Guideline sources The following summarized guidelines for the management of bleeding in patients on antithrombotics are prepared by our editorial team based on guidelines from the Canadian Cardiovascular Society (CCS 2018) and the British Society for Haematology (BSH 2013). 1 2 3 3 4 4 Definition Bleeding in patients on antithrombotics is a common complication in patients treated with both anticoagulation and antiplatelet therapy. 3 Epidemiology Bleeding in patients on antithrombotics is caused by a complex biological interaction between blood and tissue factors and extensive anticoagulation effect. 4 Disease course The complex biological interaction of blood and tissue factors, in addition to the extensive anticoagulation effect, activates bleeding cascade causing bleeding in patients on antithrombotics, which may be categorized as minor or major bleeding that may increase morbidity and mortality. 4 Prognosis and risk of recurrence Major bleeding is associated with a mortality rate of 11%. 3 https://web.pathway.md/diseases/recbAhTGe1aO1TxVZ 1/3 6/29/23, 3:18 AM Bleeding in patients on antithrombotics Pathway Guidelines 1. Medical management Patients on unfractionated heparin: discontinue heparin infusions and apply general hemostatic measures to stop bleeding in patients on UFH. B Patients on warfarin: administer 4-factor PCC (25-50 units/kg) and vitamin K (5 mg IV, for one dose) in patients with major bleeding while on warfarin. B Show 2 more Patients on danaparoid: discontinue treatment and apply general hemostatic measures to control bleeding, as there is no specific antidote for danaparoid. B Patients on fondaparinux: discontinue treatment and apply general hemostatic measures to control bleeding in patients on fondaparinux, as there is no specific antidote. B Patients on bivalirudin: discontinue treatment and apply general hemostatic measures to control bleeding, as there is no specific antidote for bivalirudin. B Patients on argatroban: discontinue argatroban and implement general hemostatic measures to control bleeding as there is no specific antidote for argatroban. B Patients on dabigatran: As per CCS 2018 guidelines, consider administering idarucizumab for emergency reversal of dabigatran's anticoagulant effect in patients with uncontrollable or potentially life-threatening bleeding and/or in patients who require urgent surgery for which normal hemostasis is necessary. B As per BSH 2013 guidelines: Discontinue treatment and start general hemostatic measures to control bleeding. B Consider administration of PCC, activated PCC and/or recombinant factor VIII in patients with ongoing life-threatening bleeding. C Patients on rivaroxaban: Discontinue treatment and start general hemostatic measures to control bleeding. B Consider administration of PCC, activated PCC and/or recombinant factor VIII in patients with ongoing life-threatening bleeding. C Patients on anti-platelets: decide to withhold antiplatelet drugs or administer pro-hemostatic agents after a careful multidisciplinary evaluation of the associated risks and benefits. B Patients on fibrinolytics: discontinue infusion of fibrinolytic and other antithrombotic drugs in patients with major bleeding within 48 hours of administration of fibrinolytic drugs. B Show 3 more 2. Specific circumstances https://web.pathway.md/diseases/recbAhTGe1aO1TxVZ 2/3 6/29/23, 3:18 AM Bleeding in patients on antithrombotics Pathway Supratherapeutic INR without bleeding: withhold 1-2 doses of warfarin and reduce the maintenance dose in patients with an INR > 5.0 but who are not bleeding. B Show 2 more Warfarin reversal prior to surgery: correct INR by giving intravenous vitamin K for surgery that requires reversal of warfarin and that can be delayed 6-12 hours. B Show 2 more Clinical findings Symptoms Past medical history Hematemesis CVD Hematuria Cancer Melena Diabetes mellitus Liver cirrhosis Social history Ulcer Current cigarette smoking Vital signs Hematological findings Hypotension systolic BP Anemia secondary to blood loss Coagulopathy ECG findings Sinus tachycardia References 1. Makris M, Van Veen JJ, Tait CR et al. Guideline on the management of bleeding in patients on antithrombotic agents. Br J Haematol. 2013 Jan;160 1 35 46. Open 2. Jason G Andrade, Atul Verma, L Brent Mitchell et al. 2018 Focused Update of the Canadian Cardiovascular Society Guidelines for the Management of Atrial Fibrillation. Can J Cardiol. 2018 Nov;34 11 1371 1392. Open 3. M E Gimbel, S C S Minderhoud, J M Ten Berg. A practical guide on how to handle patients with bleeding events while on oral antithrombotic treatment. 2018 Jun;26 6 341 351.2018 Jun;26 6 341 351. Open 4. Petras Stirbys. Review And Insights Into The Bleeding Mechanism Incited By Antithrombotic Therapy: Mechanistic Nuances Of Dual Pro-Hemorrhagic Substrate Incorporating Drug-Induced Microvascular Leakage. 2015 Aug 31;8 2 1254.2015 Aug 31;8 2 1254. Open https://web.pathway.md/diseases/recbAhTGe1aO1TxVZ 3/3