Four-factor PCC reduced the incidence of volume overload (RR, 0.34 [95% CI, 0.13-0.85]; ARR, 107 fewer episodes per 1000 [95% CI, 24 fewer to 141 fewer per 1000]; low certainty) and increased the proportion of patients who reached an INR of #1.2 to 1.3 within 0.5 to 3 hours (RR, 6.66 [95% CI, 3.82-11.61]; moderate certainty). Harms and burden. The risk of major bleeding during 45 to 90 days of follow-up, as assessed with hematoma expansion or recurrent intracranial hemorrhage (ICH), was higher following 4- factor PCC administration than following FFP administration, but the CI includes appreciable risk increases and decreases (RR, 1.34 20 fewer to 117 more per 1000]; low certainty). Administration of 4- factor PCC possibly increased the risk of PE (ARR, 148 more PE per 1000 [95% CI was not estimable]; low certainty) and DVT (ARR, 37 more DVT per 1000 [95% CI was not estimable]; low certainty), but these estimates were unreliable due to few events in the intervention group and no events in the control group. Similarly, 4-factor PCC was possibly associated with increased risk of any thromboembolism (eg, myocardial infarction, stroke, PE, or DVT), but again, the CI included appreciable risk reduction and increase [95% CI, 20 fewer to 179 more per 1000]; low certainty). Other EtD criteria and considerations. In the United States, the upfront cost of PCC is approximately threefold higher than that of FFP; in Europe, however, FFP upfront costs are higher than those of PCC. Reduction of potentially severe transfusion- associated circulatory overload reactions reduces the cost and should be factored into the resource use equation.186 In addition, FFP requires additional staff time to prepare and administer. 