Adhesive interactions of erythrocytes with neutrophils, platelets and fibrin: Implications for deep vein thrombosis

Deep vein thrombosis (DVT) is a low flow pathology often prevented by vascular compression to increase blood movement. We report heterotypic adhesive interactions of normal erythrocytes operative at low wall shear rates (γ_w) below 100 s^-1. Adhesion at γ_w = 50 s^-1 of washed RBC to fibrinogen-adherent platelets was 4-fold less (p<0.005) than to collagen-adherent platelets (279± 105 RBC/mm²). This adhesion was antagonized (> 80 % reduction) by soluble fibrinogen (3 mg/ml) and EDTA. RBC-platelet adhesion was reduced in half by antibodies against CD36 and GPIb, but not by antibodies against GPIIb/IIIa, vWF, TSP, or P-selectin. Adhesion of washed RBC to fibrinogen-adherent neutrophils was increased 6-fold in the presence of 20 μM fMLP to a level of 67 RBC per 100 neutrophils after 5 min at 50 s^-1. This adhesion was antagonized (>80%) by antibodies against CD18 (β₂-integrin) and EDTA, but not by soluble fibrinogen or antibodies against CD36 or TSP. RBC adhesion to activated platelets and activated neutrophils was prevented by wall shear stress above 1 dyne/cm² (at 100 s^-1). While washed RBC did not adhere to fibrin formed from purified fibrinogen, adhesion was marked when pure fibrin was pre-coated with TSP or when RBC were perfused over fibrin formed from recalcified plasma. Endothelial activation and unusually low flow may be a setting prone to receptor-mediated red blood cell adhesion to adherent neutrophils (or platelets/fibrin), all of which may contribute to DVT.