Department of Medicine, Division of Hematology/Oncology, San Antonio Military Medical, San Antonio, Texas.
Department of Pathology, Transfusion Service, San Antonio Military Medical, San Antonio, Texas.
Transfusion. 2020 Jan;60(1):30-35. doi: 10.1111/trf.15562. Epub 2019 Oct 23.
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.
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.
Hemolysis resolved and ferritin dramatically decreased after administration of tocilizumab, which was well tolerated. A full recovery was achieved.
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.
溶血性输血反应综合征（HHS）是一种输血后并发症，在镰状细胞病（SCD）中最为常见，其特征为输注和自身的红细胞（RBC）迅速破坏，导致网织红细胞减少和血红蛋白降至输血前水平以下。此外，输血可能危及生命。大多数患者接受静脉注射免疫球蛋白和类固醇治疗后会有所改善，但在难治性病例中，HHS 可能导致多器官衰竭和死亡，除非进行挽救性治疗。HHS 的确切病理生理学仍不确定，但新的见解表明 RBC 破坏是由激活的巨噬细胞驱动的。因此，我们提出抗巨噬细胞治疗可能是一种有效的治疗方法。
本文报道了一例镰状细胞病患者发生危及生命的难治性 HHS 病例。该患者铁蛋白显著升高，这是巨噬细胞激活的间接标志物，直接抗球蛋白试验阴性，且无 RBC 同种抗体。血红蛋白降至 2.1g/dL，低氧血症导致器官衰竭，促使使用白细胞介素 6 受体单克隆抗体托珠单抗。血红蛋白载氧体-201 是一种无细胞聚合牛血红蛋白，用于在严重贫血期间支持患者。
托珠单抗治疗后溶血得到缓解，铁蛋白显著下降，且耐受性良好。患者完全康复。
该病例突出了使用托珠单抗治疗难治性输血诱导性溶血性输血反应的新方法和成功经验，并提供了进一步的证据支持巨噬细胞激活在抗体阴性 HHS 中破坏 RBC 的作用。我们提出托珠单抗是治疗难治性 HHS 的有效且快速的挽救性治疗方法。
