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Updated: Dec 18, 2025

Comprehensive Analysis of Procoagulant Platelets Exhibiting Features of Necrosis, Apoptosis and Platelet Activation
Published on: May 23, 2025
Incidence and characteristics of spontaneous platelet macro-aggregation in acute ischemic stroke
Tomohiro Osanai1, Kasumi Mikami2, Maiko Kitajima2
1Department of Nursing Science, Hirosaki University Graduate School of Health Science, 66-1 Hon-cho, Hirosaki, 036-8564, Japan. osanait@hirosaki-u.ac.jp.
Abstract:
Spontaneous platelet aggregation is a trigger for additional development of larger thrombi. Micro-aggregation is observed in 10% of diabetes approximately and blocked by P2Y12 inhibitors, whereas macro-aggregation is associated with overexpression of platelet α2-adrenoreceptors and is not blocked by conventional anti-platelet medicines. We examined the incidence of spontaneous platelet macro-aggregation (SPMA) in acute ischemic stroke and analyzed its clinical characteristics. Out of 665 consecutive acute ischemic strokes, SPMA was found in 10 patients (1.5%, one tenth of micro-aggregation) despite no detection in 588 control subjects. Types of ischemic stroke were 4 atherothrombotic, 4 cardioembolic, and 2 lacunar strokes. Stroke with SPMA exhibited higher (worse) values of modified Rankin Scales (mRS) at discharge (3.00 ± 0.53 vs 1.93 ± 0.07, p = 0.042 by Wilcoxon) compared with stroke without SPMA despite no difference at admission. The proportion of patients who were functionally independent (score 0-2 on the mRS) at discharge was lower in stroke with SPMA compared with stroke without SPMA (p < 0.05 by chi-square test; OR 3.60, 95% CI 1.08-12.03; RR 2.04, 95% CI 1.05-2.86). It was intriguing that severe (high magnitude) SPMA was observed in 4 atherothrombotic stroke. Although anti-platelet therapy underwent, the proportion of atherothrombotic patients who were functionally improved and independent at discharge was lower in the presence of SPMA compared with the absence of SPMA (p < 0.05 by chi-square test). The patients with SPMA were more likely to be older, having major disabilities, being less functionally improved during hospitalization, and being less functionally independent at discharge.
Insights
Spontaneous platelet macro-aggregation (SPMA) occurs in 1.5% of acute ischemic stroke patients and is linked to worse functional outcomes. This condition, unlike micro-aggregation, is not effectively treated by standard anti-platelet medications.
Area of Science:
- Cardiovascular Research
- Neurology
- Hematology
Background:
- Spontaneous platelet aggregation contributes to thrombus formation.
- Micro-aggregation is common in diabetes and responsive to P2Y12 inhibitors.
- Macro-aggregation involves platelet α2-adrenoreceptors and resists conventional anti-platelet drugs.
Purpose of the Study:
- To investigate the incidence of spontaneous platelet macro-aggregation (SPMA) in acute ischemic stroke.
- To analyze the clinical characteristics and outcomes of stroke patients with SPMA.
Main Methods:
- Retrospective analysis of 665 consecutive acute ischemic stroke patients.
- Comparison of SPMA incidence between stroke patients and 588 control subjects.
- Assessment of clinical characteristics, stroke types, and functional outcomes using modified Rankin Scale (mRS).
Main Results:
- SPMA was detected in 1.5% of acute ischemic stroke patients, with none in controls.
- Stroke patients with SPMA showed significantly worse mRS scores at discharge (3.00 ± 0.53 vs 1.93 ± 0.07).
- Patients with SPMA had lower functional independence at discharge (mRS 0-2) and poorer outcomes, especially in atherothrombotic stroke cases, despite anti-platelet therapy.
Conclusions:
- SPMA is a distinct clinical entity in acute ischemic stroke, associated with poorer functional outcomes.
- SPMA is more prevalent in older patients with major disabilities, leading to less functional improvement.
- Current anti-platelet therapies appear less effective in mitigating the negative impact of SPMA on stroke recovery.
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