Modified Red Blood Cells May Be Better to Resolve Anemia in AIHA

Joana Carvalho, PhD avatar

by Joana Carvalho, PhD |

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Modified red blood cell products may be better at counteracting anemia than red blood cell suspensions normally used in conventional blood transfusions, while posing fewer side effects to patients with autoimmune hemolytic anemia (AIHA), a review study has found.

Yet, investigators noted that additional studies will be needed to confirm these findings, and establish the safety and effectiveness of these methods separately in patients with different forms of AIHA.

The review study, “Transfusion of modified blood components for the treatment of autoimmune hemolytic anemia: a network meta-analysis,” was published in the journal Future Medicine.

AIHA is an autoimmune disease characterized by the production of self-reactive antibodies that attack and destroy red blood cells. It includes mainly two variants, cold agglutinin disease (CAD) and warm AIHA (wAIHA), depending on the temperature at which harmful autoantibodies bind to red blood cells.

In these patients, red blood cell transfusions are one of the most effective treatments to resolve the effects of red blood cell destruction and anemia.

However, the presence of autoantibodies in the bloodstream may cause complications during blood transfusions and render them less effective, since they may bind and reduce the viability of transfused red blood cells.

The use of modified red blood cell products, including washed red blood cells (WRBCs) and leukoreduced red blood cells (LRBCs), potentially may help mitigate some of the side effects and complications of traditional red blood cell transfusions in AIHA patients.

WRBCs and LRBCs are “purified” red blood cells that were subjected to specific treatments to remove certain contaminants — plasma components in the case of WRBCs, and white blood cells in LRBCs — that may increase the risk of allergic reactions and other complications during blood transfusions.

“However, there are presently no evidence-based guidelines on the use of modified blood components in AIHA patients due to the rarity of AIHA,” the researchers wrote.

Here, investigators in Canada conducted a systematic review to determine if the use of these modified red blood cell products could be more beneficial than standard suspended red blood cells (SRBCs) at treating AIHA.

After performing a thorough literature search in nine online databases, investigators identified a total of 2,855 potentially relevant studies to be included in the systematic review. After removing duplicates and excluding studies that did not meet certain inclusion criteria, they selected 16 to  include  in the final analyses.

All studies were randomized controlled trials, and involved a total of 1,061 patients; they were published from 2014 to 2019.

All trials included a treatment group in which patients received WRBCs, and compared it with patients receiving either LRBCs (14 studies) or SRBCs (three studies).

Analyses showed that treatment response rates were similar for all red blood cell products. However, when red blood cells were both washed and leukoreduced, patients had a 10% increase in treatment response rates, and greater improvements in blood parameters, compared with SRBCs.

Analyses also demonstrated that, while LRBCs led to increases in red blood cell counts and decreases in total bilirubin levels, their effectiveness at increasing hemoglobin counts or reducing the percentage of reticulocytes was similar or worse than that of SRBCs. Hemoglobin is the protein in red blood cells that carries oxygen. Bilirubin is a marker of red blood cell destruction. Reticulocytes are immature red blood cells.

Still, both WRBCs and LRBCs were associated with a lower incidence of side effects, compared with SRBCs. According to the analyses, WRBCs and LRBCs might lower the incidence of treatment side effects by 56% and 28%,  respectively, compared with SRBCs.

“The use of modified blood components may achieve increased response incidence and/or [blood parameters], as well as decreased AEs [adverse events] compared with transfusion of unmodified, SRBCs,” the researchers wrote.

“Better conducted RCTs [randomized controlled trials] with cold/warm AIHA subgroups are needed to validate our findings and to establish the efficacy of modified blood components for treating warm and cold AIHA separately,” they wrote.