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Team creates ‘more reliable’ coagulation assay


 

Hemostasis-monitoring device

Photo courtesy of the Wyss

Institute at Harvard University

Scientists have developed a blood coagulation assay that, they say, is more reliable than existing assays and could one day be used to diagnose rare bleeding disorders and prevent toxic effects of anticoagulant and antiplatelet drugs.

The team created a microfluidic device with hollow channels through which blood is flowed and devised an algorithm for analyzing patient-specific data to predict when blood clots will form.

Together, these components make up the assay, which can monitor blood coagulation and platelet function.

Donald Ingber, MD, PhD, of the Wyss Institute for Biologically Inspired Engineering at Harvard University in Boston, Massachusetts, and his colleagues described the assay in Nature Communications.

The team developed a microfluidic device in which blood flows through a life-like network of small “vessels.” The blood is subjected to true-to-life shear stresses and force gradients of the human vascular network.

The device contains hollow channels that mimic the pathology of the narrowing of small blood vessels, which can often cause a shift in the fluid mechanics of blood flow that can lead to life-threatening blood clots or internal bleeds.

The device mimics rapid changes in blood flow dynamics associated with stenosis or narrowing of small blood vessels by pumping pressurized blood flow through the device’s microfluidic channels.

Using automated pressure sensors and a proprietary algorithm, data acquired from the device is analyzed in real-time, thereby predicting the time at which a certain blood sample will obstruct the blood vessel network.

“By combining our fabricated microfluidic device that mimics blood flow dynamics of small arterioles with our novel data analysis software, we can rapidly quantitate hemostasis in real-time and predict if blood clots will develop in an individual or blood sample,” Dr Ingber explained.

He and his colleagues found they could accurately monitor the effects of anticoagulant and antiplatelet drugs in blood samples from human subjects.

The team was able to monitor platelet function as well. In particular, they found they could detect abnormal platelet function in samples from patients with Hermansky–Pudlak syndrome, a rare bleeding disorder characterized by a deficiency of platelet-dense granules that cannot be easily identified using conventional assays.

The novel assay also proved successful in large animal experiments. The scientists integrated their device directly into a vascular access line that was inserted into the femoral vein of a living pig to measure clinical clotting parameters over time. They recorded precise predictions for clotting times that were more accurate and faster than currently used clinical assays.

The team noted that their device uses inexpensive in-line pressure sensors to measure clot formation. As a result, it does not require additional instrumentation, and it can be integrated directly into the blood lines of extracorporeal devices.

The scientists said the device’s ability to be configured for lab use or real-time patient monitoring opens the door for countless potential uses that could improve patient care.

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