Revised model of the tissue factor pathway of thrombin generation: Role of the feedback activation of FXI.

Background: Biochemical reaction networks are self-regulated in part due to feedback activation mechanisms. The tissue factor (TF) pathway of blood coagulation is a complex reaction network controlled by multiple feedback loops that coalesce around the serine protease thrombin.

Objectives: Our goal was to evaluate the relative contribution of the feedback activation of coagulation factor XI (FXI) in TF-mediated thrombin generation using a comprehensive systems-based analysis.

Design of a Microfluidic Bleeding Chip to Evaluate Antithrombotic Agents for Use in COVID-19 Patients.

Introduction: Interventions that could prevent thrombosis, clinical decompensation, and respiratory compromise in patients with novel coronavirus disease (COVID-19) are key to decrease mortality rate. Studies show that profound cytokine release and excessive activation of blood coagulation appear to be key drivers of COVID-19 associated mortality. Since limited methods exist for assessing the effects of anticoagulants on hemostasis, the development of novel therapies to safely prevent thrombosis in COVID-19 patients relies on preclinical animal models and early phase human trials.

Design and Utility of a Point-of-Care Microfluidic Platform to Assess Hematocrit and Blood Coagulation.

Purpose—: To develop a small volume whole blood analyzer capable of measuring the hematocrit and coagulation kinetics of whole blood.

Methods And Results—: A co-planar microfluidic chamber designed to facilitate self-driven capillary action across an internal electrical chip was developed and used to measure the electric parameters of whole human blood that had been anticoagulated or allowed to clot. To promote blood clotting, select chip surfaces were coated with a prothrombin time (PT) reagent containing lipidated tissue factor (TF), which activates the extrinsic pathway of coagulation to promote thrombin generation and fibrin formation.

Modeling the effect of blood vessel bifurcation ratio on occlusive thrombus formation.

Vascular geometry is a major determinant of the hemodynamics that promote or prevent unnecessary vessel occlusion from thrombus formation. Bifurcations in the vascular geometry are repeating structures that introduce flow separation between parent and daughter vessels. We modelled the blood flow and shear rate in a bifurcation during thrombus formation and show that blood vessel bifurcation ratios determine the maximum shear rate on the surface of a growing thrombus.

Dynamics of blood flow and thrombus formation in a multi-bypass microfluidic ladder network.

The reaction dynamics of a complex mixture of cells and proteins, such as blood, in branched circulatory networks within the human microvasculature or extravascular therapeutic devices such as extracorporeal oxygenation machine (ECMO) remains ill-defined. In this report we utilize a multi-bypass microfluidics ladder network design with dimensions mimicking venules to study patterns of blood platelet aggregation and fibrin formation under complex shear. Complex blood fluid dynamics within multi-bypass networks under flow were modeled using COMSOL.

Biorheology of platelet activation in the bloodstream distal to thrombus formation.

Thrombus growth at the site of vascular injury is mediated by the sequential events of platelet recruitment, activation and aggregation concomitant with the initiation of the coagulation cascade, resulting in local thrombin generation and fibrin formation. While the biorheology of a localized thrombus formation has been well studied, it is unclear whether local sites of thrombin generation propagate platelet activation within the bloodstream. In order to study the physical biology of platelet activation downstream of sites of thrombus formation, we developed a platform to measure platelet activation and microaggregate formation in the bloodstream.

Origin of periodic and chaotic dynamics due to drops moving in a microfluidic loop device.

Droplets moving in a microfluidic loop device exhibit both periodic and chaotic behaviors based on the inlet droplet spacing. We observe that the periodic behavior is an outcome of carrier phase mass conservation principle, which translates into a droplet spacing quantization rule. This rule implies that the summation of exit spacing is equal to an integral multiple of inlet spacing.