Triple Antiphospholipid (aPL) Antibodies Positivity Is Associated With Pregnancy Complications in aPL Carriers: A Multicenter Study on 62 Pregnancies.

Maria-Grazia Lazzaroni,Maria-Gabriella Raimondo,Amelia Ruffatti,Micaela Fredi,Maria Gerosa,Pier-Luigi Meroni,Sonia Zatti,Anna Kuzenko,Cecilia Beatrice Chighizola,Vittorio Pengo,Teresa Del Ross,Francesca Ramazzotto,Angela Tincani,Laura Andreoli,Laura Trespidi,Andrea Lojacono

doi:10.3389/fimmu.2019.01948

Abstract

Objective: Antiphospholipid antibodies (aPL) are risk factors for thrombosis and adverse pregnancy outcomes (APO). The management of the so called “aPL carriers” (subjects with aPL positivity without the clinical criteria manifestations of APS) is still undefined. This study aims at retrospectively evaluating the outcomes and the factors associated with APO and maternal complications in 62 pregnant aPL carriers.Methods: Medical records of pregnant women regularly attending the Pregnancy Clinic of 3 Rheumatology centers from January 1994 to December 2015 were retrospectively evaluated. Patients with concomitant autoimmune diseases or other causes of pregnancy complications were excluded.Results: An aPL-related event was recorded in 8 out of 62 patients (12.9%) during pregnancy: 2 thrombosis and 6 APO. At univariate analysis, factors associated with pregnancy complications were acquired risk factors (p:0.008), non-criteria aPL manifestations (p:0.024), lupus-like manifestations (p:0.013), and triple positive aPL profile (p:0.001). At multivariate analysis, only the association with a triple aPL profile was confirmed (p:0.01, OR 21.3, CI 95% 1.84–247). Patients with triple aPL positivity had a higher rate of pregnancy complications, despite they were more frequently receiving combined treatment of low dose aspirin (LDA) and low molecular weight heparin (LMWH) at prophylactic dose.Conclusion: This study highlights the importance of risk stratification in pregnant aPL carriers, in terms of both immunologic and non-immunologic features. Combination treatment with LDA and LMWH did not prevent APO in some cases, especially in carriers of triple aPL positivity. Triple positive aPL carriers may deserve additional therapeutic strategies during pregnancy.

Highlights

Antiphospholipid antibodies are a heterogeneous group of autoantibodies reacting against phospholipids, phospholipidprotein complexes and phospholipid-binding proteins, detected by different assays: lupus anticoagulant (LA), anticardiolipin and anti-β2 glycoprotein I antibodies.The so called “aPL carriers” are individuals with persistent aPL positivity, in the absence of the clinical criteria of APS [1]
APL have been demonstrated to be pathogenic [3], they should be considered as risk factors for thrombosis or pregnancy morbidity, with several other variables modulating the final clinical expression [4, 5]
The Pregnancy Clinics’ database of each center were reviewed and 62 women met the inclusion criteria during the period comprised between 1994 and 2015. These patients had 69 pregnancies during the study period, but only the first pregnancy followed at one of the 3 participating centers was considered for further analysis, according to the inclusion and exclusion criteria listed above

Summary

Introduction

The so called “aPL carriers” are individuals with persistent aPL positivity, in the absence of the clinical criteria of APS (pregnancy morbidity or thrombosis) [1]. APL are sometimes included in the diagnostic protocols to assess infertility causes performed before assisted reproduction procedures. Despite being asymptomatic, these subjects are theoretically at increased risk of vascular and obstetric events because they carry persistently positive aPL. APL have been demonstrated to be pathogenic [3], they should be considered as risk factors for thrombosis or pregnancy morbidity, with several other variables modulating the final clinical expression [4, 5]

Methods

Results

Discussion

Conclusion