Eculizumab use may safely manage transfusion complication in SCD
Treatment effective for 2 pediatric patients with hyperhemolysis syndrome
The use of eculizumab, an immunosuppressive medication approved for several autoimmune diseases, was found to be safe and effective for treating hyperhemolysis syndrome or HHS — a serious complication of blood transfusions — in two pediatric patients with sickle cell disease (SCD), a study showed.
HHS, which can be life-threatening, is characterized by the destruction of both transfused and the patient’s own red blood cells.
In these two U.S. cases, involving patients ages 9 and 18, a single dose of eculizumab managed the complication by stabilizing levels of hemoglobin, the protein that carries oxygen in red blood cells, according to researchers.
Eculizumab “has been proposed as second-line management of HHS,” the team wrote, adding that “in our experience, eculizumab is a safe and effective option for” pediatric HHS patients who don’t respond to standard treatments.
The study, “Eculizumab for management of hyperhemolysis syndrome in pediatric patients with sickle cell disease: A single-center case series,” was published in the journal Pediatric Blood & Cancer.
HHS called ‘direst complication’ of blood transfusions
SCD is caused by mutations in the HBB gene that lead to the production of hemoglobin S, a faulty version of hemoglobin. This hemoglobin version causes healthy oval-shaped red blood cells to acquire a sickle-like shape.
Sickled red blood cells usually die more quickly than normally shaped cells, often leading to a shortage of red blood cells, or anemia. They also have difficulty passing through small blood vessels, slowing or blocking blood flow, which may reduce oxygen delivery to tissues and result in vaso-occlusive crises, or episodes of severe pain.
While blood transfusions “are crucial for management of acute SCD complications,” the researchers wrote, they “are not without risk,” and the “direst complication is hyperhemolysis syndrome (HHS) for which mortality is 12%.”
Hallmarks of HHS are hemoglobin levels lower than before the transfusion and lower than normal counts of red blood cell precursors.
The recommended first-line treatment for HHS in SCD patients is intravenous immunoglobulin, or IVIG. It is meant to neutralize potentially harmful antibodies and high-dose steroids, often given as an anti-inflammatory and immunosuppressive treatment.
Eculizumab is an antibody-based therapy sold under the brand name Soliris for a number of autoimmune diseases, in which the immune system abnormally attacks healthy cells in the body.
Given that it works by suppressing the activation of the complement cascade, a part of the immune system that has been implicated in HHS, eculizumab has been suggested as a potential second-line therapy for HHS in people with SCD. However, there is limited evidence of its utility in pediatric patients who failed to respond to standard first-line treatment.
Use of eculizumab found safe for 2 patients, ages 9 and 18
Now, researchers at Texas Children’s Hospital, in Houston, described the cases of two pediatric SCD patients, meaning their ages are younger than 21, who were treated with eculizumab for HHS after they did not respond to first-line therapies.
The 9-year-old male and 18-year-old female patients both had asthma and SCD-SS, the most severe type of SCD. The disease was complicated by previous episodes of acute chest syndrome (ACS), a common SCD complication marked by lung injury.
Both were being treated with hydroxyurea, and the boy also was receiving Oxbryta (voxelotor).
The two patients were both admitted to the hospital due to an ACS episode, and received a blood transfusion to manage it. HHS developed in both five to six days after transfusion, first showing up via with lower hemoglobin levels than before the transfusion, as well as persisting or worsening pain, dark urine, and/or fatigue.
The boy and the young woman both tested negative for the presence of antibodies against the body’s own red blood cells. At HHS diagnosis, the young woman was found to have developed an alloantibody, a type of antibody developed after exposure to foreign red blood cells, as occurs in a blood transfusion.
Both patients showed progressive anemia — with the lowest hemoglobin levels reaching 2.4 to 2.5 g/dL — despite treatment with IVIG, steroids, and erythropoietin, which is a hormone that boosts red blood cell production.
Adjunctive treatments, or secondary therapies that are used in addition to a primary treatment, also were used. These involved folic acid supplements for both patients and vitamin B12 supplements for the boy; both are known to promote red blood cell production. The young woman also received rituximab, an antibody-based treatment that seeks to reduce the production of abnormal antibodies such as alloantibodies.
After a single dose of eculizumab, hemoglobin levels stabilized in both patients. Moreover, hemoglobin levels started recovering after one or two administrations.
Prior use of eculizumab for HHS [a serious blood transfusion complication] in the literature has been limited to adult patients. … We demonstrate that eculizumab is well-tolerated and safe, providing additional evidence to consider eculizumab in the setting of refractory [hard-to-treat] pediatric HHS.
Analyses of complement components revealed the boy had elevated levels of proteins consistent with overactivation of the terminal part of the complement cascade. The teenager showed low levels of CH50, a measure of total complement activity, after her first eculizumab dose, consistent with complement suppression.
Both patients completed recommended vaccination before the use of eculizumab, which is associated with a high risk of meningococcal infections, or those caused by the Neisseria meningitidis bacterium and that can affect the brain and bloodstream. Neither developed infections as a complication of eculizumab.
“Prior use of eculizumab for HHS in the literature has been limited to adult patients,” the researchers wrote. “We demonstrate that eculizumab is well-tolerated and safe, providing additional evidence to consider eculizumab in the setting of refractory [hard-to-treat] pediatric HHS.”
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