Related | Therapeutic Dosing of Unfractionated Heparin - Adult - Inpatient/Emergency Department
Therapeutic Dosing of Unfractionated Heparin -
Adult - Inpatient/Emergency Department
Consensus Care Guideline
Population/Problem:
This consensus care guideline is intended to provide physicians, advanced practice providers,
nurses, and pharmacists with a process to standardize the initiation, maintenance, and
monitoring of intravenous unfractionated heparin in the adult population. Practices considered
include guidance on selection of dosing nomograms, initial and maintenance monitoring of
heparin infusions, initial and maintenance heparin dose adjustments, and transitioning between
dosing nomograms.
Definitions:
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.1
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.2,3
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Recommendations:
Heparin (UFH) infusions with the intent for titration to a therapeutic goal must be ordered via the Heparin
Anticoagulation Supplemental Order Set. No modifications of these nomograms are allowed. While
discouraged, if patient circumstances require heparin dosing that differs from established nomograms,
specific orders must be written.
1. Baseline laboratory monitoring4
a. Prior to starting the UFH infusion collect the following baseline labs if not already resulted in
the previous 48 hours
• PT/INR
• CBC with platelet
• Heparin anti-Xa level: only if on an oral Xa inhibitor (apixaban, rivaroxaban) prior to
starting the UFH infusion
• Drug specific anti-Xa level: only if on an oral Xa inhibitor (apixaban, rivaroxaban) in the
previous 48 hours prior to starting the UFH infusion
2. Select the indication for UFH use
Table 1. Initial UFH Dosing Based on Indication1-5 (UW Health GRADE high quality evidence, strong
recommendation)
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)
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
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3. Titration of UFH infusion
a. The nomogram for titration will be specified in the administration instructions of the heparin
infusion order
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) (UW Health GRADE low quality evidence, conditional
recommendation)
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)
(UW Health GRADE low quality evidence, conditional recommendation)
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 (UW
Health GRADE low quality evidence, conditional recommendation)
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
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4. Heparin and Direct Xa Inhibitors6-9 (apixaban, rivaroxaban) (UW Health GRADE low quality evidence,
conditional recommendation
a. In the presence of a direct Xa inhibitor the measured anti-Xa level may be relatively high in
proportion to the antithrombin activity. This may result in over estimation of the heparin
activity by the assay. To account for this, a higher anti-Xa goal may be used for patients with
recent use of direct Xa inhibitors.
b. Target a higher anti-Xa range (Table 5) in patients who received a direct Xa inhibitor in the
previous 48 hours and if the baseline heparin anti-Xa level is elevated.
c. A drug specific anti-Xa level should be drawn prior to starting the heparin infusion:
i. If the drug specific anti-Xa level is within or elevated outside of the target range, then
heparin infusion should not be started.
ii. If unable to wait for the drug specific anti-Xa level to result, then patient risk/benefit
for thrombotic and bleeding risks should be weighed prior to starting the heparin
infusion.
d. Return to the standard anti-Xa goal based on indication for unfractionated heparin 48 hours
after the last dose of the direct Xa inhibitor (apixaban, rivaroxaban) was given (See Table 1).
Table 5. Nomogram for Direct Xa inhibitor in Previous 48 hours and Elevated Baseline Heparin Anti-
Xa (UW Health GRADE low quality evidence, conditional recommendation)
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
5. Titration Pearls:
a. If the infusion is held for a procedure it is ok to resume the infusion at the previous rate
prior to the hold. (UW Health low quality evidence, conditional recommendation)
b. If goal is not reached within 24 hours for rapid nomogram or 36 hours for gradual
nomogram, with correct titration, the patient may not be an appropriate candidate for
adjustments based on these heparin nomograms. Recommend consultation with
Pharmacy and/or Hematology for assistance with dosing.
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6. Laboratory Monitoring
Table 6. Laboratory monitoring for UFH infusion4
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
7. Transitioning between nomograms and anticoagulants10-14
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
Disclaimer
Consensus care models assist clinicians by providing a framework for the evaluation and treatment of
patients. This guideline outlines the preferred approach for most patients. It is not intended to replace a
clinician’s judgment or to establish a protocol for all patients. It is understood that some patients will not fit
the clinical condition contemplated by a guideline and that a guideline will rarely establish the only
appropriate approach to a problem.
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Content Expert(s):
Name: Anne Rose, PharmD – Pharmacy Manager
Phone Number: (608) 263-9738
Email Address: arose@uwhealth.org
Contact for Changes:
Name: Philip Trapskin, PharmD, BCPS – Director, Medication Use Policy, Safety, Compliance, and
Informatics
Phone Number: (608) 263-1328
Email Address: ptrapskin@uwhealth.org
Guideline Author(s):
Anne Rose, PharmD – Pharmacy
Reviewer(s):
John Hoch, MD – Vascular Surgery
Stephanie Kraus, CNS - Nursing
Kraig Kumfer, MD - Hospitalists
Margaret Murray, CNS – Nursing
Erin Robinson, PharmD – Drug Policy Program
John Sheehan, MD- Oncology
Eliot Williams, MD – Oncology
David Yang, MD, – Clinical Laboratory
Luke Zurbriggen, MD – Oncology
Committee Approval(s):
Inpatient Anticoagulation Committee: March 2023
Pharmacy & Therapeutics Committee: ***
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Contact: CCKM@uwhealth.org Last Revised: 04/2023
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Table 1. GRADE Ranking of Evidence15
High We are confident that the effect in the study reflects the actual effect.
Moderate
We are quite confident that the effect in the study is close to the true effect, but
it is also possible it is substantially different.
Low The true effect may differ significantly from the estimate.
Very Low The true effect is likely to be substantially different from the estimated effect.
Table 2. GRADE Ratings for Recommendations for or Against Practice
Strong (S)
Generally, should be performed (i.e., the net benefit of the treatment is
clear, patient values and circumstances are unlikely to affect the decision.)
Conditional (C)
May be reasonable to perform (i.e., may be conditional upon patient values
and preferences, the resources available, or the setting in which the
intervention will be implemented.)
Revise guideline as necessary, based on workgroup feedback and continued evidence
Collateral Tools & Resources
Metrics
• VTE Performance Measure – VTE 4 – UFH with dosage and platelet monitored by protocol
• Guideline adherence: anti-Xa level monitoring, infusion rate adjustments, nomogram selection
• Time to achieve a target Xa level, supra-therapeutic Xa levels, bleeding, and thrombotic events
Order Sets & Smart Sets
• IP/ED - Heparin Anticoagulation - Adult - Supplemental [4373]
Protocols
Heparin Infusion Titration – Adult – Inpatient [4]
Other Related Documents and Tools
• Extracorporeal Membrane Oxygenation (ECMO): Initiation and Management - Adult -
Inpatient/Emergency Department Consensus Care Guideline
• UW Health Mechanical Circulatory Device (MCD) - Adult - Inpatient/Ambulatory/Emergency
Department Clinical Practice Guideline
• IP - ECMO Heparin Anticoagulation - Adult - Supplemental [5894]
• IP - Total Artificial Heart Heparin Anticoagulation - Adult - Supplemental [5559]
• IP - Ventricular Assist Device Heparin Anticoagulation - Adult - Supplemental [4999]
Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission.
Contact: CCKM@uwhealth.org Last Revised: 04/2023
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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. Writing Committee M, Jneid H, Anderson JL, et al. 2012 ACCF/AHA focused update of
the guideline for the management of patients with unstable angina/Non-ST-elevation
myocardial infarction (updating the 2007 guideline and replacing the 2011 focused
update): a report of the American College of Cardiology Foundation/American Heart
Association Task Force on practice guidelines. Circulation. 2012;126(7):875-910.
3. Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease:
Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of
Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2
Suppl):e419S-e496S.
4. Whitlock RP, Sun JC, Fremes SE, Rubens FD, Teoh KH. Antithrombotic and
thrombolytic therapy for valvular disease: Antithrombotic Therapy and Prevention of
Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical
Practice Guidelines. Chest. 2012;141(2 Suppl):e576S-e600S.
5. Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC guideline for the
management of patients with non-ST-elevation acute coronary syndromes: a report of
the American College of Cardiology/American Heart Association Task Force on Practice
Guidelines. Circulation. 2014;130(25):e344-426.
6. Smith AR, Dager WE, Gulseth MP. Transitioning hospitalized patients from rivaroxaban
or apixaban to a continuous unfractionated heparin infusion: A retrospective review. Am
J Health Syst Pharm. 2020;77(Suppl 3):S59-S65.
7. Faust AC, Kanyer D, Wittkowsky AK. Managing transitions from oral factor Xa inhibitors
to unfractionated heparin infusions. Am J Health Syst Pharm. 2016;73(24):2037-2041.
8. Plum MD, Hedrick JN, Hockman R, Bazydlo L, Palkimas S. The Relationship between
the Initial Anti-factor Xa Measurement and the Duration of Direct Oral Anticoagulant
Influence in Patients Transitioning to Heparin. Pharmacotherapy. 2020;40(9):880-888.
9. Levito MN, Coons JC, Verrico MM, et al. A Systemwide Approach for Navigating the
Dilemma of Oral Factor Xa Inhibitor Interference With Unfractionated Heparin Anti-
Factor Xa Concentrations. Ann Pharmacother. 2021;55(5):618-623.
10. Apixaban (Eliquis®) [prescribing information]. Bristol-Myers Squibb Company; Princeton,
NJ. 2021.
11. Rivaroxaban (Xarelto®) [prescribing information]. Janssen Pharmaceuticals, Inc.;
Titusville, NJ. . 2021.
12. Dabigatran (Pradaxa®) [prescribing information]. Boehringer Ingelheim Pharmaceuticals,
Inc.; Ridgefield, CT. 2021.
13. Enoxaparin (Lovenox®) [prescribing information]. Sanofi Aventis US LLC. Bridgewater,
NJ. 2020.
14. Fondaparinux [prescribing information]. Zydus Pharmaceutical USA Inc.; Pennington,
NJ. . 2020.
15. Guyatt G, Oxman AD, Akl EA, et al. GRADE guidelines: 1. Introduction-GRADE
evidence profiles and summary of findings tables. J Clin Epidemiol. 2011;64(4):383-394.
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