1. FERNE/EMRA How do we treat ICH patients with an elevated INR Andy Jagoda, MD, FACEP Professor and Vice Chair Department of Emergency Medicine Mount Sinai School of Medicine New York, NY

2. FERNE/EMRA Disclosures Astra Zeneca, NovoNordisk, UCB Pharma Advisory Boards Astra Zeneca, NovoNordisk, UCB Pharma Advisory Boards Eisai Speakers’ Bureau Eisai Speakers’ Bureau Chair, ACEP Clinical Policies Committee Chair, ACEP Clinical Policies Committee Executive Board, Brain Attach Coalition Executive Board, Brain Attach Coalition Executive Board, Foundation for Education and Research in Neurologic Emergencies Executive Board, Foundation for Education and Research in Neurologic Emergencies

3. FERNE/EMRA Common Etiologies of ICH  Incidence of anticoagulant-associated ICH rose from 5% to 18% of cases of spontaneous ICH in 1990s  INR 2.5-4.5 increases risk of ICH 10X  ICH expansion in over 50% of patients on warfarin  Doubles ICH mortality Acquired Coagulopathy – Anticoagulation

4. FERNE/EMRA Treatment ICH in patients with INR > 1.5 is life- threatening ICH in patients with INR > 1.5 is life- threatening Time until initiation of warfarin reversal is predictive of outcome Time until initiation of warfarin reversal is predictive of outcome Reversal may not occur in 1 of 6 patients Reversal may not occur in 1 of 6 patients Goldstein JN, et al. Stroke. 2006;37:151-155.

5. FERNE/EMRA Reversal Options Fresh frozen plasma (FFP)Fresh frozen plasma (FFP)  Administration time  Response time Recombinant factor VIIaRecombinant factor VIIa  Limited experience Prothrombin complex concentrates (PCC)Prothrombin complex concentrates (PCC)  Not available Vitamin KVitamin K

6. FERNE/EMRA Trauma Model Tx of trauma patients with ICH on preinjury warfarin. J Trauma 2006; 61:318-321 “Coumadin protocol” in place “Coumadin protocol” in place Mean time until FFP administration was 4.3 hours +/- 4.4 hours Mean time until FFP administration was 4.3 hours +/- 4.4 hours No difference from the preprotocol group No difference from the preprotocol group Reasons for delay: Reasons for delay: Failure to recognize urgency Failure to recognize urgency Delay in delivery from blood bank Delay in delivery from blood bank Delay in initiation of infusion Delay in initiation of infusion Delay in completion of infusion Delay in completion of infusion

7. FERNE/EMRA Stroke Model Timing of FFP administration. Stroke 2006; 37:151-155 CT to FFP time: 60 – 375 min CT to FFP time: 60 – 375 min FFP: 1 – 6 units FFP: 1 – 6 units Vit K: 0 – 10 mg Vit K: 0 – 10 mg 12 / 57 patients INR did not reverse at 24 hours 12 / 57 patients INR did not reverse at 24 hours Rapid correction of INR did not correlate with outcome Rapid correction of INR did not correlate with outcome Delay in presentation Delay in presentation Delay in administration Delay in administration Delay in reversal Delay in reversal

8. FERNE/EMRA Conclusions Protocols need to exist to facilitate rapid reversal of warfarin induced coagulopathy Protocols need to exist to facilitate rapid reversal of warfarin induced coagulopathy Protocol: Protocol: 2 - 4 units FFP; begin with 2 units of universal donor FFP 2 - 4 units FFP; begin with 2 units of universal donor FFP 10 mg Vit K slowly IV over 10 minutes 10 mg Vit K slowly IV over 10 minutes Need for further research on the role of rFactor VII and PCC Need for further research on the role of rFactor VII and PCC