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

Abstract

Background: Hyperhemolysis syndrome (HHS) is a severe delayed hemolytic transfusion reaction seen in sickle cell disease (SCD) patients, characterized by destruction of donor and recipient RBCs. It results in a drop in hemoglobin to below pretransfusion levels and frequently reticulocytopenia. Case Report: We report a case of a man in his thirties with SCD with a recent hospitalization 2 weeks prior for COVID-19. His red cell antibody history included anti-Fy(a) and warm autoantibody. At that time, he was given 2 units of RBC and discharged with a hemoglobin of 10.2 g/dl.He returned to the hospital approximately 1.5 weeks later with hemoglobin 6.0 g/dl and symptoms concerning for acute chest syndrome. Pretransfusion testing now showed 4+ pan-agglutinin in both gel-based and tube-based testing. Alloadsorption identified an anti-N and a strong cold agglutinin. Three least incompatible units were transfused to this patient over several days, with evidence of hemolysis. Further reference lab work revealed anti-Fy a , anti-Fy b , anti-Le a , anti-Le b , and an anti-KN system antibody. The patient's hemoglobin nadired at 4.4 g/dl. The patient was treated with a single dose of tocilizumab, his hemoglobin stabilized, and he was discharged. Discussion: We present a case of HHS proximate to recent SARS-CoV-2 infection with multiple allo and autoantibodies identified. Information on the relationship between SARS-CoV-2 infection and HHS is limited; however, it is possible that inflammation related to COVID-19 could predispose to HHS.Tocilizumab is an approved treatment for COVID-19. Additionally, tocilizumab appears to be a promising treatment option for patients with HHS.

Impact of the SARS-CoV-2 infection in individuals with sickle cell disease: an integrative review

“…In contrast, Alkindi et al ( 31 ) show that the impact of COVID-19 on the morbidity and mortality of vaso-occlusive crises among individuals with sickle cell anemia was not significant. The occurrence of other sickle cell complications in the context of COVID-19, such as osteonecrosis, acute hemolytic crisis, post-transfusion hyperhemolysis syndrome, and splenic sequestration, has also been reported, although in a minor incidence ( 31 , 65 , 89 , 97 ).…”

“…The administration of tocilizumab, an anti-human IL-6 receptor monoclonal antibody that inhibits signal transduction by binding to sIL-6R and mIL-6R, has been described in some case reports of sickle cell individuals infected by the SARS-CoV-2, demonstrating successful results ( 74 , 77 , 79 , 97 ). This resource, which has even been made available to the general population in some places, should be considered for patients at higher risk of developing a hyperinflammatory syndrome or sickle cell complications, for example ( 74 , 120 ).…”

An Unusual Case of Hyperhemolysis Syndrome and Delayed Hemolytic Transfusion Reaction due to Anti-Jk(a) and Anti-P1 Antibodies

“…Several potential causative mechanisms were discussed previously, including macrophage hemophagocytosis and "bystander hemolysis." In support of the activated macrophage hypothesis, recent case reports have indicated that treatment with tocilizumab can result in resolution of hemolysis in refractory or difcult cases [9][10][11]. Tocilizumab is a humanized monoclonal antibody directed against the interleukin-6 receptor (IL-6R) [12].…”

“Don’t Add Fuel to the Fire”– Hyperhemolysis Syndrome in a Pregnant Woman with Compound Sickle Cell Disease/β⁰-Thalassemia: Case Report and Review of the Literature

“…However, there are no prospective studies that confirm the effectiveness and lack of response has also been reported [60]. Furthermore, there are increasing reports of successful treatment with anti-IL-6 receptor monoclonal antibodies such as tocilizumab, particularly in patients with SCD, as they have higher levels of circulating cytokines such as IL-1, TNF-α, and IL-6 [50,61]. Although there are promising case reports, further study is needed to verify the efficacy [51,52].…”