Severe hemolytic anemia due to anti-E after renal transplantation.

Abstract

Red blood cells (RBC) antibodies arising from transplanted organs and directed against recipient RBCs represent a well-established immunohematological complication of solid organ transplantation. Most of the reported cases are due to ABO or D antibodies (1). We describe an anti-E antibody that caused a severe immune hemolytic anemia in an E-positive patient who had received a kidney transplant from an E-negative receptor. A 30-year-old male, group A, D-positive (CDe/cDE) patient received a kidney from a group A, D-positive, E-negative cadaver donor. The donor had been transfused 48 hr before kidney collection with 3 group A RBCs unit with the following Rh phenotypes: CDe/cDE, cDE/cDE, and Cde/cde. Preoperative screening of donor alloantibodies was negative. The patient underwent transplantation, and during the immediate postoperative period, he received a transfusion of 4 units of group A, D-positive packed RBCs. Immunosuppressive therapy was started the day of transplantation and consisted of cyclosporine and prednisone. The patient was discharged on the posttransplant day 23 with a hemoglobin level of 11.3 g/dl. Two months later, a hemoglobin level of 8.2 g/dl was observed in a routine control examination, but no other studies were performed. In the third posttransplant month, he was readmitted due to a severe anemic syndrome with a hemoglobin level of 2.6 g/dl, a total bilirubin level of 2.2 mg/dl, and a lactate dehydrogenase level of 1039 IU/L. Serum levels of haptoglobin were <10 mg/dl, and creatinine values were 2.3 mg/dl. Immunosuppressive therapy on readmission consisted of cyclosporine (12 mg/day) and prednisone (15 mg/day). At that moment, pretransfusional testing detected a positive direct antiglobulin test (DAT), and anti-E antibody was detected in the patient's serum and in the eluate from his RBCs. The cyclosporine dosage was reduced, high-dose prednisone therapy (2 mg/kg/day) was started immediately after admission, and 7 units of group A, E-negative RBCs were transfused. He was discharged 17 days later with a hemoglobin level of 9 g/dl and normal serum chemistry. Three months later, the DAT persisted positive and anti-E antibody was still detected in patient's serum without signs of hemolysis. Twelve months after transplantation, the DAT was negative and no anti-E activity was observed in the serum. Transplanted organs contain lymphocytes that may survive in the host, particularly when immunosuppressive therapy is being administered, and mount an immune response against host antigens. In recipients of solid organ transplants, many cases of alloantibodies of A, B, and Rh specificity directed at the patient's RBCs causing severe hemolytic syndrome have been reported (1). In most cases, the antibody-associated, immune RBC destruction develops in the recipient of an organ from a donor whose serum contained the antibody. However, in our case, an antibody screening test performed on the donor's serum immediately before transplantation was negative, and since the antibody was not detected immediately after transplantation, the hemolytic episode was not due to passive transfer of antibody with the graft. Immediately before collection of the kidney, the donor had been transfused with E-positive RBCs, so he should have been primarily immunized to E. Thus, transient anti-E alloantibody production from “passenger” immunocompetent donor lymphocytes transplanted with the donor organ could explain the hemolysis. A similar case was reported by Hjelle et al. (2) in a recipient of a cadaveric renal transplant. In this case, the donor was a D-positive subject who had been transfused with 4 units of D-positive blood (Rh phenotype unknown) a week before transplantation. The antibody implicated had anti-c specificity and was detected in the patient's serum on day 4 after transplantation, with a positive DAT observed on the postoperative day 8. No clinical hemolysis was observed, and by day 9, no antibody was detected. The authors speculated that immunosuppressive therapy given to the recipient may have protected the patient from severe hemolysis. However, in our case, severe hemolysis resulted from the donor alloantibody despite the administration of immunosuppressive therapy consisting of cyclosporine and steroids. In fact, we believe that antibody production may be associated with cyclosporine immunosuppression. Cyclosporine is a powerful immunosuppressive agent that acts primarily by blocking proliferation of T lymphocytes in response to antigen or mitogens (3). However, T-lymphocyte proliferation is not impaired when presensitized lymphocytes are re-exposed to antigen in the presence of cyclosporine (4). In our case, like in that reported by Hjelle et al., donor lymphocytes were sensitized in vivo during transfusions of RBCs before transfer to the recipient, so donor-derived red cell antibody production was a secondary immune response. This case highlights the need of performing an immunohematological study in every recipient of a solid organ transplantation in whom a decrease in hemoglobin value is detected. Luis Larrea1; Javier de la Rubia1; Francisco Arriaga1,2; Jaime Sanchez3; María Luisa Marty1 Blood Bank, Department of Hematology; Nephrology Service; La Fe University Hospital; 46009 Valencia, Spain