(1) What clinical parameters define the need for intervention with 4-factor PCC over withholding oral direct Xa inhibitor alone? (2) What is the comparative effectiveness of 4-factor PCC in real-world patients presenting with potentially life-threatening oral direct Xa inhibitor- associated bleeding vs withholding direct Xa inhibitor alone?. For patients with life-threatening bleeding during oral direct Xa inhibitor treatment of VTE, the ASH guideline panel suggests using coagulation factor Xa (recombinant), inactivated-zhzo in addition to cessation of oral direct Xa inhibitor rather than no coagulation factor Xa (recombinant), inactivated-zhzo (condi- tional recommendation based on very low certainty in the evi- dence about effects ). Remark: This recommendation does not apply to non life-threatening bleeding. No data are available comparing the efficacy of 4-factor PCC and coagulation factor Xa (recombinant), inactivated-zhzo. The guideline panel offers no recommendation for 1 approach over the other. Summary of the evidence. We found no systematic reviews that addressed this question but identified a single study that measured relevant outcomes for patients receiving direct Xa inhibitors who were experiencing major bleeding.194 The eligible study reported the effect of administration of coagulation factor Xa (recombinant), inactivated-zhzo on mortality, ineffective bleeding management, and thromboembolic The EtD framework is shown online at https://dbep. gradepro.org/profile/8FD0D118-359D-B5A1-A933-FB225270E86A. Benefits. For benefits, see the evidence profile in the EtD framework referenced at the end of the previous section, available online. Because a suitable comparator group was not available, the panel was unable to judge the benefits of administration of coagulation factor Xa (recombinant), inactivated-zhzo on outcomes associated with life-threatening bleeding during direct Xa inhibitor therapy. Harms and burden. 