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THU0029 Inflammation is Strongly Associated with Lupus Anticoagulant Positivity, Independent of Known Autoimmune Disease and Recent Venous or Arterial Thrombosis
  1. S.A. Just1,
  2. M. Nybo2,
  3. H. Laustrup3,
  4. I.M.J. Hansen1,
  5. P.J. Vinholt2
  1. 1Internal Medicine, Division of Rheumatology, Svendborg Hospital, Odense University Hospital, Svendborg
  2. 2Clinical Biochemistry and Pharmacology
  3. 3Rheumatology, Odense University Hospital, Odense, Denmark

Abstract

Background The antiphospholipid syndrome (APS) is an auto-immune disorder defined by presence of antiphospholipid antibodies and either thrombosis or obstetric complications (1). Laboratory part of the diagnosis of APS comprise of testing for lupus anticoagulant (LAC), anticardiolipin (ACA) and anti-β2-glycoprotein 1 (β2GP1) antibodies (2). Especially persistent LAC positivity is associated with thrombosis risk (1). Antiphospholipid antibodies are often found in patients with inflammatory disease and inflammation is involved in the development of thrombosis (3). Two studies found that LAC status was associated with inflammatory state (4). It may, however, be due to interference from C-reactive protein (CRP) on the LAC investigation when a LAC assay based on activated partial thromboplastin time (aPTT) is used (4). To avoid this artefact a diluted Russel viper venom test (dRVVT) can be used (4). Hence, the relation between antiphospholipid antibodies and inflammation is not fully elucidated.

Objectives The aim was to study if inflammatory markers were associated with LAC positivity independent of previous thrombosis or chronic inflammatory disease.

Methods 235 patients referred to thrombophilia testing, LAC was tested with dRVVT. Acute phase markers (CRP, fibrinogen, coagulation factor VIII (FVIII)) and leukocyte count were measured. From a diagnosis register information on previous venous and arterial thrombosis and chronic inflammatory diseases was retrieved. Groups (LAC positive versus LAC negative) were compared by logistic regression with univariate and multivariate analysis adjusted for previous disease. Moreover, analyses were repeated after exclusion of patients with possible bacterial infections (CPR ≥50 mg/l). Correlations were calculated using Pearson.

Results There was no difference in age, gender or co-morbidities between LAC positive and LAC negative patients (table 1). LAC positive patients had significantly higher CRP, fibrinogen and FVIII levels compared with LAC negative (p<0.001), but no difference in leukocyte count. Exclusion of patients with CRP ≥50mg/L (6 patients of whom 2 were LAC positive) did not alter the results. The LAC titer correlated with CRP (r=0.33), fibrinogen (r=0.26) and FVIII (r=0.14) – all p<0.05. FVIII was higher in patients with elevated titer of ACA IgM compared to those with normal ACA IgM. Other tests did not differ when comparing patients with normal versus elevated titers of specific antibodies (ACA and β2GP1).

Conclusions Inflammation is associated with LAC positivity independent of thrombosis and chronic inflammatory disease. Findings indicate that inflammation induce antibody production. Thus, one may speculate if LAC positivity reflect an underlying inflammatory state, which is the true meachanism behind the increased thrombosis risk.

References

  1. Cohen D, et al. Diagnosis and management of the antiphospholipid syndrome. BMJ 2010;340:c2541

  2. Pengo V, et al. Update of the guidelines for lupus anticoagulant detection. J Thromb Haemost 2009;7:1737-40

  3. Aksu K, et al. Inflammation-induced thrombosis:mechanisms, disease associations and management. Curr Pharm Des 2012;18:1478-93

  4. Schouwers SM, et al. LAC testing in patients with inflammatory status: does C-reactive protein interfere with LAC test results? Thromb Res 2010;125:102-4

Disclosure of Interest : None declared

DOI 10.1136/annrheumdis-2014-eular.2154

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