Erythrocyte Membrane Lipid Remodeling in High-Altitude Polycythemia and After Therapeutic Erythrocytapheresis.

High-altitude polycythemia (HAPC) remains prevalent among Tibetans despite genetic adaptations, including EPAS1/HIF2A. Excessive erythrocytosis elevates blood viscosity and increases cardiopulmonary risk, yet erythrocyte metabolic and membrane-lipid mechanisms of HAPC and of therapeutic erythrocytapheresis (TE) remain incompletely defined. We conducted integrated metabolomic and lipidomic profiling of washed erythrocytes from HAPC patients and non-HAPC (NHAPC), and from HAPC patients after TE. Relative to NHAPC, HAPC showed coordinated erythrocyte remodeling spanning amino acid and purine metabolism together with membrane phospholipid and lipid structure (unsaturation and chain length) changes. The disease contrast was multiomic, whereas the acute post-TE contrast was lipid dominant, consistent with apheresis acting primarily through erythrocyte removal. K-means stratification revealed clinically meaningful TE response heterogeneity, but erythrocyte omics did not define stable responder subtypes. These findings point to erythrocyte membrane lipids as a persistent molecular feature of HAPC and of the acute TE response.