Feasibility of platelet marker analysis in ischemic stroke patients and their association with one-year outcome. A pilot project within a subsample of the Stroke Induced Cardiac Failure in Mice and Men (SICFAIL) cohort study

Abstract

Patients with ischemic stroke (IS) are at increased risk of mortality and recurrent cerebro- or cardiovascular events. Determining prognosis after IS remains challenging but blood-based biomarkers might provide additional prognostic information. As platelets are crucially involved in the pathophysiology of vascular diseases, platelet surface proteins (PSP) are promising candidates as prognostic markers in the hyperacute stage. In this pilot study, feasibility of PSP analysis by flow cytometry (HMGB1, CD84, CXCR4, CXCR7, CD62p with and without ADP-stimulation, CD41, CD61, CD40, GPVI) was investigated in 99 (median 66 years, 67.5% male) acute IS patients admitted to Stroke Unit within a substudy of the Stroke-Induced Cardiac FAILure in mice and men (SICFAIL) cohort study. Association between PSP expression and unfavorable one-year outcome (cerebro- or cardiovascular event, all-cause mortality and care dependency defined as Barthel Index <60) was explored. PSP measurements were feasible. Several process- (e.g. temperatures, processing times) and patient-related factors (e.g. prestroke ischemic events, surgery, blood pressure, antiplatelet therapy) were identified to be potentially associated with PSP expression. Elevated CD40 levels above study population’s median were associated with unfavorable outcome. Standardized conditions during blood draw and processing within the hyperacute stroke unit setting are required and patient-related characteristics must be considered for valid measurements of PSP.

Trial registration: German Clinical Trials Register (DRKS00011615).

Keywords:

• Biomarker
• flow cytometry
• platelets
• prognosis
• stroke
• surface markers

Acknowledgments

The authors wish to thank all patients and their families for participating in the SICFAIL study. The authors thank Andrea Sauer-Weckert for laboratory assistance.

Disclosure statement

MS and KU are fellows of the Graduate School of Life Sciences at University Würzburg. MS received a doctoral thesis stipend from the Graduate School of Life Sciences at University Würzburg. FAM. is supported by the German Research Foundation (within the UNION-CVD Clinician-Scientist Programme, Project No. 413657723) and has been previously supported by the Interdisciplinary Center for Clinical Research, University Hospital Würzburg (within the MD/PhD Fellowship Programme). PK received lecture fees from Daiichi Sankyo and Pfizer, as well as research support from Daiichi Sankyo. PUH reports research grants from the German Ministry of Education and Research, German Research Foundation, European Union, Berlin Chamber of Physicians, German Parkinson Society, University Hospital Würzburg, Robert Koch Institute, German Heart Foundation, Federal Joint Committee (G‐BA) within the Innovationfond, University Hospital Heidelberg (within RASUNOA-prime; supported by an unrestricted research grant to the University Hospital Heidelberg from Bayer, BMS, Boehringer Ingelheim, and Daiichi Sankyo), Charité–Universitätsmedizin Berlin (within Mondafis; supported by an unrestricted research grant to the Charité from Bayer), and University Göttingen (within FIND-AF randomized; supported by an unrestricted research grant to the University Göttingen from Boehringer Ingelheim) outside the submitted work. SW reports grants from the German Ministry of Research and Education and Deutsche Herzstiftung e.V. VR, DM, MKS, BN, TG, DR, and CK have nothing to disclose.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website.

Data availability statement

The data that support the findings of this study are available from the corresponding author (PUH) upon reasonable request.

Additional information

Funding

The SICFAIL study was supported by the German Ministry of Research and Education BMBF 01EO1004,BMBF 01EO1504 within the Comprehensive Heart Failure Centre Würzburg (grant numbers BMBF 01EO1004 and 01EO1504). Part of the work was conducted within the Collaborative Research Center 240 “Platelets,” which is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – Projektnummer 374031971 – TRR 240).