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News from the AAN Annual Meeting
Coated-Platelets Are Reported to Be Associated With Carotid Stenosis Progression



ARTICLE IN BRIEF

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DR. ANGELIA KIRKPATRICK: “Were thinking that since coated-platelets are associated with increased thrombin production, or support increased thrombin production locally when theyre activated, then perhaps they may be contributing to progression of atherosclerosis by a thrombin-mediated mechanism, and that they may also participate in some way with recruitment and activation of inflammatory cells at the endothelium.”

Coated-platelets — a subpopulation of platelets that can be observed upon stimulation with collagen and thrombin — were found to be associated with carotid stenosis progression.

WASHINGTON—Coated-platelets are associated with carotid stenosis progression, according to a study presented here at the AAN Annual Meeting in April.

Coated-platelets — a subpopulation of platelets that can be observed upon stimulation with collagen and thrombin — support a robust prothrombinase activity, retain high levels of several procoagulant proteins on the cell surface, and are considered to be prothrombotic. They are measured using a specially designed assay that uses blood drawn from the patients.

The study is the latest to find an association between coated-platelets and stroke risk.

In a study of 86 asymptomatic carotid stenosis patients, the percentage of cells converted to coated-platelets was significantly higher in those whose stenosis worsened over more than 16 months compared with those whose stenosis did not worsen (p=0.04), researchers said.

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DR. LARRY GOLDSTEIN: “The observation of an association between the proportion of coated-platelets in an individual and progression of carotid stenosis is intriguing, and could lead to interventions to reduce progression. However, more needs to be learned about the function of this class of platelets and the results need to be replicated in a larger population.”

“The levels were about 10 percent higher among the progressors compared with the non-progressors,” said Angelia Kirkpatrick, MD, MPH, an assistant professor in the cardiovascular section of the department of medicine at the University of Oklahoma Health Sciences Center. “And that's a pretty significant range.”

Coated-platelets have emerged as an area of interest in recent years in acute coronary syndrome, stroke, diabetes, and other areas.

Researchers at the University of Oklahoma Health Sciences Center have been studying the platelets for about 10 years. They have found that increased levels of the platelets are associated with large artery stroke in the acute setting. In 2014, they reported in the journal Platelets that patients with symptomatic large artery stenosis, who also had the highest levels of coated-platelets, had the highest levels of stroke recurrence.

In another small study published last year in Stroke, they found that elevated levels of coated-platelets were associated with stroke risk in asymptomatic patients with carotid artery stenosis and a stenosis level of at least 50 percent.

STUDY METHODOLOGY

The current study analyzed data on 86 patients drawn from the 329-patient Coated-Platelets in Asymptomatic Carotic Stenosis (CoPACS) study. Patients were categorized by stenosis level using carotid duplex ultrasound. The patients were assessed at least once for carotid stenosis, at an average interval between screenings of 16.5 months. The severity of the stenosis was found to have increased in 23 patients.

Among those whose stenosis had progressed, the average coated-platelet level was 44.7 percent; for those who did not progress, it was 35 percent.

Statin use was also correlated with stenosis progression (p=0.04), but Dr. Kirkpatrick said it's likely that those patients were at a higher risk already. In an analysis of predictors of stenosis progression, researchers found that only coated-platelet levels were significant.

Dr. Kirkpatrick said she hopes that the findings help to further guide research and illuminate the role of coated-platelets in stroke risk.

“We're thinking that since coated-platelets are associated with increased thrombin production, or support increased thrombin production locally when they're activated, then perhaps they may be contributing to progression of atherosclerosis by a thrombin-mediated mechanism, and that they may also participate in some way with recruitment and activation of inflammatory cells at the endothelium,” she said.

But she added that the current study should lay the groundwork for future investigations. “This is hypothesis-generating, so we're looking to study these patients further. This is a very small study, it's 86 patients,” she said.

“Our goal is to prospectively collect patients again that are referred for ultrasound assessment, follow the ones that have more than 50 percent stenosis with ultrasounds every six months, get the baseline coated-platelet levels, and get a larger participation at follow-up.”

Then, she said, researchers can get a better handle, with larger patient numbers, on whether coated-platelets are really predictive.

“We can look at other variables that may be playing a role as well,” she said.

EXPERT COMMENTARY

Larry Goldstein, MD, director of the Duke Stroke Center and soon-to-be co-director of the Kentucky Neuroscience Institute at the University of Kentucky, said that the results were interesting, but that the role these platelets might be playing is still not well understood.

“Platelets have two major functions: adherence to the site of vascular injury, and providing a surface for thrombin generation,” he explained. “Coated-platelets are a subclass that have proteins on their surface that may promote clotting, but much about their function is unknown.

“The observation of an association between the proportion of coated-platelets in an individual and progression of carotid stenosis is intriguing, and could lead to interventions to reduce progression,” he added. “However, more needs to be learned about the function of this class of platelets and the results need to be replicated in a larger population. It also needs to be recognized that the association does not prove causality, as there is always a risk of residual confounding in this type of study.”

LINK UP TO MORE INFORMATION:


•. AAN Annual Meeting Abstract: Coated-platelet levels are associated with stenosis progression in patients with carotid atherosclerosis: http://bit.ly/coatedplatelets-NT
    •. Kirkpatrick AC, Stoner JA, Dale GL, et al. Elevated coated-platelets in symptomatic large-artery stenosis patients are associated with early stroke recurrence http://informahealthcare.com/doi/abs/10.3109/09537104.2013.775570. Platelets 2014;25(2):93–96.
    •. Kirkpatrick AC, Tafur AH, Vincent AS, et al. Coated-platelets improve prediction of stroke and transient ischemic attack in asymptomatic internal carotid artery stenosis http://stroke.ahajournals.org/content/45/10/2995.long. Stroke 2014;45(10):2995–3001.