The role of material, platelets, and complement on material-induced leukocyte activation was investigated using an in vitro bead (45 μm) assay with polystyrene (PS), polyethylene glycol-immobilized polystyrene (PS-PEG), and PS-PEG-NH₂. Blood contact with beads activated leukocytes (tissue factor (TF) expression, CD11b upregulation and association with platelets), resulting in increased procoagulant activity. In the bulk, activation was independent of material surface chemistry;​ activation of adherent leukocytes was material-dependent.

In blood, tissue factor expression on monocytes, but not CD11b upregulation on leukocytes in the bulk, was independent of material surface area. Material-induced TF expression, but not CD11b upregulation, required the presence of platelets. In fact, TF expression was dependent on the association between platelets and monocytes. Both anti-IIb/IIIa and anti-P-selectin reduced TF expression. Inhibiting complement alone with sCR1 (a specific complement inhibitor) was without effect on material-induced TF expression. However, combining sCR1 and the platelet antagonist anti-GPIIb/IIIa significantly reduced material-induced TF expression in blood.

Complement inhibition with sCR1 was only effective in reducing CD11b upregulation in the bulk in the presence of a material that strongly activated complement, such as PS-PEG, but not with the moderate activator PS. When effective, complement inhibition with sCR1 only partially reduced material-induced CD11b upregulation in the bulk, suggesting that other mechanisms exist. Platelet activation was identified as the other mechanism contributing to material-induced CD11b upregulation in blood. Inhibiting both complement (with sCR1) and platelets (with anti-GPIIb/IIIa) blocked material-induced CD11 b upregulation. The presence of pyridoxal-5-phosphate alone also significantly reduced both TF expression and CD11b upregulation in the bulk;​ this is believed to be associated with its C1q and platelet inhibitory activities.

Both adsorbed complement products and adherent platelets mediated leukocyte adhesion. TF expression on adherent monocytes was strongly dependent on the presence of adherent platelets, while adsorbed complement products regulated CD1b upregulation on adherent leukocytes.

In vitro material-induced leukocyte activation, associated with the expression of procoagulant activities, appeared to be secondary to both complement and platelet activation. Blood-material compatibility may be greatly improved with a material that minimally activates both platelets and complement, or by the use of therapeutic agents, such as P5P, that simultaneously inhibit platelets and complement.