Can drug-induced platelet dysfunction be reversed?

Antiplatelet drugs are used for treatment of arterial disease, but side effects include an increased risk of bleeding. For patients with intracerebral hemorrhage, traumatic brain injury, and lower gastrointestinal bleeding, mortality rates are higher for patients taking antiplatelet drugs. Reversing the effect of antiplatelet drugs may therefore reduce the risk of mortality and morbidity in these conditions. However, the benefits of any reversal agent must be balanced against the risk of thrombotic complications. Platelet transfusion is often used in clinical practice as a reversal agent, but the only randomized controlled trial in the setting of intracerebral hemorrhage showed an increased risk of death and disability with platelet transfusion compared with standard care. Tranexamic acid is used in a wide range of conditions to reduce bleeding. The risks and benefits of tranexamic acid appear similar in patients taking antiplatelet drugs compared with those not taking antiplatelet drugs. A feasibility trial of desmopressin to reverse the antiplatelet drug effect in intracerebral hemorrhage showed promising results, but definitive efficacy studies are needed. Lastly, unlike other antiplatelet drugs, ticagrelor binds reversibly to platelets. A reversal agent for ticagrelor, bentracimab, has been used in a single-arm clinical trial that demonstrated reversal of the antiplatelet drug effect and good hemostatic outcomes, although without a comparator arm to allow a full assessment of efficacy. This review highlights an unmet need for high-quality studies assessing the efficacy of reversal strategies for drug-induced platelet dysfunction using clinically relevant outcomes.