Table Info

Table 2.

Relationship between aPLs and recurrent thrombosis in patients with PAPS

aPL		Recurrent thrombosis		P	OR (95% CI)
aPL		Yes, n (%)	No, n (%)	P	OR (95% CI)
IgG aCL, n = 52; ELISA	+	31 (91)	9 (50)	0.002	10.33 (2.20–48.37)
IgG aCL, n = 52; ELISA	–	3 (9)	9 (50)	0.002	10.33 (2.20–48.37)
IgM aCL, n = 52; ELISA	+	7 (21)	4 (22)	0.89	0.90 (0.21–3.76)
IgM aCL, n = 52; ELISA	–	27 (79)	14 (78)	0.89	0.90 (0.21–3.76)
IgG anti-β₂-GPI, n = 52; ELISA	+	29 (85)	9 (50)	0.004	7.50 (1.79–31.36)
IgG anti-β₂-GPI, n = 52; ELISA	–	4 (15)	9 (50)	0.004	7.50 (1.79–31.36)
IgM anti-β₂-GPI, n = 52; ELISA	+	8 (23)	4 (22)	0.91	1.07 (0.26–4.36)
IgM anti-β₂-GPI, n = 52; ELISA	–	26 (77)	14 (78)	0.91	1.07 (0.26–4.36)
IgG aPS/PT, n = 52; ELISA	+	29 (85)	8 (44)	0.003	7.25 (1.85–28.35)
IgG aPS/PT, n = 52; ELISA	–	5 (15)	10 (56)	0.003	7.25 (1.85–28.35)
IgM aPS/PT, n = 52; ELISA	+	13 (38)	7 (39)	0.96	0.97 (0.29–3.23)
IgM aPS/PT, n = 52; ELISA	–	21 (62)	11 (61)	0.96	0.97 (0.29–3.23)
aCL with anti-β₂-GPI, n = 52; ELISA	+	29 (85)	9 (50)	0.009	5.79 (1.48–22.58)
aCL with anti-β₂-GPI, n = 52; ELISA	–	5 (15)	9 (50)	0.009	5.79 (1.48–22.58)
IgG aCL with IgG anti-β₂-GPI and with IgG aPS/PT, n = 52; ELISA	+	27 (79)	7 (39)	0.005	6.06 (1.66–22.09)
	–	7 (21)	11 (61)	0.005	6.06 (1.66–22.09)
IgG aCL, n = 52; CLA	+	33 (97)	11 (61)	0.007	21.00 (2.17–202.78)
IgG aCL, n = 52; CLA	–	1 (3)	7 (39)	0.007	21.00 (2.17–202.78)
IgM aCL, n = 52; CLA	+	13 (38)	6 (33)	0.72	1.23 (0.36–4.23)
IgM aCL, n = 52; CLA	–	21 (62)	12 (67)	0.72	1.23 (0.36–4.23)
IgA aCL, n = 49; CLA	+	21 (66)	5 (29)	0.01	4.58 (1.23–16.94)
IgA aCL, n = 49; CLA	–	11 (34)	12 (71)	0.01	4.58 (1.23–16.94)
IgG anti-β₂-GPI, n = 52; CLA	+	33 (97)	9 (50)	0.002	32.00 (3.33–307.02)
IgG anti-β₂-GPI, n = 52; CLA	–	1 (3)	9 (50)	0.002	32.00 (3.33–307.02)
IgM anti-β₂-GPI, n = 52; CLA	+	13 (38)	6 (33)	0.72	1.23 (0.36–4.23)
IgM anti-β₂-GPI, n = 52; CLA	–	21 (62)	12 (67)	0.72	1.23 (0.36–4.23)
IgA anti-β₂-GPI, n = 49; CLA	+	18 (37)	5 (29)	0.07	3.08 (0.84–11.20)
IgA anti-β₂-GPI, n = 49; CLA	–	14 (63)	12 (71)	0.07	3.08 (0.84–11.20)
IgG anti-β₂-GPIDI, n = 48; CLA	+	29 (93)	8 (47)	0.001	16.31 (2.77–96.03)
IgG anti-β₂-GPIDI, n = 48; CLA	–	2 (7)	9 (53)	0.001	16.31 (2.77–96.03)
aCL with anti-β₂-GPI, n = 52; CLA	+	32 (94)	11 (61)	0.008	10.18 (1.74–59.24)
aCL with anti-β₂-GPI, n = 52; CLA	–	2 (6)	7 (39)	0.008	10.18 (1.74–59.24)
IgG aCL with IgG anti-β₂-GPI and with IgG anti-β₂-GPIDI, n = 48; CLA	+	29 (93)	7 (41)	0.0006	20.71 (3.48–123.00)
	–	2 (7)	10 (59)	0.0006	20.71 (3.48–123.00)

+: positive aPLs; –: negative aPLs. P: reliability. P value ≤ 0.05 represents significance difference

Declarations

Acknowledgments

The study conducted within the framework of fundamental research project FURS-2022-003 [1021051402790].

Author contributions

FAC: Conceptualization, Validation, Writing—original draft, Writing—review & editing, Project administration. AAS: Writing—original draft, Writing—review & editing, Project administration. MVC and SIG: Validation. AML: Project administration. ELN: Project administration, Supervision. TMR: Methodology, Writing—original draft, Writing—review & editing, Project administration, Supervision. All authors read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

The study was conducted in accordance with the Declaration of Helsinki, and approved by Ethics Committee of V.A. Nasonova Research Institute of Rheumatology (Protocol No. 25 dated December 19, 2019).

Consent to participate

Informed consent to participate in the study was obtained from all participants.

Consent to publication

Informed consent to publication was obtained from relevant participants.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

References

Gómez-Puerta JA, Cervera R. Diagnosis and classification of the antiphospholipid syndrome. J Autoimmun. 2014;48–49:20–5. [DOI] [PubMed]

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;4:295–306. [DOI] [PubMed]

Reshetnyak TM. Antiphospholipid syndrome: diagnosis and clinical manifestation (a lecture). Rheumatol Sci Prac. 2014;52:56–71. Russian.

Sciascia S, Amigo MC, Roccatello D, Khamashta M. Diagnosing antiphospholipid syndrome: ‘extra-criteria’ manifestations and technical advances. Nat Rev Rheumatol. 2017;13:548–60. [DOI] [PubMed]

Navarro-Carpentieri D, Del Carmen Castillo-Hernandez M, Majluf-Cruz K, Espejo-Godinez G, Carmona-Olvera P, Moreno-Hernandez M, et al. Impact of classical risk factors for arterial or venous thrombosis in patients with antiphospholipid syndrome. Clin Appl Thromb Hemost. 2018;24:834–40. [DOI] [PubMed] [PMC]

Aleksandrova EN, Novikov AA, Reshetnyak TM, Nasonov EL. Antibodies to β2-glycoprotein 1 and antibodies to cardiolipin in antiphospholipid syndrome: sensitivity and specificity analysis. Klin Med (Mosk). 2003;81:25–31. Russian. [PubMed]

Zhang S, Wu Z, Li P, Bai Y, Zhang F, Li Y. Evaluation of the clinical performance of a novel chemiluminescent immunoassay for detection of anticardiolipin and anti-beta2-glycoprotein 1 antibodies in the diagnosis of antiphospholipid syndrome. Medicine (Baltimore). 2015;94:e2059. [DOI] [PubMed] [PMC]

Ünlü O, Zuily S, Erkan D. The clinical significance of antiphospholipid antibodies in systemic lupus erythematosus. Eur J Rheumatol. 2016;3:75–84. [DOI] [PubMed] [PMC]

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;78:1296–304. [DOI] [PubMed] [PMC]

10.

Kearon C, Parpia S, Spencer FA, Baglin T, Stevens SM, Bauer KA, et al. Antiphospholipid antibodies and recurrent thrombosis after a first unprovoked venous thromboembolism. Blood. 2018;131:2151–60. [DOI] [PubMed] [PMC]

11.

Wilson WA, Gharavi AE, Koike T, Lockshin MD, Branch DW, Piette JC, et al. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthritis Rheum. 1999;42:1309–11. [DOI] [PubMed]

12.

Pengo V, Ruffatti A, Legnani C, Gresele P, Barcellona D, Erba N, et al. Clinical course of high-risk patients diagnosed with antiphospholipid syndrome. J Thromb Haemost. 2010;8:237–42. [DOI] [PubMed]

13.

Dufrost V, Risse J, Reshetnyak T, Satybaldyeva M, Du Y, Yan XX, et al. Increased risk of thrombosis in antiphospholipid syndrome patients treated with direct oral anticoagulants. Results from an international patient-level data meta-analysis. Autoimmun Rev. 2018;17:1011–21. [DOI] [PubMed]

14.

Cheldieva FA, Reshetnyak TM, Cherkasova MV, Lila AM. Study of antiphospholipid antibodies by enzyme immunoassay and chemiluminescent methods in patients with antiphospholipid syndrome and systemic lupus erythematosus (preliminary data). Klin Lab Diagn. 2021;66:546–51. [PubMed]

15.

Tkachenko OY, Lapin SV, Mazing AV, Blinova TV, Butina SE, Emanuel VL. New methods for detecting antiphospholipid antibodies. Dr Ru. 2019;10:57–62. Russian. [DOI]

16.

Devreese K, Hoylaerts MF. Laboratory diagnosis of the antiphospholipid syndrome: a plethora of obstacles to overcome. Eur J Haematol. 2009;83:1–16. [DOI] [PubMed]

17.

DE Moerloose P, Reber G, Musial J, Arnout J. Analytical and clinical performance of a new, automated assay panel for the diagnosis of antiphospholipid syndrome. J Thromb Haemost. 2010;8:1540–6. [DOI] [PubMed]

18.

Cheldieva FA, Reshetnyak TM, Cherkasova MV, Glukhova SI, Lila AM, Nasonov EL. Antibodies to domain I β2-glycoprotein 1 in patients with antiphospholipid syndrome and systemic lupus erythematosus. Rheumatol Sci Prac. 2022;60:353–9. Russian. [DOI]

19.

Pericleous C, Ferreira I, Borghi O, Pregnolato F, McDonnell T, Garza-Garcia A, et al. Measuring IgA anti-β2-glycoprotein I and IgG/IgA anti-domain I antibodies adds value to current serological assays for the antiphospholipid syndrome. PLoS One. 2016;11:e0156407. [DOI] [PubMed] [PMC]

20.

Mahler M, Albesa R, Zohoury N, Bertolaccini ML, Ateka-Barrutia O, Rodriguez-Garcia JL, et al. Autoantibodies to domain 1 of beta 2 glycoprotein I determined using a novel chemiluminescence immunoassay demonstrate association with thrombosis in patients with antiphospholipid syndrome. Lupus. 2016;25:911–6. [DOI] [PubMed]

21.

Liu T, Gu J, Wan L, Hu Q, Teng J, Liu H, et al. “Non-criteria” antiphospholipid antibodies add value to antiphospholipid syndrome diagnoses in a large Chinese cohort. Arthritis Res Ther. 2020;22:33. [DOI] [PubMed] [PMC]

22.

Shen YM, Lee R, Frenkel E, Sarode R. IgA antiphospholipid antibodies are an independent risk factor for thromboses. Lupus. 2008;17:996–1003. [DOI] [PubMed]

23.

Tortosa C, Cabrera-Marante O, Serrano M, Martínez-Flores JA, Pérez D, Lora D, et al. Incidence of thromboembolic events in asymptomatic carriers of IgA anti β2 glycoprotein-I antibodies. PLoS One. 2017;12:e0178889. [DOI] [PubMed] [PMC]

24.

Sciascia S, Sanna G, Murru V, Roccatello D, Khamashta MA, Bertolaccini ML. Anti-prothrombin (aPT) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies and the risk of thrombosis in the antiphospholipid syndrome. Thromb Haemost. 2014;111:354–64. [DOI] [PubMed]

25.

Galli M, Borrelli G, Jacobsen EM, Marfisi RM, Finazzi G, Marchioli R, et al. Clinical significance of different antiphospholipid antibodies in the WAPS (warfarin in the antiphospholipid syndrome) study. Blood. 2007;110:1178–83. [DOI] [PubMed]

26.

Devreese K, Peerlinck K, Hoylaerts MF. Thrombotic risk assessment in the antiphospholipid syndrome requires more than the quantification of lupus anticoagulants. Blood. 2010;115:870–8. [DOI] [PubMed]

27.

De Laat B, Derksen RH, Reber G, Musial J, Swadzba J, Bozic B, et al. An international multicentre-laboratory evaluation of a new assay to detect specifically lupus anticoagulants dependent on the presence of anti-beta2-glycoprotein autoantibodies. J Thromb Haemost. 2011;9:149–53. [DOI] [PubMed]

28.

Otomo K, Atsumi T, Amengual O, Fujieda Y, Kato M, Oku K, et al. Efficacy of the antiphospholipid score for the diagnosis of antiphospholipid syndrome and its predictive value for thrombotic events. Arthritis Rheum. 2012;64:504–12. [DOI] [PubMed]

29.

Sciascia S, Sanna G, Murru V, Roccatello D, Khamashta MA, Bertolaccini ML. GAPSS: the global anti-phospholipid syndrome score. Rheumatology (Oxford). 2013;52:1397–403. [DOI] [PubMed]

30.

Tikhonova TL, Reshetnyak TM, Patrushev MI, Stukacheva EA, Miroshnikov AI, Nasonov EL, et al. Leiden, G20210A mutations in the prothrombin gene and antiphospholipid antibodies in systemic lupus erythematosus and antiphospholipid syndrome. Ter Archive. 2000;72:34–8. Russian. [PubMed]

31.

Erkan D, Salmon J, Lockshin M. Antiphospholipid syndrome. In: Firestein GS, Budd RC, Gabriel SE, McInnes IB, O’Dell JR, editors. Kelley and Firestein’s textbook of rheumatology. Philadelphia: Elsevier; 2017. pp. 1389–99.

32.

Bazzan M, Vaccarino A, Stella S, Sciascia S, Montaruli B, Bertero MT, et al. Patients with antiphospholipid syndrome and thrombotic recurrences: a real world observation (the Piedmont cohort study). Lupus. 2016;25:479–85. [DOI] [PubMed]

33.

Saraiva SdS, Custódio IF, Mazetto Bde M, Collela MP, de Paula EV, Appenzeller S, et al. Recurrent thrombosis in antiphospholipid syndrome may be associated with cardiovascular risk factors and inflammatory response. Thromb Res. 2015;136:1174–8. [DOI] [PubMed]

34.

Berman H, Ugarte-Gil MF, Espinosa G, Tàssies D, Monteagudo J, Reverter JC, et al. Can inherited thrombophilia modulate the clinical phenotype of patients with antiphospholipid syndrome? Clin Exp Rheumatol. 2013;31:926–32. [PubMed]

35.

Diz-Kucukkaya R, Hancer VS, Artim-Esen B, Pekcelen Y, Inanc M. The prevalence and clinical significance of inherited thrombophilic risk factors in patients with antiphospholipid syndrome. J Thromb Thrombolysis. 2010;29:303–9. [DOI] [PubMed]