Contributed by Lara Berklite, MD
A 70-80 year old female with a history of mantle cell lymphoma with abdominal involvement on chemotherapy status post day 13 of bendamustine-rituximab presented for transfusion of red blood cells for anemia. The patient was pre-medicated with acetaminophen and received 2 units of RBCs. One hour after receiving the second unit, she had nausea, vomiting, acute abdominal pain, and back pain with frank hematuria. The patient additionally became hypertensive with a rise in blood pressure from 117/67 to 177/86 mmHg. The patient was transfused through a port without a blood warmer. No other medications were infused through the line at the same time as the transfusion. The patient had previously been transfused through the port without problem. The patient was treated for her symptoms with IV normal saline and received two additional units of RBCs with no further problems.
Hemoglobin level pre-transfusion was 7.5 g/dL and rose to 8.2 g/dL post-transfusion (ref range 11.6-14.6 g/dL). DAT was negative, but plasma was observed to be slightly pink in the lab. Antibody screen on pretransfusion and posttransfusion blood samples were both negative. Urinalysis was positive for protein, urobilinogen, bilirubin, blood, and leukocyte esterase. Total bilirubin and liver function tests were within normal limits both before and after transfusion. Pretransfusion LDH was elevated at 736 IU/L (ref range <171 IU/L), but increased to 1433 IU/L post-transfusion and continued to be elevated several days post-transfusion with a peak level of 1669 IU/L. Post-transfusion haptoglobin was <30 mg/dL (ref range 36-195 mg/dL) and free plasma hemoglobin was 134.4 mg/dL (ref range <6 mg/dL). The patient also had an increase in creatinine from a baseline of 0.7 to 1.5 mg/dL (ref range 0.5-1.4 mg/dL) and decline in eGFR from 87 to 35 mL/min/1.73m2 (normal >60 mL/min/1.73m2).
No RBC alloantibodies were detected when the serum was tested against reagent red blood cells at room temperature and 37C with albumin, ficin and PEG enhancement. Enhancement of autocontrol testing with PEG and polybrene were negative. The acid eluate was nonreactive. Enhanced direct antiglobulin testing was performed. DAT was negative using polyspecific anti-human globulin, monospecific anti-IgG, monospecific anti-C3d, monospecific anti-IgM, and monospecific anti-IgA. Given the patient's history of bendamustine use, testing was performed for drug-induced antibodies by immune complex mechanism. No antibody was detected against bendamustine when serum was tested by the drug solution addition method. The serum was tested neat and using a 1:10 and 1:20 dilution. Flow cytometry was performed to detect low levels of IgG, IgA, and IgM on the patient's cells. Pre- and post-transfusion samples were within normal range for IgG at 3.05 and 1.09%M2 respectively. IgM was slightly elevated in both samples at 9.49%M2 in the pre-transfusion sample and 4.88%M2 post-transfusion. IgA flow cytometry was negative. Testing for paroxysmal nocturnal hemoglobinuria was negative. The patient's serum was also sent to a reference lab for RBC membrane sequencing. Drug adsorption mechanism testing is pending.