Date: July 29, 2024 Reference: Connolly SJ et al (ANNEXA-I investigators) Andexanet for Factor Xa Inhibitor–Associated Acute Intracerebral Hemorrhage. NEJM May 2024 Guest Skeptic: Dr. Vasisht Srinivasan is an Emergency Medicine physician and neurointensivist at the University of Washington and Harborview Medical Center in Seattle, WA. He is an assistant professor in Emergency Medicine, Neurology, and Neurosurgery at the School of Medicine at the University of Washington. Case: A 65-year-old man is brought into the emergency department (ED) by emergency medical services (EMS) after his family saw him slump over at the dinner table. He was confused, slurring his speech, and had trouble moving his right side. Initial evaluation by medics revealed right arm weakness, a right facial droop, and decreased responsiveness. When he arrives at your ED, the family tells you he was doing fine until dinner. A code stroke is activated, and a CT head shows a left basal ganglia hemorrhage with no vascular lesions on CT angiography. Vital signs show a blood pressure (BP) of 190/110, heart rate (HR) 117 and irregularly irregular, respiratory rate (RR) 18, SpO2 99% on room air. You ask the patient’s family about any other medical conditions, and they report he has high blood pressure and atrial fibrillation. He takes metoprolol and apixaban and last took his medications that morning about eight hours before. As you begin to lower his blood pressure, you start thinking about reversal agents for his anticoagulation. Background: In hemorrhagic stroke, the ABCs for resuscitation remain the same, but can also be categorized as: Airway Management: This is an important aspect for patients with a poor neurologic exam or those who are not protecting their airways. Blood Pressure Control: There is a lot of debate about the aggressiveness of blood pressure lowering. Numerous trials have attempted to determine the optimal blood pressure target to balance the two goals of minimizing hemorrhage expansion and limiting brain ischemia. INTERACT-2 demonstrated that in patients with ICH, intensive lowering of blood pressure did not result in a significant reduction in the rate of the primary outcome of death or severe disability (SGEM#73). ATACH-2 showed that intensive blood pressure reduction (SBP 110-139 mm Hg) does not provide benefit over standard blood pressure reduction (SBP 140-179 mm Hg) in patients with acute intracerebral hemorrhage (SGEM#172). INTERACT-3 reported the odds of a poor functional outcome were lower in the goal-directed intensive care bundle group compared to usual care (SGEM#413). Coagulopathy Reversal: It makes pathophysiologic sense that patients who take anticoagulants should have the drug rapidly reversed to prevent worsening hemorrhage and poor outcomes. However, the evidence regarding the impact of anticoagulation reversal on patient-oriented outcomes such as decreased mortality or improved neurologic function in patients with acute hemorrhagic stroke is mixed and somewhat limited. Reversal of Warfarin: Freeman et al. (2004) found that recombinant factor VIIa can rapidly reverse warfarin anticoagulation in cases of acute intracranial hemorrhage, but the study did not conclusively demonstrate a reduction in mortality or an improvement in functional outcomes. Direct Oral Anticoagulants (DOACs): Compared to warfarin, DOACs like dabigatran, apixaban, and rivaroxaban have shown lower rates of ICH in randomized controlled trials. However, the management of ICH in the setting of DOAC use remains complex. Hemodialysis can help clear dabigatran, and activated charcoal may be used for recent ingestion. Prothrombin complex concentrate (PCC) may offer some benefit in reversing DOAC-related hemorrhage. The 2022 AHA/ASA guidelines give several recommendations on blood pressure lowering and coagulopathy reversal along with an algorithm. Blood Pressure Lowering: