OBJECTIVE:Enhanced red blood cell (RBC) aggregation has an adverse effect on microcirculatory blood flow and tissue oxygenation. It has been previously shown that obesity is associated with increased RBC aggregation. The objectives of the present study were to further characterize obesity-related RBC aggregation and to examine whether the enhanced aggregation is a plasma-or cellular-dependent process. METHODS: Obese (body mass index (BMI) ¼ 4076.3 kg/m 2 , n ¼ 22) and nonobese (BMI ¼ 2473.4 kg/m 2 , n ¼ 18) individuals were evaluated for inflammation markers and aggregation parameters. Aggregation parameters were derived from the distribution of RBC population into aggregate sizes, and from the variation of the distribution as a function of flow-derived shear stress, using a cell flow properties analyzer. To differentiate plasmatic from cellular factors, we determined the aggregation in the presence of autologous plasma or dextran-500kDa and calculated the plasma factor (PF) in the obese group. PF ranges from 0 to 1. When the PF ¼ 1, the aggregation is all due to plasmatic factors, when PF ¼ 0, the altered aggregation depends entirely on cellular factors, whereas 0oPFo1 reflects the joint contribution of cellular and plasmatic factors. RESULTS: Obese subjects had relatively larger aggregates that were more resistant to dispersion by flow. The calculated PF in the obese group was 0.9, indicating a pronounced contribution of plasma to RBC aggregation in obesity. DISCUSSION: Our results suggest that obese individuals present pathological plasma-dependent RBC aggregation, which is probably triggered by plasma macromolecules associated with the inflammatory response. These findings impact the future attempts to develop strategies aimed at attenuation of the enhanced RBC aggregation in obese individuals.