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Thromb Haemost 2018; 118(05): 873-882
DOI: 10.1055/s-0038-1641565
Cellular Haemostasis and Platelets
Schattauer GmbH Stuttgart

Clinical Determinants of Thrombin Generation Measured in Presence and Absence of Platelets—Results from the Gutenberg Health Study

Marina Panova-Noeva
1   Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg–University Mainz, Mainz, Germany
2   Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg–University Mainz, Mainz, Germany
,
Andreas Schulz
2   Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg–University Mainz, Mainz, Germany
,
Henri M. Spronk
3   Laboratory for Clinical Thrombosis and Hemostasis, Department of Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands
,
Aline Beicht
1   Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg–University Mainz, Mainz, Germany
,
Dagmar Laubert-Reh
2   Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg–University Mainz, Mainz, Germany
,
Rene van Oerle
3   Laboratory for Clinical Thrombosis and Hemostasis, Department of Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands
,
Natalie Arnold
2   Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg–University Mainz, Mainz, Germany
,
Jürgen H. Prochaska
1   Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg–University Mainz, Mainz, Germany
2   Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg–University Mainz, Mainz, Germany
4   DZHK (German Center for Cardiovascular Research), Partner Site Rhine-Main, Mainz, Germany
,
Maria Blettner
5   Institute of Medical Biostatistics, Epidemiology and Informatics at the University Medical Center Mainz, Mainz, Germany
,
Manfred Beutel
6   Department of Psychosomatic Medicine and Psychotherapy, University Medical Center Mainz, Mainz, Germany
,
Norbert Pfeiffer
7   Department of Ophthalmology, University Medical Center Mainz, Mainz, Germany
,
Thomas Münzel
4   DZHK (German Center for Cardiovascular Research), Partner Site Rhine-Main, Mainz, Germany
8   Center for Cardiology I, University Medical Center of the Johannes Gutenberg–University Mainz, Mainz, Germany
,
Karl J. Lackner
4   DZHK (German Center for Cardiovascular Research), Partner Site Rhine-Main, Mainz, Germany
9   Institute for Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg–University Mainz, Mainz, Germany
,
Hugo ten Cate
3   Laboratory for Clinical Thrombosis and Hemostasis, Department of Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands
,
Philipp S. Wild
1   Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg–University Mainz, Mainz, Germany
2   Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg–University Mainz, Mainz, Germany
4   DZHK (German Center for Cardiovascular Research), Partner Site Rhine-Main, Mainz, Germany
› Author Affiliations Funding The Gutenberg Health Study is funded through the government of Rhineland-Palatinate (“Stiftung Rheinland-Pfalz für Innovation“, contract AZ 961-386261/733), the research programs “Wissen schafft Zukunft” and “Center for Translational Vascular Biology (CTVB)” of the Johannes Gutenberg-University of Mainz, and its contract with Boehringer Ingelheim and PHILIPS Medical Systems, including unrestricted grants for the Gutenberg Health Study.
Further Information

Publication History

17 November 2017

01 March 2018

Publication Date:
03 April 2018 (online)

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Abstract

The tendency of a plasma sample to generate thrombin, a central enzyme in blood coagulation, might be an important indicator of prothrombotic risk linked to cardiovascular disease (CVD), but the presence of platelets may be a critical determinant. Clinical data, laboratory markers and thrombin generation (TG), investigated in both platelet-rich plasma (PRP) and platelet-free plasma (PFP) at 1 pM TF, were available in 407 individuals from the Gutenberg Health Study. Given the well-known effect of anticoagulants on TG, subjects taking anticoagulants (n = 15) have been excluded resulting in 392 subjects for further analysis. Lag time, endogenous thrombin potential (ETP) and peak height were the investigated parameters of a TG curve. Multivariable linear regression analysis was used to identify TG determinants. Mean platelet volume (MPV) and platelet count were both negatively associated to lag time and positively to peak height (MPV, β:6.35 [2.66; 10.0]; platelet count, β:0.111 [0.054; 0.169]) in PRP only. C-reactive protein was positively associated with lag time and ETP in both PRP and PFP, with a stronger effect on ETP in PRP (PRP, β:76.7 [47.5; 106]; PFP, β:34.8 [10.3; 59.2]). After adjustment for fibrinogen, the relation between CRP and ETP was attenuated in PRP and PFP. Of the traditional cardiovascular risk factors (CVRFs), obesity was positively associated to TG in PRP only. Our findings support that TG, particularly in PRP, relates to traditional CVRFs in a representative sample from a population-based study. Assessment of procoagulant activity in a platelet-dependent manner by TG is a promising tool for assessing individual risk for CVD.

Keywords

platelets - C-reactive protein - thrombin generation - population - clinical epidemiology

Authors' Contributions

All authors had full access to data and contributed to drafting of the article.


Supplementary Material

 

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