1. Transfusion Support in ABO-incompatible Heart Transplants
Troy Hutchens
Clinical Pathology ACE – Blood Bank
Nov 3rd, 2016

2. Outline Background in ABO-incompatible (ABOi) heart transplants
History
Rationale
Current Policy
Outcomes
Management Guidelines for ABOi heart transplants
Candidate selection and isohemagglutinin titers
Isohemagglutinin depletion and monitoring
Selection of transfused of blood products
Examining transfusion protocols from other institutions

3. History of ABOi Heart Transplants
Pediatric organ donors are in short supply and have decreased in the past two decades (improved pediatric critical care and/or public health/safety?)
ABOi infant heart transplantation was pioneered at The Hospital for Sick Children (Toronto) in 1996
Increase donor utilization and decrease recipient wait times
% of infant heart transplants were ABOi
Henderson et al. (2012)

4. Initial ABOi Rationale
Antibodies directed at ABO antigens do not develop until 6 months and continue to rise until months
Mechanism of tolerance is not dependent on lack of development of donor-specific isohemagglutinins
Detectable titers of donor-specific isohemagglutinins are not a contraindication to ABOi heart transplant
27% of ABOi recipients develop donor-specific isohemagglutinins within 8 years
Adults receiving ABOi heart transplants since 2005 have equivalent outcomes as those receiving ABOc heart transplants

5. Current ABOi Heart Transplant Listing Criteria
Under 1 y/o donor hearts are allocated to recipients by clinical need regardless of ABOi
Daly (2015)

6. ABOc and ABOi Heart Transplants Have Equivalent Outcomes
Henderson et al. (2012)

7. ABOc and ABOi heart transplants have equivalent rates of rejection
ABOi heart transplants have reduced rates of infection as compared to ABOc heart transplants
Henderson et al. (2012)

8. All Transfusion-related Recommendations
LEVEL C
Very limited populations evaluated
Only consensus opinion of experts, case studies or standard of care
Class II b
Recommendation's usefulness/efficacy less well established
Only diverging expert opinion, case studies, or standard-of-care
Recommendations Covered
Candidate selection and isohemagglutinin titers
Isohemagglutinin depletion
Isohemagglutinin monitoring
Transfusion of blood products
Immunosuppression
Chronic rejection monitoring
Costanzo et al. (2010)

9. Costanzo et al. (2010)

10. Examples and Outcomes Associated with Higher ABO Titers Pre-transplant
Irving et al. (2012)

11. Costanzo et al. (2010)

12. Costanzo et al. (2010)

13. Costanzo et al. (2010)

14. Table of Recommended Match of Blood Products
I was unable to find any data or recommendations on obtaining titers on pRBC units for transfusion
Costanzo et al. (2010)

15. Transfusion Support Protocols for ABOi Heart Transplant Recipients
Institutions
Columbia
UCLA
University of Michigan

16. Additional “Pearls”
Rituximab can decrease new antibody production, however, memory plasma cells do not express CD20 which limits its efficacy in targeting established antibodies
Heart transplant recipients as compared to other solid-organ transplant recipients are at highest risk for passenger lymphocyte syndrome (PLS)
patient develops IgG antibodies from lymphocytes transplanted along with the graft
post-transplant hemolysis occurs in 2-5%
direct antiglobulin test becomes reactive 1-2 weeks after transplantation
marked hemolysis and the antibodies typically persist for a few weeks

17. References
Daly KP. Emerging science in paediatric heart transplantation: donor allocation, biomarkers, and the quest for evidence-based medicine. Cardiol Young Aug;25 Suppl 2:
Sarkar RS, Philip J, Yadav P. Transfusion medicine and solid organ transplant - Update and review of some current issues. Med J Armed Forces India Apr;69(2):162-7.
Costanzo MR, Dipchand A, Starling R, Anderson A, Chan M, Desai S, Fedson S, Fisher P, Gonzales-Stawinski G, Martinelli L, McGiffin D, Smith J, Taylor D, Meiser B, Webber S, Baran D, Carboni M, Dengler T, Feldman D, Frigerio M, Kfoury A, Kim D, Kobashigawa J, Shullo M, Stehlik J, Teuteberg J, Uber P, Zuckermann A, Hunt S, Burch M, Bhat G, Canter C, Chinnock R, Crespo-Leiro M, Delgado R, Dobbels F, Grady K, Kao W, Lamour J, Parry G, Patel J, Pini D, Towbin J, Wolfel G, Delgado D, Eisen H, Goldberg L, Hosenpud J, Johnson M, Keogh A, Lewis C, O'Connell J, Rogers J, Ross H, Russell S, Vanhaecke J; International Society of Heart and Lung Transplantation Guidelines. The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients. J Heart Lung Transplant Aug;29(8):
Irving C, Gennery A, Kirk R. Pushing the boundaries: the current status of ABO-incompatible cardiac transplantation. J Heart Lung Transplant Aug;31(8):791-6.
Henderson HT, Canter CE, Mahle WT, Dipchand AI, LaPorte K, Schechtman KB, Zheng J, Asante-Korang A, Singh RK, Kanter KR. ABO-incompatible heart transplantation: analysis of the Pediatric Heart Transplant Study (PHTS) database. J Heart Lung Transplant Feb;31(2):173-9.
Dodd DA. Pediatric heart failure and transplantation: where are we in 2013? Curr Opin Pediatr Oct;25(5):
Hageman M, Michaud N, Chinnappan I, Klein T, Mettler B. ABO-incompatible heart transplants. Perfusion Apr;30(3):
Urschel S, West L. ABO-incompatible heart transplantation. Curr Opin Pediatr Oct;28(5):613-9.