Abstract 2752: Incomplete Reversal of Anticoagulation Following Intracranial Hemorrhage with Three-Factor Prothrombin Complex Concentrate
Authors: Switzer Jeffrey A , DeSousa Keith , Mohorn Phillip , Waller Jennifer L , Fagan Susan C , Hughes Douglas , Bruno Askiel , Nichols Fenwick T , Hess David C , Rocker Jody 
Published: July 2021

Introduction:
Warfarin-associated intracranial hemorrhage (wICH) is common and associated with worse outcomes than spontaneous intracranial hemorrhages. National guidelines for treatment are vague and consensus-driven. Prothrombin complex concentrates (PCC) have been advocated as a safe and rapid means for reversing anticoagulation but the effectiveness of formulations with low levels of factor VII (three-factor PCC) have not been tested. The purpose of this study was to determine the safety and effectiveness of a three-factor PCC (Profilnine) to reverse anticoagulation in the setting of wICH.

Methods:
In November, 2007, a protocol for reversal of anticoagulation in wICH using Profilnine was instituted at our instituion. All patients with wICH received 10 mg IV vitamin K and 50 IU/kg of PCC. If the INR remained >1.4 after 30 minutes, a second dose of PCC of 25 IU/kg was infused. Additional treatment with plasma was at the discretion of the treating physician. Charts of all patients receiving PCC between November 1, 2007 and May 31, 2010 were reviewed. Patient demographics, hemorrhage subtype [intracerebral (ICH), subarachnoid (SAH) or subdural (SDH)], plasma usage, complications, and clinical outcome were determined from the chart review. Adequate correction of the INR was defined as an INR <1.4. Kaplan-Meier survival analysis examined the time to INR correction.

Results:
Fifty-one wICH patients were treated with Profilnine including 28 (55%) with ICH, 21 (41%) with SDH and 2 (4%) with SAH. The mean age was 70.3 (SD 12.7), 32 (63%) were male, 37 (74%) patients were white and the remaining African-American. The mean INR was 3.56 (SD 2.71) at baseline [30 (61%) <3.0, 11 (23%) 3.0-4.9, 8 (16%) >4.9]. Seventeen (33%) patients received plasma along with the first dose of PCC. Mean INR was 2.13 post-PCC and only 33 (67.4%; 95% CI, 54.3% - 80.5%) were corrected to an INR <1.4. Eleven (22%) patients received a second dose of PCC and 22 (43%) received subsequent plasma. The likelihood of correction was not increased by concomitant plasma (p=0.77). However, those with INRs <3.0 and those with INRs between 3.0-4.9 were more likely to have an INR that corrected to <1.4 than those with and INR >4.9 before PCC dosing (p=0.02). The median time to INR correction following initial PCC dose was 11.5 hours. If a second dose of PCC was needed, the median time to INR correction was 17.6 hours. No arterial and one (2%) venous thromboembolic adverse events occurred. Twenty-four (47%) patients died or were discharged to hospice.

Conclusions:
A three-factor PCC (Profilnine) was incompletely effective in INR correction in wICH presumably due to the relatively low concentration of factor VII. The addition of plasma to PCC did not reduce the time to effective INR correction. Presumed superiority of three-factor PCC to plasma for wICH appears premature.