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 deformability, neutrophil (polymorphonuclear neutrophil; PMN) deformability, whole-blood viscosity, and platelet-neutrophil interactions on cell filtration in subjects who were critically ill with sepsis (CIS), critically ill noninfected subjects (CINS), and healthy controls (C). We assessed cell deformability 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 antibodies to CD41 and activated CD63 platelet receptors, and to CD66b PMN receptors. Filtration pressure (Pi) far CIS was significantly greater than for C and CINS at both high and low PMN and RBC concentrations. Viscometry confirmed decreases in RBC deformability and demonstrated significant increases in RBC aggregation in CIS. Increments in Pi were significantly greater with PMN and PMN-RBC combinations suspended in platelet rich plasma (PRP) than in platelet poor plasma (PPP) for CIS as compared with CINS or C. Flow cytometry confirmed significantly greater platelet activation in CIS than in 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 fluorescence: 44.7 +/- 3.6 Ifu versus 23 +/- 4.1 Ifu, respectively) in CIS than in C. We conclude that decreased filtration of whole blood in CIS is related to decreases in RBC and PMN deformability, increases in RBC aggregation, and increased platelet-PMN interactions. Of these, the formation of ptatelet-PMN aggregates appeares to have the greatest effect in impairing cell filtration. These theologic abnormalities may contribute to impaired microvascular blood flow in patients with sepsls.