The reaction mixture contained fXa or IIa (20 nM), ATIII (200 nM), different amounts of unfractionated heparin and AnXa. Methods: Inhibition of human fXa or thrombin (IIa) by ATIII in the presence of heparin was studied in an enzymatic assay in buffered solution. Here we report new in vitro data demonstrating that AnXa can also effectively reverse anticoagulation of unfractionated heparin. We previously reported nonclinical and Phase 2 clinical data in healthy subjects with enoxaparin, a low molecular weight heparin (LMWH). Andexanet alfa (AnXa) is a recombinant modified human fXa under development for the reversal of both direct and antithrombin III (ATIII)-dependent indirect fXa inhibitors. Although protamine sulfate can be used to neutralize heparin, its administration can cause severe hypotensive and anaphylactic reactions.

Bleeding is the major complication that may result from these therapies. Too rapid administration may cause hypotension or pseudo-anaphylactoid reaction.Background: Unfractionated heparin is used in the management of venous thromboembolism, stroke prevention in atrial fibrillation as well as in cardiac surgeries (e.g., valve replacement and other procedures requiring cardiopulmonary bypass).Maximum rate of 5 mg/min, without exceeding 50 mg per 10 min period.Prefer slow IV infusion to direct IV route whenever possible.If shorter than 8 hours since last dose of LMWH:.Administration of antidote may not be necessary check with the Poison Control Center whether administration of low doses of protamine would be appropriate.If longer than 12 hours since the last dose of LMWH:.It may be necessary to repeat the same dose if the APTT remains high when measured 2 to 4 hours after the first infusion.0.5 mg of protamine per mg of enoxaparin or for every 100 anti-Xa units of LMWH.If longer than 8 hours and less than 12 hours since last dose of LMWH:.An additional dose corresponding to half of the initial dose may be necessary if the APTT remains high when measured 2 to 4 hours after the first infusion.1 mg of protamine per mg of enoxaparin or for every 100 anti-Xa units of LMWH.If shorter than 8 hours since last dose of LMWH:.1-1.5 mg of protamine per 100 standard units heparin.Standard heparin administered subcutaneously:.Repeat the APTT 5 to 15 min after the end of the IV infusion and 2 hours later (possible rebound with heparin) to assess whether an additional dose is required. Adjust the dose if necessary, depending on effect.Administer an empirical dose of 25-50 mg of protamine IV infusion over 10 min.APTT unavailable heparin dose unknown:.TIME SINCE THE INJECTION OF HEPARIN DIRECT IVĭOSE OF PROTAMINE RECOMMENDED FOR EACH 100 UNITS OF STANDARD HEPARIN APPT unavailable heparin dose known (administer by direct IV only):.Administer the dose by IV infusion over 10 min.E.g.: To neutralize 3875 standard heparin units, administer approx.Determine the dose of protamine to administer:.Example: For a patient receiving a continuous IV infusion of standard heparin of 1500 units/h with a 5000 unit bolus 3 hrs ago, should neutralize: + + = 3875 units to neutralize.Include all bolus doses and the continuous infusion in the calculation.Calculate the amount of heparin to neutralize:.Consider the elimination half-life of standard heparin is about 1 hr.APPT unavailable heparin dose known (continuous IV infusion):.Repeat the APTT 5-15 min after the end of the IV infusion and 2 hrs later (possibility of rebound with heparin) to assess whether an additional dose is required. APTT 300-400 secs: 1.2 mg/kg protamine (max 50 mg/dose) by IV infusion over 10 min.

APTT 200-300 secs: 0.6 mg/kg protamine (max 50 mg/dose) by IV infusion over 10 min.Available activated partial thromboplastin time (APTT):.WARNING: The dose of protamine to be administered should be calculated based on the remaining amount of anticoagulant to be neutralized. Évaluation des technologies et des modes d'intervention.Soins palliatifs, soins de fin de vie et décès.Centre d’expertise en sécurité de l’information (CESS).Centre d'excellence sur le vieillissement de Québec.

Colloques, congrès, conférences et formations.

Naloxone (extrahospital administration).

Chelating agents (excluding Deferoxamine).

Accès au dossier de l'usager - Archives.

Soins palliatifs et soins de fin de vie.

Bank of Interpreters of the Capitale-Nationale.

Comités des usagers (CU) et comités de résidents (CR).

Devenir fournisseur pour le CIUSSS de la Capitale-Nationale.

Bureau du partenariat avec l’usager et de l’éthique (BPUE).

Portrait of the CIUSSS de la Capitale-Nationale.

Antidote to heparin