Tocilizumab in the management of posttransfusion hyperhemolysis syndrome in sickle cell disease: The experience so far

Abstract

Background Posttransfusion hyperhemolysis syndrome is a rare but life‐threatening form of delayed hemolytic transfusion reaction with lysis of both transfused and autologous red cells, seen predominantly in patients with sickle cell disease. Macrophage activation is thought to play a major role in its pathophysiology. Standard treatment is with intravenous immunoglobulin and steroids but refractory cases pose a major clinical problem. Tocilizumab is a humanized monoclonal antibody against the IL‐6 receptor that can inhibit IL‐6 induced macrophage activation. Methods and materials We describe the case of a 33‐year‐old woman with sickle cell anemia and posttransfusion hyper hemolysis syndrome refractory to standard therapy, treated with Tocilizumab. We also review all cases reported in the literature where Tocilizumab was used for posttransfusion hyperhemolysis. Results Treatment with Tocilizumab was well tolerated with no observed adverse events. There was no further drop in Hb after day 2 of treatment with subsequent continuous gradual improvement. Her bilirubin dropped significantly after the first dose and continued to improve, while ferritin and LDH reduced significantly after day 2 of treatment with Tocilizumab and continued to drop thereafter. Like in our case, all other cases in the literature where Tocilizumab was used for posttransfusion hyperhemolysis led to rapid clinical responses and no adverse events. Discussion Even though the number of cases of posttransfusion hyper hemolysis syndrome treated with Tocilizumab are few, they have all been associated with rapid clinical responses with no observed adverse events suggesting that the role of Tocilizumab in this context needs to be further explored.

Acute Hyperhemolysis Syndrome in a Patient with Known Sickle Cell Anemia Refractory to Steroids and IVIG Treated with Tocilizumab and Erythropoietin: A Case Report and Review of Literature

“…Tocilizumab is currently approved for treating autoimmune conditions, such as rheumatoid arthritis, but has also been utilized in cases of COVID-19. There have been multiple case reports that have shown tocilizumab to be effective in treating HHS [ 22 , 23 , 24 ]. In each of the cases, including ours, there have been no reported complications to tocilizumab, with rapid clinical improvement.…”

Hyperhemolysis in a patient with sickle cell disease and recent SARS‐CoV‐2 infection, with complex auto‐ and alloantibody work‐up, successfully treated with tocilizumab

“…In our patient, tocilizumab was chosen given the proinflammatory milieu created by recent SARS‐CoV‐2 infection and concern for macrophage activation (as evidenced by peak serum ferritin of 4156 ng/ml). Clinical features of HHS such as hyperferritinemia are reminiscent of subtypes of MAS/CRS 6,11 . There have been several case reports that have shown success in treating HHS with tocilizumab 6,9,11 .…”

“…Clinical features of HHS such as hyperferritinemia are reminiscent of subtypes of MAS/CRS. 6 , 11 There have been several case reports that have shown success in treating HHS with tocilizumab. 6 , 9 , 11 Our patient showed dramatic clinical improvement after initiation of tocilizumab.…”

“…Immunosuppressive therapy should be initiated promptly in patients with life‐threatening hemolysis: glucocorticoids and intravenous immunoglobulin have been used with varying success at arresting hemolysis 7 . More recent case reports have reported good treatment outcomes with monoclonal antibodies such as rituximab, eculizumab, and tocilizumab 6,8–11 . Rituximab targets CD20 and causes B‐cell apoptosis, eculizumab blocks the C5 convertase and reduces classical and alternative complement activation of the membrane attack complex, and tocilizumab blocks the interleukin‐6 (IL‐6) receptor and prevents macrophage response to that pro‐inflammatory cytokine.…”

“… 7 More recent case reports have reported good treatment outcomes with monoclonal antibodies such as rituximab, eculizumab, and tocilizumab. 6 , 8 , 9 , 10 , 11 Rituximab targets CD20 and causes B‐cell apoptosis, eculizumab blocks the C5 convertase and reduces classical and alternative complement activation of the membrane attack complex, and tocilizumab blocks the interleukin‐6 (IL‐6) receptor and prevents macrophage response to that pro‐inflammatory cytokine. Tocilizumab has been used to treat various autoimmune conditions including macrophage activation syndrome (MAS), 12 cytokine release syndrome (CRS), and most recently, patients with severe COVID‐19 pneumonia.…”