Daniel Korya, MD
Kirkpatrick AC, Tafur AJ, Vincent AS, Dale GL, and Prodan CI. Coated-Platelets Improve Prediction of Stroke and Transient Ischemic Attack inAsymptomatic Internal Carotid Artery Stenosis. Stroke. 2014
In his published lectures of 1886, Sir William Osler, the “Father of Modern Medicine”, described platelets as colorless protoplasmic discs. He called them “blood plates” and defined them as the third corpuscle. In the mid-1800’s, the French physician Albert Donne may have been one of the first to identify platelets as a distinct entity when he claimed there was a more elusive third component to blood other than erythrocytes and leukocytes.
In 2005, Dale introduced a subset of platelets that were produced after co-activation with collagen and thrombin, called “coated-platelets”. This population of platelets was more likely to be elevated in patients with large vessel ischemic strokes as compared with small vessel ischemic strokes. Coated-platelets comprised about 30% of the total platelet population in average persons, while they made up 39.4% of platelets in patients with large vessel strokes and only 21.8% in patients with small vessel strokes. Patients with symptomatic large-artery atherosclerosis with coated-platelet levels of 50% or greater were almost 7 times more likely to have recurrent strokes as compared with patients with less than 50% coated-platelet levels.
The most famous large artery to cause ischemic stroke is the carotid artery. We know from prior studies that patients with symptomatic carotid artery stenosis (CAS) stand to benefit from carotid stenting or endarterectomy. The benefits of revascularization for patients with asymptomatic disease are less certain. In fact, the risk of stroke in patients with asymptomatic CAS has recently been reported to be as low as 1%. Predicting who the 1% will be has proved challenging. Now, thanks to Kirkpatrick and her colleagues, we may have a new weapon in the fight against stroke.
This prospective study evaluated 329 patients with asymptomatic CAS who had adequate Doppler ultrasound performed with the percentage of stenosis documented. These patients were then followed up to 39.8 months with a median of 10.1 months to determine rates of stroke, TIA, vascular death and revascularization (repeated Doppler). A coated-platelet assay was used to determine the percent of coated-platelets in these patients. Important information pertaining to these patients was also recorded; such as, use of medications that can influence coated-platelet levels (SSRI, statin or anti-platelet agent), history of hypertension, diabetes, dyslipidemia, CAD, PAD or ESRD.
The major findings of this study were quite powerful. The “magic numbers” to keep in mind here are 50% and 45%. There were patients with 50% or greater CAS and patients with less than 50% CAS. Some of these patients had 45% or greater coated-platelets and some of them had less than 45% coated-platelets. Patients who had 45% or greater coated-platelets were compared based on their level of CAS, and the patients with 50% or greater CAS had a 45.2 hazard ratio (p=.0004) and an incidence of 21.54 events (ipsilateral stroke or TIA) per 100 person-years. Patients who had less than 45% coated-platelets were then split up into their respective two groups: 50% or greater CAS versus less than 50% CAS. In patients with less than 45% coated-platelets the level of carotid artery stenosis did not make a difference (i.e. there was no difference in the hazard ratio), and the event rate was 1.27 per 100 person-years.
Based on these results, Kirkpatrick was able to stratify asymptomatic patients with 50% or greater CAS into a “low-risk” category if their coated-platelets were less than 45%. Conversely, they were also able to determine which patients may benefit from early revascularization despite not having a significant degree of stenosis. With this regard, this study is potentially a game-changer and may warrant the inclusion of coated-platelet assays in the work-up and treatment strategy of all patients with CAS.