Thrombotic recurrences and bleeding events in APS vascular patients: A review from the literature and a comparison with the APS Piedmont Cohort

Bazzan, M.; Vaccarino, A; Stella, Stefania; Bertero, MT; Carignola, R.; Montaruli, Barbara; Roccatello, Dario; Shoenfeld, Yehuda

doi:10.1016/j.autrev.2012.11.007

Cited by 24 publications

(15 citation statements)

References 39 publications

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“…Most of the studies to determine the incidence of thromboembolic events in aPL carriers were cross-sectional [10, 11] and were performed in people diagnosed with APS with thrombotic antecedents. Thus these studies evaluated the recurrence of thrombotic events.…”

Section: Introductionmentioning

confidence: 99%

Incidence of thromboembolic events in asymptomatic carriers of IgA anti ß2 glycoprotein-I antibodies

et al. 2017

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BackgroundThe antiphospholipid syndrome (APS) is defined by simultaneous presence of vascular clinical events and antiphospholipid antibodies (aPL). The aPL considered as diagnostics are lupus anticoagulant and antibodies anticardiolipin (aCL) and anti-ß2 glycoprotein-I (aB2GP1). During recent years, IgA aB2GP1 antibodies have been associated with thrombotic events both in patients positive, and mainly negative for other aPL, however its value as a pro-thrombotic risk-factor in asymptomatic patients has not been well defined.ObjectiveTo test the role of IgA anti B2GP1 as a risk factor for the development of APS-events (thrombosis or pregnancy morbidity) in asymptomatic population with a 5-year follow-up.Methods244 patients isolated positive for anti-beta2-glycoprotein I IgA (Group-1 study) and 221 negative patients (Group-2 control) were studied. All the patients were negative for IgG and IgM aCL.ResultsDuring the follow-up, 45 patients (9.7%) had APS-events, 38 positive for IgA-aB2GP1 and 7 negative (15.6% vs 3.2%, p<0.001).The incidence rate of APS-events was 3.1% per year in IgA-aB2GP1 positive patients and 0.6% per year in the control group. Arterial thrombosis were the most frequent APS-events (N = 25, 55%) and were mainly observed in Group-1 patients (21 vs 4, p = 0.001). Multivariate analysis were shown as independent risk-factors for the development of APS-events, age, sex (men) and presence of IgA-aB2GP1 (odds ratio 5.25, 95% CI 2.24 to 12.32).ConclusionThe presence of IgA-aB2GP1 in people with no history of APS-events is the main independent risk factor for the development of these types of events, mainly arterial thrombosis.

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Section: Introductionmentioning

confidence: 99%

Incidence of thromboembolic events in asymptomatic carriers of IgA anti ß2 glycoprotein-I antibodies

et al. 2017

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“…The binding site on β2GPI for the receptor responsible for the induction of procoagulant activity is unknown. Indefinite anticoagulation, which is a treatment of choice for high risk APS patients, is not always effective in preventing the recurrence of thrombosis [45–47]. A detailed understanding of how β2GPI interacts with receptors involved in cellular activation by β2GPI/anti-β2GPI complexes is essential for the development of drugs specific for antiphospholipid syndrome.…”

Section: Introductionmentioning

confidence: 99%

Dimerized Domain V of Beta2-Glycoprotein I Is Sufficient to Upregulate Procoagulant Activity in PMA-Treated U937 Monocytes and Require Intact Residues in Two Phospholipid-Binding Loops

2017

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Upregulation of the procoagulant activity of monocytes by antibodies to beta2- glycoprotein I (β2GPI) is one of the mechanisms contributing to thrombosis in antiphospholipid syndrome. Current knowledge about receptors responsible for the upregulation of procoagulant activity by β2GPI/anti-β2GPI complexes and their binding sites on β2GPI is far from complete. We quantified the procoagulant activity expressed by phorbol 12-myristate 13-acetate (PMA)- differentiated U937 cells by measuring clotting kinetics in human plasma exposed to stimulated cells. Cells stimulated with anti-β2GPI were compared to cells treated with dimerized domain V of β2GPI (β2GPI-DV) or point mutants of β2GPI-DV. We demonstrated that dimerized β2GPI-DV is sufficient to induce procoagulant activity in monocytes. Using site-directed mutagenesis, we determined that the phospholipid-binding interface on β2GPI is larger than previously thought and includes Lys308 in β2GPI-DV. Intact residues in two phospholipid-binding loops of β2GPI-DV were important for the potentiation of procoagulant activity. We did not detect a correlation between the ability of β2GPI-DV variants to bind ApoER2 and potentiation of the procoagulant activity of cells. The region on β2GPI inducing procoagulant activity in monocytes can now be narrowed down to β2GPI-DV. The ability of β2GPI-DV dimers to come close to cell membrane and attach to it is important for the stimulation of procoagulant activity.

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“…These new assays have good analytical performances. Like ELISA, their diagnostic performances strongly depend on the choice of cutoff values .…”

Section: Introductionmentioning

confidence: 99%

Analytical and clinical comparison of different immunoassay systems for the detection of antiphospholipid antibodies

Montaruli

Luna

Erroi

et al. 2016

Int J Lab Hematology

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Thrombotic recurrences and bleeding events in APS vascular patients: A review from the literature and a comparison with the APS Piedmont Cohort

Cited by 24 publications

References 39 publications

Incidence of thromboembolic events in asymptomatic carriers of IgA anti ß2 glycoprotein-I antibodies

Incidence of thromboembolic events in asymptomatic carriers of IgA anti ß2 glycoprotein-I antibodies

Dimerized Domain V of Beta2-Glycoprotein I Is Sufficient to Upregulate Procoagulant Activity in PMA-Treated U937 Monocytes and Require Intact Residues in Two Phospholipid-Binding Loops

Analytical and clinical comparison of different immunoassay systems for the detection of antiphospholipid antibodies

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