Lauren E Lee1, Bradley W Beeler1, Brendan C Graham2, Andrew P Cap1, Nay Win3, Frederick Chen4. 1. Department of Medicine, Division of Hematology/Oncology, San Antonio Military Medical, San Antonio, Texas. 2. Department of Pathology, Transfusion Service, San Antonio Military Medical, San Antonio, Texas. 3. Department of Hematology, Red Cell Immunohematology, NHS Blood and Transplant, London, UK. 4. Department of Hematology, Royal London Hospital, Barts Health NHS Trust, London, UK.
Abstract
BACKGROUND: Hyperhemolysis syndrome (HHS) is a posttransfusion complication most frequently seen in sickle cell disease (SCD), characterized by rapid destruction of transfused and autologous red blood cells (RBCs), resulting in reticulocytopenia and a decrease in hemoglobin to below pretransfusion levels. Additional RBC transfusion can be life threatening. Most patients improve with intravenous immune globulin and steroids, but in refractory cases, hyperhemolysis may result in multiorgan failure and death in the absence of salvage therapy. The exact pathophysiology of HHS remains uncertain, yet new insights suggest that RBC destruction is driven by activated macrophages. Therefore, we propose that antimacrophage therapy may represent an effective treatment. CASE REPORT: A case of life-threatening HHS, refractory to intravenous immune globulin and steroids, in a patient with SCD is presented. Marked elevation in ferritin, an indirect marker of macrophage activation, a negative direct antiglobulin test, and the absence of RBC alloantibodies was noted. A hemoglobin nadir of 2.1 g/dL and resultant hypoxemia-induced organ failure prompted the use of tocilizumab, an interleukin-6 receptor monoclonal antibody. Hemoglobin-based oxygen carrier-201, a cell-free polymerized bovine hemoglobin, was used to support the patient during critical anemia. RESULTS: Hemolysis resolved and ferritin dramatically decreased after administration of tocilizumab, which was well tolerated. A full recovery was achieved. CONCLUSION: This case highlights both a novel and successful approach to managing refractory transfusion-induced hyperhemolysis with tocilizumab and provides further evidence supporting the role for macrophage activation in the destruction of RBCs in antibody-negative HHS. We propose that tocilizumab is an effective and rapid salvage therapy for refractory HHS.
BACKGROUND:Hyperhemolysis syndrome (HHS) is a posttransfusion complication most frequently seen in sickle cell disease (SCD), characterized by rapid destruction of transfused and autologous red blood cells (RBCs), resulting in reticulocytopenia and a decrease in hemoglobin to below pretransfusion levels. Additional RBC transfusion can be life threatening. Most patients improve with intravenous immune globulin and steroids, but in refractory cases, hyperhemolysis may result in multiorgan failure and death in the absence of salvage therapy. The exact pathophysiology of HHS remains uncertain, yet new insights suggest that RBC destruction is driven by activated macrophages. Therefore, we propose that antimacrophage therapy may represent an effective treatment. CASE REPORT: A case of life-threatening HHS, refractory to intravenous immune globulin and steroids, in a patient with SCD is presented. Marked elevation in ferritin, an indirect marker of macrophage activation, a negative direct antiglobulin test, and the absence of RBC alloantibodies was noted. A hemoglobin nadir of 2.1 g/dL and resultant hypoxemia-induced organ failure prompted the use of tocilizumab, an interleukin-6 receptor monoclonal antibody. Hemoglobin-based oxygen carrier-201, a cell-free polymerized bovine hemoglobin, was used to support the patient during critical anemia. RESULTS:Hemolysis resolved and ferritin dramatically decreased after administration of tocilizumab, which was well tolerated. A full recovery was achieved. CONCLUSION: This case highlights both a novel and successful approach to managing refractory transfusion-induced hyperhemolysis with tocilizumab and provides further evidence supporting the role for macrophage activation in the destruction of RBCs in antibody-negative HHS. We propose that tocilizumab is an effective and rapid salvage therapy for refractory HHS.