Ciraparantag (PER977): Ciraparantag is a small synthetic water-soluble molecule developed as a reversal agent for unfractionated heparin (UFH), LMWHs, fondaparinux, and the oral direct Xa and IIa inhibitors. It binds to targets through noncovalent hydrogen bonding Minor bleeding NOAC: Delay 1 dose or 1 day VKA: Delay until INR 2.0 Bleeding on oral anticoagulation Severe or life-threatening bleeding Supportive measures as outlined for moderate bleeding + Reversal VKA: Consider PCC NOAC: Give NOAC-specific reversal agent or PCC if reversal agent not available Moderate bleeding Delay or discontinue NOAC or VKA Maintain diuresis/volume support Mechanical compression/intervention to establish hemostasis Transfusion: PRBCs, FFP (as plasma expander), platelets as necessary VKA: Consider adding vitamin K (1-10 mg IV) NOAC: Consider absorption- activated charcoal if last dose 2-4 h Figure 5 Management of patients with active bleeding on oral anticoagulation (NOAC and VKA). FFP fresh frozen plasma; PCC prothrombin complex concentrate; PRBC packed RBCs. See Figure 1 legend for expansion of other abbreviations. 1162 Evidence-Based Medicine [ 1 5 4 # 5 C H E S T N O V E M B E R 2 0 1 8 ] and charge-charge interactions thereby preventing the anticoagulants from binding to their endogenous Ciraparantag is earlier in its development program compared with other speci c reversal agents. Management Approach to Bleeding on NOACs: The vast majority of bleeds can be managed conservatively with temporary discontinuation of NOACs and supportive measures. Reversal agents should be used sparingly in the cases of severe and life-threatening bleeding, which includes bleeding causing hemodynamic compromise, ICH, bleeding into a critical organ or closed space, persistent bleeding despite general supportive measures and local hemostatic support, or risk of recurrent bleeding due to excess NOAC drug exposure due to delayed clearance of NOAC (eg, acute renal failure) or overdose. 