Coagulopathy and bleeding associated with salicylate toxicity

Introduction: Salicylate toxicity is a common cause of morbidity and hospitalization. Animal and human studies suggest that salicylates cause a dose-dependent inhibition of the activation of factors 2, 7, 9, and 10. However, limited reports of coagulopathy or major bleeding from salicylate toxicity exist. Methods: This is a retrospective study examining subjects from January 1, 2001 to December 31, 2011 in whom at least one serum salicylate concentration was measured above 30 mg/dL. Cases were patients with elevated salicylate concentration and coagulopathy (INR > 1.5). Major bleeding cases were those with elevated salicylate concentration who developed hemorrhagic death; or bleeding from an intracranial, intraspinal, intraocular, retroperitoneal, pericardial, intramuscular site; or hemoglobin decrease of >2 g/dL, or transfusion of at least 2 units of packed RBCs during hospitalization. Results: Twelve percent of all cases of elevated salicylate concentration developed coagulopathy, 6% developed major bleeding, and 3% died. In a multivariate model, duration of elevated salicylate concentration and renal impairment were associated with coagulopathy and no variable was associated with major bleeding. Patients were more likely to develop major bleeding if they had coagulopathy, but not all cases of major bleeding had coagulopathy. Discussion: Coagulopathy and major bleeding during salicylate toxicity has been underrecognized. Renal impairment and duration of salicylate elevation contribute to the risk of coagulopathy, but no factors predict major bleeding. Patients with coagulopathy have a high risk of bleeding but some bleeding occurs without coagulopathy, suggesting that other factors, such as platelet dysfunction, may play a role. Conclusion: Coagulopathy and major bleeding develop in a clinically relevant percentage of cases of salicylate toxicity.