Introduction: Warfarin-associated intracranial hemorrhage is associated with a high mortality rate. Ongoing coagulopathy increases the likelihood of hematoma expansion and can result in catastrophic hemorrhage if surgery is performed without reversal. The traditional agent for emergency reversal of warfarin induced coagulopathy is fresh frozen plasma (FFP). More recently, 4-factor prothrombin complex concentrate (PCC) has become available as an alternative to FFP for rapid reversal of warfarin-associated coagulopathy. We sought to determine the feasibility and outcomes of using PCC for patients with intracranial hemorrhage.

Methods: A prospective, observational study of all patients undergoing reversal of warfarin-associated coagulopathy for intracranial hemorrhage was undertaken at a single, tertiary care center from April to December 2013. Records of 1400 consecutive neurosurgical consultations in the emergency department were reviewed. 44 (3%) of the consultations were for warfarin-associated intracranial hemorrhage in subdural, subarachnoid or intraparenchymal locations. 20 out of 44 (45%) patients underwent surgical or procedural intervention.

Results: 33 patients underwent emergent reversal of coagulopathy using either FFP or PCC at the discretion of the treating physician. FFP was used in 28 patients and PCC was used in five patients. International normalized ratio of prothrombin time (INR) at presentation was similar between groups (FFP 2.9, PCC 3.1, p = 0.89). The time to normalization of INR was significantly shorter in the PCC group (FFP 256 minutes, PCC 65 minutes, p < 0.05). When surgical procedures were performed, the time delay to perform procedures was also significantly shorter in the PCC group (FFP 307 minutes, PCC 159 minutes, p < 0.05).

Conclusions: In this preliminary experience, PCC provided a more rapid reversal of warfarin-induced coagulopathy and a shorter delay in the performance of surgical or procedural intervention than FFP. Faster normalization of coagulation parameters may prevent further expansion of intracranial hematoma, facilitate earlier surgical evacuation and improve neurological outcomes.

Patient Care: Use of 4-factor prothrombin complex concentrate would reduce the time required for reversal of warfarin-associated intracranial hemorrhage, facilitate rapid surgical evacuation and improve neurological outcomes.

Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe the importance of warfarin-associated intracranial hemorrhage 2) Discuss, in small groups, the relative efficacy of 4-factor prothrombin complex concentrate vs. fresh frozen plasma in correcting warfarin-associated coagulopathy

References: [1] Lavoie A, Ratte S, Clas D, et al. Preinjury warfarin use among elderly patients with closed head injuries in a trauma center. J Trauma 2004;56:802–7. [2] Mina AA, Bair HA, Howells GA, et al. Complications of preinjury warfarin use in the trauma patient. J rauma 2003;54:842–7. [3] Rådberg JA, Olsson JE, Rådberg CT. Prognostic parameters in spontaneous intracerebral hematomas with special reference to anticoagulant treatment. Stroke 1991;22:571–6. [4] Rossi EC, Simon TL. Rossi’s principles of transfusion medicine. 4th ed. Chichester, UK; Hoboken, NJ: Wiley-Blackwell/AABB Press; 2009. [5] Bershad EM, Farhadi S, Suri MF, et al. Coagulopathy and inhospital deaths in patients with acute subdural hematoma. J Neurosurg 2008;109:664–9. [6] Pabinger I, Brenner B, Kalina U, et al. Prothrombin complex concentrate (Beriplex P/N) for emergency anticoagulation reversal: a prospective multinational clinical trial. J Thromb Haemost 2008;6:622–31. [7] Zubkov AY, Mandrekar JN, Claassen DO, et al. Predictors of outcome in warfarin-related intracerebral hemorrhage. Arch Neurol 2008;65:1320–5. [8] Sarode R, Milling TJ Jr, Refaai MA, et al. Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding: a randomized, plasma-controlled, phase IIIb study. Circulation 2013;128:1234–43. [9] Hickey M, Gatien M, Taljaard M, et al. Outcomes of urgent warfarin reversal with frozen plasma versus prothrombin complex concentrate in the emergency department. Circulation 2013;128:360–4. [10] Awad AJ, Walcott BP, Stapleton CJ, et al. Dabigatran, intracranial hemorrhage,and the neurosurgeon. Neurosurg Focus 2013;34:E7.