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Rapid reversal of coagulopathy in warfarin-related intracranial haemorrhages with prothrombin complex concentrates

Departments of Anaesthesiology and Laboratory Medicine, Tan Tock Seng Hospital, National Healthcare Group, Tan Tock Seng, Singapore


We report our initial experience using Proflinine SD, a 3-Factor prothrombin complex concentrate (PCC) in combination with fresh frozen plasma and vitamin K in seven patients admitted to our neurointensive care unit with oral anticoagulation therapy-related intracranial haemorrhage over a six-month period, to achieve rapid normalisation of the international normalised ratio (INR) and allow surgical evacuation when indicated.
Four patients presented with subdural haematomas while three had intracerebral haematomas. Six of seven patients had admission INR in the appropriate therapeutic range for oral anticoagulation therapy. The median dose of PCC administered was 28.5 IU/kg body weight (interquartile range 21.3 to 38.5 IU/kg). All four patients with subdural haematoma underwent surgical evacuation once INR was less than 1.5. Median time from computed tomography diagnosis to surgery was 275 minutes (range 102 to 420 minutes). The median time to INR normalisation post-PCC administration was shorter, at 85 minutes (range 50 to 420 minutes) for the four patients who survived, versus 10 hours (range 9 to 44 hours) in the three patients who died. Two of the three patients who died had haematoma increase, worsening midline shift and subfalcine herniation, leading to withdrawal of therapy.
Prothrombin complex concentrates should be considered for use in the urgent reversal of INR in oral anticoagulation therapy-related intracranial haemorrhage, potentially halting haematoma expansion and expediting urgent neurosurgical intervention, although data from randomised controlled trials is still lacking. The literature supporting the use of PCC is reviewed and a protocolised emergent treatment algorithm is proposed, which may help achieve earlier consistent normalisation of the INR.

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