Cold Agglutinin Screen vs Cold Agglutinin Titer What

Cold Agglutinin Screen vs Cold Agglutinin Titer What is the financial impact of implementing a cold agglutinin screen for the diagnosis of cold agglutinin disease? Penny Szklarski, MLT Vanderbilt University Medical Center

Healthcare Costs

Anemia The World Health Organization defines anemia as a hemoglobin level less than 13 g/dl in men and less than 12 g/dl in premenopausal, nonpregnant women. AABB Technical Manual – 18 Edition th

Autoimmune Hemolytic Anemia (AIHA) �Warm AIHA �Cold agglutinin disease �Mixed-type AIHA �Paroxysmal cold hemoglobinuria AABB Technical Manual – 18 th Edition

What is Cold Agglutinin Disease? Cold Agglutinin Disease is rare and accounts for 15% of patients with autoimmune hemolytic anemia (AIHA) Blood, 15 August 2013 Volume 122, Number 7

Bound Ig. M Molecule

Polyclonal Antibodies Monoclonal Antibodies �Typically seen in post infectious setting �Most commonly seen in pediatrics �Mycoplasma �Long term disease �Often resists treatment �May be associated with an underlying lymphoproliferative disorder �Seen in geriatrics Blood, 15 August 2013 – Volume 122, Number 7

Wright Stain Blood Smears Normal Cold Agglutinin Disease

Wright Stain Blood Smears Normal Cold Agglutinin Disease

Specimen tubes from a patient with cold agglutinin disease Photo complements of Dr. Garrett Booth, Vanderbilt University Medical Center

Primary Study Hypothesis Was the assumption correct that providers were ordering cold agglutinin titers instead of cold agglutinin screens?

Research Methodology �Institutional Review Board (IRB) approval was obtained. �Retrospective chart review was performed �Titers from 1/1/2010 to 10/31/2013 �Screens from 4/2012 to 10/31/2013 �Cold agglutinin titers of >1: 64 were considered clinically significant

Limitations �Ordering provider’s field of expertise �Small sample size due to the rarity of the disease

What is the most cost effective blood bank test for the diagnosis of cold agglutinin disease?

Cold agglutinin titer � Titers are performed at 4°C � Low titers of cold agglutinins can be found in normal individuals

How common is cold agglutinins in blood donors? �A recent study revealed that 5% of donors tested for cold agglutinins had titers of >1: 4 �Retrospective review of 276 healthy donors ( 2014 Transfusion, 54: 1294 -1297

Cold agglutinin screen �Ig. G and C 3 d Direct Antiglobulin Test (DAT) �Room temperature and 30°C saline antibody screens with auto controls �Thermal amplitude if positive *Immune Hemolytic Anemias – Second Edition Lawrence D. Petz, MD George Garratty, Ph. D

Diagnostic for Cold Agglutinin Disease � 70% of all clinically significant cold agglutinins react at 37°C � 100% of all clinically significant cold agglutinins react at 30°C �Positive C 3 D and Negative Ig. G DAT �Positive RT and 30°C saline antibody screen with positive auto controls Immune Hemolytic Anemias-Second Edition , Dr. Lawrence Petz and Dr. George Garratty

Results: Cold Agglutinin Titer � 80 Titers were ordered prior to inception of the screen � 5 (6. 3%) were clinically significant 2 were diagnosed with Stevens-Johnson Syndrome 1 was diagnosed with B-Cell Lymphoma 2 were newly diagnosed with Cold Agglutinin Disease � 68 (85%) had a negative C 3 d

Why is a negative C 3 d significant? Cold agglutinin disease is strongly supported with a positive C 3 d and a negative Ig. G DAT

Results: Cold Agglutinin Screen � 17 Cold agglutinin screens were ordered. � 7 (41%) were positive requiring thermal amplitude 3 (17. 6%) diagnosed with cold agglutinin disease 1 diagnosed with Systemic Lupus Erythematosus 1 diagnosed with Myelofibrosis 2 were outpatients and lost to follow-up

Since implementation of the cold agglutinin screen. � 38 Titers were ordered independent of the screen � 3 (7. 8%) were true positive with titers of >1: 64

What are the financial implications of ordering titers instead of screens for diagnosis?

Cost Analysis Cold Agglutinin Titer Cold Agglutinin Screen Consumables Cost per Units Total 10 X 75 Tubes $ 0. 02 11 $ 0. 22 Screen Cell 1 $ 0. 49 10 $ 4. 90 Cost per Units Total 10 X 75 Tubes $ 0. 02 1 $ 0. 02 12 x 75 Tubes $ 0. 06 1 $ 0. 06 MTS Gel Card $ 0. 80 1 $ 0. 80 C 3 d Reagent $ 1. 34 1 $ 1. 34 Total Consuma bles $ 2. 22 Total Consumab les $ 5. 12 Salary and Benefits Tech Time Hrly Rate Hrs Total $ 31. 25 0. 35 $ 10. 94 Total Cost per Test $ 16. 06 Salary and Benefits Tech Time Hrly Rate Hrs Total $ 31. 25 0. 48 $ 15. 10 Total Cost per Test $ 17. 32

Positive Pretest Probability � 6. 3% using the titer � 17. 6% using the screen

Cost of inappropriately ordered tests � 38 Independently ordered titers � 35 (92. 1%) rendered no new cold agglutinin disease diagnosis at a cost of $562. 10

Conclusion �Cold agglutinin disease is rare �Knowledge of correct test for diagnosis is essential �Inappropriate testing cost money �Inappropriate testing takes time away from more important projects

Acknowledgements Garrett Booth, M. D. , Associate Medical Director Allison Paroskie, M. D, Associate Medical Director Emily Coberly, M. D. , Transfusion Medicine Fellow Stephanie Sephel, MLS, SBB, Transfusion Medicine Manager Mary Johnson, MLS, SBB, Transfusion Medicine Supervisor The entire Vanderbilt Transfusion Medicine Staff

Thank You!