ABO Blood Group as a Boundary-Condition Modifier in Sepsis and Sepsis-Associated HLH: A Sympathetic Harmonic Resonance Framework Interpretation

Abstract Sepsis and sepsis-associated hemophagocytic lymphohistiocytosis (HLH/MAS) exhibit overlapping clinical and biological features that challenge binary diagnostic frameworks and contribute to delayed recognition of immune termination failure. Within the Sympathetic Harmonic Resonance Framework (SHRF), these conditions are modeled as distinct attractor states within a coupled immune, vascular, and bioenergetic system, differentiated by effective feedback gain and termination capacity rather than pathogen burden alone. This study proposes that ABO blood group functions as a boundary-condition modifier within this system, subtly altering immune-vascular coupling strength and thereby influencing disease trajectory without determining disease onset. Using retrospective analysis of intensive care unit cohorts with serial laboratory data, we emphasize trajectory-based metrics, including slopes and curvature of ferritin, coagulation markers, and lactate, over static thresholds. We hypothesize that non-O blood groups exhibit earlier and steeper signatures of vascular decoherence and immune amplification under comparable inflammatory load, biasing trajectories toward HLH-like runaway dynamics, while blood group O remains closer to recovery basins until termination failure dominates. The framework yields explicit, falsifiable predictions centered on time-dependent instability rather than categorical risk, offering a systems-level interpretation of heterogeneity in severe inflammatory syndromes and a testable path toward improved phenotyping of sepsis-HLH continua. sepsis; hemophagocytic lymphohistiocytosis; macrophage activation syndrome; immune dysregulation; ferritin; immunothrombosis; systems biology; trajectory analysis; critical care; Sympathetic Harmonic Resonance Framework