Monocyte-derived macrophage microparticles impart tissue factor activity to biomaterial surfaces

The initiation of coagulation on biomaterials is attributed to the contact pathway of coagulation. However, recent discoveries of blood-borne tissue factor (TF) activity suggest that the TF pathway of coagulation may contribute to thrombosis on biomaterials. To evaluate the role of TF bearing microparticles to biomaterial thrombogenicity, the adhesion of monocyte-derived macrophage microparticles (MMPs) to bare, bovine serum albumin (BSA) blocked, and plasma-coated materials was examined. MMP suspensions consisted of 20-37% TF positive particles that exhibited TF activity. Data from static experiments with polyethylene (PE), polydimethylsiloxane (PDMS), polystyrene (PS), and glass knitted and woven Dacron(R) grafts showed that MMPs adhered to uncoated, and plasma coated surfaces supported TF activity, whereas surfaces blocked with BSA supported less activity. Flow studies were performed on plasma-coated glass and tissue culture-treated polystyrene (TCPS) as a model system to demonstrate deposition and firm adhesion of microparticles under physiologic flow conditions. MMPs deposited and imparted TF activity to plasma-coated glass at wall shear rates of 100, 400, and 1200 sec(-1). Deposition on TCPS was comparable to glass at 100 sec(-1), but virtually nonexistent at the two higher shear rates after a 1 h perfusion, implying material and shear dependent adhesion. The localization of procoagulant MMPs to biomaterial surfaces could lead to an increased risk of thrombosis on cardiovascular implants beyond that anticipated by the contact pathway alone.