FXI Levels as Independent Risk Factor for Antiphospholipid Syndrome: Development of a New Predictive Score, APS-FXI

M.E. de la Morena-Barrio¹, J. Pagan-Escribano², A. Miñano¹, V. Roldán¹, A. Lopez-Arribas³, J. Lozano², M.J. Hernandez-Vidal², I. de la Morena-Barrio⁴, V. Vicente¹, M.T. Herranz², J. Corral¹

¹Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Arrixaca, CIBERER, Murcia, Spain, ²Servicio de Medicina Interna, Hospital Universitario Morales Meseguer, Murcia, Spain, ³Werfen, Valencia, Spain, ⁴Servicio de Reumatologia, Hospital Clínico de Valencia, Valencia, Spain

Abstract Number: PB1929

Meeting: ISTH 2020 Congress

Theme: Thrombotic Microangiopathies » Antiphospholipid Syndrome

Background: The prothrombotic consequences of antiphospholipid antibodies (aPL) are well demonstrated. Antibodies (titer and type) and cardiovascular risk factors have been used as predictors of thrombotic or obstetric events (antiphospholipid syndrome, APS) in the aGAPSS score, but further factors might improve predictions. Factor XI (FXI), a target of aPL, has been involved both in thrombosis (>150%) or bleeding (< 70%). Moreover, FXI deficiency protects against thrombosis.

Aims: To evaluate FXI in patients with aPL.

Methods: 194 consecutive subjects with aPL, 112 primary APS and 82 asymptomatic (a-aPL) were enrolled. FXI was evaluated by coagulometric assays (FXI:C) using two contact activators (silica -SS- and ellagic acid -SF-), and by western-blotting. F11 was studied by sequencing and MLPA. Statistical analysis included binary logistic regression, Mann-Whitney U test, and ROC curves.

Results: FXI:C values were significantly higher in APS than in a-aPL. Remarkably, cases with FXI>150% were 14-times higher in APS, and cases with FXI< 70% were 4-times higher in a-aPL.

[Characteristics of subjects with antiphospholipid antibodies (aPL). Potential risk factors associated to antiphospholipid syndrome (APS).]

Two patients had congenital FXI deficiency caused by the Ashkenazy p.Glu135* variant, however, dilution analyses confirmed the presence of inhibitors in the remaining 12 patients with FXI deficiency. Multivariate analysis confirmed dyslipidemia, aB2GPI IgG, and lupus anticoagulant (LA) as independent risk factors for APS, but FXI (both excess and deficiency) showed the highest odds ratios (OR). A predictive score for APS based on b coefficients and including for the first time FXI (APS-FXI), was performed. ROC curve showed a better adjustment for APS-FXI than aGAPSS.

[Multivariate analysis by binary logistic regression and ROC curves; APS-FXI vs aGAPSS in the prediction of APS in our cohort.]

Conclusions: Our study shows a strong predictive value of FXI levels in subjects with aPL. FXI>150% are associated to APS, while FXI deficiency < 70%, which may be caused by the antibodies, protects subjects with aPL from APS. We have developed a new score for predicting APS including FXI levels with high sensitivity and specificity.PI18/00598 (ISCIII y FEDER); and 19873/GERM/15 (Fundación Séneca).

To cite this abstract in AMA style:

de la Morena-Barrio ME, Pagan-Escribano J, Miñano A, Roldán V, Lopez-Arribas A, Lozano J, Hernandez-Vidal MJ, de la Morena-Barrio I, Vicente V, Herranz MT, Corral J. FXI Levels as Independent Risk Factor for Antiphospholipid Syndrome: Development of a New Predictive Score, APS-FXI [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/fxi-levels-as-independent-risk-factor-for-antiphospholipid-syndrome-development-of-a-new-predictive-score-aps-fxi/. Accessed December 11, 2023.

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