Therapeutic Dosing of Unfractionated Heparin – Adults – Inpatient Consensus Care Guideline Summary Target Population: adult patients receiving therapeutic heparin infusions Link to Full Guideline: Therapeutic Dosing of Unfractionated Heparin – Adult – Inpatient/Emergency Department Guideline overview • Anticoagulation dosing nomograms are defined by time to achieve therapeutic range o Gradual nomogram: within 24-36 hours o Rapid nomogram: within 18-24 hours • Therapeutic heparin infusions must be ordered with the Heparin Anticoagulation Supplemental order set • Baseline labs necessary prior to initiation of infusion are defined • The indication for use determines the anti-Xa target goal, the initial bolus dose, and initial infusion rate • The administration instructions for heparin infusion orders specify the titration nomogram to use • Instructions for management of heparin infusions within 48 hours of direct Xa inhibitor (apixaban, rivaroxaban) administration are provided • Bolus doses and infusion rate changes are based on heparin levels by anti-Xa and include nomograms for: gradual, rapid, treatment of acute coronary syndrome with GP IIb/IIIa inhibitors, and direct Xa inhibitor in previous 48 hours and elevated baseline heparin anti-Xa doses • Recommendations for timing of laboratory monitoring are provided o Heparin levels by anti-Xa should be measured 6 hours after initiation or change in infusion rate • Instructions for transitioning between nomograms and to other anticoagulants is provided • References Gradual Anticoagulation Nomogram – Initiates unfractionated heparin at a lower initial infusion rate with the intent to achieve a therapeutic range within 24-36 hours. This nomogram is typically reserved for patients receiving concomitant thrombolytics, who have a new mechanical valve during current admission or when concerns for bleeding outweigh the need for quickly reaching a therapeutic goal. Rapid Anticoagulation Nomogram – Initiates unfractionated heparin with the intent to achieve a therapeutic range within 18-24 hours. This nomogram is typically reserved for venous or atrial thrombosis, acute coronary syndrome, history of mechanical valves or when therapeutic anticoagulation is needed quickly. Table 1. Initial UFH Dosing Based on Indication Indication Anti-Xa Target Goal Initial Bolus Initial Infusion Rate Anticoagulation for COVID (Rapid Nomogram unless high bleed risk) 0.3-0.7 IU/mL 80 units/kg (max 10,000 units) 18 units/kg/hr Venous Thromboembolism/ Atrial Thrombosis (Rapid Nomogram unless high bleed risk) 0.3-0.7 IU/mL 80 units/kg (max 10,000 units) 18 units/kg/hr Mechanical Heart Valve (historical) (Rapid Nomogram unless high bleed risk) 0.3-0.7 IU/mL 80 units/kg (max 10,000 units) 18 units/kg/hr Mechanical Heart Valve (new during admission) (Gradual Nomogram) 0.3-0.7 IU/mL None 12 units/kg/hr Therapeutic anticoagulation with elevated bleeding risk (Gradual Nomogram) 0.3-0.7 IU/mL None 12 units/kg/hr Systemic thrombolytics used in previous 24 hours (Gradual Nomogram) 0.3-0.7 IU/mL None 12 units/kg/hr Acute Coronary Syndrome with GP IIb/IIIa inhibitor (e.g. eptifibatide) (Gradual Nomogram) 0.1-0.3 IU/mL None 12 units/kg/hr (max 1,000 units/hr) Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 04/2023 Effective 4/20/2023. Contact CCKM@uwhealth.org for previous versions Acute Coronary Syndrome without GP IIb/IIIa inhibitor (Rapid Nomogram unless high bleed risk) 0.3- 0.7 IU/mL 60 units/kg (max 4,000 units) 12 units/kg/hr (max 1,000 units/hr) Initial boluses and infusion rates are based on actual body weight Table 2. Gradual Anticoagulation Nomogram (e.g., Therapeutic anticoagulation with elevated bleeding risk, systemic thrombolytics used in past 24 hours, mechanical heart valve (new during admission), acute coronary syndrome with GP IIb/IIIa inhibitor) Heparin Level by Anti-Xa (IU/mL) Bolus/Hold Infusion Rate Change <0.1 Bolus 20 units/kg & inform MD (max 5,000 units) increase by 2 units/kg/hr 0.1 – 0.29 None increase by 1 units/kg/hr 0.3 – 0.7 None NO CHANGE; Therapeutic Range 0.71 – 0.8 None decrease by 1 units/kg/hr 0.81 – 1.7 Hold infusion 1 hr decrease by 2 units/kg/hr >1.7 Hold infusion 1½ hr & inform MD decrease by 3 units/kg/hr Table 3. Rapid Anticoagulation Nomogram (e.g., Anticoagulation for COVID, venous thromboembolism, atrial thrombus, mechanical heart valve (historical), acute coronary syndrome without GP IIb/IIIa inhibitor) Heparin Level by Anti-Xa (IU/mL) Bolus/Hold Infusion Rate Change <0.1 Bolus 40 units/kg & inform MD (max 10,000 units) increase by 3 units/kg/hr 0.1 – 0.19 Bolus 20 units/kg & inform MD (max 5,000 units) increase by 2 units/kg/hr 0.2 – 0.29 None increase by 1 units/kg/hr 0.3 – 0.7 None NO CHANGE; Therapeutic Range 0.71 – 0.8 None decrease by 1 units/kg/hr 0.81 – 1.7 Hold infusion 1 hr decrease by 2 units/kg/hr >1.7 Hold infusion 1½ hr & inform MD decrease by 3 units/kg/hr Table 4. Nomogram for Treatment of Acute Coronary Syndrome with GP IIb/IIIa inhibitor Heparin Level by Anti-Xa (IU/mL) Bolus/Hold Infusion Rate Change < 0.1 Bolus 20 units/kg & inform MD (max 5,000 units) increase by 3 units/kg/hr 0.1 – 0.3 None NO CHANGE; Therapeutic Range 0.31 – 0.5 None decrease by 1 units/kg/hr 0.51 – 0.8 None decrease by 2 units/kg/hr > 0.8 Hold infusion 1 hr & inform MD decrease by 3 units/kg/hr Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 04/2023 Effective 4/20/2023. Contact CCKM@uwhealth.org for previous versions Table 5. Nomogram for Direct Xa Inhibitor in Previous 48 hours and Elevated Baseline Heparin Anti-Xa Heparin Level by Anti-Xa (IU/mL) Bolus/Hold Infusion Rate Change < 0.1 Bolus 40 units/kg & inform MD (max 10,000 units) increase by 3 units/kg/hr 0.1 – 0.39 Bolus 20 units/kg & inform MD (max 5,000 units) increase by 2 units/kg/hr 0.4 – 0.69 None increase by 1 units/kg/hr 0.7 – 1.0 None NO CHANGE; Therapeutic Range 1.1 – 1.4 None decrease by 1 units/kg/hr 1.5 – 1.7 Hold infusion 1 hr decrease by 2 units/kg/hr > 1.7 Hold infusion 1½ hr & inform MD decrease by 3 units/kg/hr Table 6. Laboratory monitoring for UFH infusion Lab Initiation/Titration Maintenance Heparin level by anti-Xa 6 hours after initiation or resumption of infusion following a hold 6 hours after any rate change Once 3 consecutive levels are in target range, then check daily Hemoglobin 24 hours after initiation Every other day for up to 14 days Platelets 24 hours after initiation Every other day for up to 14 days Table 7. Transitioning between UFH and other anticoagulants Gradual to Rapid Rapid to Gradual Continue current infusion rate When next level results titrate with new nomogram Heparin to Enoxaparin Stop heparin Administer enoxaparin 2-4 hours later Heparin to DOAC Stop heparin Give oral anticoagulant at the same time Heparin to Fondaparinux Stop heparin Administer fondaparinux 2-4 hours later Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 04/2023 Effective 4/20/2023. Contact CCKM@uwhealth.org for previous versions References 1. O'Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127(4):529-555. 2. 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