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Stroke Clot Composition Linked to Functional Outcomes, Death
Study hints at personalized treatment potential
The relative composition of ischemic stroke clots was associated with mortality and disability prognosis, according to a large study.
Those who had clots rich in red blood cells (RBCs) had better outcomes, while platelet content contributed to greater risk, reported Raul G. Nogueira, MD, of the University of Pittsburgh, during the American Stroke Association's International Stroke Conference (ISC), held virtually and in person in New Orleans.
For each 10% increase in RBC content of a clot, the odds ratio of functional independence at 90 days after a stroke (modified Rankin Scale score 0-2 or return to baseline function) rose a relative 18% and the odds of death fell 16%, both statistically significant.
For each 10% higher platelet content in the clot, the unadjusted odds of such a good neurologic outcome fell by a relative 11% and odds of mortality rose 16%, again both significant.
While RBC content has long been tied to softer clots easier to remove with endovascular therapy, the role of platelets has been "somewhat neglected," Nogueira noted at an ISC press conference.
Still, "they have the potential to modify the mechanical properties of the clot and therefore affect the outcomes after thrombectomy," he said. "Also, the more erythrocytic components you have, the more friable the clot is, so it has a higher tendency to break apart and cause distal embolization."
Indeed, in the study, platelet composition appeared to modify the advantage of an RBC-rich clot, with significant interaction terms. Good functional outcome at 90 days was seen in 62.8% of patients with RBC-rich, platelet-poor clots, and 50.8% of those with RBC-rich, platelet-rich clots (P=0.052). Mortality at 90 days occurred in 10.0% and 18.8%, respectively (P=0.045).
The study utilized clot samples retrieved as part of the observational EXCELLENT registry for first-line, real-world use of the EmboTrap thrombectomy device in an "all-comer" population. Of the 36 participating centers, 25 collected clots for immunohistological and MSB staining analysis, yielding 543 for analysis at central laboratories in the U.S. and Europe.
RBC-rich clots were defined as those with more than 45% RBCs, which were then subdivided into those with more than the median 30.7% platelet composition, deemed platelet rich, and those with a platelet-to-fibrin ratio at or below the median 1.52, considered low in fibrin. The samples were fairly evenly divided among the subtypes.
Fibrin content wasn't a significant factor in mortality and functional outcomes, nor was there a significant interaction of platelet contribution to RBC-poor clots.
"These nuances are important," commented ISC program vice-chair Tudor G. Jovin, MD, of the Cooper Neurological Institute in Camden, New Jersey, at the press conference.
The next step for research is to identify clot composition, not histologically after removal, but through imaging, biomarkers, or some other means before thrombectomy, he suggested. "This study is getting us a step closer to this paradigm of individualized medicine where we figure out before the clot is removed what the essential component of the clot composition is, so that we can tailor treatments accordingly."
Analyses accounting for other variables, such as anticoagulation use by the patient and calcification in the clot, are ongoing, Nogueira noted.
Conference program chair Louise McCullough, MD, PhD, of the University of Texas Health Science Center at Houston, pointed to other results presented at the conference showing benefits from adding intra-arterial thrombolytics after complete revascularization with thrombectomy.
If we could quickly determine if a clot is RBC-rich right in the interventional suite, "it may be we could stratify who would benefit," she said during the press conference that she moderated.
It's possible that high-RBC clots, which are more prone to embolization, could benefit even more from this type of "cleaning-up approach," Nogueira agreed.
Other potential personalization would be to give an intra-arterial antiplatelet for platelet-rich clots compared with adjunctive tissue plasminogen activator, McCullough told MedPage Today.
Another key question that clot composition could potentially answer in the future is how to prevent subsequent strokes, commented Tapan Mehta, MD, MPH, of the Ayer Neuroscience Institute at Hartford Hospital in Connecticut, who has also researched clot composition.
Looking for the source of the clot after the fact -- whether carotid artery or cardiac emboli -- is the best clinicians can do now, he told MedPage Today. "But if somehow we could correlate the red blood cell, fibrin, and platelet content consistently to the origin of the clot, that would be a huge help ... because we can change the type of prophylactic medication we use: whether we use aspirin, whether we use Coumadin [warfarin], or whether we use one of the newer anticoagulants."
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Disclosures
The EXCELLENT registry was sponsored by Cerenovus.
Nogueira disclosed consulting fees for advisory roles with Anaconda, Biogen, Cerenovus, Genentech, Hybernia, Imperative Care, Medtronic, Phenox, Philips, Prolong Pharmaceuticals, Stryker Neurovascular, Shanghai Wallaby, and Synchron, as well as stock options for advisory roles with Astrocyte, Brainomix, Cerebrotech, Ceretrieve, Corindus Vascular Robotics, Vesalio, Viz-AI, RapidPulse, and Perfuze.
Primary Source
International Stroke Conference
Source Reference: Nogueira RG, et al "Outcomes and clot composition in the EXCELLENT registry" ISC 2022; Abstract LB20.
