Ciclosporin/tacrolimus

Abstract

Passenger lymphocyte syndrome: case report A 69-year-old man developed passenger lymphocyte syndrome during treatment with ciclosporin and tacrolimus as immunosuppressant [dosages, routes and duration of treatment to reactions onsets not stated]. The man, who had a history of cirrhosis and hepatocellular carcinoma, underwent orthotopic liver transplantation. Early immunosuppression with tacrolimus and mycophenolate was later transitioned to ciclosporin [cyclosporine] and prednisone. Five days after discharge, he was readmitted for hypotension, exertional dyspnoea, anaemia and mildly elevated total bilirubin. The anaemia was suspected secondary to acute blood loss compounded by suppression of erythropoiesis secondary to immunosuppressive medications. Historical medical records included AB RhD-positive blood type and negative antibody screen prior to transplant. Upon ABO typing, his RBC’s demonstrated possible spontaneous agglutination. Spontaneous agglutination dispersed when washed with phosphate-buffered saline. This was interpreted as rouleaux, and the ABO type was reported as AB RhD-positive with a negative antibody screen. The man received three units of AB RBC’s transfusion. Post-transfusion, laboratory results showed Hb 7.0 g/dL, elevated lactate dehydrogenase (LDH) and decreased haptoglobin. Over the next 3 days, he remained anaemic despite transfusion of five additional units of RBC’s. LDH continued to rise and haptoglobin remained <8 mg/dL. Peripheral blood revealed polychromasia, reticulocytosis and microand macro-spherocytes. Direct antiglobulin testing (DAT) showed C3 (1+ reactivity), but no IgG bound to RBC’s. He was initially diagnosed with cold agglutinin syndrome (CAS) by the haematology clinical team. A second ABO type and screen demonstrated ABO discrepancy. A forward type consistent with type AB, but agglutination on reverse typing when patient plasma was tested against A1 reagent RBC’s. This discrepancy was presumably secondary to CAs given the initial diagnosis of CAS. Subsequently, plasma exchange (PLEX) with type AB plasma was performed for 5 days for transfusion-refractory anaemia. At this time, 10 additional units of AB RBC’s were transfused. Extensive evaluation for infectious organisms was negative. After PLEX, his Hb, haptoglobin and LDH normalised. He remained above the transfusion threshold for 5 days before requiring three additional units of AB RBC’s over the following 2 days. During transfusion of the third unit of RBC’s, administered immediately following the second unit, he experienced a sudden onset of dyspnoea, chills, hypotension, tachycardia and tachypnea. A transfusion reaction evaluation was performed. A chest radiograph showed no significant interval change. The preand post-transfusion samples showed an ABO discrepancy with agglutination on reverse typing with A1 reagent RBC’s. DAT on the post-transfusion sample was negative for IgG and C3. Laboratory results were significant for LDH of 526 U/L, haptoglobin <8 mg/dL and total bilirubin 17.4 mg/dL. On further evaluation, it was revealed that he had received a minor ABO incompatible transplanted liver from a blood type B donor. An anti-A1 titre was significant for a titre of 8. Testing of the RBC’s with anti-A1 Dolichos bifloris lectin did not led to RBC agglutination. However, his plasma agglutinated both A1 RBC’s (3+ reactivity) and A2 RBC’s (1+ reactivity), indicating the original agglutination seen in the reverse type with A1 reagent RBC’s was due to anti-A, and not specifically anti-A1. The findings suggested PLS secondary to a type B liver allograft containing lymphocytes producing anti-A. Therefore, he was switched to type O RBC’s and immunosuppression was increased. Afterwards, his condition stabilised, haemolysis biomarkers normalised, and he was discharged 3 days later.