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Prepublished online as a Blood First Edition Paper on July 5, 2002; DOI 10.1182/blood-2002-03-0712.

Submitted March 6, 2002
Accepted June 26, 2002
Adhesion of normal erythrocytes at depressed venous shear rates to activated neutrophils, activated platelets, and fibrin polymerized from plasma
Mukul S Goel and Scott L Diamond*
Department of Chemical Engineering, University of Pennsylvania, Philadelphia, PA, USA
* Corresponding author; email: sls{at}seas.upenn.edu.
Deep vein thrombosis (DVT) is a low flow pathology often prevented by vascular compression to increase blood movement. We report new heterotypic adhesive interactions of normal erythrocytes operative at low wall shear rates ( w) below 100 s-1. Adhesion at 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 GPVI-triggered 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, P-selectin, ß1, v, or CD47. Adhesion of washed RBC to fibrinogen-adherent neutrophils was increased 6-fold in the presence of 20 mM fMLP to a level of 67 RBC per 100 neutrophils after 5 min at 50 s-1. RBC-neutrophil adhesion was diminished by anti-CD11b (76%), anti-RBC LW (ICAM4; 40%), or by EDTA (>80%), but not by soluble fibrinogen or antibodies against CD11a, CD11c, CD36, TSP, ß1, v, or CD47. 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.

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