Patients with Sickle Cell Disease Benefit Most from Interventions That Reduce Hemolytic Anemia

Interventions that reduce hemolytic anemia in patients with sickle cell disease may be the best therapeutic target for the population, according to research presented at the 60th ASH Annual Meeting & Exposition in San Diego, California, this past weekend.

Patients with sickle cell disease often experience chronic hemolytic anemia in varying degrees of severity and it can reduce the capacity of oxygen delivered to the body. It can result in multiple types of complications, including fatigue and organ damage.

Investigators from the University of Tennessee Health Science Center (UTHSC) in Memphis, Tennessee, conducted a meta-analysis to review the current literature for hemoglobin modification outcomes in patients with sickle cell disease. The team searched Embase and Medline databases for relevant studies published between 1998 and 2017, as well as abstracts from the past 2 years of scientific conferences, and found 139 appropriate studies to include. Some of the complications the investigators were specifically examining were overt stroke, kidney disease, elevated estimated pulmonary artery systolic pressure, and death.

“If we are able to improve the [hemolytic] anemia that these patients have, then perhaps we will decrease the frequency at risk for sickle cell complications,” presenter Kenneth I. Ataga, MD, director at the UTHSC Center for Sickle Cell Disease said when explaining the investigation’s hypothesis to Rare Disease Report®.

The team separated the study findings into categories based on the outcomes related to hemoglobin. Lower hemoglobin levels were shown to have an association with several factors, the investigators learned, including lower hemoglobin levels and a history of stroke, silent cerebral infarct, or increased transcranial Doppler-measured cerebral artery velocity; the presence of microalbuminuria; and elevated estimated pulmonary artery systolic pressure.

Six studies in the meta-analysis representing 3196 patients examined sickle cell disease and the risk for mortality. Five of those studies showed that hemoglobin levels were lower in deceased compared with living patients.

“We found that patients who have these complications had lower hemoglobin levels compared with those patients [with sickle cell disease] who did not have those complications,” Dr. Ataga said. “That was interesting, and it confirms what we have thought before we embarked on this study.”

In the second part of their study, the investigators modeled the risk of reduction in each of these complications if the patients were treated with some kind of intervention to increase their hemoglobin levels. They learned that there was a decrease in decrease in risk for each of these complications—stroke, kidney disease, death—for every hemoglobin increase of 1 g/dL or greater.

According to the investigators, over the last 20 years, published research demonstrates a significant relationship between chronic anemia and worsening clinical outcomes in sickle cell disease patients.

“What we suggested was that perhaps in interventions in which patients have improvement in anemia, this may be beneficial for patients with sickle cell disease,” Dr. Ataga said, noting that so far, all of this is theoretical, and more research is needed to support these findings.

The abstract, “Low Hemoglobin Increases Risk for Stroke, Kidney Disease, Elevated Estimated Pulmonary Artery Systolic Pressure, and Premature Death in Sickle Cell Disease: A Systematic Literature Review and Meta-Analysis,” was published online.