Collaboration between inpatient anticoagulation service and hospital reference

laboratory to reduce misdiagnosis of Heparin Induced Thrombocytopenia

Harmony Bowles, PharmDPGY1 Pharmacy Resident

University of New Mexico Hospital

IRB Approval Received

Category C1

Abstract # 49

Disclosure Statement

• Harmony Bowles• Investigators have no conflict of interest to

disclose• This study was not funded• Proprietary information or results may be subject

to different interpretations• Speaker’s presentation of this slide indicates

agreement to abide by the non-commercialism guidelines provided in the CE Requirements page

Learning Objectives

• Objective #1: – Describe the role of a multidisciplinary collaboration in

reducing overdiagnosis of HIT

• Objective #2:– List financial and clinical benefits of having a

multidisciplinary team involved in diagnosis and management of HIT

Target Audience: Pharmacists

• Level 1 trauma center

• 646 bed tertiary care teaching hospital

• ~50 full-time pharmacists

• Pharmacy-driven inpatient anticoagulation service seven days a week

Pre-Test Assessment Questions

• T/F: The use of a validated pre-test probability tool known as the 4T’s score has been shown to improve the process of identifying patients at low risk for HIT.

• T/F: Collaboration between inpatient anticoagulation service and the reference laboratory will lead to a reduction in the number of inappropriate HIT antibody ELISA tests performed.

• T/F: Multidisciplinary collaboration leads to cost savings by decreasing the number of patients being inappropriately tested and treated for HIT.

Background• Heparin Induced Thrombocytopenia (HIT) is a pro-

thrombotic, immune- mediated adverse reaction to heparin or low-molecular weight heparin (LMWH) therapy1

• Accurate diagnosis requires:– Patient clinical presentation – Laboratory results

• Most institutions utilize an enzyme-immunoassay (ELISA) to detect HIT antibodies (Ab)– High sensitivity: >90% negative predictive value – Low specificity: high potential for false positives2

1. Arepally G, Ortel T. N Engl J Med 2006;355:809-17.2. Lo G, Sigouin C, Warkentin T. Am J Heamatol. 2007;82:1043-1043.

Background• Hospitalized patients have multiple reasons for developing

thrombocytopenia

• Inappropriately ordered non-specific ELISA Ab increases potential for overdiagnosis of HIT

• The 4T’s score3 –Validated assessment tool to identify patients at risk for HIT–Based on 4 patient parameters:

• Magnitude of platelet drop• Timing of thrombocytopenia in relation to heparin exposure• Presence of new thrombosis• Other possible reasons for thrombocytopenia

–High negative predictive value

3. Lo G, Juhl D, Warkentin T, et al. J Thromb Heamost 2006; 4:759-765.

Study Objectives• Primary objective:

– Evaluate impact of multidisciplinary collaboration in reducing number of inappropriate Ab tests performed, thereby reducing the misdiagnosis of HIT

• Secondary objective:– Evaluate potential cost savings of decreasing Ab testing

and use of direct thrombin inhibitors (DTIs) for inappropriate treatment of HIT

Methods – Study Design

• Study design: Single center, pre-post prospective study with retrospective chart review

• Inclusion criteria: All patients for whom Ab was ordered during study period – ≥ 18 years of age– Sufficient data available to calculate 4T’s score

Methods – Intervention Outline

Methods – Data Collection• At risk population

– Patients exposed to unfractionated heparin (UFH) or low molecular weight heparin (LMWH) products

– Patients for whom an Ab tests ordered during pre- and post-intervention period obtained from reference laboratory

• Patients with Ab ordered – Manual chart review for patient demographics, characteristics,

pre-defined bleeding and thrombotic events

• 4T’s score independently and retrospectively calculated by 3 evaluators to establish inter-rater reliability (IRR)

Methods – Data Collection• Cost:

– Hospital cost for performing Ab test obtained from reference laboratory

– Drug treatment cost per patient for those receiving direct thrombin inhibitor (DTI) in pre-intervention period evaluated by:

• DTI acquisition cost• Number of patients treated • Number of doses dispensed

Methods – Data Analysis

• Fleiss kappa performed to assess IRR between 3 evaluators

• Chi-square used to analyze categorical variables

• Student t-test used to analyze continuous variables

• All data entered and analyzed with SPSS software version 19.0

Results – IRR

• IRR– Fleiss kappa = (0.643)– Interpretation: Good IRR4

4. Fleiss J. Statistical Methods for Rates and Proportions, 2nd ed. New York: John Wiley and Sons; 1987.

Results – Study Population

*NS: No statistical difference

At Risk Population (# of patients)

Pre- Intervention

Post- Intervention p-value

Admitted to UNMH 19,312 19,422 -

Exposed to UFH/LMWH 6,867 7,809 NS

Patients with Ab ordered(% of total exposed patients)

176(2.5%)

108(1.4%)

<0.001

Results – Demographics

Patients with Ab ordered

CharacteristicPre-Intervention

(n=176)Post-Intervention

(n=108) p-value

Age, mean (SD), years 56.9 (14.5)

56.4 (16.2)

NS

Male 87 (49.4%) 55 (50.9%) NS

*NS: No statistical difference

Results – Ab Testing

Results – Ab Testing

n=127 n=127n=74

n=33

Results – Cost

Cost incurred

Hospital cost per Ab test $35.00

Hospital drug cost per patient treated for HIT(Pre-intervention)

$6400.00

Patients with Ab ordered

Pre-Intervention(n=176)

Post-Intervention(n=108) p-value

Patients treated for HIT 16(9.1%)

9(8.3%)

0.912

# of Ab tests cancelled 0 46 <0.001

Results – Cost Savings

Estimated annual cost savings=($15.92 – $7.66) x 7809= $64,502.34

Results – Adverse EventsPatients with Ab ordered

Adverse outcomePre-

(n=176)Post-

(n=108) p-value

Bleeding event 10.2% 6.5% 0.279

Thrombotic event 0.6% 0% 0.433

• No bleeding events directly associated with HIT treatment during hospitalization

• Single thrombotic event in the pre-intervention period in patient with negative HIT Ab result

Study Limitations

• Calculation of 4T’s score performed retrospectively

• Data collected from chart review dependent on accurate documentation

• Patients could have received treatment for bleeding or thrombosis events at another facility

• Total cost evaluation did not include pharmacist time to perform intervention

• Limited external validity as not all hospitals have dedicated inpatient anticoagulation service

Conclusions• Impact of multidisciplinary collaboration

– Reduction in inappropriate HIT testing – Reduction in misdiagnosis of HIT without causing

adverse clinical outcomes

• Use of the 4T’s score by a pharmacists is a means to improving accuracy of HIT testing and diagnosis and improving patient outcomes

• Substantial cost savings may be realized through decreased lab testing, decreased DTI use and avoidance of unnecessarily treating patients for HIT

Post-Test Assessment Questions

• T/F: The use of a validated pre-test probability tool known as the 4T’s score has been shown to improve the process of identifying patients at low risk for HIT

• T/F: Collaboration between inpatient anticoagulation service and the reference laboratory will lead to a reduction in the number of inappropriate HIT ELISA tests performed

• T/F: Multidisciplinary collaboration leads to cost savings by decreasing the number of patients being inappropriately treated for HIT

Acknowledgements

• Allison Burnett, PharmD

• Richard D’Angio, PharmD, BCPS

• Matthew Borrego, Ph.D., M.S

• Tiffany Montoya, PharmD