Hemostatic efficacy of four factor prothrombin complex concentrate in intracerebral hemorrhage patients receiving warfarin vs. factor Xa inhibitors.

INTRODUCTION: 4-F PCC is administered for reversal of factor Xa inhibitor-associated coagulopathy despite a lack of quality evidence demonstrating hemostatic efficacy. The aim of this study was to evaluate the hemostatic efficacy of 4-F PCC in intracerebral hemorrhage patients who received factor Xa inhibitors versus warfarin. MATERIALS AND METHODS: This was a multi-center, retrospective, observational cohort study at a large healthcare system. Patients taking warfarin received 4-F PCC 25-50 units/kg based on the presenting INR, while patients taking a factor Xa inhibitor received 35 units/kg. The primary outcome was the percentage of patients with good or excellent hemostatic efficacy as assessed by modified Sarode scale, with neurologic outcomes assessed as a secondary endpoint. Patients were included in the primary outcome population if they had a repeat CT scan within 24 h. RESULTS: One hundred fifty-seven patients were included in the primary outcome population; [warfarin (n = 76), factor Xa inhibitors (n = 81)]. Hemostatic efficacy was 83 % in the warfarin group versus 75 % in the factor Xa inhibitor group (p = 0.24). The hemostatic efficacy risk difference between the groups was 7.6 % (95 % CI 5.1 %, 20.2 %). Good neurologic outcome (mRS 0-2) at discharge was 17 % in warfarin patients versus 12 % in the factor Xa inhibitor patients (p = 0.40). CONCLUSIONS: There was no significant difference in hemostatic efficacy or clinical outcomes between patients taking warfarin or a factor Xa inhibitor following reversal with 4-F PCC. This study provides further support that 4-F PCC can be used for the reversal of factor Xa inhibitor-associated coagulopathy.

Direct to Angiography vs Repeated Imaging Approaches in Transferred Patients Undergoing Endovascular Thrombectomy.

Importance: A direct to angiography (DTA) treatment paradigm without repeated imaging for transferred patients with large vessel occlusion (LVO) may reduce time to endovascular thrombectomy (EVT). Whether DTA is safe and associated with better outcomes in the late (>6 hours) window is unknown. Also, DTA feasibility and effectiveness in reducing time to EVT during on-call vs regular-work hours and the association of interfacility transfer times with DTA outcomes have not been established. Objective: To evaluate the functional and safety outcomes of DTA vs repeated imaging in the different treatment windows and on-call hours vs regular hours. Design, Setting, and Participants: This pooled retrospective cohort study at 6 US and European comprehensive stroke centers enrolled adults (aged ≥18 years) with anterior circulation LVO (internal cerebral artery or middle cerebral artery subdivisions M1/M2) and transferred for EVT within 24 hours of the last-known-well time from January 1, 2014, to February 29, 2020. Exposures: Repeated imaging (computed tomography with or without computed tomographic angiography or computed tomography perfusion) before EVT vs DTA. Main Outcomes and Measures: Functional independence (90-day modified Rankin Scale score, 0-2) was the primary outcome. Symptomatic intracerebral hemorrhage, mortality, and time metrics were also compared between the DTA and repeated imaging groups. Results: A total of 1140 patients with LVO received EVT after transfer, including 327 (28.7%) in the DTA group and 813 (71.3%) in the repeated imaging group. The median age was 69 (interquartile range [IQR], 59-78) years; 529 were female (46.4%) and 609 (53.4%) were male. Patients undergoing DTA had greater use of intravenous alteplase (200 of 327 [61.2%] vs 412 of 808 [51.0%]; P = .002), but otherwise groups were similar. Median time from EVT center arrival to groin puncture was faster with DTA (34 [IQR, 20-62] vs 60 [IQR, 37-95] minutes; P < .001), overall and in both regular and on-call hours. Three-month functional independence was higher with DTA overall (164 of 312 [52.6%] vs 282 of 763 [37.0%]; adjusted odds ratio [aOR], 1.85 [95% CI, 1.33-2.57]; P < .001) and during regular (77 of 143 [53.8%] vs 118 of 292 [40.4%]; P = .008) and on-call (87 of 169 [51.5%] vs 164 of 471 [34.8%]; P < .001) hours. The results did not vary by time window (0-6 vs >6 to 24 hours; P = .88 for interaction). Three-month mortality was lower with DTA (53 of 312 [17.0%] vs 186 of 763 [24.4%]; P = .008). A 10-minute increase in EVT-center arrival to groin puncture in the repeated imaging group correlated with 5% reduction in the functional independence odds (aOR, 0.95 [95% CI, 0.91-0.99]; P = .01). The rates of modified Rankin Scale score of 0 to 2 decreased with interfacility transfer times of greater than 3 hours in the DTA group (96 of 161 [59.6%] vs 15 of 42 [35.7%]; P = .006), but not in the repeated imaging group (75 of 208 [36.1%] vs 71 of 192 [37.0%]; P = .85). Conclusions and Relevance: The DTA approach may be associated with faster treatment and better functional outcomes during all hours and treatment windows, and repeated imaging may be reasonable with prolonged transfer times. Optimal EVT workflow in transfers may be associated with faster, safe reperfusion with improved outcomes.