Anticoagulant Reversal Prepared by Shane Barclay MD

Objectives Define the role for anticoagulant reversal. Review of bleeding management – general principles. Coagulation assays. Reversal treatment options.

Role for anticoagulant reversal Major life threatening bleeding for patients on any type of anticoagulation can be problematic. In addition to standard bleeding management, one should be aware of specific treatment options for specific anticoagulants.

Bleeding Management – acute case Discontinue anticoagulants. Control active bleeding (pressure). Appropriate IV fluids, oxygen, CV support. Packed red blood if available. If available, FFP for patients on ASA, Clopidogrel, or other platelet inhibitors. Other specific measures as discussed next.

Remember this?! Tissue trauma, vascular injury

Where anticoagulants work Heparin/Low Molecular Weight Heparin: - Inhibits Xa, Ixa, XIIa and Thrombin - measured by PTT Warfarin: - Inhibits VII, IX, X - measured by INR Direct Oral Anticoagulants (DOAC) - Direct Thrombin Inhibitors (Dabigatran) - Direct Factor Xa inhibitors (“Xabans”) (Rivaroxaban, Apixaban…)

Where anticoagulants work

Where DOACs work

Coagulation Assays PTT – measures the intrinsic pathway - of some use with Unfractionated Heparin. INR and PT – measures extrinsic pathway. - useful for Warfarin Thrombin Time (TT) - can be used if patient on Dabigatran. DOACs generally have little or no effect on PT/INR or PTT

Anticoagulation Reversal Options Protamine sulfate Vitamin K Tranexamic Acid Activated Charcoal Packed Red Blood cells Platelets Prothrombin Complex Concentrates (PCCs) Specific DOAC reversal agents

Anticoagulation Reversal Options DRUG REVERSAL AGENT Heparin Protamine Sulfate 1mg per 100 units heparin at 5 mg/min. Max 50 mg Check PPT at 15 min, then 2-8 hrs.

Anticoagulation Reversal Options DRUG REVERSAL AGENT LMWH Protamine Sulfate 1mg per mg LMWH if last injection < 8 hrs. 0.5 mg per mg LMWH if last injection > 8 hrs. 0.5 mg per mg if bleeding persists after 4 hrs of first dose. Max infusion 5 mg/min Single dose not to exceed 50 mg

Anticoagulation Reversal Options DRUG REVERSAL AGENT Warfarin Vitamin K 2 – 10 mg IV Prothrombin Complex (Beriplex) INR 2-3.9 25 units/kg (max 2500u) INR 4-5.9 35 units/kg (max 3500u) INR > 6 50 units/kg (max 5000u) If PCC not available Fresh Frozen Plasma 10 – 20 ml/kg plus Vitamin K 5 – 10 mg IV

Anticoagulation Reversal Options DRUG REVERSAL AGENT Dabigatran Idarucizumab (Praxbind) 25 mg q 15 min x 2 doses. Activated Charcoal 100 g PO if ingestion < 2 hrs. Tranexamic acid 25 mg/kg IV Desmopressin 0.3 mcg/kg SQ or IV

Anticoagulation Reversal Options DRUG REVERSAL AGENT Apixaban/ Activated Charcoal 100 g PO Rivaroxaban if ingestion < 6 hrs. PCC 50 units/kg max 5000 units. Tranexamic acid 25 mg/kg IV Desmopressin 0.3 mg/kg SQ/IV FFP not recommended.

Summary Patients presenting with acute life threatening bleeding and who are on anticoagulants need special management and often very specific treatment to reverse their bleeding. You need to be aware of the various types of anticoagulants and the treatment options available in your center.