Warfarin-related intracerebral haemorrhage: better outcomes when reversal includes prothrombin complex concentrates

H C Hanger, J A A Geddes, T J Wilkinson, M Lee, A E Baker
Internal Medicine Journal 2013, 43 (3): 308-16

BACKGROUND: Warfarin-related intracerebral haemorrhage (WRICH) has high mortality. Haematoma expansion is prolonged in WRICH and independently predicts worse outcomes. Guidelines recommend prompt reversal of the warfarin coagulopathy, but evidence of benefit is lacking.

AIMS: To determine whether the introduction of a WRICH reversal protocol (late 2008), which includes prothrombin complex concentrates (PCC), improves outcomes

METHODS: All patients presenting with WRICH between January 2004 and July 2010 were included. Retrospective case note and radiology review was performed, collecting data on intracerebral haemorrhage (ICH) severity, degree and timeliness of reversal, and patient outcomes. Cox's proportional hazards analysis was used to compare outcomes associated with and without PCC after controlling for ICH severity.

RESULTS: Eighty-eight patients were included (27 treated palliatively). Mean international normalised ratio was 2.9. Vitamin K, PCC and fresh frozen plasma were given alone or in combination to 68, 23 and 44 patients, and mean time from computed tomography scanning to administration was 2.2, 3.3 and 3.1 h respectively. Four patients received PCC pre-protocol (none before 2007), two during development and seventeen patients post-protocol. Those who received PCC had improved survival (P < 0.001). After controlling for ICH score, hazard ratio for death was 0.27 (P < 0.01) for use of PCC. Survival tended to be greater with earlier administration of PCC (P = 0.053). Despite improved survival, discharge domicile and function were not significantly worse.

CONCLUSIONS: PCC reversal was associated with improved survival without worsened disability. Delays in administration may have reduced the potential benefits.

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