Influence of rheologic changes and platelet-neutrophil interactions on cell filtration in sepsis

We examined the role of erythrocyte (red brood cell; RBC) aggregation and d eformability, neutrophil (polymorphonuclear neutrophil; PMN) deformability, whole-blood viscosity, and platelet-neutrophil interactions on cell filtra tion in subjects who were critically ill with sepsis (CIS), critically ill noninfected subjects (CINS), and healthy controls (C). We assessed cell def ormability by filtration through filters of 5-mu m pore size. Whole blood, RBC, PMN, and combinations of PMN and RBC were studied. Viscometry was done on isolated RBC. Platelet-PMN interactions were assessed with monoclonal a ntibodies to CD41 and activated CD63 platelet receptors, and to CD66b PMN r eceptors. Filtration pressure (Pi) far CIS was significantly greater than f or C and CINS at both high and low PMN and RBC concentrations. Viscometry c onfirmed decreases in RBC deformability and demonstrated significant increa ses in RBC aggregation in CIS. Increments in Pi were significantly greater with PMN and PMN-RBC combinations suspended in platelet rich plasma (PRP) t han in platelet poor plasma (PPP) for CIS as compared with CINS or C. Flow cytometry confirmed significantly greater platelet activation in CIS than i n CINS or C (mean fluorescence: 39 +/- 9 Ifu versus 18.7 +/- 4.0 Ifu and 17 .1 +/- 2.3 Ifu, respectively) and greater platelet-PMN aggregation (mean fl uorescence: 44.7 +/- 3.6 Ifu versus 23 +/- 4.1 Ifu, respectively) in CIS th an in C. We conclude that decreased filtration of whole blood in CIS is rel ated to decreases in RBC and PMN deformability, increases in RBC aggregatio n, and increased platelet-PMN interactions. Of these, the formation of ptat elet-PMN aggregates appeares to have the greatest effect in impairing cell filtration. These theologic abnormalities may contribute to impaired microv ascular blood flow in patients with sepsls.