Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1
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Index Copernicus  – 161.11; MEiN – 140 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

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Advances in Clinical and Experimental Medicine

2018, vol. 27, nr 6, June, p. 827–832

doi: 10.17219/acem/78361

Publication type: original article

Language: English

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High prevalence of antinuclear antibodies in patients following venous thromboembolism

Joanna Natorska1,B,C,D, Magdalena Celińska-Löwenhoff2,D,E, Anetta I. Undas1,A,E,F

1 Institute of Cardiology, Jagiellonian University Medical College, Kraków, Poland

2 Department of Internal Medicine, Jagiellonian University Medical College, Kraków, Poland


Background. Growing evidence suggests that activation of blood coagulation exerts protective functions during inflammation. However, it has been hypothesized that dysregulated immunothrombosis may lead to venous thromboembolism (VTE). Antinuclear antibodies (ANAs) are considered to promote the thrombotic tendency but there have been no reports on the association between ANAs and VTE.
Objectives. The objective of this study was to investigate if the presence of ANAs is associated with VTE.
Material and Methods. We enrolled 283 consecutive patients, aged 18–66 years old, following a VTE episode, and 165 age-matched healthy controls. Patients with documented autoimmune diseases (n = 56, 19.79%), including antiphospholipid syndrome (n = 48, 16.9%), were excluded. Antinuclear antibodies were determined based on immunofluorescence. The specific immunofluorescence patterns observed at serum dilution equal to or greater than 1:100 were considered as positive ANAs.
Results. The final analysis included 227 patients (aged 41.07 ±11.4, 98 males, 129 females) following provoked (n = 111) or unprovoked (n = 116) VTE. Ninety-four (42.2%) patients had positive ANAs, including 32 (33.3%) with ANAs titer ≥1:320, whereas as few as 14 (8.4%) controls had positive ANAs (p < 0.007). ANA-positive patients were more commonly diagnosed with unprovoked (n = 55; 57.4%) than provoked VTE (n = 39; 40.6%) (p = 0.03). A similar observation was made for ANAs titer ≥1: 320 (26 patients with unprovoked vs 20 patients with provoked VTE, p = 0.04). The presence of ANAs in the patient group did not correlate with age, sex, time since the VTE event, type of anticoagulation and its quality, inflammatory markers and D-dimer.
Conclusion. The prevalence of positive ANAs was 5 times higher among VTE patients than in controls. Antinuclear antibodies occur commonly in VTE and might be involved in the pathogenesis of unprovoked VTE.

Key words

venous thromboembolism, deep vein thrombosis, antinuclear antibodies

References (22)

  1. Rosendaal FR. Venous thrombosis: A multicausal disease. Lancet. 1999;353:1167–1173.
  2. Konstantinides SV, Torbicki A, Agnelli G, et al.; Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J. 2014;43:3033–3069.
  3. Jenkins PV, Rawley O, Smith OP, O’Donnell JS. Elevated factor VIII levels and risk of venous thrombosis. Br J Haematol. 2012;157:653–663.
  4. de Groot PG, Derksen B, Lisman T, Meijers JC, Rosendaal FR. Lupus anticoagulants and the risk of a first episode of deep venous thrombosis. J Thromb Haemost. 2005;3:1993–1997.
  5. von Brühl ML, Stark K, Steinhart A, et al. Monocytes, neutrophils and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo. J Exp Med. 2012;209:819–835.
  6. Yamazaki M. Antiphospholipid antibody syndrome. In: Ichinose A, ed. Sciences of Thrombi, Hemostasis, and Angiology. Tokyo, Japan: Chugai-Igakusha; 2005:410–421.
  7. Kobayashi Y, Numano F. Angiitis. In: Morishita R, ed. Vascular Medicine. Tokyo, Japan: Medical Review; 2001:565–576.
  8. Agmon-Levin N, Damoiseaux J, Kallenberg C, et al. International recommendations for the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies. Ann Rheum Dis. 2014;73:17–23.
  9. Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4:295–306.
  10. Pengo V, Tripodi A, Reber G, et al.; Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. Update of the guidelines for lupus anticoagulant detection. J Thromb Haemost. 2009;7:1737–1740.
  11. Tripodi A, de Groot PE, Pengo V. Antiphospholipid syndrome: Laboratory detection, mechanisms of action and treatment. J Intern Med. 2011;270:110–122.
  12. Aviña-Zubieta JA, Vostretsova K, De Vera MA, Sayre EC, Choi HK. The risk of pulmonary embolism and deep venous thrombosis in systemic lupuserythematosus: A general population-based study. Semin Arthritis Rheum. 2015;45:195–201.
  13. Merkel PA, Lo GH, Holbrook JT, et al.; Wegener's Granulomatosis Etanercept Trial Research Group. High incidence of venous thrombotic events among patients with Wegener granulomatosis: The Wegener’s Clinical Occurrence of Thrombosis (WeCLOT) study. Ann Intern Med. 2005;142:620–626.
  14. Mustonen P, Lehtonen KV, Javela K, Puurunen M. Persistent antiphospholipid antibody (aPL) in asymptomatic carriers as a risk factor for future thrombotic events: A nationwide prospective study. Lupus. 2014;23:1468–1476.
  15. Pierangeli SS, Chen PP, Raschi E, et al. Antiphospholipid antibodies and the antiphospholipid syndrome: Pathogenic mechanisms. Semin Thromb Hemost. 2008;34:236–250.
  16. Roubey RA. Immunology of the antiphospholipid antibody syndrome. Arthritis Rheum. 1996;391:1444–1454.
  17. Vlachoyiannopoulos PG, Routsias JG. A novel mechanism of thrombosis in antiphospholipid antibody syndrome. J Autoimmun. 2010;35:248–255.
  18. Roubey RA, Hoffman M. From antiphospholipid syndrome to antibody-mediated thrombosis. Lancet. 1997;350:1491–1493.
  19. Yalavarthi S, Gould TJ, Rao AN, et al. Release of neutrophil extracellular traps by neutrophils stimulated with antiphospholipid antibodies: A newly identified mechanism of thrombosis in the antiphospholipid syndrome. Arthritis Rheumatol. 2015;67:2990–3003.
  20. Ortel TL. Thrombosis and the antiphospholipid syndrome. Hematology Am Soc Hematol Educ Program. 2005;1:462–468.
  21. Basu A, Sanchez TW, Casiano CA. DFS70/LEDGFp75: An enigmatic autoantigen at the interface between autoimmunity, AIDS and cancer. Front Immunol. 2015;6:116. doi: 10.3389/fimmu.2015.00116
  22. Marlet J, Ankri A, Charuel JL, et al. Thrombophilia associated with anti-DFS70 autoantibodies. PLoS One. 2015;10(9):e0138671. doi: 10.1371/journal.pone.0138671