UMEM Educational Pearls

Prothrombin complex concentrate (PCC) and fresh frozen plasma (FFP) are used for INR reversal in patients on vitamin K antagonists (VKA) (e.g., warfarin) with life-threatening bleeding. Guidelines from the Neurocritical Care Society and Society of Critical Care Medicine recommend using PCC over FFP for patients with VKA-associated hemorrhage and an INR >=1.4.

New study-INCH trial:

  • Multi-center, prospective, randomized, open-label trial comparing FFP IV 20 ml/kg + phytonadione IV 10 mg versus 4-factor PCC IV 30 IU/kg + phytonadione IV 10 mg
  • Adult patients on VKA with intracerebral or subdural hemorrhage with INR >=2.0 were included. Patients with traumatic intracranial hemorrhage were excluded.

What they found:

  • Analysis included 50 (23 FFP and 27 PCC) patients (trial was stopped early after a safety analysis)
  • 2 (9%) patients in the FFP group and 18 (67%) patients in the PCC group achieved an INR <=1.2 within 3 hours (adjusted OR 30.6, 95% CI 4.7-197.9; p=0.0003)
  • Hematoma expansion at 3 hours was higher in those treated with FFP than PCC (adjusted difference 16.9 ml, 95% CI 2.5-31.3; p=0.023)
  • Time until INR <=1.2 was longer in the FFP group than the PCC group (1482 vs 40 minutes; p=0.050)

Application to clinical practice:

  • Of note, FFP 30 ml/kg has been suggested to provide more complete coagulation factor correction (this trial used 20 ml/kg), and package inserts for PCCs recommend doses based on INR and weight (this trial used 30 IU/kg for all patients)
  • Although the sample size was small, this study suggests that in patients with VKA-associated non-traumatic intracranial hemorrhage and an elevated INR, PCC may provide faster INR correction than FFP, and may additionally be associated with a smaller degree of hematoma expansion.


  1. Frontera JA, Lewin JJ, Rabinstein AA, et al. Guideline for reversal of antithrombotics in intracranial hemorrhage. Neurocrit Care 2016; 24:6-46. (PMID 26714677)

  2. Steiner T, Poli S, Griebe M, et al. Fresh frozen plasma versus prothrombin complex concentrate in patients with intracranial haemorrhage related to vitamin K antagonists (INCH): a randomised trial. Lancet Neurol 2016; 15:566-73. (PMID 27302126)

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