Hemostasis and thrombosis beyond biochemistry: roles of geometry, flow and diffusion

Panteleev, Mikhail A.; Dashkevich, Natalia M.; Ataullakhanov, Fazoil I.

doi:10.1016/j.thromres.2015.07.025

Cited by 54 publications

(45 citation statements)

References 90 publications

(136 reference statements)

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“…[1][2][3] Activated platelets are believed to be important contributors of the phosphatidylserine (PS)-rich surface for the procoagulant membranedependent reactions in thrombosis and hemostasis. 4 They are heterogeneous, with the overwhelming majority of coagulation proteins binding to the single PS-exposing subpopulation of activated platelets.…”

Section: Introductionmentioning

confidence: 99%

Coagulation factors bound to procoagulant platelets concentrate in cap structures to promote clotting

Подоплелова¹,

Sveshnikova

Kotova

et al. 2016

Blood

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106

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Key Points• All blood coagulation factors predominantly bind to a small "cap"-like region on procoagulant-activated platelets.• Their concentration in this small region promotes acceleration of the membrane-dependent reactions of coagulation.Binding of coagulation factors to phosphatidylserine (PS)-exposing procoagulant-activated platelets followed by formation of the membrane-dependent enzyme complexes is critical for blood coagulation. Procoagulant platelets formed upon strong platelet stimulation, usually with thrombin plus collagen, are large "balloons" with a small (∼1 mm radius) "cap"-like convex region that is enriched with adhesive proteins. Spatial distribution of blood coagulation factors on the surface of procoagulant platelets was investigated using confocal microscopy. All of them, including factors IXa (FIXa), FXa/FX, FVa, FVIII, prothrombin, and PS-sensitive marker Annexin V were distributed nonhomogeneously: they were primarily localized in the "cap," where their mean concentration was by at least an order of magnitude, higher than on the "balloon." Assembly of intrinsic tenase on liposomes with various PS densities while keeping the PS content constant demonstrated that such enrichment can accelerate this reaction by 2 orders of magnitude. The mechanisms of such acceleration were investigated using a 3-dimensional computer simulation model of intrinsic tenase based on these data. Transmission electron microscopy and focal ion beam-scanning electron microscopy with Annexin V immunogold-labeling revealed a complex organization of the "caps." In platelet thrombi formed in whole blood on collagen under arterial shear conditions, ubiquitous "caps" with increased Annexin V, FX, and FXa binding were observed, indicating relevance of this mechanism for surface-attached platelets under physiological flow. These results reveal an essential heterogeneity in the surface distribution of major coagulation factors on the surface of procoagulant platelets and suggest its importance in promoting membrane-dependent coagulation reactions. (Blood. 2016;128(13):1745-1755

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Section: Introductionmentioning

confidence: 99%

Coagulation factors bound to procoagulant platelets concentrate in cap structures to promote clotting

Подоплелова¹,

Sveshnikova

Kotova

et al. 2016

Blood

Self Cite

106

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“…Our focus, however, is not to the formation and the evolution of actual calcifications and clots. These are very complicated biochemical phenomena [28] and their full dynamics is beyond the scope of this article. The goal is here to illustrate how, given a criterion for aggregation, this can be implemented in our model.…”

Section: Resultsmentioning

confidence: 99%

Discrete multi-physics: A mesh-free model of blood flow in flexible biological valve including solid aggregate formation

et al. 2017

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We propose a mesh-free and discrete (particle-based) multi-physics approach for modelling the hydrodynamics in flexible biological valves. In the first part of this study, the method is successfully validated against both traditional modelling techniques and experimental data. In the second part, it is further developed to account for the formation of solid aggregates in the flow and at the membrane surface. Simulations of various types of aggregates highlight the main benefits of discrete multi-physics and indicate the potential of this approach for coupling the hydrodynamics with phenomena such as clotting and calcification in biological valves.

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“…The in vivo progress of blood coagulation was initially described by Orfeo et al [28] to occur in three stages (initiation, propagation, and termination) in three distinct compartments (extravascular space exposed by injury, the region enclosed by the clot, and surrounding intravascular space) that are spatially disjoint. This view has been further expanded, and it is now recognized that, in vivo, the various reactions of blood coagulation occur at different sites on different cell surfaces which are part of different tissues making flow, transport, and diffusion-of participating enzymes and platelets-the important factors that link the distinct compartments into a single functional system [29]. Succinctly put, the new understanding of coagulation necessitates models that capture spatio-temporal changes, as opposed to temporal changes alone, and those which span interactions at multiple scales (sub-cellular coagulation reactions and fibril generation, cellular interactions of platelets with each other and with the flow, and macro-scale vessel wall-level blood flow and reactant transport) as opposed to single scale (macro-scale continuum level) alone.…”

Section: Models For Clot Formation and Lysismentioning

confidence: 99%

A Short Review of Advances in the Modelling of Blood Rheology and Clot Formation

Mohan

Rajagopal

2017

Fluids

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Several advances have taken place since the early 2000s in the field of blood flow modelling. These advances have been driven by the development of assist devices such as Left Ventricular Assist Devices (LVADs), etc., and by the acceptance of in silico tests for the generation of hypotheses concerning clot formation and lysis. We give an overview of the developments in modelling of blood rheology and clot formation/lysis in the last 10 to 15 years. In blood rheology, advances are increasingly supplemented by flow simulation studies. In clot formation (or coagulation), advances have taken place in both single-scale modeling under quiescent conditions as well as in multi-scale modeling in the presence of flow. The future will possibly see more blood flow simulations in complex geometries and, simultaneously, development and simulation of multi-scale models for clot formation and lysis.

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Hemostasis and thrombosis beyond biochemistry: roles of geometry, flow and diffusion

Cited by 54 publications

References 90 publications

Coagulation factors bound to procoagulant platelets concentrate in cap structures to promote clotting

Coagulation factors bound to procoagulant platelets concentrate in cap structures to promote clotting

Discrete multi-physics: A mesh-free model of blood flow in flexible biological valve including solid aggregate formation

A Short Review of Advances in the Modelling of Blood Rheology and Clot Formation

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