Optimal dose of prothrombin complex concentrate for acute reversal of oral anticoagulation

We investigated optimal dose of prothrombin complex concentrate (PCC) for acute reversal of oral anticoagulation in patients with major hemorrhagic complications or who required invasive procedures. We also checked how rapidly international normalized ratio (INR) was reversed after PCC administration. INR was measured before and 10-60 min after administration of PCC with or without vitamin K in 42 patients (men 28, women 14, median age of 70 years old) who had received warfarin but required rapid reversal of INR because of a hemorrhagic complication or medical procedure. The amount of PCC administered was 200 IU in six patients, 500 IU in 30, 1000 IU in 3, and 1500 IU in the other 3. Additional administration of PCC was performed when the correction of INR was inadequate. In 10 of the 42 cases, INR was measured serially, before, 10 and 60 min and 12-24 h after the administration of PCC and vitamin K. In the six patients who received PCC of 200 IU, INR values of 3.34 median (range 2.06 to 5.08) decreased to 1.85 (range 1.23 to 2.43) significantly (Wilcoxon's rank sum test, p=0.028), but in three patients (50%), INR values were still above 2.0 after the administration. In 30 patients treated with PCC of 500 IU, values decreased from 2.49 median (range 1.54 to 10.00) to 1.19 (range 0.87 to 1.55) significantly (p<0.0001). The corrected INR values were below 1.5 in 25 of 26 patients (96%) who had initial INR values from 2.0 to 4.9. In four patients with initial INR of 5.0 or more, the reversed INR was below 1.5 in one (25%), between 1.5 and 2.0 in two (50%), and above 2.0 in one (25%) who had additional administration of 500 IU PCC lowering INR from 2.01 to 1.48. Values of INR in the six patients receiving 1000 IU or 1500 IU, INR decreased from 2.33 median (range 1.96 to 4.00) to 0.96 (range 0.87 to 1.24, p=0.028). In the 10 patients with serial measurement, INR changed from 2.67 median (range 2.05 to 10.00) to 1.17 (range 0.99 to 1.60) 10 min after the administration. The INR values remained stable 60 min and 12-24 h after the PCC administration. The 500 IU of PCC is likely to be optimal dose of PCC for emergent reversal of INR in patients requiring rapid correction of INR below 5.0, but to be inadequate dose in patients with INR of 5.0 or more. PCC administration with vitamin K may finish reversing INR rapidly within 10 min and keep the reversed INR values for 12-24 h.