Can C1-inhibitor Improve Transfusion in Autoimmune Hemolytic Anemia?

Administration of C1 esterase inhibitor (C1-INH) during transfusions “temporarily reduced complement activation,” but did not significantly suppress hemolytic activity among patients with severe transfusion-dependent, complement-mediated autoimmune hemolytic anemia (CM-AIHA), according to a report in Blood Advances.

“Peritransfusional C1-INH temporarily reduced complement activation,” summarized the study’s lead author, Esther de Boer, MD, PhD, from Amsterdam Infection and Immunity Institute in the Netherlands. “However, C1-INH failed to halt hemolytic activity in severe transfusion-dependent-CM-AIHA.”

The prospective, single-center, phase II trial enrolled 10 patients with confirmed CM-AIHA who were indicated for transfusion of two units of red blood cells (RBCs). Participants received four doses of intravenous C1-INH at 12-hour intervals around transfusion. Blood samples were taken and evaluated for hemolytic activity, RBC opsonization, complement activation, and markers of inflammation.

Transfusions Not Significantly Improved with C1-inhibitor

Reportedly, patients showed increased plasma C1-INH antigen and activity that peaked at 48 hours after administration, as well as a significant reduction of C3d deposition on RBCs. Hemoglobin levels briefly increased after transfusion but returned to baseline within 48 hours. Five grade 3 and one grade 4 adverse events occurred that were judged unrelated to the peritransfusional C1-INH.

The authors judged that markers of hemolysis, complement activation, and inflammation did not change overall, though they added that they could not exclude that post-transfusional hemolytic activity would have been higher without C1-INH administration.

“In conclusion, these data do not support the clinical use of C1-INH in the tested dose in patients with severe CM-AIHA but add to the increasing experience with proximal complement inhibitors in this patient population,” Dr. de Boer and colleagues concluded.

Reference

de Boer ECW, Jalink M, Delvasto-Nuñez L, et al. C1-inhibitor treatment in patients with severe complement-mediated autoimmune hemolytic anemia. Blood Adv. 2023;7(13):3128-3139. doi:10.1182/bloodadvances.2022009402