Granulomonocytapheresis for Sepsis: Mechanistic Rationale, Therapeutic Potential, and Potential Concerns in Thromboinflammatory Critical Illness

Abstract

Granulomonocytapheresis (GMA) is an extracorporeal leukocyte adsorption therapy that selectively removes activated granulocytes and monocytes through interactions involving Fcγ receptors (FcγR) and complement receptor 3 (CR3). Initially developed for chronic inflammatory diseases such as ulcerative colitis, GMA has recently attracted attention as a potential adjunctive therapy for sepsis. Contemporary understanding of sepsis emphasizes thromboinflammation, immunothrombosis, endothelial injury, and inflammatory cell death as central mechanisms underlying organ dysfunction. Activated FcγR-positive and CR3-positive myeloid cells contribute to cytokine storm, neutrophil extracellular trap (NET) formation, oxidative injury, coagulation activation, and release of damage-associated molecular patterns (DAMPs). These processes amplify endothelial dysfunction, microvascular thrombosis, and disseminated intravascular coagulation. GMA may interrupt these self-amplifying inflammatory and thromboinflammatory loops by selectively depleting activated inflammatory leukocytes while relatively preserving adaptive immunity. Mechanistically, removal of FcγR-positive cells may suppress inflammasome activation, pyroptosis, and DAMP-mediated cytokine amplification, whereas removal of CR3-positive cells may attenuate NETosis, oxidative burst, endothelial adhesion, and microvascular injury. Although preliminary clinical and experimental studies suggest potential benefits in sepsis, important concerns remain regarding patient selection, optimal timing, infection risk, thrombocytopenia, and cost-effectiveness. Further phenotype-oriented clinical trials are required to define the therapeutic role of GMA in sepsis and thromboinflammatory critical illness.