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Background: The use of anticoagulants and antithrombotic agents in the population is increasing as the population ages with a concomitant rise in chronic diseases such as atrial fibrillation. The incidence of intracranial hemorrhage (ICH) with these agents is small but clinically significant. The purpose of this article is to illustrate how a single institution developed anticoagulation-associated ICH treatment guidelines. Methodology: A literature review of the topic was performed using the PubMed and Cochrane Evidence-Based Medicine review databases using keywords including antithrombotic agents, antiplatelet agents, traumatic brain injury, and intracranial hemorrhage. The results of the search were reviewed, and relevant English-language manuscripts were retained. The pharmacology of each agent was reviewed. Results: Anticoagulants increase the risk and severity of ICH; the association is not as clear with the use of antithrombotic agents. Each agent’s pharmacology and development is discussed, and reversal strategies are reviewed. Whereas some agents may be reversed medically, others are dialyzable, and a few agents have no effective reversal mechanism currently available. Conclusion: ICH, either primary or traumatic, that is complicated by these agents must be rapidly recognized and appropriately treated. Use of a common, simple clinical practice guideline will assist clinicians in intervening rapidly for this patient group.