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 make a judgment on the benefits of 4-factor PCC on outcomes associated with life-threatening bleeding during oral direct Xa inhibitor therapy for VTE. Harms and burden. Because a suitable comparator group was not available, the panel was unable to make a judgment on the harms and burdens of 4-factor PCC on outcomes associated with life-threatening bleeding during oral direct Xa inhibitor therapy. Studies did report that bleeding either worsened or did not improve in 32% of patients receiving 4-factor PCC. Other EtD criteria and considerations. There was very limited evidence to inform other considerations. Conclusions and research needs for this recommendation. Lack of evidence left the net health benefit/harm from using 4-factor PCC as an addition to cessation of direct Xa inhibitors very uncertain. The ASH guideline panel therefore suggests that either 4-factor PCC administration as an addition to temporary cessation of oral direct Xa inhibitor or cessation of oral direct Xa inhibitor alone be used for patients with life-threatening bleeding during treatment of VTE (conditional recommendation based on very low certainty in the evidence). In a life-threatening situation, the experience and judgment of the prescriber weighing individual risks and benefits would likely be the deciding factors. This recommendation does not apply to non life-threatening bleeding because cost likely outweighs potential benefit and there is likely a small but quantifiable increased risk of thromboembolism associated with administration of PCC.193 The panel identified the following additional research questions. (1) What clinical parameters define the need for intervention with 4-factor PCC over withholding oral direct Xa inhibitor alone? 