Passenger lymphocyte syndrome, an unusual cause of anemia after liver transplantation

Abstract

Introduction and Objectives

The prevalence of anemia after liver transplantation ranges from 4.3% to 28.2%. Causes that occur in the first two weeks include bleeding, sepsis, medications, and hemolysis. Immune hemolysis represents less than 1% of the cases and includes graft-versus-host disease and hemolysis associated with ABO incompatibility. We present a case of passenger lymphocyte syndrome as a cause of immune hemolytic anemia two weeks after a liver transplant.

Materials and Patients

A 43-year-old woman, blood group A+, with a history of HCV-related liver cirrhosis and BCLC-A hepatocellular carcinoma, was chosen for a liver transplant. Surgery was uneventful, requiring the transfusion of an O+ blood unit. The postoperative evolution was carried out without complications. On day 10, after the transplant, she presented a drop of 3 g/dL in hemoglobin, leukocytosis, elevated acute phase reactants, and mixed hyperbilirubinemia. An esophagogastroduodenoscopy and colonoscopy showed no active bleeding. The hemolysis profile showed a decrease in the haptoglobin value and an increase in DHL, negative Coombs, without schistocytes. An MRCP was requested, with no evidence of bile leakage or active bleeding. Because of the suspicion of hemolysis due to drugs, tacrolimus was changed to mycophenolate mofetil, and because of possible hemolysis due to sepsis, broad-spectrum antibiotic coverage was added without improvement. On day 14, there was a suspicion of transient lymphocyte syndrome. Isohemagglutinin levels were requested and became positive, and two O+ blood units were transfused. The following day, she presented a significant improvement in all laboratory parameters, and on day 20 she was discharged from the hospital without any abnormality in her laboratory parameters.

Results

In our management of hemolytic anemia after liver transplantation, two theories initially emerged: 1) Hemolysis due to tacrolimus, for which it was suspended and changed to mycophenolate mofetil, and 2) Hemolysis due to sepsis, due to leukocytosis and inflammation, initiating coverage with meropenem and vancomycin. But without improvement after both interventions. Finally, due to suspicion of transient lymphocyte syndrome, isohemagglutitins were requested and were positive, and after the transfusion of 2 O+ blood units, containing anti-A+ antibodies, she showed improvement, confirming the diagnosis.

Conclusions

In the passenger lymphocyte syndrome, there is a donor B lymphocyte production of antibodies causing a primary or secondary response to recipient erythrocytes. The incidence is higher in the heart-lung transplant, followed by liver transplantation. The risk also increases according to the donor-recipient ABO mismatch, being more common with group O donors and group A recipient (61%), followed by group O donors and group B recipients (22%). The clinical picture is characterized by fever, diarrhea, rash and hemolysis. The hemolysis usually occurs on days 3 to 24 after the liver transplantation and tends to be mild and self-limited. The diagnosis is made when the recipient had a positive direct antiglobulin test and there were donor antibodies in the serum against the recipient's red blood cell antigens. Treatment options include the transfusion of O red blood cell units and, in cases of severe hemolysis, immunosuppressors or plasmapheresis.