<i>Ex vivo</i> evaluation of erythrocytosis‐enhanced platelet thrombus formation using the cone and plate(let) analyzer: effect of platelet antagonists

Peerschke, Ellinor I.B.; Silver, Richard T.; Weksler, Babette B.; Grigg, Sage E.; Savion, Naphtali; Varon, David

doi:10.1111/j.1365-2141.2004.05190.x

Cited by 19 publications

(16 citation statements)

References 42 publications

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“…Direct measurements indicate that platelet transport to vessel walls increases several hundred times when red blood cells are added. 7,21,27,39 Aarts et al 1,2 studied the motion of the platelets with and without the presence of the RBCs. In the absence of RBCs, platelets simulated by a distribution of rigid model spherical particles, migrated to an average radial position of 0.6 times the radius from the tube centerline.…”

Section: Function and Behavior Of Plateletsmentioning

confidence: 99%

Micro-scale Dynamic Simulation of Erythrocyte–Platelet Interaction in Blood Flow

et al. 2008

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Platelet activation, adhesion, and aggregation on the blood vessel and implants result in the formation of mural thrombi. Platelet dynamics in blood flow is influenced by the far more numerous erythrocytes (RBCs). This is particularly the case in the smaller blood vessels (arterioles) and in constricted regions of blood flow (such as in valve leakage and hinge regions) where the dimensions of formed elements of blood become comparable with that of the flow geometry. In such regions, models to predict platelet motion, activation, aggregation and adhesion must account for platelet-RBC interactions. This paper studies platelet-RBC interactions in shear flows by performing simulations of micro-scale dynamics using a computational fluid dynamics (CFD) model. A level-set sharp-interface immersed boundary method is employed in the computations in which RBC and platelet boundaries are tracked on a two-dimensional Cartesian grid. The RBCs are assumed to have an elliptical shape and to deform elastically under fluid forces while the platelets are assumed to behave as rigid particles of circular shape. Forces and torques between colliding blood cells are modeled using an extension of the soft-sphere model for elliptical particles. RBCs and platelets are transported under the forces and torques induced by fluid flow and cell-cell and cell-platelet collisions. The simulations show that platelet migration toward the wall is enhanced with increasing hematocrit, in agreement with past experimental observations. This margination is seen to occur due to hydrodynamic forces rather than collisional forces or volumetric exclusion effects. The effect of fluid shear forces on the platelets increases exponentially as a function of hematocrit for the range of parameters covered in this study. The micro-scale analysis can be potentially employed to obtain a deterministic relationship between fluid forces and platelet activation and aggregation in blood flow past cardiovascular implants.

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Section: Function and Behavior Of Plateletsmentioning

confidence: 99%

Micro-scale Dynamic Simulation of Erythrocyte–Platelet Interaction in Blood Flow

et al. 2008

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“…The correlation between the platelet thrombus volume and hematocrit has been thoroughly discussed. Thrombus formation did not occur at a high shear stress in platelet-rich plasma or in whole blood with reduced hematocrit [17][18][19][20][21][22].…”

Section: Discussionmentioning

confidence: 99%

“…RBCs may, as a result of shear-induced lytic or sublytic injury, liberate ADP, which may activate platelets and promote platelet-platelet, as well as plateletsurface, interaction (chemical mechanism) [17][18][19]. Both RBC-derived ADP and RBC-mediated platelet surface transport are involved in the potentiation by RBCs of platelet aggregation by shear stress [17].…”

Section: Discussionmentioning

confidence: 99%

“…RBCs, by concentrating in the center of the blood stream and colliding with platelets, may facilitate transport of platelets toward the vessel wall (physical mechanism) [17][18][19]. RBCs may, as a result of shear-induced lytic or sublytic injury, liberate ADP, which may activate platelets and promote platelet-platelet, as well as plateletsurface, interaction (chemical mechanism) [17][18][19].…”

Section: Discussionmentioning

confidence: 99%

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Gorog Thrombosis Test: analysis of factors influencing occlusive thrombus formation

Nishida

Murata

Miyaki

et al. 2006

Blood Coagulation &Amp; Fibrinolysis

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We used the Gorog Thrombosis Test to analyze the factors influencing the occlusion time, which represents platelet activation and subsequent occlusive thrombus formation, in 132 healthy Japanese volunteers (116 men, 16 women; mean age, 45.0 +/- 12.0 years). The Gorog Thrombosis Test was designed to evaluate platelet aggregation and thrombolytic activity under a high shear stress condition (175 dynes/cm) in a native blood sample in vitro. The mean +/- SD occlusion time was 154.8 +/- 64.7 s (men, 153.4 +/- 64.2 s and women, 165.4 +/- 56.5 s). The occlusion time was inversely correlated with von Willebrand factor ristocetin cofactor activity (VWF:Rco) (r = -0.242, P = 0.0055) and von Willebrand factor antigen (r = -0.230, P = 0.0080). The mean occlusion time in the group with VWF:Rco of at least 170% (137 s) was significantly shorter than that in the group with VWF:Rco less than 170% (156 s, P < 0.05). Platelet counts, other coagulation markers and smoking showed no significant correlations with occlusion time. Red blood cells (r = -0.177, P = 0.0365), hemoglobin (r = -0.191, P = 0.0245) and hematocrit (r = -0.182, P = 0.0329) also showed inverse correlations with the occlusion time. This report is the first to clearly demonstrate the role of von Willebrand factor in the formation of occlusive thrombi in the Gorog Thrombosis Test.

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“…The system is mounted on top of an inverted microscope and real-time microscopy of changes in the cells is thus facilitated. More recent applications thus include the effect of shear stress on mechanotransduction and morphological response of ECs [49,50], the interaction between platelets and ECs or ligand coated surfaces [51,52], and the interaction between platelets and RBC in pathology [53].…”

Section: Cone and Plate Viscometers Backgroundmentioning

confidence: 99%

Biological effects of dynamic shear stress in cardiovascular pathologies and devices

Girdhar

Bluestein

2008

Expert Review of Medical Devices

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Altered and highly dynamic shear stress conditions have been implicated in endothelial dysfunction leading to cardiovascular disease, and in thromboembolic complications in prosthetic cardiovascular devices. In addition to vascular damage, the pathological flow patterns characterizing cardiovascular pathologies and blood flow in prosthetic devices induce shear activation and damage to blood constituents. Investigation of the specific and accentuated effects of such flow-induced perturbations on individual cell-types in vitro is critical for the optimization of device design, whereby specific design modifications can be made to minimize such perturbations. Such effects are also critical in understanding the development of cardiovascular disease. This review addresses limitations to replicate such dynamic flow conditions in vitro and also introduces the idea of modified in vitro devices, one of which is developed in the authors' laboratory, with dynamic capabilities to investigate the aforementioned effects in greater detail.Keywords cardiovascular disease; cone-plate viscometers; dynamic shear stress; platelet activation; prosthetic heart valves; turbulence Implantable blood recirculation devices, artificial hearts and heart valves, have long been used as life-saving alternatives for people with severe cardiovascular diseases. However, such devices require complex anticoagulation therapy and, as a consequence, are linked to postimplant complications, such as hemorrhage. Despite the anticoagulation therapy, the risk for cardioembolic stroke is not eliminated. Although biocompatibility of these recirculation devices is of utmost importance, optimizing the geometric design of these devices is also critical to avoid flow-induced trauma to blood. Over the years, a definite link between fluid shearstress-induced damage and activation of blood constituents such as platelets and red blood cells, has been established. Irregular flow patterns arising around complex geometries (e.g., the hinge regions of mechanical heart valves [MHV]) have been recently characterized by numerical calculations and noninvasive flow measurements, and are implicated in causing flow-induced thromboembolism (TE). For instance, the Medtronic Parallel™ valve exhibited regions of elevated turbulent stress around the hinges due to its specific geometry, which, in †Author for correspondence: Department of Biomedical Engineering, State University of New York at Stony Brook, Stony Brook, NY 11794-8181, USA, Tel.: +1 631 444 1259, Fax: +1 631 444 6646, danny.bluestein@sunysb.edu. Financial & competing interests disclosure:The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manu...

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Ex vivo evaluation of erythrocytosis‐enhanced platelet thrombus formation using the cone and plate(let) analyzer: effect of platelet antagonists

Cited by 19 publications

References 42 publications

Micro-scale Dynamic Simulation of Erythrocyte–Platelet Interaction in Blood Flow

Micro-scale Dynamic Simulation of Erythrocyte–Platelet Interaction in Blood Flow

Gorog Thrombosis Test: analysis of factors influencing occlusive thrombus formation

Biological effects of dynamic shear stress in cardiovascular pathologies and devices

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