing a context-dependent strategy that balances hemostatic benefit against potential harm to optimize patient outcomes and steward a precious resource.