Contact activation of the plasma coagulation cascade. I. Procoagulant surface chemistry and energy

Abstract

Contact activation of the intrinsic pathway of porcine blood plasma coagulation is shown to be a steep exponential-like function of procoagulant surface energy, with low activation observed for poorly water-wettable surfaces and very high activation for fully water-wettable surfaces. Test procoagulants studied were a system of oxidized polystyrene films with varying wettability (surface energy) and glass discs bearing close-packed self-assembled silane monolayers (SAMs) with well-defined chemistry consisting of 12 different terminating chemical functionalities. A monotonic trend of increasing coagulation activation with increasing water wettability was observed for the oxidized polystyrene system whereas results with SAM procoagulants suggested a level of chemical specificity over and above the surface energy trend. In particular, it was noted that coagulation activation by SAMs terminated with--CO2H was much higher than anticipated based on surface wettability whereas--NH3(+)-terminated SAMs exhibited very low procoagulant activity. SAMs terminated in--(CH2)2(CF2)7CF3 behaved as anticipated based on surface energy with very low procoagulant activity and did not exhibit special properties sometimes attributed to perfluorinated compounds. Quantitative ranking of the inherent coagulation activation properties of procoagulant surfaces was obtained by application of a straightforward phenomenological model expressed in a closed-form mathematical equation relating coagulation time to procoagulant surface area. Fit of the model with a single adjustable parameter to experimental measurements of porcine platelet-poor plasma coagulation time was very good, implying that assertions and simplifications of the model adequately simulated reality. Two important propositions of the model were that (1) the number of putative "activating sites" scaled linearly with procoagulant surface area, and (2) contact activation of the plasma coagulation cascade was catalytic in the sense that these activating sites were not consumed or "poisoned" by irreversible or slowly reversible protein adsorption during coagulation. An extension of the coagulation model proposed that procoagulant activation properties scale exponentially with the surface density of polar (acid-base) sites, which, in turn, was related to procoagulant wettability.

Use of surface-modifying macromolecules to enhance the biostability of segmented polyurethanes

“…The reduced levels of fibrinogen adsorption that are shown in Figure 7 are significant, implying that the material has a relatively lower affinity to retain fibrinogen, a protein that is dominant in the formation of blood clots 35 and that has been associated with platelet activation on polyurethane surface. 32,36,37 Recently, Vogler et al 38,39 used glass discs bearing 12 kinds of close-packed self-assembled monolayers to investigate the relationship between coagulation and surface wettability. The results showed that the -(CH 2 ) 2 (CF 2 ) 7 CF 3 surface, the least wettable surface among their testing substrates, induced the least plasma coagulation.…”

Effects of surface wettability and contact time on protein adhesion to biomaterial surfaces

“…Wettability affects protein adsorption, platelet adhesion/activation, blood coagulation and cell and bacterial adhesion [12][13][14][15][16][17]. However, observations regarding the effects of surface wettability on protein adhesion have not always been consistent.…”

Protein conformational changes induced by adsorption onto material surfaces: an important issue for biomedical applications of material science

“…Besides cell culture, the behavior of materials in contact with biological fluid is of tremendous importance for biocompatibility in medicine and pharmacy. It has long been recognized that several negatively charged materials (glass, kaolin, celite, dextran sulfate polymers) induce fast blood clotting [3,4]. The "contact activation pathway" of the plasma coagulation cascade is due to factor XII activation.…”