Evidence Unclear About Superiority of Exchange Transfusion Types in Sickle Cell Disease

A systematic review and meta-analysis found no clear advantage for automated red cell exchange.

For patients with sickle cell disease (SCD), exchange transfusion has benefits over simple transfusion (ST), but a new meta-analysis and systematic review suggests there is insufficient evidence to say which type of exchange transfusion is superior.

The report was published in Vox Sanguinis.

According to the authors, there are 3 main therapies for SCD: blood transfusion, hydroxyurea, and bone marrow transplantation (BMT). Of the 3, only BMT is considered a potential cure, although many patients do not qualify for the procedure, which can come with significant complications. Hydroxyurea can improve vaso-occlusive crisis and acute chest syndrome, but transfusion therapy appears to be able to also reduce the risk of stroke and other complications.

The question facing physicians and patients, however, is which type of transfusion to choose: ST, automated red cell exchange (aRBX), or manual red cell exchange transfusion (MET).

The study authors said aRBX and MET, both types of exchange transfusion, are generally preferable to ST, since exchange transfusion “maintains the hemoglobin S [HbS] level within target ranges or even rapidly decreases the level of HbS, prevents iron overload and volume overload, and minimizes the rise in blood viscosity.”

MET, in which whole blood is phlebotomized right before transfusion, can reduce the net iron load. It is typically indicated for patients with a lack of high-flow venous access, patients with a low body weight, or patients in low-resource areas. aRBX is faster and can further reduce iron load, they said, but it requires apheresis equipment, good venous access, and anticoagulation.

The authors said it is important to understand the comparative safety and efficacy of aRBX compared with MET, but they said the existing evidence is limited and sometimes contradictory. They therefore decided to conduct a systematic review and meta-analysis to see whether a wider lens would yield clarity.

They searched for published literature that evaluated the effect of red cell exchange in decreasing HbS percentage. After exclusions, they found 9 studies that met the inclusion criteria: 8 were prospective or retrospective observational studies and the ninth was a randomized controlled trial.

When the authors pooled the results, however, they found they were inconclusive. Although most studies showed aRBX led to a greater reduction in HbS vs MET, the overall difference was not statistically significant. In terms of serum ferritin levels, aRBX appeared to outperform MET.

“However, there was significant heterogeneity among the studies as revealed in the meta-analysis,” they wrote.

In terms of adverse events, the investigators said there was no statistically significant added risk for aRBX.

The authors said they believe this is the first meta-analysis that compared safety and efficacy between the 2 procedures, but they said their analysis shows more work is needed.

“[M]ore high-quality evidence from large randomized controlled trials designed and powered is desirable to reach any conclusion on the efficacy of aRBX over MET as well as on the safety profile of aRBX in both children and adult patients with SCD,” they wrote.

In the meantime, they said, there is no clear advantage for aRBX.

“This meta-analysis did not reveal any significant benefit of aRBX in reducing HbS percentage and attenuating the serum ferritin level when compared with MET,” they wrote.

Reference

Mukherjee S, Sahu A, Ray GK, Maiti R, Prakash S. Comparative evaluation of efficacy and safety of automated versus manual red cell exchange in sickle cell disease: a systematic review and meta-analysis. Vox Sang. Published online May 30, 2022. doi:10.1111/vox.13288