Skip to main content

Advertisement

Log in

Can we predict thrombotic tendency in rheumatoid arthritis? A thromboelastographic analysis (with ROTEM)

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

The higher incidence of arterial and venous events is well established in patients with rheumatoid arthritis (RA). Our aim here was to investigate whether there is a prothrombotic state in RA patients by using rotational thromboelastometry (ROTEM) method and to demonstrate whether the disease variables play a role in this process. A total of 85 patients who met the 2010 RA classification criteria were consecutively included in the study. The patients with RA who have been using antiaggregant, anticoagulant, or nonsteroidal anti-inflammatory drugs (NSAIDs) and had a history of arterial or venous thromboembolism were excluded from the study. Their complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fibrinogen, D-dimer, and lipid profiles were measured, DAS-28 disease activation scores were calculated, and simultaneous ROTEM analysis was performed to determine the predisposition to thrombosis. Of the ROTEM parameters, clotting time (CT, seconds (s)), clot formation time (CFT, s), and maximum clot firmness (MCF) were evaluated. Having a shorter CT and/or CFT in intrinsic (I) or extrinsic (E) pathway and/or a longer MCF compared to the healthy controls was considered as “predisposition to hypercoagulability”. The mean age of the 85 RA patients were 54.12 ± 13 years, and 77.6% of the patients were female (n = 66). Of the patients, 52.9% (n = 45) were using methotrexate (MTX) ± hydroxychloroquine (HCQ) ± corticosteroid (CS), while 43.5% (n = 37) were using anti-tumor necrosis factor (TNF) ± MTX. Active steroid usage was ongoing in 64.7% of the patients (n = 55). When evaluated according to DAS-28, in those with higher disease activity, a shorter I-CFT and greater I-MCF were determined (p = 0.020 and p = 0.033, respectively). In those with higher disease activity based on the correlation analysis, I-CFT and E-CFT were shorter and I-MCF and E-MCF were longer, indicating a higher predisposition to thrombosis. Using linear regression, variables with a major effect on ROTEM parameters were identified as DAS-28, CRP, and platelet count. As the first study in the literature, we identified that disease activation is the most important risk factor for prothrombotic state in RA patients irrespective of the drugs used. ROTEM can be used in clinical practice to predict thrombotic events in RA patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Brasington RD (2011) Rheumatoid arthritis. In: Hochberg MC, Silman AJ, Smolen JS, Weinblatt ME, Weismna MH (eds) Rheumatology. Philadelphia:Elsevier, pp 829–838

    Chapter  Google Scholar 

  2. Liang KP, Liang KV, Matteson EL, Mcclelland RL, Christianson TJ, Turesson C (2006) Incidence of noncardiac vascular disease in rheumatoid arthritis and relationship to extraarticular disease manifestations. Arthritis Rheum 54:642–648

    Article  PubMed  PubMed Central  Google Scholar 

  3. Bacani AK, Gabriel SE, Crowson CS, Heit JA, Matteson EL (2012) Noncardiac vascular disease in rheumatoid arthritis: increase in venous thromboembolic events? Arthritis Rheum 64:53–61

    Article  PubMed  PubMed Central  Google Scholar 

  4. Chung WS, Peng CL, Lin CL, Chang YJ, Chen YF, Chiang JY, Sung FC, Kao CH (2014) Rheumatoid arthritis increases the risk of deep vein thrombosis and pulmonary thromboembolism: a nationwide cohort study. Ann Rheum Dis 73:1774–1780

    Article  PubMed  Google Scholar 

  5. Mameli A, Barcellona D (2009) Marongiu F (2009). Rheumatoid arthritis and thrombosis. Clin Exp Rheumatol 27:846–855

    PubMed  CAS  Google Scholar 

  6. van den Oever IA, Sattar N, Nurmohamed MT (2014) Thromboembolic and cardiovascular risk in rheumatoid arthritis: role of the haemostatic system. Ann Rheum Dis 73:954–957

    Article  PubMed  CAS  Google Scholar 

  7. Aksu K, Donmez A, Keser G (2012) Inflammation-induced thrombosis: mechanisms, disease associations and management. Curr Pharm Des 18:1478–1493

    Article  PubMed  CAS  Google Scholar 

  8. Whiting D, DiNardo JA (2014) TEG and ROTEM: technology and clinical applications. Am J Hematol 89:228–232

    Article  PubMed  CAS  Google Scholar 

  9. Akay OM, Ustuner Z, Canturk Z, Mutlu FS, Gulbas Z (2009) Laboratory investigation of hypercoagulability in cancer patients using rotation thrombelastography. Med Oncol 26:358–364

    Article  PubMed  Google Scholar 

  10. Yaşar Bilge NŞ, Akay OM, Kaşifoğlu T, Kuş G, Korkmaz C (2013) The role of hemostatic mechanisms in the development of thrombosis in Behcet's disease: an analysis by modified rotation thromboelastogram (ROTEM). Clin Rheumatol 32:1815–1818

    Article  PubMed  Google Scholar 

  11. Collins KS, Balasubramaniam K, Viswanathan G, Natasari A, Tarn J, Lendrem D, Mitchell S, Zaman A, Ng WF (2013) Assessment of blood clot formation and platelet receptor function ex vivo in patients with primary Sjogren’s syndrome. BMJ Open 3:e002739

    Article  PubMed  PubMed Central  Google Scholar 

  12. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd et al (2010) 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 62:2569–2581

    Article  PubMed  Google Scholar 

  13. Goren Sahin D, Sahin A, Akay OM (2016) Comparison of rotational thromboelastography findings in pseudoexfoliation syndrome patients and healthy controls. J Glaucoma 25:879–882

    Article  PubMed  Google Scholar 

  14. Stanford SN, Sabra A, Lawrence M, Morris RH, Storton S, Wani M, Hawkins K, Williams PR, Potter JF, Evans PA (2015) Prospective evaluation of blood coagulability and effect of treatment in patients with stroke using rotational thromboelastometry. J Stroke Cerebrovasc Dis 24:304–311

    Article  PubMed  Google Scholar 

  15. Solomon DH, Karlson EW, Rimm EB, Cannuscio CC, Mandl LA, Manson JE, Stampfer MJ, Curhan GC (2003) Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis. Circulation 107:1303–1307

    Article  PubMed  Google Scholar 

  16. Kim KJ, Baek IW, Park KS, Kim WU, Cho CS (2017) Association between antiphospholipid antibodies and arterial thrombosis in patients with rheumatoid arthritis. Lupus 26:88–94

    Article  PubMed  CAS  Google Scholar 

  17. Chung CP, Oeser A, Raggi P, Gebretsadik T, Shintani AK, Sokka T, Pincus T, Avalos I, Stein CM (2005) Increased coronary-artery atherosclerosis in rheumatoid arthritis: relationship to disease duration and cardiovascular risk factors. Arthritis Rheum 52:3045–3053

    Article  PubMed  Google Scholar 

  18. Turesson C, Jacobsson L, Bergström U (1999) Extra-articular rheumatoid arthritis: prevalence and mortality. Rheumatology (Oxford) 38:668–674

    Article  CAS  Google Scholar 

  19. Lippi G, Emmanuel J, Favaloro EJ, Montagnana M, Franchini M (2010) C-reactive protein and venous thromboembolism: causal or casual association? Clin Chem Lab Med 48:1693–1701

    PubMed  CAS  Google Scholar 

  20. Davis JM 3rd, Maradit Kremers H, Crowson CS, Nicola PJ, Ballman KV, Therneau TM, Roger VL, Gabriel SE (2007) Glucocorticoids and cardiovascular events in rheumatoid arthritis: a population-based cohort study. Arthritis Rheum 56:820–830

    Article  PubMed  CAS  Google Scholar 

  21. Ridker PM, Buring JE, Shih J, Matias M, Hennekens CH (1998) Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation 98:731–733

    Article  PubMed  CAS  Google Scholar 

  22. Wallberg-Jonsson S, Johansson H, Ohman ML, Rantapaa-Dahlqvist S (1999) Extent of inflammation predicts cardiovascular disease and overall mortality in seropositive rheumatoid arthritis: a retrospective cohort study from disease onset. J Rheumatol 26:2562–2571

    PubMed  CAS  Google Scholar 

  23. Gasparyan AY, Ayvazyan L, Mikhailidis DP, Kitas GD (2011) Mean platelet volume: a link between thrombosis and inflammation? Curr Pharm Des 17:47–58

    Article  PubMed  CAS  Google Scholar 

  24. McEntegart A, Capell HA, Creran D, Rumley A, Woodward M, Lowe GD (2001) Cardiovascular risk factors, including thrombotic variables, in a population with rheumatoid arthritis. Rheumatology (Oxford) 40:640–644

    Article  CAS  Google Scholar 

  25. Schmidt M, Christiansen CF, Horváth-Puhó E, Glynn RJ, Rothman KJ, Sørensen HT (2011) Non-steroidal anti-inflammatory drug use and risk of venous thromboembolism. J Thromb Haemost 9:1326–1333

    Article  PubMed  CAS  Google Scholar 

  26. Aviña-Zubieta JA, Abrahamowicz M, De Vera MA, Choi HK, Sayre EC, Rahman MM, Sylvestre MP, Wynant W, Esdaile JM, Lacaille D (2013) Immediate and past cumulative effects of oral glucocorticoids on the risk of acute myocardial infarction in rheumatoid arthritis: a population-based study. Rheumatology (Oxford) 52:68–75

    Article  CAS  Google Scholar 

  27. Rempenault C, Combe B, Barnetche T, Gaujoux-Viala C, Lukas C, Morel J, Hua Cİ (2018) Metabolic and cardiovascular benefits of hydroxychloroquine in patients with rheumatoid arthritis: a systematic review and meta-analysis. Ann Rheum Dis 77:98–103

    Article  PubMed  Google Scholar 

  28. van Halm VP, Nurmohamed MT, Twisk JW, Dijkmans BA, Voskuyl AE (2006) Disease-modifying antirheumatic drugs are associated with a reduced risk for cardiovascular disease in patients with rheumatoid arthritis: a case control study. Arthritis Res Ther 8:R151

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Wallace DJ, Linker-Israeli M, Metzger AL, Stecher VJ (1993) The relevance of antimalarial therapy with regard to thrombosis, hypercholesterolemia and cytokines in SLE. Lupus 2(Suppl. 1):S13–S15

    PubMed  Google Scholar 

  30. Davies R, Galloway JB, Watson KD, Lunt M, Symmons DP, Hyrich KL, BSRBR Control Centre Consortium, British Society for Rheumatology Biologics Register (2011) Venous thrombotic events are not increased in patients with rheumatoid arthritis treated with anti-TNF therapy: results from the British Society for Rheumatology Biologics Register. Ann Rheum Dis 70:1831–1834

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Financial support

The study was supported by Eskisehir Osmangazi University Scientific Research Projects Commission (No. 20151106).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Döndü Üsküdar Cansu.

Ethics declarations

Ethical approval

Ethical approval was obtained from Eskisehir Osmangazi University Clinical Studies Ethics Committee (27 April 2016, No. 06).

Disclosures

None.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Türk, S.M., Cansu, D.Ü., Teke, H.Ü. et al. Can we predict thrombotic tendency in rheumatoid arthritis? A thromboelastographic analysis (with ROTEM). Clin Rheumatol 37, 2341–2349 (2018). https://doi.org/10.1007/s10067-018-4134-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-018-4134-y

Keywords

Navigation