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Salvage of refractory post-transfusion hyperhaemolysis by targeting hyperinflammation and macrophage activation with tocilizumab He was not on a regular transfusion programme and had not received further transfusion since the last operation in 2018. Treatment of post-transfusion hyperhaemolysis syndrome in sickle cell disease with the anti-IL6R humanised monoclonal antibody tocilizumab. Hyperhaemolysis syndrome (HHS) is a severe post-transfusion complication that can develop rapidly and cause life-threatening anaemia and death unless recognised and treated promptly.1,2 It is mostly, but not exclusively, seen in sickle cell patients, often after multiple previous transfusions. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary: Post‐transfusion hyperhaemolysis syndrome (PTHS) is a rare life‐threatening transfusion complication reported mainly in sickle cell patients. Its pathogenesis is poorly understood. Antibody‐mediated haemolysis and bystander effect have been proposed as putative mechanisms, but in half of cases, red cell antibodies are undetectable, and PTHS develops despite transfusion of cross‐matched compatible RBC. An alternate hypothesis proposes activated macrophages as the main drivers of red cell destruction through direct phagocytosis. We report the histopathological findings of two patients with PTHS showing extensive macrophage expansion and erythrophagocytosis, supportive of macrophage activation driving PTHS. This supports a possible role for novel therapies that target macrophage activation. [ABSTRACT FROM AUTHOR]

The article focuses on guidelines regarding red cell transfusion among patients associated with sickle cell diseases (SCD). Topics discussed include consideration of haemoglobin (Hb) concentration among SCD patients; avoidance of hyperviscosity with post-transfusion Hb through analysis of Hb baseline; observation of alloimmunisation rate among SCD patients regarding transfusion; and description of life-threatening conditions among Hyperhaemolysis patient over delayed transfusion.

The article focuses on guidelines regarding red cell transfusion among patients associated with sickle cell diseases (SCD). Topics include consideration of transcranial doppler ultrasonography (TCD) as treatment method for stroke treatment among children; consideration of Preoperative transfusion among SCD patient undergoing medium-risk surgery; illustration of several emergency cases of transfusion such as aplastic anaemia; and suggestion of hydroxycarbamide treatment for acute chest syndrome.

Treatment of post-transfusion hyperhaemolysis syndrome in Sickle Cell Disease with the anti-IL6R humanised monoclonal antibody Tocilizumab It is characterised by brisk haemolysis of both transfused and recipient red cells, also known as "By-stander" haemolysis, with a haemoglobin (Hb) drop below pre-transfusion levels, marked increase in serum ferritin (SF) and a fall in reticulocyte count. 1 Hb, haemoglobin, LDH, lactate dehydrogenase; PTHS, post-transfusion hyperhaemolysis syndrome; RTC, reticulocytes; SF, serum ferritin. [Extracted from the article]

A letter to the editor is presented in response to the article "Immunoglobulin-resistant delayed hemolytic transfusion reaction treated with rituximab in an adult sickle cell patient" by Delmonte L. and collegues in the previous issue.