The Role of Platelet Aggregation and Activation as Biomarkers for Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage.

Background

Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) is increasingly attributed to thromboinflammation and microvascular platelet activation. Accordingly, we aimed to characterize longitudinal platelet aggregation, platelet activation, and platelet morphology in patients with aSAH and assessed their association with DCI.

Methods

This single-center prospective cohort consisted of 206 patients with aSAH. Of the 206 patients, 144 were analyzed via platelet aggregometry, 148 via flow cytometry, and 129 had both aggregometry and flow cytometry data. An additional 52 patients had morphology data. Peripheral blood was sampled on post-bleed days 1, 2, 4, 7, and 10. Platelet aggregation was measured by Chrono-Log aggregometry; platelet activation (PAC-1, CD62P) was measured by flow cytometry; platelet morphology was measured by microscopy. Patient-level area-under-the-curve summaries were entered into binary logistic regression. Benjamini-Hochberg false-discovery rate (FDR) was applied across the analyte × parameter grid.

Results

Sixty patients (29.1%) developed DCI. Across days 1-10, no agonist-stimulated aggregation parameter and no flow cytometric activation parameter was significantly associated with DCI after FDR correction (all q ≥ 0.42). Only morphologically activated platelets were more prevalent in DCI patients at day 2 (73.8 ± 4.9% vs. 55.6 ± 18.6%; p = 0.001), a difference that survived FDR correction (q = 0.005).

Conclusions

Peripheral platelet function assays do not reliably stratify DCI risk after aSAH. These findings may align with the preferential consumption of the hyperactive platelets, though these findings are hypothesis-generating only and need further investigation.