Case presentation
A 45-year-old gentleman of Chinese ethnicity presented to the thalassemia ward with high grade fever associated with black urine, generalised bone pain and worsening jaundice 36 hours after being transfused with 2 units of ABO and Rh matched leukoreduced cross match compatible red blood cells. He was a known beta thalassemia major, in which, he underwent regular two-weekly transfusion since childhood. However, he was occasionally non-compliant to his transfusion schedule with the latest blood transfusion being 6-weeks prior. He had extramedullary hematopoiesis in the liver, spleen and paraverterbra with mild liver hemosiderosis. He was on dual oral iron chelation therapy. He had a family history of beta thalassemia. He was a non-smoker, a teetotaler and never consumed traditional drugs. He worked as a lawyer.
Physical examination revealed a thin-built gentleman who was significantly pallor and jaundiced. He was febrile at 39.50C with a blood pressure of 140/80 mmHg and tachycardic at 112 beats/minute. He did not demonstrate any cutaneous rash. He had a palpable liver of 5 cm and a spleen of 15 cm. Other systemic examinations were unremarkable.
His pre-transfusion hemoglobin (Hb) of 5.2g/dL decreased further to 4.6 g/dL after 2 units of red cell transfusion. He had a steady state mild pancytopenia (total white cell count: 3.2 x 109/L and platelet: 75 x 109/L) which was attributed to his extramedullary haematopoiesis-related-hypersplenism. His hemolytic markers and peripheral blood film on day 2 of transfusion were consistent with acute intravascular hemolysis. He also had marked hyperferritinemia (his baseline serum ferritin: 200-300 ug/L). His blood and urine cultures were both sterile excluding the possibility of bacterial contamination. The other laboratory parameters are tabulated in Table 1.
Further investigations were performed at the blood bank on Day 2 of transfusion. His ABO and Rh blood grouping on conventional tube technique was O Rh(D) positive, R1R1 phenotype which were the same previously. The micro Coombs (Direct antiglobulin test-DAT) using low ionic strength saline (LISS)/anti-human globulin (AHG) column agglutination card was 2+ for anti-C3d and negative for anti-IgG. The antibody screening on patient’s serum using ID Diacell Asia I-II-III (LISS/AHG column agglutination card) at 370C did not demonstrate any unexpected antibodies on Day 2. A repeated micro Coombs test at Day 15 was negative for both anti-IgG and C3d. Furthermore, the antibody screening showed presence of alloantibody in cell III on Day 15 as shown in Table 2. A 11-cell antibody identification panel (Table 3) identified anti-Cw in the patient’s serum. The patient’s RBCs were genotyped using sequence specific primer-polymerase chain reaction (SSP-PCR) molecular method as RHCE*C/C, RHD*01/01, RHCE*e/e, JK*A, JK*B, KEL*k, FY*A, GYPA*N, GYPB*s. Hence, the RBC phenotype was predicted as R1R1, Cw-, Jka+b-, Fya+b-, kk, NN, ss.
A diagnosis of hyperhemolysis syndrome was made. He was treated with a synergistic combination therapy of intravenous methylprednisolone 8mg/kg daily and intravenous immunoglobulin (IVIg) at a dose of 0.4g/kg daily for a 5-day duration. He was also hydrated adequately with isotonic saline, given subcutaneous erythropoietin-alpha and prophylaxis anticoagulation with enoxaparin 40mg daily (weight 58kg) to prevent hemolysis-induced-thrombosis. The Hb decreased to a nadir of 3.5g/dL at day 10 before increasing to 5.8g/dL at day 15 without any blood transfusion. He was counselled for splenectomy, in which, he refused for the fear of surgery. He is currently on two weekly crossmatch compatible leukoreduced RBC phenotype matched red blood cell transfusion at our thalassemia daycare center.