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Early circulating levels of endothelial cell activation markers in aneurysmal subarachnoid haemorrhage: associations with cerebral ischaemic events and outcome

¹ Department of Neurology, University Medical Centre Utrecht, Utrecht, Netherlands
² Department of Haematology, Research Laboratory, University Medical Centre Utrecht
³ Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht
⁴ Department of Plasma Proteins, Sanquin Research at CLB and Department of Vascular Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands

Correspondence to:
Correspondence to:
Dr C J M Frijns
Department of Neurology, C03.228, University Medical Centre, PO Box 85500, 3508 GA Utrecht, Netherlands; c.j.m.frijns{at}neuro.azu.nl

Objective: To investigate the relation of endothelial cell activation with delayed cerebral ischaemia (DCI) and outcome after subarachnoid haemorrhage (SAH).

Methods: Concentrations of soluble (s) intercellular adhesion molecule-1, sE-selectin, sP-selectin, ED1-fibronectin, von Willebrand Factor (vWf), and vWf propeptide were measured within three days of SAH onset. The associations with poor outcome were investigated at three months in 106 patients. In 90 patients in whom the occurrence of cerebral ischaemia could be dated accurately, two analyses were undertaken: one for all ischaemic events (n = 32), including those related to treatment, and another for spontaneous DCI (n = 11). Concentrations of markers were dichotomised at their medians. The associations of endothelial cell activation markers with outcome were expressed as odds ratios (OR) from logistic regression and those with ischaemic events as hazard ratios (HR) derived from Cox regression.

Results: Early vWf concentrations were associated with poor outcome (crude OR = 4.6 (95% CI, 2.0 to 10.9; adjusted OR = 3.3 (1.1 to 9.8). Early levels of vWf were also positively related to occurrence of all ischaemic events (crude HR = 2.3 (1.1 to 4.9); adjusted HR = 1.8 (0.8 to 3.9) and with occurrence of spontaneous DCI (crude HR = 3.5 (0.9 to 13.1); adjusted HR = 2.2 (0.5 to 9.8). None of the other markers showed any associations.

Conclusions: Concentrations of sICAM-1, sP-selectin, sE-selectin, and ED1-fibronectin do not predict the occurrence of DCI or outcome. The positive associations of raised early vWf concentrations with ischaemic events and poor outcome after SAH may reflect a predisposition to further ischaemic injury through formation of microthrombi in the cerebral circulation.

Abbreviations: DCI, delayed cerebral ischaemia; GCS, Glasgow coma scale; mRs, modified Rankin scale; SAH, subarachnoid haemorrhage; vWf, von Willebrand factor

Keywords: subarachnoid haemorrhage; endothelial adhesion molecules; Von Willebrand factor

This article has been cited by other articles:

				C J M Frijns, K M Kasius, A Algra, R Fijnheer, and G J E Rinkel Endothelial cell activation markers and delayed cerebral ischaemia in patients with subarachnoid haemorrhage J. Neurol. Neurosurg. Psychiatry, July 1, 2006; 77(7): 863 - 867. [Abstract] [Full Text] [PDF]