a case of passenger lymphocyte syndrome following minor abo incompatible renal transplantation

Case Report A case of passenger lymphocyte syndrome following minor ABO incompatible renal transplantation Anju Dubey1, Hemchandra Pandey1, Atul Sonker1, Rajendra K Chaudhary1 Department of Transfusion Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India Abstract Immune hemolysis is one of the adverse effects that can occur following solid organ transplantation Understanding the clinical settings and the various causes is necessary for prompt diagnosis and appropriate management One such condition is passenger lymphocyte syndrome (PLS) This case report describes the case of a 27-year-old male renal allograft recipient of the B-positive blood group who received a kidney from an O-positive donor Postoperatively, the patient showed declining hemoglobin (Hb) level and was transfused with B-group packed RBCs (PRBCs), following which there was steep fall in Hb level A request for PRBCs was sent to the blood bank and this time cross-match with B-group PRBCs showed incompatibility The patient’s RBCs were found to be strongly DAT (direct anti-globulin test) positive and the eluate showed the presence of anti-B with a titer of 32 Thus, diagnosis of probable PLS was made The patient was managed with methylprednisolone, plasmapheresis and O-group PRBCs Gradually his condition improved and was discharged in stable condition Key words: Antibody titer, DAT, hemolysis, passenger lymphocyte syndrome, transplantation Introduction Access this article online Website: www.ajts.org DOI: 10.4103/0973-6247.126694 Quick Response Code: Correspondence to: Dr Anju Dubey, Department of Transfusion Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow-226 014, Uttar Pradesh, India E-mail: dranjudubey@ gmail.com 56 Recipients of minor ABO-mismatched transplantation may experience delayed hemolysis mediated by donor lymphocytes contained in the graft Donor lymphocytes produce iso-agglutinins capable of destroying the recipient’s red cells, resulting in varying degrees of hemolysis This condition is known as passenger lymphocyte syndrome (PLS) Onset is between and weeks post transplantation and the course is self-limiting as ABO antibodies clear out within a maximum span of months.[1] Case Report Here we report one such case of PLS in a 27-yearold male renal allograft recipient of the B Rh D-positive blood group who received a kidney from a donor of the O Rh D-positive blood group Indication for transplantation was end-stage renal disease and basiliximab induction was given The patient was transfused with B Rh D-positive packed RBCs (PRBCs), units during the surgery and units postoperatively in the next 24 hours The postoperative course of the patient was uneventful and graft function was normal by day However, day 10 onwards, the patient showed a declining hemoglobin (Hb) level from 7.4 to 6.6 g% His blood sample was sent to the blood bank, requesting for 1 unit of PRBCs It showed no group discrepancy or unexpected antibody The patient was transfused with U of cross-match-compatible PRBCs of the B Rh D-positive blood group, following which there was a steep fall in his Hb level from 6.6g to 3.2g% over a period of 12 hour Investigations showed that platelet count and coagulation parameters were normal, reticulocyte count was 11.1%, lactate dehydrogenase (LDH) level was 990 U/l and unconjugated bilirubin level was 2.4 mg/dl The treating unit suspected hemolytic uremic syndrome associated with tacrolimus administration in the patient, which was excluded on the basis of absence of fragmented red cells on peripheral blood smear A request for units of PRBCs was again sent to the blood bank ABO and Rh grouping were performed using the conventional test tube technique at room temperature, which showed no discrepancy; however, cross-match with B Rh D-positive PRBCs using the LISS Coomb column agglutination technique (Bio-Rad, Diamed GmbH, Cressier FR, Switzerland) at 37°C showed incompatibility On performing direct anti-globulin test (DAT) using the LISS Coomb column agglutination technique (BioRad, Diamed GmbH, Cressier FR, Switzerland), the patient’s red cells were found to be strongly positive (4+) Elution was performed using the gentle heating method and the eluate showed the presence of anti-B Indirect anti-globulin test of the patient’s serum using a three-cell panel of O group (Diacell, BioRad, Diamed GmbH, Cressier FR, Switzerland) was negative, ruling out the presence of any unexpected Asian Journal of Transfusion Science - Vol 8, Issue 1, January - June 2014 Dubey, et al.: Case of passenger lymphocyte syndrome antibody and anti-B was detectable in the serum Titration of anti-B using B-group red cells showed a titer of 32 in the indirect anti-globulin test phase The antibody was probably of IgG class The antibody was reactive only at 37°C and was unaffected by dithiothreitol treatment The cross-match showed compatibility with O group so units of O Rh D-positive PRBCs were issued for the patient and a provisional diagnosis of PLS was made Serial titration of the kidney donor’s serum in the indirect antiglobulin test phase showed anti-A and anti-B titers of 64 and 1024, respectively Hemolysin test showed a positive result with B cells, indicating that the donor’s blood group was the dangerous O-type The patient was treated with three doses of intravenous methylprednisolone His Hb level did not show significant elevation and investigations showed a persistently raised reticulocyte count, LDH and creatinine [Table 1] He was subsequently transfused with PRBCs of O group and underwent two sessions of plasmapheresis One volume exchange was done every alternate day and replacement was done with 5% albumin solution The patient was serially monitored and the sequence of events that followed is depicted in Figure Nineteen days postoperatively, his Hb rose to 6.7 g% and anti-B titer was Thereafter, his condition improved gradually and was discharged on day 29 in stable condition with good urine output, a serum creatinine level of 1.2 mg %, Hb level of g% and an anti-B titer of Discussion donor had a high titer of anti-B; however, it has been established that the titer of antibody in the donor is not a reliable means of prediction of the occurrence of hemolysis in the recipient in the postoperative period.[7] Post-transplantation hemolysis due to the formation of antibodies within the ABO system is self-limiting and often mild, but our patient had severe intravascular hemolysis, due to transfusion of a significant amount of group-B PRBCs in the postoperative period Several other cases of severe hemolysis after minor ABOincompatible solid organ transplantation have been reported previously.[8-10] Hemolysis in such cases can be managed by transfusion with group-O RBCs, avoidance of ABO-incompatible plasma products and maintenance of adequate renal perfusion Corticosteroids are often used empirically In patients with more severe hemolysis, plasma exchange may be used to decrease antibody titer Other strategies include an increase or change in immunosuppression, intravenous immunoglobulin, red-cell exchange and using monoclonal antibodies such as rituximab Conclusion The study highlights the importance of routinely monitoring patients receiving ABO-mismatched transplant for developing PLS, which is indicated by the presence of signs of hemolysis, positive PLS is a well-recognized syndrome of immune hemolysis following a minor ABO-mismatch solid organ transplantation Most cases of PLS are due to ABO mismatch, but antibodies against Rh, Kidd and Lewis blood group systems have also been reported to cause PLS.[2-4] Clinical findings include hemolysis of abrupt onset, a rapidly declining Hb level, signs of intravascular hemolysis (hemoglobinemia and hemoglobinuria) and renal failure, associated with elevation of serum bilirubin and LDH Hemolysis is generally short-lived, evidently because the lymphocytes transferred with the donor organ are able to proliferate only temporarily and are not permanently engrafted The serum antibody is predominantly IgG, but it may also be IgM Antibody production gradually decreases as the passenger lymphocytes reach the end of their life span.[5] The antibodies persist for a median of weeks in kidney transplant recipients.[6] The risk and degree of hemolysis is lowest in kidney (antibody in 17%, hemolysis in 9%), followed by liver (antibody in 40%, hemolysis in 29%) and highest in heart–lung transplants (antibody in 70%, hemolysis in 70%).[6] In this case, we found that the Table 1: Serial variation of patient’s parameters Days after transplantation 10 11 12 15 17 19 Hb (g%) 7.4 6.6 2.3 3.1 6.2 6.5 6.7 LDH (IU/l) — — 990 — 668 — 450 Figure 1: Serial variation of DAT, antibody titer, Hb level and management details of the patient Unconjugated bilirubin (mg/dl) — — 2.4 — 2.2 — 1.7 Asian Journal of Transfusion Science - Vol 8, Issue 1, January - June 2014 Reticulocyte count (%) — — 19.4 — 11.1 — 7.9 Creatinine (mg%) 7.8 4.56 2.48 1.91 1.76 1.83 1.20 Urine output (l) 9.08 8.50 — — — — 5.50 57 Dubey, et al.: Case of passenger lymphocyte syndrome DAT and presence of relevant antibody (anti-A or anti-B) in the patients’ serum and RBC eluate The most important safeguard is awareness of both the operating surgeon and the transfusion medicine physician of the syndrome, which will enable it to be recognized and treated earlier References Smith EP Hematologic disorders after solid organ transplantation Hematology Am Soc Hematol Educ Program 2010;2010:281-6 Saba NF, Sweeney JD, Penn LC, Lawton JC, Yankee RL, Huang Ch, et al Anti-D in a D-positive renal transplant patient Transfusion 1997;37:321-4 Hareuveni M, Merchav H, Austerlite N, Rahimi-Leveen N, Ben-Tal O Donor anti Jk(a) causing hemolysis in a liver transplant recipient Transfusion 2002;42:363-7 Ting A, Pun A, Dodds AJ, Atkinson K, Biggs JC Red cell alloantibodies produced after bone marrow transplantation Transfusion 1987;27:145-7 Petz LD Immune hemolysis associated with transplantation Semin Hematol 2005;42:145-55 Ramsey G Red cell antibodies arising from solid organ transplants 58 Transfusion 1991;31:76-86 Hows J, Beddow K, Gordon-Smith E, Branch DR, Spurce W, Sniecinski I, et al Donor-derived red blood cell antibodies and immune hemolysis after allogeneic bone marrow transplantation Blood 1986;67:177-81 Orchard J, Young NT, Smith C, Thomas S, Darke C Severe intravascular haemolysis in a renal transplant recipient due to anti-B of donor origin Vox Sang 1990;59:172-5 Davis SL, Vaidya A, Timbs A, Schuh A, Staves J, Murphy MF Severe haemolysis due to passenger lymphocyte syndrome after an ABO mismatched bowel transplant — a case report Transfus Med 2011;21:65-9 10 Panaro F, DeChristopher PJ, Rondelli D, Testa G, Sankary H, Popescu M, et al Severe hemolytic anemia due to passenger lymphocytes after living-related bowel transplant Clin Transplant 2004;18:332-5 Cite this article as: Dubey A, Pandey H, Sonker A, Chaudhary RK A case of passenger lymphocyte syndrome following minor ABO incompatible renal transplantation Asian J Transfus Sci 2014;8:56-8 Source of Support: Nil, Conflicting Interest: None declared Asian Journal of Transfusion Science - Vol 8, Issue 1, January - June 2014 Copyright of Asian Journal of Transfusion Science is the property of Medknow Publications & Media Pvt Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission However, users may print, download, or email articles for individual use  ... transplant Clin Transplant 2004;18:332-5 Cite this article as: Dubey A, Pandey H, Sonker A, Chaudhary RK A case of passenger lymphocyte syndrome following minor ABO incompatible renal transplantation. .. syndrome of immune hemolysis following a minor ABO- mismatch solid organ transplantation Most cases of PLS are due to ABO mismatch, but antibodies against Rh, Kidd and Lewis blood group systems have also... Dubey, et al.: Case of passenger lymphocyte syndrome DAT and presence of relevant antibody (anti -A or anti-B) in the patients’ serum and RBC eluate The most important safeguard is awareness of both