Clot's Platelet Content May Affect Thrombectomy Outcomes

Erik Greb

February 28, 2022

The platelet content of a clot may be at least as strong a predictor of outcome and mortality following mechanical thrombectomy as fibrin content, new data suggest.

Researchers analyzed clot composition for about 1000 patients with acute ischemic stroke who were included in a prospective, multicenter registry. Among clots rich in red blood cells (RBCs), higher platelet content was associated with reduced likelihood of a good patient outcome at 90 days (odds ratio [OR], 0.89 per 10% increase in platelet content).

"This is all about precision medicine: how you attack these different types of clots," said investigator Raul Nogueira, MD, director of the University of Pittsburgh Medical Center Stroke Institute, Pittsburgh, Pennsylvania.

The findings were presented at the recent International Stroke Conference 2022, which was held in New Orleans and virtually because of the pandemic.

Examining EXCELLENT Data

Mechanical thrombectomy has become an established and effective treatment for ischemic stroke. Clots that are rich in RBCs are more deformable and considered easier to remove, the researchers note. Clots rich in fibrin, on the other hand, have a higher coefficient of friction and are more challenging to extract.

Platelets are another important component of clots, but their effects on the mechanical properties of clots have not been examined as extensively as those of RBCs and fibrin. The current investigators hypothesized that platelets would affect the outcomes of mechanical thrombectomy.

They examined data from the EXCELLENT registry, which includes prospective, observational data for patients with acute ischemic stroke who underwent first-line mechanical thrombectomy using the EmboTrap device. Participants were enrolled at 36 US and European sites from September 2018 to March 2021.

The registry includes procedural, clinical, and imaging data. Most study sites also collected clot material for immunohistologic analysis. The current investigators classified clots as RBC-rich if RBCs represented more than 45% of their content. Otherwise, clots were considered RBC-poor. The investigators further divided these two groups according to median platelet content (30.7%) and median platelet-to-fibrin ratio (1.52).

The investigators conducted a univariate logistic analysis to identify predictors of outcomes that were significantly different between the four types of clot composition.

Fewer Platelets, Better Outcomes

In all, 999 patients were included in this analysis. The population's mean age was 70 years, and approximately 52% of patients were women. Mean baseline NIH Stroke Scale score was 15.6, and 47.4% of patients had wake-up stroke or unwitnessed stroke. In addition, 38% of patients received tissue plasminogen activator (t-PA).

The time from stroke onset to first device deployment was less than 6 hours for 55.1% of patients. The median number of passes was one, and 85.2% of patients had three or fewer passes. In addition, 38.1% of patients achieved a modified thrombolysis in cerebral infarction (mTICI) flow of 2c or greater on the first pass.

Approximately 47% of patients had a modified Rankin Scale (mRS) score of 0 to 2, or a score less than or equal to baseline, at 90 days. The rate of all-cause mortality at 90 days was 19.1%.

Patients with RBC-poor clots were more likely to be older (P = .024) and female (P = .033) than patients with RBC-rich clots. Other baseline demographic characteristics were similar between these two groups.

Among patients with RBC-rich clots, the rate of mRS 0-2 at 90 days was 50.8% in patients with platelet-rich clots and 62.8% in patients with platelet-poor clots (P = .052). The rate of all-cause mortality at 90 days was 18.8% for platelet-rich clots and 10% for platelet-poor clots (P = .045).

In patients with RBC-poor clots, outcomes associated with platelet-rich and platelet-poor clots were similar. The overall rate of mRS of 0-2 at 90 days was about 38%. The overall rate of all-cause mortality at 90 days was approximately 25%.

"This is one of the first large, prospective registries to incorporate clot analysis," said Nogueira.

"There is no difference according to platelet content if you are RBC-poor," he said. "If you are in an RBC-rich clot, you can see that low platelets will give you higher chances of good outcome and lower mortality."

Nogueira acknowledged that the study findings were limited by baseline imbalances in clot characteristics between the four subgroups. "We await our multivariable analysis to confirm these results," he said.

Device "Looks Promising"

Commenting on the findings for Medscape Medical News, Louis R. Caplan, MD, professor of neurology at Harvard Medical School, Boston, Massachusetts, said that the EmboTrap device that was used in the study to remove clots "hasn't been popularized but looks promising and seems to be safe." The device is better able to retrieve intact clots than previously was possible, he added.

The long-accepted hypothesis was that clots that form in the blood vessels (or "white clots") mostly contained platelets and fibrin, and that clots forming in the heart ("red clots") mostly contained red blood cells and fibrin, but few platelets. The current data indicate that the story is not that simple, said Caplan, who was not involved in the study.

For some cardiogenic clots, antiplatelet drugs can be an important treatment for secondary prevention, with or without anticoagulants, Caplan added. More research is needed to study which heart lesions involve platelets.

Clot composition may also affect thrombolytic efficacy. "There's good evidence that thrombolytic drugs lyse red-cell-rich clots and don't do anything to platelets," said Caplan. "If it's a platelet-rich clot, then t-PA wouldn't be effective." Mechanical thrombectomy should be considered in this case, he added.

The study was funded by Cerenovus. Nogueira has received consulting fees from Anaconda, Biogen, Cerenovus, Genentech, Hybernia, Imperative Care, Medtronic, Phenox, Philips, Prolong Pharmaceuticals, Stryker Neurovascular, Shanghai Wallaby, and Synchron. He has received stock options from Astrocyte, Brainomix, Cerebrotech, Ceretrieve, Corindus Vascular Robotics, Vesalio, Viz-AI, RapidPulse and Perfuze. Caplan has disclosed no relevant financial relationships.

International Stroke Conference (ISC) 2022: Presentation LB20. Presented February 11, 2022.

Follow Erik Greb on Twitter: @MedscapeErik .

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