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.