Severe Clotting During Extracorporeal Dialysis Procedures

Boyer, C; Swartz, Richard D.

doi:10.1111/j.1525-139x.1991.tb00417.x

Cited by 10 publications

(9 citation statements)

References 47 publications

(5 reference statements)

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“…For example, a major limitation of these assays is that they measure clotting behaviour under static (no flow) or irrelevant flow conditions, and thus, they fail to incorporate the effects of haemodynamic forces (pressure, flow and shear stress) and related cellular interactions that are known to significantly impact whole blood thrombosis in the living vasculature 3 13 . Notably, flow acceleration and deceleration (fluid shear gradients) have been shown to initiate platelet aggregation during arterial thrombosis in vivo 14 15 , and clotting in extracorporeal devices usually occurs at sites of sudden flow disturbances, stagnation points and stenosed sections of tubing 16 17 . However, none of the routinely used haemostasis assays incorporate these physiological conditions in their assessment of blood coagulation.…”

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confidence: 99%

A shear gradient-activated microfluidic device for automated monitoring of whole blood haemostasis and platelet function

et al. 2016

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Accurate assessment of blood haemostasis is essential for the management of patients who use extracorporeal devices, receive anticoagulation therapy or experience coagulopathies. However, current monitoring devices do not measure effects of haemodynamic forces that contribute significantly to platelet function and thrombus formation. Here we describe a microfluidic device that mimics a network of stenosed arteriolar vessels, permitting evaluation of blood clotting within small sample volumes under pathophysiological flow. By applying a clotting time analysis based on a phenomenological mathematical model of thrombus formation, coagulation and platelet function can be accurately measured in vitro in patient blood samples. When the device is integrated into an extracorporeal circuit in pig endotoxemia or heparin therapy models, it produces real-time readouts of alterations in coagulation ex vivo that are more reliable than standard clotting assays. Thus, this disposable device may be useful for personalized diagnostics and for real-time surveillance of antithrombotic therapy in clinic.

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confidence: 99%

A shear gradient-activated microfluidic device for automated monitoring of whole blood haemostasis and platelet function

et al. 2016

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“…There is an obvious trend that longer duration would result in more rescued subjects, at least in the earlier stages of sepsis. However, the use of extracorporeal blood filtration devices leads to increased risk of trombogenesis 40 and other undesired side effects 41 . That is why it is commonly administered with the use of anticoagulants like heparin.…”

Section: Resultsmentioning

confidence: 99%

Effectiveness of Multiple Blood-Cleansing Interventions in Sepsis, Characterized in Rats

Stojković

Ghalwash

Cao

et al. 2016

Sci Rep

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Sepsis is a serious, life-threatening condition that presents a growing problem in medicine, but there is still no satisfying solution for treating it. Several blood cleansing approaches recently gained attention as promising interventions that target the main site of problem development-the blood. The focus of this study is an evaluation of the theoretical effectiveness of hemoadsorption therapy and pathogen reduction therapy. This is evaluated using the mathematical model of Murine sepsis, and the results of over 2,200 configurations of single and multiple intervention therapies simulated on 5,000 virtual subjects suggest the advantage of pathogen reduction over hemoadsorption therapy. However, a combination of two approaches is found to take advantage of their complementary effects and outperform either therapy alone. The conducted computational experiments provide unprecedented evidence that the combination of two therapies synergistically enhances the positive effects beyond the simple superposition of the benefits of two approaches. Such a characteristic could have a profound influence on the way sepsis treatment is conducted.

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“…25,26,29,36 However, the role of the microfluidic network geometry in the thrombogenicity of devices such as extracorporeal oxygenation machine (ECMO), left ventricular assist devices, and nanomembrane hemodialysis cassettes is not well defined. 6,8,67 An integrated approach of studying blood flow and thrombus formation within microfluidic networks in the presence of coagulation may be useful in understanding how the physical biology of a microfluidic device promotes thrombus formation, which may help in the development of safer therapeutic device designs. Moreover, this approach may further help predict the risk of thrombus formation within physiological microvascular network geometries found in human organs, such as the spleen, placenta, kidney and brain.…”

Section: Discussionmentioning

confidence: 99%

Dynamics of Blood Flow and Thrombus Formation in a Multi-Bypass Microfluidic Ladder Network

et al. 2016

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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. Red blood cells and platelets were assumed to be non-interacting spherical particles transported by the bulk fluid flow, and convection of the activated coagulation factor II, thrombin, was assumed to be governed by mass transfer. This model served as the basis for predicting formation of local shear rate gradients, stagnation points and recirculation zones as dictated by the bypass geometry. Based on the insights from these models, we were able to predict the patterns of blood clot formation at specific locations in the device. Our experimental data was then used to adjust the model to account for the dynamical presence of thrombus formation in the biorheology of blood flow. The model predictions were then compared to results from experiments using recalcified whole human blood. Microfluidic devices were coated with the extracellular matrix protein, fibrillar collagen, and the initiator of the extrinsic pathway of coagulation, tissue factor. Blood was perfused through the devices at a flow rate of 2 µL/min, translating to physiologically relevant initial shear rates of 300 and 700 s−1 for main channels and bypasses, respectively. Using fluorescent and light microscopy, we observed distinct flow and thrombus formation patterns near channel intersections at bypass points, within recirculation zones and at stagnation points. Findings from this proof-of-principle ladder network model suggest a specific correlation between microvascular geometry and thrombus formation dynamics under shear. This model holds potential for use as an integrative approach to identify regions susceptible to intravascular thrombus formation within the microvasculature as well as extravascular devices such as ECMO.

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Severe Clotting During Extracorporeal Dialysis Procedures

Cited by 10 publications

References 47 publications

A shear gradient-activated microfluidic device for automated monitoring of whole blood haemostasis and platelet function

A shear gradient-activated microfluidic device for automated monitoring of whole blood haemostasis and platelet function

Effectiveness of Multiple Blood-Cleansing Interventions in Sepsis, Characterized in Rats

Dynamics of Blood Flow and Thrombus Formation in a Multi-Bypass Microfluidic Ladder Network

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