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  • Blood flow  (1)
  • Modelling thrombogenesis  (1)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Annals of biomedical engineering 18 (1990), S. 685-709 
    ISSN: 1573-9686
    Keywords: Thrombosis ; Transport in flowing blood ; Coagulation cascade ; Modelling thrombogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract The paper presents a mathematical analysis of the contributions of flow and mass transport to a single reactive event at a blood vessel wall. The intent is to prepare the ground for a comprehensive study of the intertwining of these contributions with the reaction network of the coagulation cascade. We show that in all vessels with local mural activity, or in “large” vessels (d〉0.1 mm) with global reactivity, events at the tubular wall can be rigorously described by algebraic equations under steady conditions, or by ordinary differential forms (ODEs) during transient conditions. this opens up important ways for analyzing the combined roles of flow, transport, and coagulation reactions in thrombosis, a task hitherto considered to be completely intractable. We report extensively on the dependence of transport coefficient kL and mural coagulant concentration Cw on flow, vessel geometry, and reaction kinetics. It is shown that for protein transport, kL varies only weakly with shear rate $$\dot \gamma $$ in large vessels, and not at all in the smaller tubes (d〈10−2 mm). For a typical protein, kL∼10−3 cm s−1 within a factor of 3 in most geometries, irrespective of the mural reaction kinetics. Significant reductions in kL (1/10–1/1,000) leading to high-coagulant accumulation are seen mainly in stagnant zones vicinal to abrupt expansions and in small elliptical tubules. This is in accord with known physical observations. More unexpected are the dramatic increases in accumulation which can come about through the intervention of an autocatalytic reaction step, with Cw rising sharply toward infinity as the ratio of reaction to transport coefficient approaches unity. Such self-catalyzed reactions have the ability to act as powerful amplifiers of an otherwise modest influence of flow and transport on coagulant concentration. The paper considers as well the effect on mass transport of transient conditions occasioned by coagulation initiation or pulsatile flow. During initiation, instantaneous flux varies with diffusivity and bulk concentration, favouring the early adsorption/consumption of proteins with the highest abundance and mobility. This is akin to the ‘Vroman effect’ seen in narrow, stagnant spaces. The effect of flow pulsatility on kL has the potential, after prolonged cycling, of bringing about segregation or accumulation of proteins, with consequences for the coagulation process.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Annals of biomedical engineering 22 (1994), S. 357-370 
    ISSN: 1573-9686
    Keywords: Mathematical modeling ; Blood coagulation ; Thrombin ; Blood flow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract This paper presents the first attempt to model the blood coagulation reactions in flowing blood. The model focuses on the common pathway and includes activation of factor X and prothrombin, including feedback activation of cofactors VIII and V by thrombin, and plasma inhibition of factor Xa and thrombin. In this paper, the first of two, the sparsely covered membrane (SCM) case is presented. This considers the limiting situation where platelet membrane binding sites are in excess, such that no membrane saturation or binding competition occurs. Under these conditions, the model predicts that the two positive feedback loops lead to multiple steady-state behavior in the range of intermediate mass transfer rates. It will be shown that this results in three parameter regions exhibiting very different thrombin production patterns. The model predicts the effect of flow on steady-state and dynamic thrombin production and attempts to explain the difference between venous and arterial thrombi. The reliance of thrombin production on precursor procoagulant protein concentrations is also assessed.
    Type of Medium: Electronic Resource
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