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Thromb Haemost 2018; 118(08): 1461-1469
DOI: 10.1055/s-0038-1666858
Atherosclerosis and Ischaemic Disease
Georg Thieme Verlag KG Stuttgart · New York

No Association between Thrombin Generation and Intra-Plaque Haemorrhage in Symptomatic Carotid Atherosclerotic Plaques: The Plaque at RISK (PARISK) Study

Geneviève A. J. C. Crombag
1   Department of Radiology and Nuclear Medicine, Maastricht University Medical Centre, Maastricht University, Maastricht, The Netherlands
2   CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht University, Maastricht, The Netherlands
,
Henri M. Spronk
2   CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht University, Maastricht, The Netherlands
3   Department of Internal Medicine, Clinical Thrombosis and Haemostasis Laboratory, Maastricht University Medical Centre, Maastricht University, Maastricht, The Netherlands
,
Patty Nelemans
4   Department of Epidemiology, Maastricht University Medical Centre, Maastricht University, Maastricht, The Netherlands
,
Floris H. B. M. Schreuder
5   Department of Neurology, Maastricht University Medical Centre, Maastricht University, Maastricht, The Netherlands
6   Department of Clinical Neurophysiology, Maastricht University Medical Centre, Maastricht University, Maastricht, The Netherlands
,
Martine T. B. Truijman
5   Department of Neurology, Maastricht University Medical Centre, Maastricht University, Maastricht, The Netherlands
6   Department of Clinical Neurophysiology, Maastricht University Medical Centre, Maastricht University, Maastricht, The Netherlands
,
Anouk C. van Dijk
7   Department of Radiology, Erasmus Medical Centre, Erasmus University, Rotterdam, The Netherlands
8   Department of Neurology, Erasmus Medical Centre, Erasmus University, Rotterdam, The Netherlands
,
Alexandra A. J. de Rotte
9   Department of Radiology, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands
,
Madieke I. Liem
10   Department of Neurology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
,
Mat J. A. P. Daemen
11   Department of Pathology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
,
Anton F. W. van der Steen
12   Department of Biomedical Engineering, Erasmus Medical Centre, Erasmus University, Rotterdam, The Netherlands
,
Werner H. Mess
2   CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht University, Maastricht, The Netherlands
6   Department of Clinical Neurophysiology, Maastricht University Medical Centre, Maastricht University, Maastricht, The Netherlands
,
Paul J. Nederkoorn
10   Department of Neurology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
,
Jeroen Hendrikse
9   Department of Radiology, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands
,
Aad van der Lugt
7   Department of Radiology, Erasmus Medical Centre, Erasmus University, Rotterdam, The Netherlands
,
Joachim E. Wildberger
1   Department of Radiology and Nuclear Medicine, Maastricht University Medical Centre, Maastricht University, Maastricht, The Netherlands
2   CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht University, Maastricht, The Netherlands
,
Hugo ten Cate
2   CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht University, Maastricht, The Netherlands
3   Department of Internal Medicine, Clinical Thrombosis and Haemostasis Laboratory, Maastricht University Medical Centre, Maastricht University, Maastricht, The Netherlands
,
Robert J. van Oostenbrugge
2   CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht University, Maastricht, The Netherlands
4   Department of Epidemiology, Maastricht University Medical Centre, Maastricht University, Maastricht, The Netherlands
,
M. Eline Kooi
1   Department of Radiology and Nuclear Medicine, Maastricht University Medical Centre, Maastricht University, Maastricht, The Netherlands
2   CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht University, Maastricht, The Netherlands
› Author Affiliations Funding This research was performed within the framework of CTMM, project PARISk (grant 01C-202), and supported by the Dutch Heart Foundation. This project has received funding from the European Union (EU) Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 722609.
Further Information

Publication History

03 November 2017

20 May 2018

Publication Date:
04 July 2018 (online)

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Abstract

Background Carotid atherosclerosis is an important cause of stroke. Intra-plaque haemorrhage (IPH) on magnetic resonance imaging (MRI) increases stroke risk. Development of IPH is only partly understood. Thrombin is an essential enzyme in haemostasis. Experimental animal studies have shown conflicting results on the relation between thrombin and plaque vulnerability. We hypothesize that decreased thrombin generation (TG) is associated with IPH and plaque vulnerability.

Objective This article investigates whether TG is associated with IPH and other features of plaque vulnerability in stroke patients.

Methods Recently symptomatic stroke patients underwent carotid MRI and blood sampling. MRI plaque features include plaque burden, presence of IPH, amount of lipid-rich necrotic core (LRNC), calcified tissue and fibrous tissue (% of total wall volume). TG was assessed in platelet-poor plasma and expressed as: peak height (PH) and endogenous thrombin potential (ETP). MR images could be analysed in 224 patients. Blood samples were available in 161 of 224 patients. Binary multivariate logistic and linear regression were used to investigate the association between TG and MRI plaque features.

Results IPH and LRNC were present in 65 (40%) and 102 (63%) of plaques. There were no significant associations between TG and IPH; PH odds ratio (OR) = 1, 95% confidence interval (CI): 0.76 to 1.45 and ETP OR = 1, 95% CI: 0.73 to 1.37. After correction for age, sex and hypercholesterolaemia, the association was weak but non-significant; PH: OR = 0.76, 95% CI: 0.52 to 1.10 and ETP: OR = 0.73, 95% CI: 0.53 to 1.37.

Conclusion Features of carotid plaque on MRI show no significant association with TG in stroke patients. Systemic TG does not seem to be an important factor in IPH development.

Keywords

carotid stenosis - ischaemic attack - transient - magnetic resonance imaging - stroke - thrombin

Note

ClinicalTrials.gov Identifier, NCT Number: NCT01208025.


 

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