Salvage of refractory post-transfusion hyperhaemolysis by targeting hyperinflammation and macrophage activation with tocilizumab.

Abstract

To the Editor 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. It is mostly, but not exclusively, seen in sickle cell patients, often after multiple previous transfusions. In patients with previous history of hyperhaemolysis, further transfusions should be avoided, but if essential, transfusion should be administered with prophylactic intravenous immunoglobulins (IVIG) and steroids, antigen-negative red cells if there are known alloantibodies, matching the patient's full extended phenotype if feasible. However, as this case demonstrates, prophylaxis with standard first line therapy and compatible phenotyped blood may not be sufficient to prevent further episodes of HHS. HHS is characterised by the destruction of transfused and autologous red cells resulting in a fall in haemoglobin (Hb) to below pretransfusion levels, and by reticulocytopenia. Typically, in the acute type of HHS, no new alloantibodies are detected, other than preexisting antibodies, and in half the cases the DAT remains negative. The pathogenesis of HHS remains unclear, but is associated with systemic symptoms of inflammation and extreme hyperferritinaemia that are indicative of macrophage activation. Histopathological studies in patients with HHS have demonstrated the presence of widespread macrophage erythrophagocytosis in the liver, spleen and bone marrow, suggesting that macrophage activation and direct erythrophagocytosis is an important mechanism of red blood cell destruction. Recently, two cases of HHS have been successfully treated with immunomodulating drug tocilizumab, a humanised monoclonal antibody against the interleukin-6 receptor that has been successfully used in other hyperinflammatory macrophage activation syndromes (MAS) including COVID19. We describe another case of HHS responding to tocilizumab after failed treatment with IVIG and steroids.