Artificial blood vessels

on a microfluidic chip

Credit: Rob Felt

New research suggests a microfluidic device could help physicians choose the appropriate antiplatelet therapy for patients in need of thromboprophylaxis.

Study investigators ran patient blood samples through the microfluidic device to compare the effects of 3 antiplatelet agents—aspirin, eptifibatide, and heparin—on occlusion times and thrombus detachment.

They found that shear rates had a significant impact on treatment effects.

Although aspirin was effective at low shear rates, it proved largely ineffective at high shear rates, even with increasing doses. And the same was true of heparin.

Eptifibatide was affected by shear rates but still lengthened occlusion times and decreased the risk of thrombus detachment. At higher doses, the drug could prevent occlusion regardless of shear rate.

Melissa Li, PhD, of the University of Washington in Seattle, and her colleagues reported these results in PLOS ONE.

“Doctors have many drug options, and it is difficult for them to determine how well each of those options is going to work for a patient,” Dr Li said. “This study is the first time that a prototype benchtop diagnostic device has tried to address this problem using varying shear rates and patient dosing and tried to make it more personalized.”

The researchers used the microfluidic device to measure occlusion times and thrombus detachment for a range of shear rates (500, 1500, 4000, and 10000 s^-1) and drug concentrations (0-2.4 μM for eptifibatide, 0-2 mM for aspirin, and 3.5-40 units/L for heparin).

The team took blood samples from healthy patients, added the drugs to the samples, and ran them through the device. The device has 4 channels that mimic the coronary arteries, which allowed the investigators to study clotting under a variety of conditions.

Results showed that eptifibatide lengthened occlusion time, but the time decreased as shear rates increased. Increasing doses of the drug reduced the risk of occlusion, however. At doses greater than 1.2 μM, eptifibatide prevented occlusion at all shear rates.

Aspirin was unable to fully prevent occlusive thrombosis at high shear rates (4000 and 10000 s^-1), even at doses of 2 mM, which is 20 times the recommended daily oral dose.

However, the drug did prevent nearly all occlusive thromboses at low shear rates (500 and 1500 s^-1), even at the lowest doses tested. The researchers said they observed identical trends in aspirin and heparin.

When they controlled for shear rate, dosage, and inter-subject variability, the investigators found that occlusion rates were significantly different with the 3 therapies.

Compared to samples treated with eptifibatide, those treated with aspirin had a 4-fold greater risk of occlusion, and those treated with heparin had a 9-fold greater risk. An untreated sample had 14 times the risk of occlusion as an eptifibatide-treated sample.

The researchers also assessed the risk of thrombus detachment and found that eptifibatide lowered the risk, while aspirin raised it. Compared to no therapy, the odds ratios were 0.72 for eptifibatide and 4.48 for aspirin.

Dr Li said this evidence suggests that aspirin can prevent thrombosis in some patients but may not be effective in others, particularly those with atherosclerosis. The team’s device could one day help physicians identify which patients can benefit from aspirin and which cannot, although more testing is needed.

“This finding is something that’s been echoed in the literature by physicians who would find that a number of patients who would take aspirin were not receiving any clinical benefit,” Dr Li said. “What we showed is a good explanation for the conditions under which aspirin resistance occurs and one that matches up with what other people have found.”

On the other hand, as eptifibatide could prevent thrombosis across all shear rates, this research suggests the drug (and other GPIIb/IIIa inhibitors) could be effective for patients whether or not they had atherosclerosis. Dr Li noted that clinical evidence supports this finding.

Device measures drugs’ antithrombotic activity