Determination of Critical Parameters in Platelet Margination

Reasor, Daniel A.; Mehrabadi, Marmar; Ku, David N.; Aidun, Cyrus K.

doi:10.1007/s10439-012-0648-7

Cited by 120 publications

(124 citation statements)

References 49 publications

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“…The higher the fluorescence intensity, the higher the margination propensity. In simulation studies, where the exact center of mass of particles is known, margination is conveniently defined as the number of particles at a given characteristic distance from the wall (e.g., the CFL thickness or adhesion distance) (15,20,21,23,37,49). In this study, each segment width was 9.5 mm, which is close to the CFL thickness, as shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Direct Tracking of Particles and Quantification of Margination in Blood Flow

Carboni

Bognet

Bouchillon

et al. 2016

Biophysical Journal

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Margination refers to the migration of particles toward blood vessel walls during blood flow. Understanding the mechanisms that lead to margination will aid in tailoring the attributes of drug-carrying particles for effective drug delivery. Most previous studies evaluated the margination propensity of these particles via an adhesion mechanism, i.e., by measuring the number of particles that adhered to the channel wall. Although particle adhesion and margination are related, adhesion also depends on other factors. In this study, we quantified the margination propensity of particles of varying diameters (0.53, 0.84, and 2.11 mm) and apparent wall shear rates (30, 61, and 121 s À1 ) by directly tracking fluorescent particles flowing through a microfluidic channel. The margination parameter, M, is defined as the total number of particles found within the cell-free layers normalized by the total number of particles that passed through the channel. In this study, an M-value of 0.2 indicated no margination, which was observed for all particle sizes in water. In the case of blood, larger particles were found to have higher M-values and thus marginated more effectively than smaller particles. The corresponding M-values at the device outlet were 0.203, 0.223, and 0.285 for 0.53-, 0.84-, and 2.11-mm particles, respectively. At the inlet, the M-values for all particle sizes in blood were <0.2, suggesting that non-fully-developed flow and constriction may lead to demargination. For particle velocities transverse to the flow direction (v y ), all particle sizes showed a larger standard deviation of v y as well as a higher effective diffusivity when the particles were suspended in blood relative to water. These higher values are attributed to collisions between the blood cells and particles, further supporting recent simulation results. In terms of flow rates, for a given particle size, the higher the flow rate, the higher the M-value.

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Section: Resultsmentioning

confidence: 99%

Direct Tracking of Particles and Quantification of Margination in Blood Flow

Carboni

Bognet

Bouchillon

et al. 2016

Biophysical Journal

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“…Smaller scale studies of blood flow are preferred for qualitative studies. For example, Crowl & Fogelson [25,26] simulated the lateral motion of platelets in a two-dimensional channel, whereas three-dimensional studies have focused on varying parameters and examining their effect on the margination [27,28]. At this cellular scale, models have either emphasized flows in straight channels or used a haematocrit significantly lower than the physiological value.…”

Section: Introductionmentioning

confidence: 99%

Where do the platelets go? A simulation study of fully resolved blood flow through aneurysmal vessels

2013

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One contribution of 25 to a Theme Issue 'The virtual physiological human: integrative approaches to computational biomedicine'. Despite the importance of platelets in the formation of a thrombus, their transport in complex flows has not yet been studied in detail. In this paper we simulated red blood cells and platelets to explore their transport behaviour in aneurysmal geometries. We considered two aneurysms with different aspect ratios (AR ¼ 1.0, 2.0) in the presence of fast and slow blood flows (Re ¼ 10, 100), and examined the distributions of the cells. Low velocities in the parent vessel resulted in a large stagnation zone inside the cavity, leaving the initial distribution almost unchanged. In fast flows, an influx of platelets into the aneurysm was observed, leading to an elevated concentration. The connection of the platelet-rich cellfree layer (CFL) with the outer regions of the recirculation zones leads to their increased platelet concentration. These platelet-enhanced recirculation zones produced a diverse distribution of cells inside the aneurysm, for the different aspect ratios. A thin red blood CFL that was occupied by platelets was observed on the top of the wide-necked aneurysm, whereas a high-haematocrit region very close to the vessel wall was present in the narrow-necked case. The simulations revealed that non-trivial distributions of red blood cells and platelets are possible inside aneurysmal geometries, giving rise to several hypotheses on the formation of a thrombus, as well as to the wall weakening and the possible rupture of an aneurysm.

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“…35 Computational models of whole blood, which simulate the motion of collections of red blood cells and platelets suspended in plasma, show the temporal development of the red-cell depletion zone and the subsequent margination of platelets. [36][37][38] These studies also show that the red blood cells along the edge of the red-cell depletion zone form an effective barrier which strongly inhibits the movement of platelets from the near-wall region back into the core flow. 36,37 In the context of our flow assay, this implies that most of the platelets that contact the upstream priming region will remain within a few microns of the wall during their transit through the chamber to the downstream capture region, and so have a significant chance of contact with the capture region.…”

Section: Discussionmentioning

confidence: 81%

Functional assay of antiplatelet drugs based on margination of platelets in flowing blood

2016

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A novel functional assay of antiplatelet drug efficacy was designed by utilizing the phenomena of platelet margination in flowing blood and transient platelet contacts with surface-immobilized platelet agonists. Flow margination enhances transient contacts of platelets with the walls of flow chambers covered with surface-immobilized proteins. Depending on the type and the surface density of the immobilized agonists, such transient interactions could "prime" the marginated platelet subpopulation for enhanced activation and adhesion downstream. By creating an upstream surface patch with an immobilized platelet agonist, platelet flow margination was used to test how effective antiplatelet drugs are in suppressing downstream platelet activation and adhesion. The platelet adhesion downstream was measured by a so-called "capture" patch region close to the distal end of the flow chamber. Platelet adhesion downstream was found to be dose-dependent on the upstream surface coverage of the "priming" patch, with immobilized fibrinogen acting as a platelet agonist. Several antiplatelet agents (acetylsalicylic acid, eptifibatide, and tirofiban) were evaluated for their efficacy in attenuating downstream adhesion after upstream platelet priming. The activation of the platelet population was found to be dependent on both the extent of the upstream agonist stimulus and the antiplatelet drug concentration. Such a relationship provides an opportunity to measure the efficacy of specific antiplatelet agents against the type and concentration of upstream platelet agonists.

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Determination of Critical Parameters in Platelet Margination

Cited by 120 publications

References 49 publications

Direct Tracking of Particles and Quantification of Margination in Blood Flow

Direct Tracking of Particles and Quantification of Margination in Blood Flow

Where do the platelets go? A simulation study of fully resolved blood flow through aneurysmal vessels

Functional assay of antiplatelet drugs based on margination of platelets in flowing blood

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