Hemolytic anemia blunts the cytokine response to transfusion of older red blood cells in mice and dogs.

Abstract

BACKGROUND\nTransfusion of red blood cells (RBCs) stored for longer durations induces hemolysis and inflammatory cytokine production in murine and canine models. Despite immune system activation by stored RBCs, human randomized trials suggest that fresher RBC transfusions do not improve clinical outcomes. We hypothesized that underlying recipient hemolysis may affect cytokine responses to older RBC transfusions.\n\n\nSTUDY DESIGN AND METHODS\nC57BL/6 mouse cohorts were infused with anti-TER119 antibody to induce hemolysis, rabbit anti-platelet antiserum to induce immune thrombocytopenia (ITP), or appropriate control antibodies. Two days later, mice were transfused with fresh or stored RBCs. Furthermore, in a prospective, randomized, blinded trial, 38 client-owned dogs with primary autoimmune hemolytic anemia (AIHA) and two dogs with ITP, requiring RBC transfusion, were enrolled and randomized to receive fresh (≤7\u2009days) or old (≥21\u2009days) stored RBC transfusions. Monocyte chemoattractant protein (MCP)-1 levels were assessed at defined times after transfusion.\n\n\nRESULTS\nPrior immune-mediated hemolysis blunted the MCP-1 response to stored RBC transfusion in mice (361\u2009±\u2009111\u2009pg/ml vs. 6836\u2009±\u20091528\u2009pg/ml in mice with immune hemolysis vs. ITP, respectively; mean\u2009±\u2009SD; p\xa0<\u2009.0001). Although hemolysis markers increased after transfusion of older RBCs, the cytokine response was also muted in dogs with AIHA. No differences in morbidity or mortality were evident comparing dogs randomized to fresh or old RBCs.\n\n\nCONCLUSION\nThese data suggest that underlying hemolysis blunts inflammatory responses to old RBC transfusions. The canine data support randomized trial results suggesting a lack of clinical benefit with fresh RBC transfusions in subjects with underlying, baseline hemolysis.