1. Collaboration between inpatient anticoagulation service and hospital reference laboratory to reduce misdiagnosis of Heparin Induced Thrombocytopenia Harmony Bowles, PharmD PGY1 Pharmacy Resident University of New Mexico Hospital IRB Approval Received Category C1Abstract # 49

2. 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

3. 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

4. Level 1 trauma center 646 bed tertiary care teaching hospital ~50 full-time pharmacists Pharmacy-driven inpatient anticoagulation service seven days a week

5. 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.

6. Background Heparin Induced Thrombocytopenia (HIT) is a pro- thrombotic, immune- mediated adverse reaction to heparin or low-molecular weight heparin (LMWH) therapy 1 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 positives 2 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.

7. Background Hospitalized patients have multiple reasons for developing thrombocytopenia Inappropriately ordered non-specific ELISA Ab increases potential for overdiagnosis of HIT The 4T’s score 3 –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.

8. 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

9. 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

10. Methods – Intervention Outline

11. 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)

12. 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

13. 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

14. Results – IRR IRR –Fleiss kappa = (0.643) –Interpretation: Good IRR 4 4. Fleiss J. Statistical Methods for Rates and Proportions, 2nd ed. New York: John Wiley and Sons; 1987.

15. Results – Study Population *NS: No statistical difference At Risk Population (# of patients) Pre- Intervention Post- Interventionp-value Admitted to UNMH19,31219,422- Exposed to UFH/LMWH6,8677,809NS Patients with Ab ordered (% of total exposed patients) 176 (2.5%) 108 (1.4%) <0.001

16. Results – Demographics Patients with Ab ordered Characteristic Pre-Intervention (n=176) Post-Intervention (n=108)p-value Age, mean (SD), years56.9 (14.5) 56.4 (16.2) NS Male87 (49.4%)55 (50.9%)NS *NS: No statistical difference

17. Results – Ab Testing

18. n=127 n=74 n=33

19. 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 HIT16 (9.1%) 9 (8.3%) 0.912 # of Ab tests cancelled046<0.001

20. Results – Cost Savings Estimated annual cost savings=($15.92 – $7.66) x 7809= $64,502.34

21. Results – Adverse Events Patients with Ab ordered Adverse outcome Pre- (n=176) Post- (n=108)p-value Bleeding event10.2%6.5%0.279 Thrombotic event0.6%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

22. 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

23. 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

24. 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

25. Acknowledgements Allison Burnett, PharmD Richard D’Angio, PharmD, BCPS Matthew Borrego, Ph.D., M.S Tiffany Montoya, PharmD