The risk of stroke (RR, 0.87 [95% CI, more per 1000]; very low certainty) and myocardial infarction (RR, fewer to 4 more per 1000]; very low certainty) did not differ among those receiving protamine and controls. Other EtD criteria and considerations. Compared with planned use of protamine at the conclusion of an invasive procedure, the panel considered that in a life-threatening bleeding situation, ordering protamine and having it prepared and infused may prove more difficult. Therefore, the feasibility of this intervention might vary according to whether centers perform invasive cardiac procedures where routine use of protamine is common. Conclusions and research needs for this recommendation. The guideline panel determined that though there is very low certainty evidence for a net health benefit associated with administering protamine to patients receiving heparin (LMWH or UFH) who develop life-threatening bleeding in addition to heparin therapy cessation, the possibility of benefit warranted a conditional recommendation in favor of protamine administra- tion. The recommendation does not, however, apply to patients with less serious bleeding when cessation of LMWH/UFH alone is likely to be sufficient. Although most studies did not specify whether heparin included UFH or LMWH, protamine should primarily be used for patients on UFH due to complete rather than partial reversal of the anticoagulant effect, as is seen with administration to patients who have been treated with The panel identified the following additional research question. What is the comparative effectiveness of protamine administration for management of life-threatening bleeding in VTE or other patients on UFH/LMWH compared with UFH/LMWH cessation alone? Anticoagulant resumption following bleeding Question: For patients receiving anticoagulant treatment of VTE who survive an episode of major bleeding, should resumption of oral anticoagulation therapy vs discontinuation of oral anticoagu- lation therapy be used? 