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. A cost- effectiveness analysis based on a systematic review and UK National Health Service perspective estimated that the cost per quality-adjusted life-year gained with PCC vs FFP was 3000 or less, depending on hemorrhage type.187 Conclusions and research needs for this recommendation. The guideline panel s assessment was that the benefits and harms with 4-factor PCC vs FFP were balanced based on very low Table 4. VTE recurrence risk stratification High risk Moderate risk Low risk VTE within past 3 mo VTE within past 3-12 mo VTE . 12 mo previously No other risk factors Deficiency of protein C, protein S, or antithrombin Heterozygous factor V Leiden Antiphospholipid antibody syndrome mutation Multiple thrombophilic abnormalities Recurrent VTE Active cancer certainty evidence. Nevertheless, the panel favored 4-factor PCC over FFP because of ease of administration, the increased probability of achieving a near-normalized INR, and the lower risk of volume overload. The panel determined that this recommendation most directly applies to intracranial bleeding, where speed of reversal is likely to be a particularly important consideration. The panel identified the following additional research questions. (1) What is the cost-effectiveness of 4-factor PCC vs FFP from the payer perspective in various health care systems? (2) What is the true magnitude of increased thromboembolic risk associated with 4-factor PCC administration compared with the same risk for patients treated with FFP? Question: For patients with life-threatening bleeding during oral direct Xa inhibitor treatment of VTE, should cessation of direct Xa inhibitor plus reversal of the direct Xa inhibitor anticoagulant effect vs cessation of direct Xa inhibitor alone be used? 