Portable device rapidly assesses blood clotting

SAN DIEGO — ClotChip, a novel dielectric microfluidic sensor, uses a single drop of blood to rapidly provide a complete report on a patient’s ability to clot blood, according to study results presented at the ASH Annual Meeting and Exposition.

Perspective from Howard Liebman, MD

The device demonstrated sensitivity to multiple coagulation factors and platelet activity and has the potential to be used as point-of-care coagulation testing for the diagnosis of a bleeding patient — to help clinicians know if they have taken anticoagulant or antiplatelet medications to assess whether an antidote is needed — or in trauma-induced coagulopathy.

Evi X. Stavrou

Such an assessment was previously only available through specialized laboratory testing.

“Early indication of bleeding risk is important for patients who are critically ill, severely injured, or on anticoagulation and antiplatelet therapy,” Evi X. Stavrou, MD, assistant professor of medicine at Case Western Reserve School of Medicine, said during a press conference. “We know that conventional laboratory tests, such as the PT and the aPTT, are costly, labor intensive and provide an assessment of blood coagulation only.

“Existing handheld point-of-care devices used to monitor specific patients provide the crude assessment of the coagulation process, but they do not account for the distribution of platelet and leukocytes to the hemostatic process,” Stavrou added. “There is a need for a low-cost and easy-to-use portable platform that will enable the point-of-care assessment of the entire hemostatic process outside of a central laboratory.”

Stavrou and colleagues developed ClotChip, a dielectric microsensor that uses dielectric spectroscopy, which is a fully electrical technique, to monitor blood coagulation using a single drop of blood.

Researchers evaluated ClotChip compared with conventional tests using blood samples from 11 healthy donors. This analysis showed the time to peak normalized permittivity readout levels correlated with coagulation time.

Researchers then evaluated ClotChip in 12 patients with clotting disorders, including hemophilia A and B, acquired von Willebrand factor defect and mild congenital hypo-dysfibrinogenemia.

Compared with normal samples, the permittivity curves from the samples of clotting disorders had significant prolongation in the time to peak parameter from the normal range of 4.5 to 6 minutes, to 6.5 to 15 minutes (P = .0002).

Results showed ClotChip had a greater degree of sensitivity for the diagnosis of a coagulation defect. Further, the device results in a lower rate of false-negative results.

In vitro platelet inhibition studies with whole blood from healthy volunteers treated with prostaglandin E2 to inhibit platelet function showed the addition of prostaglandin E2 causes a significant decrease in peak permittivity (P < .02).

“These data show that the ClotChip is not only able to capture platelet function defects, but it also gives a discriminatory reading compared with coagulation defects,” Stavrou said.

Since this analysis, researchers have developed a second-generation device that measures the anticoagulant effect of target-specific oral anticoagulant agents.

“Our device gives you different information — and more information — than other devices out there,” Stavrou said in a press release. “The sensitivity and discriminatory ability of the devices, when compared to standard coagulation tests, is what excites me very much.” – by Alexandra Todak

Reference:

Stavrou EX, et al. Abstract 3754. Presented at: ASH Annual Meeting and Exposition; Dec. 3-6, 2016; San Diego.

Disclosure: The study was funded in part by the Case-Coulter Translational Research Partnership and the Advanced Platform Technology Center, a Veterans Affairs Research Center of Excellence at Case Western Reserve University. The researchers report no relevant financial disclosures.

Perspective

Howard Liebman, MD

This report is very preliminary. A number of new technologies are developed that have no immediate applications. Even when you look at the theoretical application of a novel point-of-care hemostatic assay, it does not solve the clinical issues of identifying the underlying defect. This assay system is based upon the application of a new chip that could potentially be put into a handheld point-of-care device that can take a miniscule amount of whole blood and show that there is a defect in the generation of a clot in that whole blood. Beyond this, defining the underlying defect requires well-established laboratory studies. It will not necessarily differentiate a platelet defect from a hemostatic protein deficiency or defect.
It could have application in monitoring the hemostatic effect of various antithrombotic (anticoagulant) agents or the effect of an antiplatelet agent. Therapeutic ranges would have to be determined for each hemostatic modulating agent. Therefore, a lot more work is needed to determine how to best utilize this tool. The investigators used the chip to determine the time to peak thrombin generation and could assess the height of the peak. In most of the patients with clotting-protein deficiencies, it just shifts the lag time. Researchers only evaluated seven patients with very significant coagulation defects. They did not include patients with subtle coagulation defects. There was an effort to produce an acquired platelet defect, but the researchers did not look at patients with known platelet defects.
How would the investigators determine the therapeutic lag-time shift for various indications when used either to assess factor replacement in a hemophiliac or assess the effect of an oral Factor Xa inhibitor? It might have value in warfarin monitoring, but would it be better than the present home monitoring devices? At present, I do not see this as being a significant advance in hemostatic monitoring. It is a fantastic technology, but the researchers are going to have to find some way of showing that it is applicable to clinical situations, and there is nothing in this preliminary report to support it is clinically applicable.

Howard Liebman, MD

Keck School of Medicine

University of Southern California

Disclosures: Liebman reports no relevant financial disclosures.