1. health and fitness
2. therapy

5/5/2015
Where Do Our Heparin Doses Come From?
Heparin nomogram assessment and
revision based on anticoagulation
indication
CHEST 2012
AHA/ACC
2014
VTE: 80 units/kg bolus +
18 units/kg/hr infusion
VTE: No comment
ACS: 60-70 units/kg
bolus + 12-15 units/kg/hr
infusion
ACS: 60 units/kg bolus +
12 units/kg/hr infusion
AF: No comment
AF: No comment
Minu Jacob, PharmD
PGY-2 Pharmacotherapy Resident
Harper University Hospital, Detroit Medical Center
The speaker has no actual or potential conflicts of interest in relation to this presentation.
Why is Timing Important?
VTE Mortality Data
• Examine the relationship between achieving
therapeutic anticoagulation and mortality in
PE patients.
Secondary
Outcomes
3.0%
7.7%
Mortality Based on Timing of Heparin
Administration
Heparin in ED
Mortality Based on Timing of
Therapeutic aPTT
Heparin After Admission
aPTT < 24 hours
20.00%
aPTT > 24 hours
20.00%
15.30%
15.00%
• In-hospital and 30-day all-cause mortality
Mortality
Primary
Outcomes
N = 400
30-day mortality
• Retrospective study of 400 patients admitted
to the Mayo Clinic with acute, symptomatic
PE
Methods
Primary Outcome
In-hospital mortality
• Length of stay, hemorrhage events on
heparin, recurrent VTE within 90 days
10.00%
4.40%
5.00%
4.70%
10.00%
5.60%
5.60%
5.00%
1.40%
1.50%
0.00%
Smith SB, et al. CHEST 2010;137:1382-1390.
14.80%
15.00%
Mortality
Objective
0.00%
Hospital Mortality (p=0.009) 30-Day Mortality (p < 0.01)
Hospital Mortality (p=0.091) 30-Day Mortality (p=0.037)
Smith SB, et al. CHEST 2010;137:1382-1390.
Study Rationale
Study Objectives
• Recent quality assurance data has shown inconsistency
in achieving target aPTT with 24 hours of heparin
initiation.
• Cardiology sub-committee identified a need to evaluate
and improve the heparin dosing nomogram.
Current Heparin Dosing Nomogram
Indication
Bolus
Infusion Rate
VTE
80 units/kg
18 units/kg/hr
ACS
AF
PAD
Valve
60 units/kg
12 units/kg/hr
Optimize heparin dosing nomogram
 Patients on heparin IV who reach
target aPTT within 24 hours
Identify barriers to reaching target aPTT
within 24 hours (protocol and practice)
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5/5/2015
Outcomes
Study Design
• Number of patients who reach
target aPTT within 24 hours preand post- nomogram revision
implementation
Primary
Endpoint
Secondary
Endpoints
• Rates of major and minor
bleeding
• New thrombosis
• Time to target aPTT
Study Methods
• Site/system
committee
approval
• Education
• Data collection
• New nomogram
assessment
Phase 1
Phase 3
Data Collection
Inclusion
Criteria
• Age 18-89 years
• Heparin pharmacy to dose consult
for at least 36 hours
Exclusion
Criteria
• Patients admitted to Children’s
Hospital of Michigan
• Heparin physician dosing
• Off-protocol aPTT targets
• Heparin monitored by thrombin times
Phase I Results: Patients
Heparin
Dosing
Demographics
• Baseline labs
• Co-morbidities
Adverse
Effects
• Heparin dose
changes
• Corresponding
aPTTs
• Bleeding
• New thrombosis
Descriptive statistics used for Phase I statistical analysis
Phase I Results: Demographics
151 admissions in July
2014 that met inclusion
criteria
19 admissions excluded
for improperly drawn
aPTTs and inadequate
documentation
Phase 2
• Data collection
• Pharmacists
survey
• Nomogram
revision
131 unique patients
included in analysis
Baseline Characteristics
N = 131
Age, mean ± SD
65 ± 14.5 years
Male, n (%)
63 (48)
ABW 30% > IBW, n (%)
73 (55.7)
Heparin Indication, n (%)
•ACS
•VTE
•AF
•PAD
•Valve
53 (40)
43 (33)
28 (21)
5 (4)
3 (2)
132 admissions included
in analysis
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5/5/2015
Patients Reaching Target aPTT within 24 Hours of
Heparin Initiation
Average Heparin Dose to Achieve Target aPTT
19
70.0%
18.3
62.8%
Current nomogram initial heparin dosing
18 17.7
18
60.0%
Heparin Dose (units/kg/hr)
46.4%
40.0%
40.0%
33.3%
30.0%
20.0%
17.1
16.2
16
16
15.5
15.5
15
15
14.8
14.7
Overall
Non-obese
Obese
14
13
10.0%
12
0.0%
Overall (n=132)
VTE (n=43)
ACS (n=53)
AF (n=28)
Heparin Indication
PAD (n=5)
11
Valve (n=3)
VTE (n=41)
Adverse Effects
ACS (n=43)
AF (n=28)
Heparin Indication
PAD (n=4)
Valve (n=3)
Survey Says…
Phase I Results: Safety
Incidence, No (%)
Bleeding events* (n = 10)
Major
Minor
4 (40)
6 (60)
Thrombosis
0
*Bleeding definitions based on ESSENCE trial
Cohen M, et al. N Engl J Med 1997;337:447-52.
> 10
Q2: When dosing heparin, what percent of the time
do you deviate from the nomogram? (N = 64)
42%
6-10
14%
3-5
20%
0-2
24%
0%
5%
10%
15%
20%
25%
Percent of Pharmacists
30%
35%
40%
45%
Percent Deviation from Nomogram
Q1: How many years of experience do you have
dosing heparin? (N = 64)
Years of Experience
Percent of Patients
49.1%
17
16.9
17
50.0%
50.0%
> 40
3%
21-40
22%
11-20
31%
0-10
44%
0%
5%
10%
15%
20%
25%
30%
35%
40%
45%
50%
Percent of Pharmacists
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5/5/2015
Association of Protocol Deviation and Achieving
Target aPTT
Study Results: Heparin Initiation
Number of Patients With Deviations From Protocol (N = 75 out
of 132 total admissions)
Different bolus
7
3
No bolus
9
30
No bolus and different infusion rate
Different bolus and different infusion rate
9
Different infusion rate
17
Wrong weight
Percent of Patients in Target aPTT Range within 24
Hours
60.0%
Upon heparin initiation , we deviate from protocol
approximately 57% of the time!
35.0%
30.0%
25.0%
With Deviation
Increased risk of bleeding
95%
36%
68%
Other responses:
Elevated baseline coags
•Thrombocytopenia
•ESRD on hemodialysis
Decreased Hgb/Hct
•ABW > 180% IBW
42%
34%
24%
ABW < IBW
19%
0%
10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
10%
20%
Q5: Patient characteristics that cause deviation on
follow-up for bolus (N = 63)
89%
Increased risk of bleeding
86%
Decreased Hgb/Hct
54%
Increased age
10%
20%
41%
34%
26%
23%
21%
ABW < IBW
30%
40%
50%
60%
70%
80%
80%
57%
Elevated baseline coagulation labs
17%
0%
70%
75%
Increased risk of bleeding
ABW > 130% IBW
19%
ABW > 130% IBW
60%
Proximity of aPTT to target
Heparin indication with lower risk of thrombosis
21%
ABW < IBW
50%
Q6: Patient characteristics that cause deviation on
follow-up for infusion rate (N = 61)
Increased age
38%
Elevated baseline coagulation labs
40%
Decreased Hgb/Hct
44%
Heparin indication with lower risk of thrombosis
30%
Percent of Pharmacists
Percent of Pharmacists
Proximity of aPTT to target
59%
53%
Increased age
ABW > 130% IBW
Heparin indication with lower risk of thrombosis
25%
23%
0%
40.0%
Q4: Patient characteristics that cause deviation for
initial infusion rate (N = 59)
Patient Characteristic
Patient Characteristic
Increased risk of bleeding
ABW < IBW
45.6%
45.0%
No Deviation
Other responses:
•Oral anticoagulant
prior to admission
Elevated baseline coags
75%
•Thrombocytopenia
•ESRD on hemodialysis
Decreased Hgb/Hct
56%
•Recent administration of heparin SubQ (< 8 hours)
•If INR is > 2 Increased age
52%
•Patient continues on heparin after cardiac catheterization
ABW > 130% IBW
50.0%
20.0%
Q3: Patient Characteristics that cause deviation for
initial bolus (N = 64)
Heparin indication with lower risk of thrombosis
54.7%
55.0%
90% 100%
15%
0%
10%
20%
30%
40%
50%
60%
70%
80%
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5/5/2015
Q7: If aPTT is ≤ 5 seconds below target range, for
which indications would you most likely bolus per
nomogram? (N = 64)
Heparin Indication
VTE
Heparin Nomogram Changes
95%
Valve
64%
ACS
33%
PAD
25%
AF
23%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Percent of Pharmacists
Heparin Nomogram Changes
Study Design
• Data collection
• Pharmacists
survey
• Nomogram
revision
Phase 2
• Site/system
committee
approval
• Education
Phase 1
• Data collection
• New nomogram
assessment
Phase 3
Study Limitations
Future Directions
• Retrospective study design
• ESRD and liver disease patients not well
represented
• Small sample size
• High variability in outcomes for obese patients
• Documentation
• Phase III post-implementation assessment
– Evaluate rates of reaching target aPTT within 24
hours after nomogram revision
– Assess the impact of pharmacy education on
adherence to nomogram
• Nursing and laboratory personnel education
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5/5/2015
Conclusions
• Therapeutic aPTT within 24 hours of heparin initiation
improves outcomes in VTE patient population.
• Results showed that current nomogram initiated heparin
at lower bolus and infusion rates for ACS than required.
• Pharmacist-perceived bleeding risk and elevated baseline
coagulation labs were common reasons for deviation.
• Nomogram revisions will need to be assessed at regular
intervals for safety, efficacy, and adherence to protocol.
Learning Question #1
• For which of the following indications has
achieving a target aPTT within 24 hours
shown to decrease mortality?
A.
B.
C.
D.
Acute coronary syndromes
Pulmonary embolus
Peripheral arterial disease
Mitral valve replacement
Learning Question #2
Acknowledgments
• What is the heparin dosing
recommendation for NSTE-ACS according
to the CHEST 2012 guidelines?
• Elizabeth Petrovitch, Pharm.D., BCPS
• Lynette Moser, Pharm.D.
• Joanne MacDonald, Pharm.D.
A. 70 units/kg bolus and 15 units/kg/hr infusion
B. Target 1.8 to 2.3 times the baseline aPTT
C. Target 1.5 to 2.5 times the baseline aPTT
D. Fondaparinux is recommended over
unfractionated heparin
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