Ann Thorac Surg 2006;81:1105-1107
© 2006 The Society of Thoracic Surgeons
Case report
Exchange Transfusion During Extra Corporeal Membrane Oxygenation Used as a Bridge to ABO-Mismatch Cardiac Transplantation
Phil Botha, MRCS
a
,
*
,
Asif Hasan, FRCS
a
,
Simon Haynes, FRCA
b
,
Jane Cassidy, FRCA
b
,
Joe Roe, FRCA
b
,
John Wallis, FRCPath
c
,
Jon Smith, FRCA
b
a Department of Cardiothoracic Surgery and Transplantation, Freeman Hospital, High Heaton, Newcastle upon Tyne, United Kingdom
b Department of Paediatric Intensive Care, Freeman Hospital, High Heaton, Newcastle upon Tyne, United Kingdom
c Department of Haematology, Freeman Hospital, High Heaton, Newcastle upon Tyne, United Kingdom
Accepted for publication January 20, 2005.
* Address correspondence to Dr Botha, c/o Ward 27A, Freeman Hospital, Newcastle upon Tyne, NE7 7DN United Kingdom (Email: phil.botha{at}nuth.northy.nhs.uk).
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Abstract
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We report a case in which exchange transfusion was performed directly from the extracorporeal membrane oxygenation circuit in a child being bridged to cardiac transplantation. This allowed preparation for ABO-mismatched heart transplant in a child dependent on extracorporeal support, awaiting a suitable ABO-matched donor. Exchange transfusion or plasmapheresis in this setting would normally be performed on cardiopulmonary bypass to allow exsanguinations under hypothermia immediately pre-transplant. This allows little time for depletion of isohemagglutinins, occasionally leading to prolonged bypass times. We believe our method to be a safe alternative, allowing ample time for immunological preparation for ABO-incompatible transplant.
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Introduction
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The use of extracorporeal membrane oxygenation (ECMO) as a bridge to cardiac transplantation in the infant gives results similar to those in non-bridged transplants. Donor organs remain in short supply, necessitating long periods of extracorporeal support. By using ABO-mismatched hearts for transplantation, the donor pool can be expanded with excellent results in infants as old as 14 months of age. This requires the removal of pre-formed anti-A or anti-B antibodies by plasmapheresis or exchange transfusion to prevent acute rejection. This is normally performed intraoperatively on full cardiopulmonary bypass by exsanguinations under hypothermia, allowing little time for repeated cycles of exchange with measurement of haemagglutinin levels. This case demonstrates that exchange transfusion can safely be performed while on ECMO to prepare the child for ABO-mismatched transplantation.
A 13-month-old boy presented with a 3-day history of irritability and cough. An echocardiogram showed a dilated left ventricle with a 20% ejection fraction and an otherwise structurally normal heart. Despite supportive therapy, multiple episodes of bradycardia and hypoxia had developed over the ensuing 2 days, and he was referred to a supra-regional transplant center. While in transit to the transplant center, cardiac arrest occurred, requiring cardiopulmonary resuscitation. On arrival, cardiopulmonary resuscitation had been in progress for 35 minutes and the child had become markedly acidotic (pH 7.12). The jugular vessels were cannulated and ECMO commenced at a flow of 150 mL/kg/min. Ominously, neurological examination revealed a fixed, dilated right pupil and a reactive but dilated left pupil.
After ECMO was established the boy became hemodynamically stable. Electroencephalogram showed signs of minor cortical injury only and a day later some spontaneous movement, eye opening, coughing and gag reflexes returned. With signs of neurological recovery apparent, the patient was listed for transplantation. Chest roentgenogram showed signs of pulmonary edema, and a transvenous atrial septostomy was performed to decompress the left heart. By day 7 after admission, both pupils were reacting to light. The possibility of ABO-mismatched transplantation was discussed with the family and consent was obtained, the child being O Rhesus positive with anti-A titres of 1:64 and anti-B of 1:8 in the absence of previous blood product transfusions. Institutional review board approval had been granted for a program of ABO-mismatched cardiac transplantation.
On day 11 at 16:00 hours, an AB positive donor heart became available and exchange transfusion was performed from the ECMO circuit. This was done by clamping the circuit directly before the bladder reservoir and removing blood from the circuit 500 mL (±67% of estimated blood volume) at a time through a side infusion port proximal to the clamp. The circuit was kept primed with volume by connecting 3 units of packed red blood cells, 3 units of fresh frozen plasma, and 4 units of human albumin solution in turn to a side infusion port (Fig 1). We performed five cycles of exchange transfusion and repeated isohemagglutinin titres after each cycle. (The resultant titre profiles are displayed in Fig 2). Blood removed from the circuit was passed through a cell saver (CellSaver 5 System, Haemonetics, MA) allowing the red cells to be re-infused. Exchange transfusion rapidly eliminated circulating drugs including sedatives. This required repeated bolus doses of sedatives to maintain appropriate levels of sedation. After five cycles, the patient's isohemagglutinins had been rendered undetectable by conventional testing.
Orthotopic heart transplant was undertaken. Iso-haemagglutinin titres remained undetectable at termination of bypass. Immunosuppression consisted of methylprednisolone, cyclosporin A, azathioprine, and anti-thymocyte globulin for 2 days. Rituximab (Roche, Hertfordshire, UK), an anti-CD20 monoclonal antibody, was administered as a single dose of 375mg/m2 in an attempt to minimize allo-antibody production. Inotropic and ventilatory support was rapidly weaned, and the patient was extubated on postoperative day 2. Anti-A titres also rose to 1:8, but the patient remained clinically well with no evidence of graft dysfunction on echocardiography.
A full neurological recovery was soon evident. Haemagglutinin titres continued to fluctuate between 1:8 to 1:32 for anti-A, and 1:2 to 1:8 for anti-B. It was decided to monitor graft function by echocardiography alone and cardiac biopsy was not undertaken. The patient remained clinically and echocardiographically stable until his discharge on postoperative day 27 and remained so at 120-day follow-up.
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Comment
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In infants with acquired myopathy and those with cardiac failure secondary to congenital heart disease, orthotopic heart transplantation remains the only definitive therapeutic option. Donor organs for these patients are in short supply leading to long waiting times and end-organ dysfunction [1, 2]. Extracorporeal membrane oxygenation as a bridge to transplantation has provided an effective way of decreasing morbidity and mortality in those listed for transplantation. Survival to discharge in patients bridged in this manner has been shown to range from 58% to 83% [3, 4].
In the United Kingdom, 45% of the population are of blood group O. In this group especially, small organs suitable for infants are in very short supply. The use of ABO mismatched hearts for transplantation in the immunologically immature infant is a safe way of improving use of the existing donor pool, shortening waiting times, and minimizing organ wastage [5, 6]. West and colleagues [5] demonstrated a decrease of waiting list mortality from 58% to 7% and similar survival rates with the use of ABO-incompatible transplantation. Two of the patients from their series were 14 months of age at transplantation, having preformed antibodies to A and B blood group antigens. This is believed to be due to cross-reactivity with surface antigens of intestinal flora and develops in the first 2 years of life. Both of these patients were treated with intraoperative plasma exchange as sole means of removing these antibodies. In our own center, ABO mismatch transplantation has been performed successfully in ages to 21 months [6]. Hyper-acute rejection did not occur in any of these patients and an element of immune accommodation was observed postoperatively with only low levels of antibody re-accumulation. Importantly, re-accumulation of antibody was not associated with graft damage. Plasma exchange performed intraoperatively from the bypass circuit, allows little time to achieve complete elimination of antibody. We chose to perform plasmapheresis from the ECMO circuit while on the intensive care unit, allowing ample time to achieve zero titres in preparation for transplantation.
We have demonstrated that exchange transfusion can be performed safely on a child being bridged to transplantation with ECMO. This allows preparation for ABO incompatible heart transplantation. The safe upper age limit for ABO mismatched cardiac transplantation remains to be defined.
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References
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- Goldman AP, Cassidy J, de Leval M, et al. The waiting gamebridging to paediatric heart transplantation. Lancet 2003;362:1967-1970.[Medline]
- Reddy SLC, Hasan A, Hamilton JRL, et al. Mechanical versus medical bridge to transplantation in children. What is the best timing for mechanical bridge? Eur J Cardiothorac Surg 2004;25:605-609.[Abstract/Free Full Text]
- Gajarski RJ, Mosca RS, Obye RG, et al. Use of extracorporeal life support as a bridge to paediatric cardiac transplantation J Heart Lung Transplant 2003;22:28-34.[Medline]
- Kirschbom PM, Bridges ND, Myung RJ, Gaynor JW, Clark BJ, Spray TL. Use of extracorporeal membrane oxygenation in pediatric thoracic organ transplantation J Thorac Cardiovasc Surg 2002;128:150-156.
- West LJ, Pollock-Barziv SM, Dipchand AI, et al. ABO-incompatible heart transplantation in infants N Engl J Med 2001;344:793-800.[Abstract/Free Full Text]
- Rao JN, Hasan A, Hamilton JRL, et al. ABO-incompatible heart transplantation in infantsthe Freeman hospital experience. Transplantation 2004;77:1389-1394.[Medline]
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Abstract
Introduction
