Investigation of platelet margination phenomena at elevated shear stress.

Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
Biorheology (Impact Factor: 1.29). 02/2007; 44(3):161-77.
Source: PubMed

ABSTRACT Thrombosis is a common complication following the surgical implantation of blood contacting artificial organs. Platelet transport, which is an important process of thrombosis and strongly modulated by flow dynamics, has not been investigated under the shear stress level associated with these devices, which may range from tens to several hundred Pascal.The current research investigated platelet transport within blood under supra-physiological shear stress conditions through a micro flow visualization approach. Images of platelet-sized fluorescent particles in the blood flow were recorded within microchannels (2 cm x 100 microm x 100 microm). The results successfully demonstrated the occurrence of platelet-sized particle margination under shear stresses up to 193 Pa, revealing a platelet near-wall excess up to 8.7 near the wall (within 15 microm) at the highest shear stress. The concentration of red blood cells was found to influence the stream-wise development of platelet margination which was clearly observed in the 20% Ht sample but not the 40% Ht sample. Shear stress had a less dramatic effect on the margination phenomenon than did hematocrit. The results imply that cell-cell collision is an important factor for platelet transport under supra-physiologic shear stress conditions. It is anticipated that these results will contribute to the future design and optimization of artificial organs.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Thrombus formation over a ruptured atherosclerotic plaque cap can occlude an artery with fatal consequences. We describe a computational model of platelet transport and binding to interpret rate-limiting steps seen in experimental thrombus formation over a collagen-coated stenosis. The model is used to compute shear rates in stenoses with growing boundaries. In the model, moving erythrocytes influence platelet transport based on shear-dependent enhanced diffusivity and a nonuniform platelet distribution. Adhesion is modeled as platelet-platelet binding kinetics. The results indicate that observed thrombus growth rates are limited by platelet transport to the wall for shear rates up to 6000 s(-1). Above 7000 s(-1), the thrombus growth rate is likely limited by binding kinetics (10(-4) m/s). Thrombus growth computed from these rate-limiting steps match the thrombus location and occlusion times for experimental conditions if a lag time for platelet activation is included. Using fitted parameters, the model is then used to predict thrombus size and shape at a higher Reynolds number flow consistent with coronary artery disease.
    Biophysical Journal 07/2013; 105(2):502-11. · 3.67 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The mainstay of treatment for thrombosis, the formation of occlusive platelet aggregates that often lead to heart attack and stroke, is antiplatelet therapy. Antiplatelet therapy dosing and resistance are poorly understood, leading to potential incorrect and ineffective dosing. Shear rate is also suspected to play a major role in thrombosis, but instrumentation to measure its influence has been limited by flow conditions, agonist use, and non-systematic and/or non-quantitative studies. In this work we measured occlusion times and thrombus detachment for a range of initial shear rates (500, 1500, 4000, and 10000 s(-1)) and therapy concentrations (0-2.4 µM for eptifibatide, 0-2 mM for acetyl-salicylic acid (ASA), 3.5-40 Units/L for heparin) using a microfluidic device. We also measured complete blood counts (CBC) and platelet activity using whole blood impedance aggregometry. Effects of shear rate and dose were analyzed using general linear models, logistic regressions, and Cox proportional hazards models. Shear rates have significant effects on thrombosis/dose-response curves for all tested therapies. ASA has little effect on high shear occlusion times, even at very high doses (up to 20 times the recommended dose). Under ASA therapy, thrombi formed at high shear rates were 4 times more prone to detachment compared to those formed under control conditions. Eptifibatide reduced occlusion when controlling for shear rate and its efficacy increased with dose concentration. In contrast, the hazard of occlusion from ASA was several orders of magnitude higher than that of eptifibatide. Our results show similar dose efficacy to our low shear measurements using whole blood aggregometry. This quantitative and statistically validated study of the effects of a wide range of shear rate and antiplatelet therapy doses on occlusive thrombosis contributes to more accurate understanding of thrombosis and to models for optimizing patient treatment.
    PLoS ONE 01/2014; 9(1):e82493. · 3.73 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Although the thrombogenic nature of the surfaces of cardiovascular devices is an important aspect of blood biocompatibility, few studies have examined platelet deposition onto opaque materials used for these devices in real time. This is particularly true for the metallic surfaces used in current ventricular assist devices (VADs). Using hemoglobin depleted red blood cells (RBC ghosts) and long working distance optics to visualize platelet deposition, we sought to perform such an evaluation. Fluorescently labeled platelets mixed with human RBC ghosts were perfused across 6 opaque materials (a titanium alloy (Ti6Al4V), silicon carbide (SiC), alumina (Al2O3), 2-methacryloyloxyethyl phosphorylcholine polymer coated Ti6Al4V (MPC-Ti6Al4V), yttria partially stabilized zirconia (YZTP), and zirconia toughened alumina (ZTA)) for 5 min at wall shear rates of 400 and 1000 sec-1. Ti6Al4V had significantly increased platelet deposition relative to MPC-Ti6Al4V, Al2O3, YZTP, and ZTA at both wall shear rates (P <0.01). For all test surfaces, increasing the wall shear rate produced a trend of decreased platelet adhesion. The described system can be a utilized as a tool for comparative analysis of candidate blood-contacting materials with acute blood contact.
    Journal of Biomedical Materials Research Part A 04/2014; · 2.83 Impact Factor