Brigham and Women's Hospital Brookline, Massachusetts, United States
Background/Case Studies: Delayed hemolytic transfusion reactions can be complicated by hyperhemolysis, a syndrome in which the patients hemolyze autologous red cells in addition to transfused donor red cells. Patients can die from the severe anemia and immune activation induced by free heme. Hyperhemolysis is usually treated with intravenous immunoglobulin and high dose steroids, along with erythropoietin support as most patients are reticulocytopenic. Current American Society of Hematology guidelines recommend against further transfusions as they are thought to exacerbate hemolysis in an “adding fuel to fire” manner. Reports in recent years demonstrate complement activation in patients with hyperhemolysis, and the anti-C5 antibody eculizumab is recommended for second-line therapy. However, it is unclear how or when eculizumab could be best deployed during a patient’s course.
Study
Design/Methods: We present a case of hyperhemolysis with profound thrombocytopenia that was successfully treated with eculizumab, immunosuppressants/immunomodulators, and hematopoiesis stimulators. The patient is a 29-year-old hemoglobin SS female with anti-C, anti-E, and anti-M alloantibodies. She was transfused with three units of CEK-matched red blood cells prior to hip surgery, including one unit positive for S antigen. Five days later she presented with symptoms of a delayed hemolytic transfusion reaction that evolved into hyperhemolysis with hemoglobin below 3g/µL at nadir.
Results/Findings: The patient’s post-transfusion testing was positive for a new anti-S antibody and direct antiglobulin positive for both IgG and complement C3b/C3d. Interestingly, she developed concurrent thrombocytopenia, with platelet count dropping from 411K/µL pre-op to 9K/µL at nadir. Eculizumab, intravenous immunoglobulin, steroids, and erythropoietin were initiated, which rapidly reduced the patient’s bilirubin levels. To prevent end organ damage and death, five additional units of CEKS-matched red cells were transfused over four days, which the patient largely tolerated. After the second dose of eculizumab the patient did not require further transfusions. One dose of romiplostim was administered for thrombopoiesis support. Her platelet count recovered as her hemoglobin stabilized. Conclusions: In summary, this is a case of hyperhemolysis with profound thrombocytopenia where the patient tolerated several life-saving red cell units after the administration of eculizumab and other immunosuppressive agents. Although red cell transfusions are currently contraindicated in hyperhemolysis, eculizumab may prevent exacerbation in direct antiglobulin test-positive cases and tip the balance in favor of transfusion to prevent death from severe anemia.
Importance of research: RBC transfusions are generally contra-indicated in hyperhemolysis syndrome. However, when patients with hyperhemolysis experience profound life-threatening anemia, transfusions may be required to avert end-organ damage and death. We present a case that illustrates how anti-complement therapy in conjunction with other agents could be used to help patients tolerate RBC transfusions during hyperhemolysis.
