Tocilizumab proves effective against sickle cell-related hyperhemolysis
Case analysis urges therapy be considered as a cost-effective alternative
Using tocilizumab off-label in four young adults with sickle cell disease (SCD) who developed hyperhemolysis syndrome as a complication of a blood transfusion stopped the premature destruction of red blood cells, suggesting it may be safe and effective when other options fail.
While tocilizumab is not approved for SCD or hyperhemolysis syndrome, “it is generally widely available and should be considered a suitable and cost-effective alternative to currently available options,” the researchers wrote.
The four cases appear in “Tocilizumab provides a potential therapeutic option for the management of hyperhaemolysis syndrome in sickle cell disease: A case series and brief narrative overview of the literature,” published in Transfusion Medicine.
Defining the hyperhemolysis complication
Hyperhemolysis syndrome is a rare but serious complication that can follow a blood transfusion. Both the patient’s own and transfused red blood cells are rapidly destroyed, leading to severe anemia. It most often affects people with SCD, whose red blood cells are abnormally shaped.
The exact cause of hyperhemolysis syndrome is unclear. It may involve antibodies triggering a part of the immune system called the complement pathway or the activation of macrophages — immune cells that can destroy red blood cells. Treating hyperhemolysis syndrome is challenging because first-line therapies, like intravenous immunoglobulin (IVIG) and corticosteroids or other medications, do not always work.
Tocilizumab — marketed as Actemra and other brand names for certain types of arthritis and other diseases — works by blocking the receptor for interleukin-6 (IL-6), a molecule that drives inflammation. Because IL-6 activates macrophages, blocking its signaling with tocilizumab may be of therapeutic value for hyperhemolysis syndrome.
Previous reports suggest it can be effective and result in shorter hospital stays compared with eculizumab, a complement inhibitor that has been used off-label to treat hyperhemolysis syndrome in SCD, but evidence remains limited to a few cases.
Here, researchers reviewed the cases of two men and two women who returned to the hospital four to 19 days after receiving a blood transfusion with severe pain, dark urine, and/or fever. Three tested positive for alloantibodies, which often form in response to a blood transfusion, leading to transfusion reactions.
All four received IVIG and corticosteroids as first-line treatment for hyperhemolysis syndrome, followed by tocilizumab at a dose of 8 mg/kg. One person (a 34-year-old man) received a second course of tocilizumab. In all four, tocilizumab was effective in rapidly stopping hemolysis.
The two men subsequently received blood transfusions without any signs or symptoms of hemolysis. However, both died due to problems unrelated to hyperhemolysis syndrome. The two women required no further blood transfusions and remained alive after a stay of 11 and 43 days in the hospital, respectively.
“We suggest that the use of tocilizumab could be considered as an alternative to eculizumab in uncomplicated [hyperhemolysis syndrome] in sickle cell disease, where there is evidence of an inflammatory response, indicated by fever or macrophage activation,” the researchers wrote.
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