AT ASH 2016

SAN DIEGO (FRONTLINE MEDICAL NEWS) – Using less than a drop of blood, a portable microsensor provided a comprehensive coagulation profile in less than 15 minutes and perfectly distinguished various coagulopathies from normal blood samples – handily beating the results with both activated partial thromboplastin time (aPTT) and prothrombin time (PT).

Dubbed ClotChip, the disposable device detects coagulation factors and platelet activity using dielectric spectroscopy, Evi X. Stavrou, MD, said at the annual meeting of the American Society of Hematology. The development points the way for comprehensive, rapid, point-of-care assessment of critically ill or severely injured patients and those who need ongoing monitoring to evaluate response to anticoagulant therapy, she added.

Existing point-of-care coagulation assays have several shortcomings, Dr. Stavrou, of Case Western Reserve University, Cleveland, said during a press briefing at the conference. They are relatively insensitive, fail to measure platelet activity, or are only approved for specific subgroups of patients, such as those on warfarin, she specified.

To develop an alternative, Dr. Stavrou and her associates added a parallel-plate capacitive sensing structure to an inexpensive, disposable microfluidic biochip designed to test 9 microliters (less than one drop) of blood. They built the microsensor from biocompatible and chemically inert materials to minimize the chances of artificial contact activation.

To test the device, the researchers used calcium dichloride to induce coagulation in whole blood samples from 11 controls with normal aPTT and PT values. Time curves of output from the microsensor showed that coagulation consistently peaked within 4.5 to 6 minutes.

Next, the investigators tested blood from 12 patients with coagulopathies, including hemophilia A, hemophilia B, acquired von Willebrand factor defect, and congenital hypodysfibrinogenemia. These samples all yielded abnormal curves, with prolonged times to peak that ranged between 7 and 15 minutes – significantly exceeding those of healthy controls (P = .0002).

By plotting rates of true positives against rates of true negatives, the researchers obtained areas under the receiver operating curves of 100% for ClotChip, 78% for aPTT, and 57% for PT. In other words, ClotChip correctly identified all cases and controls in this small patient cohort, which neither aPTT or PT did.

Finally, the researchers used the microsensor to measure coagulation activity in normal blood samples that they treated with prostaglandin E2 to inhibit platelet aggregation. Normalized permittivity (an electrical measure) was significantly lower than in untreated control samples (P = .03), but time to peak values were the same in both groups. This finding confirms that the chip can identify abnormal platelet function, Dr. Stavrou said. “ClotChip is sensitive to the complete hemostasis process, exhibits better sensitivity and specificity than conventional coagulation assays, and discriminates between coagulation and platelet defects,” she concluded.

The investigators are recruiting volunteers for an expanded round of testing for the device, and are working to optimize construction to further enhance its sensitivity.

Dr. Stavrou and her coinvestigators had no relevant financial disclosures.