Two-thirds of our populace presented with a baseline INR below 7.5. The target INR used in our study is in line with Dutch common practice Tipifarnib (Zarnestra) for non-cranial bleeding emergencies. and successful clinical Tipifarnib (Zarnestra) outcome. Results Target International Normalized Rate was reached in 92% of the fixed dose patients (n=101) 95% of variable dose patients (n=139) resulting in a risk difference of -2.99% (90% CI: – 8.6 to 2.7) (non-inferiority not confirmed). Clinical outcome was successful in 96% and 88% of fixed variable dose, respectively, with a risk difference of 8.3% (90% CI: 2.7-13.9; non-inferiority confirmed). Conclusions Although a lower fixed prothrombin complex concentrate dose was associated with successful clinical end result, Tipifarnib (Zarnestra) fewer patients reached the target International Normalized Rate. the variable dose regimen of PCC for VKA reversal in bleeding patients. Design and Methods Study design This prospective, observational two-cohort study compares the outcome of treatment with PCC for VKA reversal according to two different dosing strategies in two Dutch teaching hospitals. Both hospitals are located close to each other in one Dutch city. These hospitals are comparable regarding total number of beds, the size of the Emergency Department, Intensive Care Unit (ICU), and Traumatology, Surgery, and Internal Medicine Departments. Patients Patients were eligible for inclusion if reversal of VKA treatment with PCC was indicated for major or clinically relevant, nonintracranial bleeding. Patients with an indication for PCC because of an intracranial bleeding event, an urgent invasive process, and patients not using VKA treated with PCC were excluded. Prothrombin complex concentrate regimen Both participating hospitals used Cofact? (Sanquin BV, Amsterdam, The Netherlands) as PCC. This product contains factors II, VII, IX and X. Cofact does not contain either activated factors or heparin. Stocks of this product were adequate and promptly available in both hospitals. The participating hospitals applied different PCC dosing strategies in routine clinical practice. Patients entering one hospital were treated with a low fixed dose of 1 1,040 IU F IX. The other hospital applied a variable dose regimen (84% of patients in the fixed dose and the variable dose cohort, respectively). The mean duration of hospitalization, during which patients were followed up, was six days. Main patients’ characteristics are shown in Table 1. Table 1. Patients’ characteristic. Open in a separate window Prothrombin complex concentrate treatment The range of concentration of the vitamin K dependent factors in PCC batches used during the period of evaluation was 23-26 IU F IX, 10-14 IU F VII, 19-24 IU F II, and 18-23 IU F X mL-1; 26 IU FIX per mL was used for dose calculation. The most frequent indication for PCC treatment was gastrointestinal bleeding (57% in each cohort; 4 (2.9%) patients in the variable dose regimen cohort (94.7% of patients in the fixed dose and the variable dose cohorts, respectively, resulting in a risk difference of -2.99% (90% CI: -8.64 to 2.66) for non-inferiority with the limit set to 4%, indicating that non-inferiority was not established (Table 3). Table 3. Overall results. Open in a separate window In the fixed dose cohort, median INR declined Tipifarnib (Zarnestra) from 5.1 (range 1.5 to above 7.6) at baseline to 1 1.5 (range 1 to 2 2.9) and in the variable dose cohort, from 5.9 (range 1.8 to above 7.6) to 1 1.4 Tipifarnib (Zarnestra) (range 0.9 to 3.4), after PCC treatment (Figure 2). Open in a separate window Figure 2. PCC administration. Prothrombin IKK-alpha Complex Concentrate (PCC) administered per patient. Graphic conventions as in figure 1. In cohort 1, median dosage is the same line as upper interquartile range. Cohort 1: fixed dose regimen, cohort 2: variable dose regimen. Furthermore, the results on the planned subgroup analysis of baseline INR below 5 showed that non-inferiority was established for.