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The Role of Platelet Activation and Inflammation in Early Brain Injury Following Subarachnoid Hemorrhage

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Abstract

Background

Early brain injury (EBI) following aneurysmal subarachnoid hemorrhage (SAH) is an important predictor of poor functional outcome, yet the underlying mechanism is not well understood. Animal studies suggest that platelet activation and inflammation with subsequent microthrombosis and ischemia may be a mechanism of EBI.

Methods

A prospective, hypothesis-driven study of spontaneous, SAH patients and controls was conducted. Platelet activation [thromboelastography maximum amplitude (MA)] and inflammation [C-reactive protein (CRP)] were measured serially over time during the first 72 h following SAH onset. Platelet activation and inflammatory markers were compared between controls and SAH patients with mild [Hunt–Hess (HH) 1–3] versus severe (HH 4–5) EBI. The association of these biomarkers with 3-month functional outcomes was evaluated.

Results

We enrolled 127 patients (106 SAH; 21 controls). Platelet activation and CRP increased incrementally with worse EBI/HH grade, and both increased over 72 h (all P < 0.01). Both were higher in severe versus mild EBI (MA 68.9 vs. 64.8 mm, P = 0.001; CRP 12.5 vs. 1.5 mg/L, P = 0.003) and compared to controls (both P < 0.003). Patients with delayed cerebral ischemia (DCI) had more platelet activation (66.6 vs. 64.9 in those without DCI, P = 0.02) within 72 h of ictus. At 3 months, death or severe disability was more likely with higher levels of platelet activation (mRS4–6 OR 1.18, 95 % CI 1.05–1.32, P = 0.007) and CRP (mRS4–6 OR 1.02, 95 % CI 1.00–1.03, P = 0.041).

Conclusions

Platelet activation and inflammation occur acutely after SAH and are associated with worse EBI, DCI and poor 3-month functional outcomes. These markers may provide insight into the mechanism of EBI following SAH.

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Acknowledgments

Dr. Frontera received funding for this project from the American Heart Association (11CRP5270003) and the Research Program Committee of the Cleveland Clinic (RPC # 2013-1014).

Author contributions

J.A. Frontera was responsible for study design, collecting, analyzing and interpreting data, writing the manuscript, and final approval of the version to be published. J.J. Provencio was responsible for interpreting the data, revising the intellectual content, and final approval of the version to be published. F.A. Sehba was responsible for study design, analyzing and interpreting data, revising the intellectual content and final approval of the version to be published. T.M. McIntyre was responsible for revising the intellectual content, and final approval of the version to be published. A.S. Nowacki was responsible for analyzing and interpreting data and final approval of the version to be published. E. Gordon was responsible for collecting data and final approval of the version to be published. J.M. Weimer was responsible for collecting data and final approval of the version to be published. L. Aledort was responsible for study design, analyzing and interpreting data, revising the intellectual content, and final approval of the version to be published.

Author information

Authors and Affiliations

  1. Cerebrovascular Center of the Neurological Institute, Cleveland Clinic, 9500 Euclid Ave. S80, Cleveland, OH, 44195, USA

    Jennifer A. Frontera & Jonathan M. Weimer

  2. Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA

    Jennifer A. Frontera & Thomas M. McIntyre

  3. Department of Neurology and Neuroscience, Brain Immunology and Glia Center, University of Virginia, Charlottesville, VA, USA

    J. Javier Provencio

  4. Department of Neurosurgery, Mount Sinai School of Medicine, New York, NY, USA

    Fatima A. Sehba

  5. Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA

    Amy S. Nowacki

  6. Department of Critical Care, Mount Sinai School of Medicine, New York, NY, USA

    Errol Gordon

  7. Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA

    Louis Aledort

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  1. Jennifer A. Frontera
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  2. J. Javier Provencio
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Correspondence to Jennifer A. Frontera.

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12028_2016_292_MOESM1_ESM.tif

Supplementary Figure 1. Platelet activation, C-reactive protein (CRP) in jugular and peripheral venous blood over the first 72 hours following aneurysm rupture. Whisker bars represent the standard error of the mean. MA = maximum amplitude, SAH = subarachnoid hemorrhage (TIF 71 kb)

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Frontera, J.A., Provencio, J.J., Sehba, F.A. et al. The Role of Platelet Activation and Inflammation in Early Brain Injury Following Subarachnoid Hemorrhage. Neurocrit Care 26, 48–57 (2017). https://doi.org/10.1007/s12028-016-0292-4

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