Using microfluidics to understand the effect of spatial distribution of tissue factor on blood coagulation

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Abstract

Initiation of blood coagulation by tissue factor (TF) is a robust, highly regulated process. Both the spatial distribution of TF and the geometry of the vasculature may play important roles in regulating coagulation. As this review describes, microfluidic systems provide a unique opportunity for investigating the spatiotemporal dynamics of blood coagulation in vitro. Microfluidic systems with surfaces of phospholipid bilayers patterned with TF have been used to demonstrate experimentally the threshold responses of initiation of coagulation to the size and shape of surfaces presenting TF. These systems have also been used to demonstrate experimentally that propagation of coagulation is regulated by the shear rate of blood flow in microcapillaries and microchannels. By understanding these and other aspects of the spatial dynamics that regulate blood coagulation, many new methods for treating clotting disorders, such as venous thromboembolism (VTE) and sepsis, could arise.

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Cited by (16)

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    This same technique can also be used to examine how characteristics of the injury surface affect coagulation and thrombosis, as well as to define the kinetics of platelet recruitment, adhesion, and clot contraction. By designing a microfluidic device that incorporated varied spatial distributions of tissue factor, studies were able to demonstrate that the initiation of coagulation requires a large patch of tissue factor or a close distribution of many small patches, since a spread out distribution of small patches with the same total surface area did not initiate coagulation [41]. Atherosclerotic geometries have also been incorporated into microfluidic devices to study how disease states affect thrombosis.

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    As sepsis can be associated with systemic intravascular activation of coagulation (Aird, 2005), it is useful to learn about the spatial distribution and location of tissue factor (TF) and the geometry of the vasculature that regulate coagulation. Shen et al. developed microfluidic systems with surfaces of phospholipid bilayers patterned with TF to demonstrate experimentally the threshold responses of initiation of coagulation to the size and shape of surfaces presenting TF (Shen et al., 2008). Thermal injury can trigger an inflammatory cascade that heralds shock, SIRS and even death (D'Avignon et al., 2010).

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    Perhaps such an evaluation could soon be possible with recent advances in microfluidic assays that have provided the ability to investigate pathological shear stresses in channels that mimic stenotic vessels [41] or those with resultant turbulent flow. Similarly, microfluidic assays have been used to evaluate the spatial distribution of tissue factor on coagulation, which may have bearing on treatment of sepsis-related disseminated intravascular coagulation or venous thromboembolism [42]. Another promising trend is the use of microfluidics to evaluate patient-specific thrombotic potential and response to specific pro-coagulant agents such as chemotherapy [43].

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    The first one is the group of Prof. Ataullakhanov that after the initial publications [21,33–35] continued to explore the processes of clot growth in non-convective systems in vitro [46–51,56–64]. The second one is the group of Prof. Ismagilov that carried out a series of significant research works using the microfluidics technique [52–54,65–71]. The propagation of self-sustained traveling waves in various homogeneous active media progresses at a constant stationary speed that does not depend on the manner of the wave initiation [31].

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