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Therapeutic Dosing of Unfractionated Heparin – Adult – Inpatient –
Clinical Practice Guideline
Cover Sheet
Target Population: Inpatient
CPG Contact:
Name: Sara Shull, PharmD, MBA, Drug Policy Manager
Phone Number: 608-262-1817
Email address: [email protected]
Guideline Author(s):
Anne Rose, Pharm.D.
Coordinating Team Members:
Eliot Williams, MD; John Hoch, MD; Teresa Darcy, MD, MMM;
John Sheehan MD
Review Individuals/Bodies:
Inpatient Anticoagulation Committee
Committee Approvals/Dates:
Anticoagulation Committee: August 2011; May 2012
Pharmacy and Therapeutics: November 2011; May 2012
Release Date: April 2011
UW Health – University of Wisconsin Hospital and Clinics
Clinical Practice Guideline (CPG)
Executive Summary
Guideline Title:
Therapeutic Dosing of Unfractionated Heparin– Adult – Inpatient – Clinical Practice
Guideline
Guideline Overview
The following guideline provides recommendations for how to initiate, dose adjust and
monitor a therapeutic unfractionated heparin infusion. There is new literature to suggest
that monitoring unfractionated heparin infusions with anti-Xa levels may improve time to
therapeutic range and warrant less lab testing, however, this data is limited and
monitoring with aPTT is still the preferred method.
Practice Recommendations
1. The order must specify the intended regimen, lab monitoring and if an initial bolus is desired. The
following regimens are available:
1.1
Gradual Anticoagulation Regimen:
1.1.1 All acute coronary syndrome patients
1.1.2 Patients treated with alteplase, tenecteplase or abciximab/eptifibatide/tirofiban
1.1.3 New mechanical valve
(note: no bolus is recommended if less than 6 hours from arterial sheath removal)
1.2
Rapid Anticoagulation Regimen:
1.2.1 Deep vein thrombosis
1.2.2 Pulmonary embolism
1.2.3 Ventricular or atrial thrombus
1.2.4 Therapeutic anticoagulation
2. Initial Heparin Bolus
2.1
Initial heparin bolus orders are based on the dosing regimen (gradual or rapid)
Regimen
Gradual
Rapid
Bolus Dose
(units/kg)
60
80
Maximum Bolus
(units)
4000
10,000
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Initial Infusion
(units/kg/hr)
12
18
3. Algorithms for adjusting heparin infusion by aPTT levels
Gradual Anticoagulation Regimen Heparin Anticoagulation Dose Adjustments by aPTT
*aPTT should be rounded to the nearest whole number (If < 0.5 round down, if ≥ 0.5 round up)
aPTT (seconds)*
<36
36-37
38-46
47-56
57-66
67-86
87-100
>100
Bolus/Hold
Bolus 20 units/kg & inform MD
0
0
0
0
Hold infusion 1 hour & inform MD
Hold infusion 1 hour & inform MD
Hold infusion 1 ½ hour & inform MD
Infusion Rate Change
↑ 2 units/kg/hr
↑ 1 unit/kg/hr
NO CHANGE
↓ 1 unit/kg/hr
↓ 2 units/kg/hr
↓ 2 units/kg/hr
↓ 3 units/kg/hr
↓ 4 units/kg/hr
Rapid Anticoagulation Regimen Heparin Anticoagulation Dose Adjustments by aPTT
*aPTT should be rounded to the nearest whole number (If < 0.5 round down, if ≥ 0.5 round up)
aPTT (seconds)*
<35
35-38
39-44
45-60
Bolus/Hold
Bolus 40 units/kg & inform MD
Bolus 20 units/kg & inform MD
0
0
61-75
76-90
91-115
>115
0
Hold infusion 1 hour & inform MD
Hold infusion 1 hour & inform MD
Hold infusion 1 ½ hour & inform MD
Infusion Rate Change
↑ 3 units/kg/hr
↑ 2 units/kg/hr
↑ 1 units/kg/hr
No Change; Therapeutic
Range
È by 1 unit/kg/hr
È by 2 units/kg/hr
È by 3 units/kg/hr
È by 4 units/kg/hr
4. Algorithm for adjusting heparin infusion with heparin levels by anti-Xa
Gradual Anticoagulation Regimen Heparin Anticoagulation Dose Adjustments by anti-Xa
Heparin Level by
Anti-Xa (IU/mL)
<0.1
Bolus/Hold
Infusion Rate Change
Bolus 20 units/kg & inform MD
Ç by 3 units/kg/hr
0.1 - 0.3
0.31 - 0.5
0.51 - 0.8
> 0.8
0
0
0
Hold infusion 1 hr & inform MD
No Change
È by 1 unit/kg/hr
È by 2 units/kg/hr
È by 3 units/kg/hr
Rapid Anticoagulation Regimen Heparin Anticoagulation Dose Adjustments by anti-Xa
Heparin Level by
Anti-Xa (IU/mL)
< 0.1
0.10 - 0.19
0.2 - 0.29
Bolus/Hold
Infusion Rate Change
Bolus 40 units/kg & inform MD
Bolus 20 units/kg & inform MD
None
Ç by 3 units/kg/hr
Ç by 2 units/kg/hr
Ç by 1 unit/kg/hr
0.3 - 0.7
0.71 - 0.8
0.81 - 1.6
1.61-2.4
> 2.4
0
None
Hold infusion ½ hr & inform MD
Hold infusion 1 hr & inform MD
Hold infusion 1½ hr & inform MD
No Change; Therapeutic Range
È by 1 unit/kg/hr
È by 2 units/kg/hr
È by 3 units/kg/hr
È by 4 units/kg/hr
UW Health – University of Wisconsin Hospital and Clinics
Therapeutic Dosing of Unfractionated Heparin – Adult – Inpatient – Clinical Practice Guideline
A. Scope
1. Hospitalized patients receiving intravenous unfractionated heparin intended for therapeutic dosing
B. Methodology
C. Definitions
1. Heparin is a high-alert medication. An additional double-check is required as specified in Hospital
Administrative Policy 8.33 must be performed on all boluses, when IV pump programming is
outside of the established IV pump decision support software (Alaris Guardrails®) limits, when a
new bag of heparin is hung and at each shift change.
D. Introduction
1. The following guideline provides recommendations for how to initiate, dose adjust and monitor a
therapeutic unfractionated heparin infusion. There is new literature to suggest that monitoring
unfractionated heparin infusions with anti-Xa levels may improve time to therapeutic range and
warrant less lab testing, however, this data is limited and monitoring with aPTT is still the
preferred method.
UW Health – University of Wisconsin Hospital and Clinics
E. Recommendations
1. Therapeutic heparin infusions should be ordered by order sets that include a dose adjustment algorithm:
1.1
Monitor heparin infusion with aPTT if the baseline aPTT 23 - 40 seconds (Class IIb, Level C)
1.2
Monitor heparin infusion with anti-Xa levels if the baseline aPTT < 23 seconds or > 40
seconds or for patients weighing ≥ 120 kg (Class IIb, Level C)
1.3
Do NOT monitor the heparin infusion with both aPTT and anti-Xa
1.4
For therapeutic heparin infusions, no modifications of these algorithms are allowed.
1.4.1 While discouraged, if patient circumstances require heparin dosing that differs
from established algorithms, specific orders must be written.
1.4.2 Separate heparin order sets are available for patients on extracorporeal
membrane oxygenation or ventricular assist devices.
2. The order must specify the intended regimen, lab monitoring and if an initial bolus is desired. The
following regimens are available:
2.1
Gradual Anticoagulation Regimen: (Class I, Level C)
2.1.1 All acute coronary syndrome patients
2.1.2 Patients treated with alteplase, tenecteplase or abciximab/eptifibatide/tirofiban
2.1.3 New mechanical valve
(note: no bolus is recommended if less than 6 hours from arterial sheath removal)
2.2
Rapid Anticoagulation Regimen: (Class I, Level B)
2.2.1 Deep vein thrombosis
2.2.2 Pulmonary embolism
2.2.3 Ventricular or atrial thrombus
2.2.4 Therapeutic anticoagulation
3. Initial Laboratory Monitoring
3.1
STAT baseline aPTT and PT/INR prior to initiating heparin infusion if not available
(Class IIa, Level B)
3.2
STAT baseline CBC and platelet if not available (Class I, Level A)
3.3
Labs must be drawn prior to initiating the heparin infusion
4. Initiation of Heparin Infusion
4.1
Bolus doses are based on actual body weight (Class I, Level B)
4.1.1 Round the bolus dose to the nearest 100 units for ease of preparation
4.1.2 Document the administered bolus in the flow sheet
4.1.3 Use heparin 1000 units/mL vial for bolus from floor stock
Regimen
Gradual
Rapid
4.2
4.3
4.4
4.5
Bolus Dose
(units/kg)
60
80
Maximum Bolus
(units)
4000
10,000
Initial Infusion
(units/kg/hr)
12
18
Initial starting rates are based on the weight specified in the order
4.2.1 Actual, ideal or adjusted body weight may be used
If actual body weight is used obtain a weight before initiating the heparin infusion order
4.3.1 Use best estimate of true weight if unable to weigh patient
4.3.1 Record the new weight in electronic record if not already documented
For patients > 120 kg consider using an adjusted body weight for dosing (Class IIb, Level C)
4.4.1 If a dosing weight is used this should be reflected in the heparin infusion order
4.4.2 If a dosing weight is used the heparin infusion should be run on a separate
programming module
Use heparin 25,000 units/500 mL D5W premixed bags
4.5.1 Other heparin concentrations are not allowed for use
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5. Titration of Heparin Infusion (Class IIb, Level C)
5.1
Check STAT aPTT or anti-Xa 6 hours after initiation and 6 hours after any rate change
6.1.1 For patients ≥ 120 kg and if using anti-Xa check anti-Xa 4 hours after initiation
and 4 hours after any rate change
5.2
Prior to adjusting the heparin infusion confirm the ordered regimen
5.3
Adjust the rate as indicated by the appropriate dosing table
5.4
Record each heparin rate adjustment in mL/hr in the heparin flow sheet
5.5
Once 3 consecutive aPTTs or anti-Xa levels are therapeutic, order routine aPTT or anti-Xa
every 24 hours with the am labs
5.6
If a rate adjustment becomes necessary or the infusion is held for any reason and
restarted, recheck aPTT or anti-Xa in 6 hours and repeat the above process
5.7
Adjust infusions by either aPTT or anti-Xa levels and NOT by both methods
6. Algorithms for adjusting heparin infusion by aPTT levels (Class IIa, Level B)
Gradual Anticoagulation Regimen Heparin Anticoagulation Dose Adjustments by aPTT
*aPTT should be rounded to the nearest whole number (If < 0.5 round down, if ≥ 0.5 round up)
aPTT (seconds)*
<36
36-37
38-46
47-56
57-66
67-86
87-100
>100
Bolus/Hold
Bolus 20 units/kg & inform MD
0
0
0
0
Hold infusion 1 hour & inform MD
Hold infusion 1 hour & inform MD
Hold infusion 1 ½ hour & inform
MD
Infusion Rate Change
↑ 2 units/kg/hr
↑ 1 unit/kg/hr
NO CHANGE
↓ 1 unit/kg/hr
↓ 2 units/kg/hr
↓ 2 units/kg/hr
↓ 3 units/kg/hr
↓ 4 units/kg/hr
Rapid Anticoagulation Regimen Heparin Anticoagulation Dose Adjustments by aPTT
*aPTT should be rounded to the nearest whole number (If < 0.5 round down, if ≥ 0.5 round up)
aPTT (seconds)*
<35
35-38
39-44
45-60
Bolus/Hold
Bolus 40 units/kg & inform MD
Bolus 20 units/kg & inform MD
0
0
61-75
76-90
91-115
>115
0
Hold infusion 1 hour & inform MD
Hold infusion 1 hour & inform MD
Hold infusion 1 ½ hour & inform
MD
Infusion Rate Change
↑ 3 units/kg/hr
↑ 2 units/kg/hr
↑ 1 units/kg/hr
No Change; Therapeutic
Range
È by 1 unit/kg/hr
È by 2 units/kg/hr
È by 3 units/kg/hr
È by 4 units/kg/hr
6.1
If unable to reach therapeutic aPTT levels, after 3 consecutive aPTTs and appropriate infusion
adjustment, change to monitoring infusion with heparin levels by anti-xa (Class IIb, Level C)
6.2
If two consecutive aPTTs are greater than 115 seconds, check a heparin level by anti-xa, if levels
do not correlate begin monitoring infusion with heparin levels by anti-xa (Class IIb, Level C)
6.2.1 A non-correlating aPTT to anti-Xa is one that would prompt a different action as
described by each algorithm when comparing results
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6.3
If a therapeutic goal is not reached within 24 hours with correct titration the patient may not be
an appropriate candidate for adjustments based on the heparin algorithm. Recommend
consultation with Pharmacy and/or Hematology for assistance with dosing. (Class IIb, Level C)
7. Algorithm for adjusting heparin infusion with heparin levels by anti-Xa (Class IIa, Level B)
Gradual Anticoagulation Regimen Heparin Anticoagulation Dose Adjustments by anti-Xa
Heparin Level by
Anti-Xa (IU/mL)
<0.1
0.1 - 0.3
0.31 - 0.5
0.51 - 0.8
> 0.8
Bolus/Hold
Infusion Rate Change
Bolus 20 units/kg & inform MD
0
0
0
Hold infusion 1 hr & inform MD
Ç by 3 units/kg/hr
No Change
È by 1 unit/kg/hr
È by 2 units/kg/hr
È by 3 units/kg/hr
Rapid Anticoagulation Regimen Heparin Anticoagulation Dose Adjustments by anti-Xa
Heparin Level by
Anti-Xa (IU/mL)
< 0.1
0.10 - 0.19
0.2 - 0.29
0.3 - 0.7
0.71 - 0.8
0.81 - 1.6
1.61-2.4
> 2.4
Bolus/Hold
Infusion Rate Change
Bolus 40 units/kg & inform MD
Bolus 20 units/kg & inform MD
None
0
Ç by 3 units/kg/hr
Ç by 2 units/kg/hr
Ç by 1 unit/kg/hr
No Change; Therapeutic
Range
È by 1 unit/kg/hr
È by 2 units/kg/hr
È by 3 units/kg/hr
È by 4 units/kg/hr
None
Hold infusion ½ hr & inform MD
Hold infusion 1 hr & inform MD
Hold infusion 1½ hr & inform
MD
8. Transitioning Between Regimens (Class IIb, Level C)
8.1
If the aPTT or anti-Xa level is within therapeutic goal than continue the current infusion
rate and adjust based on the newly ordered algorithm
8.2
If the aPTT or anti-Xa level is not at goal when transitioning to new regimen see algorithm:
aPTT or anti-Xa level is NOT at goal
based on the new algorithm
aPTT or anti-Xa level low
Calculated infusion rate
higher than current rate
Increase infusion rate to newly
calculated rate and check aPTT or
anti-Xa level in 6 hours
aPTT or anti-Xa level high
Calculated infusion rate
lower than current rate
Calculated infusion rate
higher than current rate
Do not lower infusion rate
Adjust infusion based on new
algorithm
Consider bolus if not ordered
Do not increase infusion rate
Adjust infusion based on new
algorithm
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Calculated infusion rate
lower than current rate
Decrease infusion rate to newly
calculated rate and check aPTT
or anti-Xa level in 6 hours
9. Maintenance Laboratory Monitoring (Class I, Level A)
9.1
Hemoglobin and platelets must be followed 24 hours after initiating heparin therapy and
every other day thereafter for up to 14 days or until therapy is discontinued
10. Monitoring (Class IIb, Level C)
10.1
Every eight hours: Inspect line/surgical/wound sites for bleeding and check patient for
symptoms indicating bleeding such as hematomas, bruising, and respiratory symptoms.
Contact MD for any signs of bleeding.
11. Provider should be notified if:
11.1
Baseline aPTT > 34 seconds or baseline INR > 1.2
9
11.2
Platelet count decreases > 50% from baseline or if count falls below 100 x10 /L
11.3
Hemoglobin decreases by > 2 g/dL from baseline
11.4
aPTT is < 36 seconds or > 66 seconds if patient is on the gradual anticoagulation regimen
11.5
aPTT is < 39 seconds or > 75 seconds if patient is on the rapid anticoagulation regimen
11.6
Patient has any deterioration in neurologic status
12. Therapeutic heparin infusions should be used with caution in patients with: (Class I, Level C)
12.1
Hypersensitivity to heparin
12.2
Increased risk for hemorrhagic complications
12.3
Patients who are actively bleeding
12.4
Thrombocytopenia
12.5
Less than 72 hours post-op
12.6
Hemorrhagic stroke in the past 4 weeks
F. References
1. Antithrombotic and thrombolytic therapy: American College of Chest Physicians Evidence-Based
Clinical Practice Guidelines (8th Edition). Chest. 2008;133(6 Suppl):67S-887S.
2. Smith ML and Wheeler KE. Weight based heparin protocol using antifactor Xa monitoring. Am J
Health-Syst Pharm. 2010;67:371-374
3. Rosborough TK. Monitoring unfractionated heparin therapy with anti-Xa activity results in fewer
monitoring tests and dosages changes thank monitoring with the activated partial thromboplastin
time. Pharmacotherapy. 1999;19:760-6.
4. Guervil DJ. Activated partial thromboplastin time versus antifactor Xa heparin assay in monitoring
unfractionated heparin by continuous intravenous infusion. Ann Pharmacother. 2011;45:861-8.
G. Benefits/Harms of Implementation
1. Benefit: Provides a standardized approach for management and monitoring of therapeutic
unfractionated heparin
2. Harms: Anticoagulation therapy may increase bleeding risk or result in acute bleeding
H. Qualifying Statements - none
I.
Implementation Strategy –
1. Recommendations provided by this guideline will be disseminated to clinical staff through the use
of implementation tools outlined below.
J. Implementation Tools/Plan –
1. Email notification to hospital staff through the Clinical In-brief
2. Notification to the hospital pharmacists at a staff meeting
3. Update of the therapeutic heparin infusion order sets in Health Link that will include a hyperlink to
these guidelines
K. Disclaimer
It is understood that occasionally patients will not match the conditions considered in the guideline
and clinical judgment should be used when developing a treatment plan.
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