Background— Patients experiencing major bleeding while taking vitamin K antagonists require rapid vitamin K antagonist reversal. We performed a prospective clinical trial to compare nonactivated 4-factor prothrombin complex concentrate (4F-PCC) with plasma for urgent vitamin K antagonist reversal. Methods and Results— In this phase IIIb, multicenter, open-label, noninferiority trial, nonsurgical patients were randomized to 4F-PCC (containing coagulation factors II, VII, IX, and X and proteins C and S) or plasma. Primary analyses examined whether 4F-PCC was noninferior to plasma for the coprimary end points of 24-hour hemostatic efficacy from start of infusion and international normalized ratio correction (≤1.3) at 0.5 hour after end of infusion. The intention-to-treat efficacy population comprised 202 patients (4F-PCC, n=98; plasma, n=104). Median (range) baseline international normalized ratio was 3.90 (1.8–20.0) for the 4F-PCC group and 3.60 (1.9–38.9) for the plasma group. Effective hemostasis was achieved in 72.4% of patients receiving 4F-PCC versus 65.4% receiving plasma, demonstrating noninferiority (difference, 7.1% [95% confidence interval, −5.8 to 19.9]). Rapid international normalized ratio reduction was achieved in 62.2% of patients receiving 4F-PCC versus 9.6% receiving plasma, demonstrating 4F-PCC superiority (difference, 52.6% [95% confidence interval, 39.4 to 65.9]). Assessed coagulation factors were higher in the 4F-PCC group than in the plasma group from 0.5 to 3 hours after infusion start (P<0.02). The safety profile (adverse events, serious adverse events, thromboembolic events, and deaths) was similar between groups; 66 of 103 (4F-PCC group) and 71 of 109 (plasma group) patients experienced ≥1 adverse event. Conclusions— 4F-PCC is an effective alternative to plasma for urgent reversal of vitamin K antagonist therapy in major bleeding events, as demonstrated by clinical assessments of bleeding and laboratory measurements of international normalized ratio and factor levels. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: .

CSL Behring.

Background: Anemia is frequent in patients with cancer, but there are concerns regarding treatment with erythropoiesis-stimulating agents. Blood transfusions are commonly used as an alternative, but with little data regarding outcomes.Methods: In a retrospective cohort study, we investigated the associations between transfusions and venous thromboembolism, arterial thromboembolism, and mortality in hospitalized patients with cancer using the discharge database of the University HealthSystem Consortium, which included 504 208 hospitalizations of patients with cancer between 1995 and 2003 at 60 US medical centers.Results: Of the patients included, 70 542 (14.0%) received at least 1 red blood cell (RBC) transfusion and 15 237 (3.0%) received at least 1 platelet transfusion. Of patients receiving RBC transfusions, 7.2% developed venous thromboembolism and 5.2% developed arterial thromboembolism, and this was significantly greater than the rates of 3.8% and 3.1%, respectively, for the remaining study population (P Ͻ.001). In multivariate analysis, RBC transfusion (odds ratio [OR], 1.60; 95% confidence interval [CI], 1.53-1.67) and platelet transfusion (1.20; 1.11-1.29) were independently associated with an increased risk of venous thromboembolism. Both RBC transfusion (OR, 1.53; 95% CI, 1.46-1.61) and platelet transfusion (1.55; 1.40-1.71) were also associated with arterial thromboembolism (P Ͻ.001 for each). Transfusions were also associated with an increased risk of inhospital mortality (RBCs: OR, 1.34; 95% CI, 1.29-1.38; platelets: 2.40; 2.27-2.52; PϽ .001).Conclusions: Both RBC and platelet transfusions are associated with increased risks of venous and arterial thrombotic events and mortality in hospitalized patients with cancer. Further investigation is necessary to determine whether this relationship is causal.