C1-inhibitor treatment in patients with severe complement-mediated autoimmune hemolytic anemia

•Human plasma–derived C1-INH temporarily reduced complement deposition on RBCs but not systemic complement activation.•C1-INH did not halt hemolytic activity in patients with severe CM-AIHA. [Display omitted] Complement-mediated (CM) autoimmune hemolytic anemia (AIHA) is characterized by the destruc...

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Published in:Blood advances 2023-07, Vol.7 (13), p.3128-3139
Main Authors: de Boer, Esther C. W., Jalink, Marit, Delvasto-Nuñez, Laura, Meulenbroek, Elisabeth M., Baas, Inge, Janssen, Susanne R., Folman, Claudia C., Gelderman, Kyra A., Wouters, Diana, Engel, Marije D., de Haas, Masja, Kersten, Marie José, Jongerius, Ilse, Zeerleder, Sacha, Vos, Josephine M. I.
Format: Article
Language:English
Subjects:
Anemia, Hemolytic, Autoimmune - therapy
Autoantibodies
Clinical Trials and Observations
Complement System Proteins
Hemolysis
Humans
Inflammation
Prospective Studies
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Summary:•Human plasma–derived C1-INH temporarily reduced complement deposition on RBCs but not systemic complement activation.•C1-INH did not halt hemolytic activity in patients with severe CM-AIHA. [Display omitted] Complement-mediated (CM) autoimmune hemolytic anemia (AIHA) is characterized by the destruction of red blood cells (RBCs) by autoantibodies that activate the classical complement pathway. These antibodies also reduce transfusion efficacy via the lysis of donor RBCs. Because C1-inhibitor (C1-INH) is an endogenous regulator of the classical complement pathway, we hypothesized that peritransfusional C1-INH in patients with severe CM-AIHA reduces complement activation and hemolysis, and thus enhances RBC transfusion efficacy. We conducted a prospective, single-center, phase 2, open-label trial (EudraCT2012-003710-13). Patients with confirmed CM-AIHA and indication for the transfusion of 2 RBC units were eligible for inclusion. Four IV C1-INH doses (6000, 3000, 2000, and 1000 U) were administered with 12-hour intervals around RBC transfusion. Serial blood samples were analyzed for hemolytic activity, RBC opsonization, complement activation, and inflammation markers. Ten patients were included in the study. C1-INH administration increased plasma C1-INH antigen and activity, peaking at 48 hours after the first dose and accompanied by a significant reduction of RBC C3d deposition. Hemoglobin levels increased briefly after transfusion but returned to baseline within 48 hours. Overall, markers of hemolysis, inflammation, and complement activation remained unchanged. Five grade 3 and 1 grade 4 adverse event occurred but were considered unrelated to the study medication. In conclusion, peritransfusional C1-INH temporarily reduced complement activation. However, C1-INH failed to halt hemolytic activity in severe transfusion-dependent–CM-AIHA. We cannot exclude that posttransfusional hemolytic activity would have been even higher without C1-INH. The potential of complement inhibition on transfusion efficacy in severe CM-AIHA remains to be determined.
ISSN:2473-9529
2473-9537
DOI:10.1182/bloodadvances.2022009402