Abstract
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.
Highlights
Accurate assessment of blood haemostasis is essential for the management of patients who use extracorporeal devices, receive anticoagulation therapy or experience coagulopathies
Various tests and devices have been developed over many decades to assess blood clotting and platelet function in vitro, including assays for bleeding time, activated clotting time (ACT), activated partial thromboplastin time, thromboelastography and platelet aggregometry
While these tests provide useful information regarding coagulation status or platelet function, they are limited in terms of their ability to predict thrombotic or bleeding risk in clinical settings[10,11,12] at least in part because they fail to incorporate many of the key contributors to haemostasis control that exist in vivo
Summary
Accurate assessment of blood haemostasis is essential for the management of patients who use extracorporeal devices, receive anticoagulation therapy or experience coagulopathies. Microfluidic devices and parallel plate flow chambers that mimic atherosclerotic confinement of vessels and reconstitute physiological shear rates and gradients have been developed for basic research studies using human whole blood in combination with extracellular matrix (for example, collagen) surface coatings[15,18,19] These studies confirmed that haemostasis induced by blood contact with matrix varies depending on local flow conditions; the basic insights gained from these studies have not been translated into clinical practice, mainly because these devices are not designed for bedside use or they require highly specialized instrumentation and imaging systems[19,20,21,22,23]. We show that the device can be integrated directly into vascular access lines and blood-contacting medical devices for real-time ex vivo monitoring of changes in haemostasis within native flowing blood
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