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Thromb Haemost 2010; 104(02): 224-230
DOI: 10.1160/TH10-02-0091
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Thrombin generation in rheumatoid arthritis: Dependence on plasma factor composition

Anetta Undas
1   Institute of Cardiology, Jagiellonian University School of Medicine, Krakow, Poland
,
Matthew Gissel
2   Department of Biochemistry, University of Vermont, Burlington, Vermont
,
Beata Kwasny-Krochin
3   Department of Rheumatology, Jagiellonian University School of Medicine, Krakow, Poland
,
Piotr Gluszko
3   Department of Rheumatology, Jagiellonian University School of Medicine, Krakow, Poland
,
Kenneth G. Mann
2   Department of Biochemistry, University of Vermont, Burlington, Vermont
,
Kathleen E. Brummel-Ziedins
2   Department of Biochemistry, University of Vermont, Burlington, Vermont
› Author Affiliations Financial support: This research was supported by a grant from the Jagiellonian University School of Medicine (no K/ZDS/000565, to A.U.) and an NIH grant HL46703 (Project 5).
Further Information

Publication History

Received: 03 February 2010

Accepted after minor revision: 12 March 2010

Publication Date:
24 November 2017 (online)

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Summary

Growing evidence indicates that rheumatoid arthritis (RA) is associated with an increased risk for thromboembolic cardiovascular events. We investigated thrombin generation profiles in RA patients and their dependence on plasma factor/inhibitor composition. Plasma factor (F) compositions (II, V, VII, VIII, IX, X), antithrombin and free tissue factor pathway inhibitor (TFPI) from 46 consecutive RA patients with no cardiovascular events (39 female, 7 male, aged 57 [range, 23–75] years; DAS28 [Disease Activity Score] 5.2 ± 1.1) were compared with those obtained in age- and sex-matched apparently healthy controls. Using each individual’s plasma coagulation protein composition, tissue factor- initiated thrombin generation was assessed both computationally and empirically. RA patients had higher fibrinogen (4.18 [IQR 1.09] vs. 2.56 [0.41] g/l, p<0.0001), FVIII (226 ± 40 vs. 113 ± 15%, p<0.001), PC (107 [16] vs. 100 [14]%, p<0.001), and free TFPI levels (22.3 [2.2] vs. 14.7 [2.1] ng/ml, p<0.001). DAS28, but not age, RA duration, or C-reac- tive protein, was associated with FV, FVIII, FIX, FX, antithrombin, and free TFPI (r from 0.27 to 0.48, p<0.05). Intergroup comparison of computational thrombin generation profiles showed that in RA patients, maximum thrombin levels (p=0.01) and the rate of thrombin formation (p<0.0001) were higher, whereas the initiation phase of thrombin generation (p<0.0001) and the time to maximum thrombin levels (p<0.0001) were longer. Empirical reconstructions of the populations reproduced the thrombin generation profiles generated by the computational model. Simulations of thrombin formation suggest that blood plasma composition, i.e. a marked increase in FVIII, somewhat counterbalanced by free TFPI, contributes to the prothrombotic phenotype in RA patients.

Keywords

Inflammation - plasma composition - prothrombotic phenotype - rheumatoid arthritis - thrombin generation
 

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