• Anita Tsen, Linda A Kirschenbaum, Catherine LaRow, Raymond Khan, Susannah Kurtz, Sandeep Bansal, and Mark E Astiz.
• Department of Medicine, New York Medical College, Valhalla; and Department of Medicine, Manhattan, New York, USA.
• Shock. 2009 Feb 1;31(2):120-4.

AbstractTo examine the effects of anticoagulants and the role of thrombin on neutrophil-platelet-endothelial cell interactions in septic shock. Controlled experiments using phase-contrast microscopy to study neutrophil, platelet, and endothelial cell interactions in flowing cell suspensions under simulated physiologic conditions. University research laboratory. Adult patients with septic shock and normal volunteers. Microslides were coated with human umbilical vein endothelial cells. Neutrophils and platelets removed from control subjects were stimulated with plasma from patients in septic shock and perfused over endothelial cells. Heparin (H), argatroban (A), antithrombin III (ATIII), and recombinant human activated protein C (rhAPC) with and without thrombin were added to cells suspended in septic plasma and normal plasma. The number of neutrophils adherent to endothelial cells, neutrophil rolling velocity, and the number of neutrophils in aggregates were determined. Flow cytometric analysis of cells was used to identify cell activation and the formation of platelet-neutrophil aggregates. Heparin, A, ATIII, rhAPC all significantly decreased neutrophil adhesion and aggregation, and increased rolling velocity of neutrophils suspended in septic plasma. These results are similar to those observed with normal plasma but present greater absolute changes. Platelet-neutrophil aggregation, platelet activation, and neutrophil activation were significantly decreased by each of the anticoagulants. The addition of thrombin to cell suspensions containing anticoagulants reversed the effects of H, A, ATIII, rhAPC on neutrophil adhesion, adherence, and rolling velocity. In addition, thrombin attenuated the effects of each of these agents on platelet-neutrophil aggregation, platelet activation, and neutrophil activation. These data suggest that H, A, ATIII, and rhAPC decrease sepsis-induced neutrophil-endothelial cell interactions. The reversal of this effect by thrombin suggests that these agents alter neutrophil-endothelial interactions through their anticoagulant effects and the resulting decrease in thrombin activity.

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