Laboratory and Clinical Correlates of Lupus Anticoagulant Positivity in an Albanian Cohort

ORIGINAL ARTICLE
Ina Toska, Ervin Rapushi, Rexhep Shkurti, Anila Mitre, Ervin Toçi

 
For citation: Toska I, Rapushi E, Shkurti R, Mitre A, Toçi E. Laboratory and Clinical Correlates of Lupus Anticoagulant Positivity in an Albanian Cohort. International Journal of Biomedicine. 2026;16(2):223-226. doi:10.21103/Article16(2)_OA11
 
Originally published June 5, 2026

Abstract: 

Background: Antiphospholipid syndrome (APS) is an autoimmune disease in which immune-mediated mechanisms promote a chronic prothrombotic state, leading to an increased risk for thrombotic events and obstetric complications. Particularly during their reproductive ages, females are disproportionately affected, making APS a major clinical concern in female populations. Lupus anticoagulant (LAC) is recognized as the strongest laboratory predictor for thrombosis and adverse pregnancy outcomes, among antiphospholipid antibodies. However, the clinical and laboratory correlates of LAC in women, including thrombosis, homocysteine metabolism, genetic thrombophilia, and reproductive complications, remain poorly understood.
Methods and Results: This observational study included 522 individuals with a thrombotic event or pregnancy morbidity, suspected of having APS. They were tested for LAC, homocysteine (HCY), and antiphospholipid antibodies. Subsequent analyses were conducted exclusively among female participants to provide a more clinically meaningful and statistically reliable evaluation. Association between LAC levels and APS classification, thrombotic events, homocysteine levels, the MTHFR gene mutations (C677T and A1298C), and other conditions of pregnancy losses were evaluated using chi-square tests, Welch two-sample t-test, and Pearson correlation as appropriate. Statistical analyses were performed using R software.
Among female participants (n=452), LAC positivity was observed in 35.2%, elevated homocysteine levels in 18.8%, and APS in 11.3%. Lupus anticoagulant levels were highly significant in participants with thrombotic events and APS classified. No significant linear correlation was observed between LAC and homocysteine levels. In contrast, significant differences in LAC levels were observed according to the MTHFR mutation status and history of other pregnancy losses.
Conclusion: This study highlights the central role of lupus anticoagulant as a key laboratory marker associated with thrombotic events and APS-related manifestations in women. The lack of association with homocysteine further supports the concept of independent pathogenic pathways. These findings underscore the importance of LAC assessment in the clinical evaluation and risk stratification of patients with suspected antiphospholipid syndrome.

Keywords: 
antiphospholipid syndrome • lupus anticoagulant • homocysteine • MTHFR gene
References: 
  1. Cervera R, Piette JC, Font J, Khamashta MA, Shoenfeld Y, Camps MT, et al.; Euro-Phospholipid Project Group. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum. 2002 Apr;46(4):1019-27. doi: 10.1002/art.10187. PMID: 11953980.
  2. Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006 Feb;4(2):295-306. doi: 10.1111/j.1538-7836.2006.01753.x. PMID: 16420554.
  3. Galli M, Luciani D, Bertolini G, Barbui T. Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature. Blood. 2003 Mar 1;101(5):1827-32. doi: 10.1182/blood-2002-02-0441. Epub 2002 Oct 3. PMID: 12393574.
  4. Den Heijer M, Lewington S, Clarke R. Homocysteine, MTHFR and risk of venous thrombosis: a meta-analysis of published epidemiological studies. J Thromb Haemost. 2005 Feb;3(2):292-9. doi: 10.1111/j.1538-7836.2005.01141.x. PMID: 15670035.
  5. Pengo V, Tripodi A, Reber G, Rand JH, Ortel TL, Galli M, De Groot PG; 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. Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. J Thromb Haemost. 2009 Oct;7(10):1737-40. doi: 10.1111/j.1538-7836.2009.03555.x. Epub 2009 Jul 17. PMID: 19624461.
  6. Meroni PL, Borghi MO, Raschi E, Tedesco F. Pathogenesis of antiphospholipid syndrome: understanding the antibodies. Nat Rev Rheumatol. 2011 Jun;7(6):330-9. doi: 10.1038/nrrheum.2011.52. Epub 2011 May 10. PMID: 21556027.
  7. Salmon JE, Girardi G. The Role of Complement in the Antiphospholipid Syndrome. KARGER eBooks. 2003 Jan 1;133–48.
  8. Tektonidou MG, Andreoli L, Limper M, Amoura Z, Cervera R, Costedoat-Chalumeau N, et al. EULAR recommendations for the management of antiphospholipid syndrome in adults. Ann Rheum Dis. 2019 Oct;78(10):1296-1304. doi: 10.1136/annrheumdis-2019-215213. Epub 2019 May 15. PMID: 31092409; PMCID: PMC11034817.
  9. Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ. 2002 Nov 23;325(7374):1202. doi: 10.1136/bmj.325.7374.1202. PMID: 12446535; PMCID: PMC135491.
  10. Bezemer ID, Doggen CJ, Vos HL, Rosendaal FR. No association between the common MTHFR 677C->T polymorphism and venous thrombosis: results from the MEGA study. Arch Intern Med. 2007 Mar 12;167(5):497-501. doi: 10.1001/archinte.167.5.497. PMID: 17353498.
  11. ‌Hickey S, Curry C, Toriello H. ACMG Practice Guideline: lack of evidence for MTHFR polymorphism testing. Genet Med. 2013;15:153–156. doi:10.1038/gim.2012.165
  12. de Laat HB, Derksen RH, Urbanus RT, Roest M, de Groot PG. beta2-glycoprotein I-dependent lupus anticoagulant highly correlates with thrombosis in the antiphospholipid syndrome. Blood. 2004 Dec 1;104(12):3598-602. doi: 10.1182/blood-2004-03-1107. Epub 2004 Aug 17. PMID: 15315975.

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Received March 9, 2026.
Accepted April 27, 2026.
© 2026 The Author(s). International Journal of Biomedicine is published by IMRDC.
This is an open access article under the CC BY-NC-ND 4.0 license.