Pediatric Cardiac Transplantation of a Highly Sensitized Patient After Mechanical Support and Exchange Transfusions: A Case Report

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1 Pediatric Cardiac Transplantation of a Highly Sensitized Patient After Mechanical Support and Exchange Transfusions: A Case Report Dafne Andrea Chianella, CCP Alicia Sievert, CCP, FPP; Mary McCall, CCP,FPP; Jeffery Acsell, CCP; Anthony Shackelford, DHA, CCP..

2 I have no disclosures Disclosures

3 Sensitization Overview Define Therapeutic Options Causes Effects Case Report

4 What is Sensitization? The development of circulation antibodies directed against human leukocyte antigen (HLA) system. HLA System= genes responsible for regulating the human immune system Diversity in humans Defense against disease HLA exposure = AB production= sensitivity

5 Panel reactive antibody test. (PRA)=% of incompatible donors in a population. scouring: Measures of Sensitivity? 0% - 99%. PRA 10% = elevated Aka Sensitized Mean fluorescence intensity (MFI)= represents the strength of antibody binding. MFI>8000 =strong binding MFI = moderate binding MFI <2000 = weak binding.

6 What Causes Sensitization? Previous blood transfusions Previous transplantations Exposure to VADs and ECMO Exposure to allograft material Pregnancy

7 Effects Of Sensitivity Pre-op Restrictions on possible donors Exclusion from transplant lists Prolonged waiting times Post-op Cardiac transplant rejection manifestations Acute cell-mediated rejection Antibody-mediated rejection (AMR) Cardiac allograft vasculopathy

8 Therapeutic Options for Dealing with Sensitized Patients Pre-, Intra-, and Post-operative desensitization Plasmapheresis Intravenous immunoglobulin (IVIG) anti-t-cell and anti-b-cell agents and other meds. Exchange transfusions

9 Exchange Transfusion: Perfusion Strategy Toronto, Hospital for Sick Children: - West LJ, Pollock-Barziv SM, Dipchand AI et al. - ABO-incompatible heart transplantation in infants. Summery: Neonatal Grace Period of immunological immaturity. ABO-incompatible heart transplantation Exchange transfusion: prime components plasma discarded, RBC s washed and returned Anti-A and anti-b AB titer levels tested.

10 Case Report 16 y.o. male with history of dilated cardiomyopathy/heart failure. 5/20/2013: listed for cardiac transplant Heartware? 6/3/13: acutely decompensated Multi organ failure

11 Emergent Centrimag Insertion Pending Heartware approval Ascending aorta- 21 Fr cannula RSPV/left atrial junction- 28 Fr angled metaltipped MANY blood products liver and kidney function slowly improved

12 PROCEDURE: Heartware 1. Centrimag LVAD explantation. 2. Tricuspid valve annuloplasty 3. Primary repair of ASD (PFO) 4. Heartware LVAD implantation. Aorta and LV apex cannulation. 4 L per minute at 2700 RPM TEE = severe RV dysfunction, mild TR Several transfusions.

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14 Pathway to Sensitization VADs and high number of transfusions PRA= 86% Positive autocross-match Possibly viral??=> Caused cardiomyopathy MFI of 20,000 to himself. Donor Qualifications: virtual cross-match= MFI< Prospective cross-match showed less reaction than autocross-match

15 MUSC Clinical Protocol for a Highly Sensitized Patient Pre-Transplant and Peri-Operative Guidelines: Tacrolimus, Mycophenolate mofetil, and Solumedrol Intra-operative 3X volume exchange Remove the whole blood Transfuse PRBC and FFP cocktail Initiate CPB Separate/discard plasma (source of circulating AB) Return washed pt PRC

16 Exchange Transfusion Patient Parameters: Ht: 180cm Wt: 60 kg BSA: 1.8 m2 3x Exchange Cocktail: 19.5 units PRBC 19.5 units FFP 1.5x Exchange Cocktail 9.8 units PRBC 9.8 units FFP

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18 OHT Heartware and AICD explant. CPB Exchange Transfusion OHT total ischemic time= 224 min. MUSC anti-rejection Post-Transplant guidelines: 1. Immunosuppression Cellcept, Solumedrol, tacolimus 2. Rejection Monitoring Endomyocardial biopsy

19 Current ECHO 1 Year Post-Op RESULTS EF= 57.8% Pathology 9/4/2014 elevated donor-specific antibodies complement deposition on his graft. Immunofluorescence Microscopy: -(+) capillary deposition of C4d AMR (antibody-mediated rejection) Treatment: medically and with plasmapheresis.

20 Conclusion VAD therapy and multiple transfusions can bridge a cardiac patient to transplant, but is associated with many risks. The development of HLA antibodies can lead to sensitization, severely limiting the possible donor pool. An exchange transfusion, in combination with pre-, intra, and post-op desensitization therapies may help delay/decrease rejection. With the number of sensitized patients awaiting OHT increasing, we must continue to research and develop strategies to decrease morbidity and mortality.

21 Social Media Update:

22 References 1. Castleberry C, Ryan T, Chin C. Transplantation in highly sensitized pediatric patient. Circulation.2014;129: Conway J, Dipchand A. Challenges with sensitized recipients in pediatric heart transplantation. Clinics.2014;69: George I, Colley P, Russo M, Martens T, Burke E, Oz M, Deng M, Mancini D, Naka Y. Association of device surface and biomaterials with immulologic sensitization after mechanical support. J Thorac Cardiovasc Surg. 2008;135: Shaddy1 RE, Hawkins J. Immunology and failure of valves allografts in children. Ann Thorac Surg.2002;74: Asante-Korang A, Jacobs JP, Ringwald J, Carapellucci J, Rosenberg K, McKenna D, McCormack J, Wilmot I, Gjeldum A, Lopez-Cepero M, Sleasman J. Management of children undergoing cardiac transplantation with high Panel Reactive Antibodies. Cardiol Young ;21 : O Connor M, Menteer J, Christant M, Monos D, Lind C, Levine S, Gaynor J, Hanna B, Paridon S, Ravishankar C, Kaufan B. Ventricular assist device-associated anti-human leukocyte antigen antibody sensitization in pediatric patients bridged to heart transplantation. J Heart Lung Transplant.2010;29: McKenna D, Eastlund T, Segall M, Noreen H, Park S. HLA alloimmunization in patients requiring ventricular assist device support. J Heart Lung Transplant. 2002;21: Pollock-BarZiv S, Den Hollander N, Ngan B, Kantor p, McCrindle B, West L, Dipchand A. Pediatric heart transplantation in human leukocyte antigen-sensitized patients. Evolving management and assessment on intermediate-term outcomes in a high-risk population. Circulation.2007;116:

23 References Cont. 8. Stevenson L, Hamilton M, Tillisch I, Moriguichi J, Kobashigawa J, Creaser J, Drinkwater D, Laks H. Decreasing survival benefit from cardiac transplantation for outpatients as the waiting list lengthens. J Am Coll Cardiol. 1991;18(4): Betkowski A, Graff R, Chen J, Hauptman P. Panel-reactive antibody screening practices prior to heart transplantation. J Heart Lung Transplant. 2002;21: Mehra M, Uber P, Uber W, Scott R, Park M. Allosensitization in heart transplantation: implications and management strategies. Current Options in Cardiology.2003;18: Tambur A, Pamboukian S, Costanzo M, Herrera N, Dunlap S, Montpetit M, Heroux A, The presence of HLA-directed antibodies after heart transplantation is associated with poor allograph outcomes. Transplantation. 2005;80: Murata K, Baldwin W. Mechanisms of complement activation, C4d deposition, and their contribution to the pathogenesis of antibody-mediated rejection. Transplant Rev (Orlando) ;23: Jost C. Schmidt D, Huebler M, Balmer C, Noll G, Caduff R, Greutmann M. Heart transplantation in congenital heart disease: in whom to consider and when? J Transplant. 2013; pages. 14. Foreman C, Gruenwald C, Wes L. ABO-incompatible heart transplantation: a Perfusion strategy. Perfusion.2004;19:

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