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? This question aimed to evaluate management options for life- threatening bleeding related to administration of an oral direct Xa inhibitor. Two approaches have emerged for this situation, administra- tion of 4-factor PCC and administration of coagulation factor Xa (recombinant), inactivated-zhzo (formerly known as andexanet alpha). These approaches have not been directly compared, and the panel was unable to provide a judgment regarding which is preferred and therefore made independent recommendations regarding each intervention. For patients with life-threatening bleeding during oral direct Xa inhibitor treatment of VTE, the ASH guideline panel suggests using either 4-factor PCC administration as an addition to cessation of oral direct Xa inhibitor or cessation of oral direct Xa inhibitor alone (conditional recommendation based on very low certainty in the evidence 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 of- fers no recommendation for 1 approach over the other. Summary of the evidence. We found no systematic reviews that addressed this question, but we identified 8 individual Eligible studies included patients receiv- ing direct Xa inhibitors who were experiencing major bleeding and reported the effect of 4-factor PCC on mortality, ineffective bleeding management, and thromboembolic complications.106,110,113,188-192 The EtD framework is shown online at https://dbep.gradepro.org/ profile/2ec6099d-9b00-4bac-bc31-34653ee10737. Benefits. For benefits, see the evidence profile in the EtD framework referenced at the end of the previous section, available online. 