INR and vitamin K-dependent factor levels after vitamin K antagonist reversal with 4F-PCC or plasma

Restoration of international normalized ratio (INR) to value <1.5 is commonly targeted to achieve hemostasis in vitamin K antagonist (VKA)-treated patients with major bleeding or undergoing urgent surgery. However, the relationship between corrected INR and vitamin K-dependent factor (VKDF) levels for hemostasis is uncertain. The objectives of the study were to (1) examine the impact of 4-factor prothrombin complex concentrate (4F-PCC) or plasma on INR correction and VKDF restoration and (2) evaluate the relationship between INR values and VKDF levels in patients with acute major bleeding or requiring an urgent surgical procedure.. Adult VKA-treated patients with an elevated INR (≥2.0 within 3 hours before study treatment) who received 4F-PCC or plasma following major bleeding or prior to urgent surgery/invasive procedure were included in this retrospective analysis of data from two prospective phase IIIb randomized controlled trials. Of the 370 patients included in this analysis, 185 received 4F-PCC and 185 received plasma. In the 4F-PCC group, 85.9% (159/185) had INR ≤1.5 at 30 minutes after the end of infusion compared with only 39.1% (72/184) in the plasma group. Following 4F-PCC treatment, all VKDF levels exceeded 50% activity regardless of post-infusion INR value. However, following plasma administration, mean activity levels for factors II and X were below 50% at all time points assessed within 3 hours after starting the infusion, regardless of post-infusion INR value. This retrospective analysis demonstrated that treatment with 4F-PCC in VKA-treated patients rapidly restores VKDFs to hemostatic levels irrespective of post-infusion INR value whereas plasma does not.