Case Description
Our patient is a 19-year-old male with β-thalassemia major on chronic transfusion therapy. He received phenotypically-matched RBC transfusions (matched for E- K- S- Fya- antigens) every 3 weeks. Twelve days after a transfusion, he presented with myalgias, fatigue, and low-grade fever, and was found to have a hemoglobin (hgb) of 5.5 g/dL with concurrent evidence of hemolysis, concerning for a delayed hemolytic transfusion reaction. The direct antiglobulin test (DAT) revealed panagglutination. He was admitted and transfused one unit of matched packed red blood cells (PRBC). Immediately after the transfusion he produced dark urine with urobilinogen and proteinuria concerning for hemolysis of the transfused unit. Hyperhemolysis was suspected and aggressive immunosuppression was initiated consisting of intravenous methylprednisolone (2mg/kg) every 6 hours and intravenous immunoglobulin G (IVIG) (1 gram/kg). Despite these interventions, his hemoglobin dropped from 4.7 g/dL to 4.3 g/dL. Intravenous (IV) eculizumab (900mg) was initiated in conjunction with continued IV corticosteroids and two additional doses of IVIG. Figure 1 details the lab trend and interventions during his acute hospitalization.
The patient was monitored in the intensive care unit and further transfusions were avoided while immune control was attempted. He remained stable with hemoglobin 3.1-3.4 g/dL until hospital day 8. At that time, he had a hemoglobin of 2.9 g/dL with evidence of stable bilirubin and lactase dehydrogenase (LDH) levels. The decision was made to start him on Rituximab (375mg/m2 IV) and transfuse one half of a unit of phenotypically-matched PRBCs over four hours. He tolerated this well and followed with the second half of the unit that evening. Repeat laboratory evaluation post-transfusion remained stable. He continued to receive transfusions over several days with improvement in hgb, but without significant worsening of hemolysis.
Additional transfusions were given and tolerated over the next week, reaching a maximum hgb of 12.3 g/dL by hospital day 11. At this time, the methylprednisolone was transitioned to prednisone with a slow taper. He was able to be discharged in stable condition after 15 total days in the hospital. During the acute phase he received a total of three doses if IVIG daily in the first four days, two doses of weekly eculizumab, two doses of weekly rituximab and high dose steroids followed by taper.
As an outpatient he completed a three-week prednisone taper and he continued weekly Rituximab for four total doses. Unfortunately, 44 days after his initial presentation (three weeks from his last dose of eculizumab), hemolysis resumed with drop in hgb from 11.4g/dL to 7 g/dL and an increase in LDH. Figure 2 outlines the outpatient course with labs and interventions. Eculizumab (900mg) was restarted weekly for four weeks, along with prednisone (0.5mg/kg/day) and sirolimus (2mg) twice daily. He received a total of 11 doses of eculizumab, he was given 900mg weekly for five doses, followed by 1200mg every other week for four doses, then 1200mg every three weeks for two doses. The eculizumab treatment course was completed 176 days from his initial presentation. The patient continues to tolerate transfusions without evidence of recurrence of hemolysis on single-agent sirolimus for immunosuppression.