Effect of prothrombin complex concentrate on INR and blood coagulation system in emergency patients treated with warfarin overdose.

We investigated the effect of prothrombin complex concentrate (PCC) on the international normalized ratio (INR) and blood coagulation system in two emergent patients treated with warfarin for secondary prevention of cardioembolic stroke due to nonvalvular atrial fibrillation. An 80-year-old woman developed massive subcutaneous hemorrhage and swelling on her right upper extremity with weak pulsation of the right radial artery and had an INR above 10. An 83-year-old man had pleural effusion with an INR value of 6.69 and pleural puncture was immediately required. We administered 500 IU of PCC to the two patients (17.2 IU/kg and 12.5 IU/kg) with 10 mg of vitamin K. The INR decreased to 1.12 and 1.85, respectively, with an increase of plasma levels of protein C and coagulant factors IIa, VIIa, IXa, and Xa 10 min after administration. The plasma levels of the thrombin-antithrombin III complex increased (from 4.0 to 12.0 micro g/l and from 0.5 to 28.9 micro g/l, respectively, normal value <3.0), but prothrombin fragment 1+2 increased minimally 10 min after administration (from 0.4 to 1.1 nmol/ml and from 0.4 to 0.7 nmol/ml, respectively, normal value 0.4-1.4 nmol/ml). Plasma levels of D-dimer remained unchanged. The massive subcutaneous hemorrhage in the former patient improved in 14 days. Anticoagulation was restarted in the latter patient after 14 days of PCC administration. There were no embolic episodes during the month after PCC administration. In conclusion, a small amount of PCC may be effective in immediately correcting increased INR levels with increased plasma levels of protein C and coagulant factors IIa, VIIa, IXa, and Xa and may partially activate the coagulation system without any effects on plasma levels of D-dimer.