BackgroundMillions of patients receive vitamin K antagonist (VKA) therapy worldwide. Annually 0.2–1 % of all VKA users develops an intracranial hemorrhage (ICH). Prothrombin complex concentrate (PCC) is administered to restore the INR ≤ 1.5 in an attempt to limit hematoma growth. In order to facilitate PCC dosing, our hospital recently changed from a variable dose based on bodyweight, baseline- and target-INR, to a fixed 1000 IU fIX PCC dosing protocol for ICH.MethodsIn a before and after design, we compared successful achievement of an INR ≤ 1.5 with a fixed dosing strategy versus the variable dosing strategy of PCC in patients presenting with intracranial bleeding complications of VKA. Data of the two cohorts of patients were retrospectively collected from medical records.ResultsA median dosage of 1750 IU was given per patient in the variable dose group (n = 25) versus 1000 IU in the fixed dose group (n = 28). In the intention-to-treat analysis, 96 % achieved an INR ≤ 1.5 after an initial dose in the variable dose cohort compared to 68 % in the fixed dose cohort (p = 0.01). An additional dose was given in 2 (8 %) versus 9 (32 %) patients, respectively (p = 0.04). The median door-to-PCC-order time was 42 versus 32 min (p = 0.37) and the door-to-needle time was 81, respectively 60 min (p = 0.42).ConclusionThe fixed dose protocol necessitates additional PCC infusions more frequently to achieve a target INR ≤ 1.5. Door-to-order and door-to-needle time were shorter but, in this small cohort, not significantly so. The effect on clinical outcome remains unknown.

Background In the initial absence of specific reversal agents for factor Xa inhibitors (FXa‐Is), prothrombin complex concentrate (PCC) as a hemostatic agent has been recommended by guidelines. Since 2017, idarucizumab has been registered for dabigatran reversal. Still, data on the clinical outcome of direct oral anticoagulant (DOAC)‐related emergencies (major bleeding or urgent interventions) is scarce. In addition, it is unknown to what extent PCC restores thrombin generation in FXa‐I–related emergencies. Our aim was to describe management and clinical outcomes of DOAC‐related emergencies and to assess the laboratory effect of PCC in patients with FXa‐I emergencies. Methods In this prospective cohort study in 5 Dutch hospitals, patients presenting with DOAC‐related emergencies were eligible. The primary outcome was effective hemostasis according to the ISTH definition. Safety outcomes were 30‐day mortality and thromboembolic rate. In patients treated with PCC, additional blood samples were taken to assess the effect on thrombin generation. Results We included 101 patients with major bleeding (FXa‐I, 76; dabigatran, 25) and 21 patients requiring an urgent intervention (FXa‐I, 16; dabigatran, 5). Of patients with major bleeding, 67% were treated with PCC or idarucizumab. Effective hemostasis, 30‐day mortality, and thromboembolism rate were 67%, 22%, and 1%, respectively. In a subset of bleeding patients on FXa‐I managed with PCC, thrombin generation increased, with 96% immediately after PCC administration. In patients requiring an urgent intervention, effective hemostasis, 30‐day mortality, and thromboembolic rate were 95%, 14%, and 5%. Conclusions Effective hemostasis was achieved in the majority of patients presenting with DOAC‐related emergencies;, thromboembolic complications were rare, and mortality was quite high.

To determine if a fixed dose of 1000 IU of 4-factor prothrombin complex concentrate (4F-PCC) is as effective as traditional variable dosing based on body weight and international normalized ratio (INR) for reversal of vitamin K antagonist (VKA) anticoagulation. Methods:In this open-label, multicenter, randomized clinical trial, patients with nonintracranial bleeds requiring VKA reversal with 4F-PCC were allocated to either a 1,000-IU fixed dose of 4F-PCC or the variable dose. The primary outcome was the proportion of patients with effective hemostasis according to the International Society of Thrombosis and Haemostasis definition. The design was noninferiority with a lower 95% confidence interval of no more than À6%. When estimating sample size, we assumed that fixed dosing would be 4% superior.Results: From October 2015 until January 2020, 199 of 310 intended patients were included before study termination due to decreasing enrollment rates. Of the 199 patients, 159 were allowed in the per-protocol analysis. Effective hemostasis was achieved in 87.3% (n¼69 of 79) in fixed compared to 89.9% (n¼71 of 79) in the variable dosing cohort (risk difference 2.5%, 95% confidence interval À13.3 to 7.9%, P¼.27). Median door-to-needle times were 109 minutes (range 16 to 796) in fixed and 142 (17 to 1076) for the variable dose (P¼.027). INR less than 2.0 at 60 minutes after 4F-PCC infusion was reached in 91.2% versus 91.7% (P¼1.0). Conclusion:The large majority of patients had good clinical outcome after 4F-PCC use; however, noninferiority of the fixed dose could not be demonstrated because the design assumed the fixed dose would be 4% superior. Door-to-needle time was shortened with the fixed dose, and INR reduction was similar in both dosing regimens. [