Problem Solved? An Individual Ratio between Point-of-Care and Venous International Normalized Ratio Values in Two Patients with Antiphospholipid Syndrome: Two Case Reports

Abstract

Antiphospholipid syndrome (APS) is a rare autoimmune disorder characterized by thromboembolic and obstetric complications in the presence of persistent antiphospholipid antibodies (aPL). Treatment aims to prevent recurrent thrombosis, primarily using anticoagulation therapy with vitamin K antagonists (VKA). Monitoring of VKA therapy relies on the International Normalized Ratio (INR), which can be assessed using point-of-care testing (POCT). However, in a subset of APS patients with a high-risk aPL profile, the POCT-INR is falsely elevated, which might lead to underdosing of VKA and subsequent high risk of recurrent thrombosis. This case report describes two female patients with triple-positive thrombotic APS receiving VKA therapy. Both patients underwent biweekly paired INR measurements via POCT-INR and venous INR methods. Despite significant discrepancies, a strong individual linear correlation was observed: r = 0.77 (95% confidence interval [CI]: 0.54–0.99, p < 0.001) and r = 0.93 (95% CI: 0.88–0.97, p < 0.001), respectively. These findings suggest that individualized correction factors could be developed to improve the accuracy of POCT-INR measurements, thereby optimizing VKA dosing in these patients.

Keywords

antiphospholipid syndrome - International Normalized Ratio - point-of-care testing - vitamin-k antagonists - case report

Authors' Contributions

B.G. wrote the case report. M.R. and SS contributed clinical details and revisions, J.B. provided the patient perspective and statistical input, A.H. contributed laboratory details en revisions, R.U. contributed revisions, and M.L. supervised the project.

Publikationsverlauf

Eingereicht: 16. Januar 2025

Angenommen: 18. Februar 2025

Accepted Manuscript online:
20. Februar 2025

Artikel online veröffentlicht:
19. März 2025

• References

• 1 Barbhaiya M, Zuily S, Naden R. et al; ACR/EULAR APS Classification Criteria Collaborators. The 2023 ACR/EULAR antiphospholipid syndrome classification criteria. Arthritis Rheumatol 2023; 75 (10) 1687-1702
• 2 Knight JS, Branch DW, Ortel TL. Antiphospholipid syndrome: advances in diagnosis, pathogenesis, and management. BMJ 2023; 380: e069717
• 3 Limper M, de Leeuw K, Lely AT. et al. Diagnosing and treating antiphospholipid syndrome: a consensus paper. Neth J Med 2019; 77 (03) 98-108
• 4 Shikdar S, Vashisht R, Bhattacharya PT. International Normalized Ratio (INR). Treasure Island (FL): StatPearls Publishing LLC; 2024
• 5 Gardiner C, Williams K, Mackie IJ, Machin SJ, Cohen H. Patient self-testing is a reliable and acceptable alternative to laboratory INR monitoring. Br J Haematol 2005; 128 (02) 242-247
• 6 Noordermeer T, Urbanus RT, Wong CY. et al. Interference in point-of-care international normalized ratio monitoring in patients with lupus anticoagulant is correlated with anti-β2-glycoprotein I antibody titers. Res Pract Thromb Haemost 2022; 7 (01) 100011
• 7 Isert M, Miesbach W, Schüttfort G. et al. Monitoring anticoagulant therapy with vitamin K antagonists in patients with antiphospholipid syndrome. Ann Hematol 2015; 94 (08) 1291-1299
• 8 Laurent C, Ricard L, Nguyen Y. et al. Triple positive profile in antiphospholipid syndrome: prognosis, relapse and management from a retrospective multicentre study. RMD Open 2023; 9 (01) e002534
• 9 Tripodi A, Chantarangkul V, Clerici M, Negri B, Galli M, Mannucci PM. Laboratory control of oral anticoagulant treatment by the INR system in patients with the antiphospholipid syndrome and lupus anticoagulant. Results of a collaborative study involving nine commercial thromboplastins. Br J Haematol 2001; 115 (03) 672-678
• 10 Braun S, Spannagl M, Völler H. Patient self-testing and self-management of oral anticoagulation. Anal Bioanal Chem 2009; 393 (05) 1463-1471
• 11 Horsti J. Comparison of quick and Owren prothrombin time with regard to the harmonisation of the international normalised ratio (INR) system. Clin Chem Lab Med 2002; 40 (04) 399-403
• 12 Meijer P, Kynde K, van den Besselaar AMHP, Van Blerk M, Woods TAL. International normalized ratio (INR) testing in Europe: between-laboratory comparability of test results obtained by Quick and Owren reagents. Clin Chem Lab Med 2018; 56 (10) 1698-1703
• 13 Osman A, Lindahl TL. Plasma predilution with addition of depleted plasma in a prothrombin time reagent improves the agreement between different prothrombin time methods. Scand J Clin Lab Invest 2009; 69 (03) 395-400
• 14 Della Valle P, Crippa L, Garlando AM. et al. Interference of lupus anticoagulants in prothrombin time assays: implications for selection of adequate methods to optimize the management of thrombosis in the antiphospholipid-antibody syndrome. Haematologica 1999; 84 (12) 1065-1074
• 15 Noordermeer T, Molhoek JE, Schutgens REG. et al. Anti-β2-glycoprotein I and anti-prothrombin antibodies cause lupus anticoagulant through different mechanisms of action. J Thromb Haemost 2021; 19 (04) 1018-1028