The impact of hydroxychloroquine on obstetric outcomes in refractory obstetric antiphospholipid syndrome

Conventional treatment of obstetric antiphospholipid syndrome fails in approximately 20–30% of pregnant women without any clearly identified risk factor. It is important to identify risk factors that are associated with these treatment failures. This study aimed to assess the impact of risk factors on pregnancy outcomes in women with obstetric antiphospholipid syndrome treated with conventional treatment. We carefully retrospectively selected 106 pregnancies in women with obstetric antiphospholipid syndrome treated with heparin + aspirin. Pregnancy outcomes were evaluated according to the following associated risk factors: triple positivity profile, double positivity profile, single positivity profile, history of thrombosis, autoimmune disease, more than four pregnancy losses, and high titers of anticardiolipin antibodies and/or anti-βeta-2-glycoprotein-I (aβ2GPI) antibodies. To establish the association between pregnancy outcomes and risk factors, a single binary logistic regressions analysis was performed. Risk factors associated with pregnancy loss with conventional treatment were: the presence of triple positivity (OR = 5.0, CI = 1.4–16.9, p = 0.01), high titers of aβ2GPI (OR = 4.4, CI = 1.2–16.1, p = 0.023) and a history of more than four pregnancy losses (OR = 3.5, CI = 1.2–10.0, p = 0.018). The presence of triple positivity was an independent risk factor associated with gestational complications (OR = 4.1, CI = 1.2–13.9, p = 0.02). Our findings reinforce the idea that triple positivity is a categorical risk factor for poor response to conventional treatment.

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Women with isolated antiphospholipid antibodies (APL) have better obstetric outcomes compared to those with obstetric antiphospholipid syndrome (APS): Abstract PM.08 Table

Archives of Disease in Childhood - Fetal and Neonatal Edition ◽

10.1136/fetalneonatal-2012-301809.103 ◽

2012 ◽

Vol 97 (Suppl 1) ◽

pp. A32.2-A32 ◽

Cited By ~ 1

Author(s):

MC Soh ◽

D Pasupathy ◽

G Gray ◽

J McLaren ◽

C Nelson-Piercy

Keyword(s):

Antiphospholipid Syndrome ◽

Antiphospholipid Antibodies ◽

Obstetric Outcomes ◽

Obstetric Antiphospholipid Syndrome

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Risk factors for early severe preeclampsia in obstetric antiphospholipid syndrome with conventional treatment. The impact of hydroxychloroquine

Lupus ◽

10.1177/0961203320952850 ◽

2020 ◽

Vol 29 (13) ◽

pp. 1736-1742

Author(s):

José Omar Latino ◽

Sebastián Udry ◽

Federico Aranda ◽

Silvia Perés Wingeyer ◽

Diego Santiago Fernández Romero ◽

...

Keyword(s):

Risk Factors ◽

High Risk ◽

Antiphospholipid Syndrome ◽

Conventional Treatment ◽

Severe Preeclampsia ◽

Factors Associated ◽

High Risk Factors ◽

History Of ◽

Obstetric Antiphospholipid Syndrome ◽

The Impact

Objective The first aim was to retrospectively identify risk factors for the development of early severe preeclampsia (sPE) in patients with obstetric antiphospholipid syndrome (OAPS) who received conventional treatment (CT). The second aim was to evaluate the impact of hydroxychloroquine (HCQ) in preventing early sPE among a subgroup of patients considered at high risk. Methods A total of 102 women diagnosed with OAPS and treated with CT since the diagnosis of pregnancy were selected. At the end of pregnancy, we identified risk factors associated with early sPE. According to these risk factors, we collected a new cohort of 42 patients who presented high-risk factors for developing early sPE and split them into two groups according to the treatment received: group A, CT (30 patients); and group B, CT+HCQ (12 patients). We evaluated and compared pregnancy outcomes in both groups. Results According to the multivariate analysis, risk factors associated with early sPE and CT were triple positivity for antiphospholipid antibodies (aPL) (OR = 24.70, [4.27–142.92], p < 0.001) and a history of early sPE (OR = 7.11, [1.13–44.64], p = 0.036). A low-risk aPL profile was associated with a good response to CT in preventing early sPE (OR = 0.073, [0.014–0.382], p = 0.002). High-risk patients treated with CT+HCQ had a significantly lower early sPE rate than those treated with CT only (8.3% vs 40.0%; p = 0.03). Conclusion Triple positivity for aPL and a history of early sPE are potential strong risk factors for the development of early sPE. HCQ might be an interesting therapeutic option for patients with high-risk factors for early sPE.

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Obstetric outcomes in patients with primary thrombotic and obstetric antiphospholipid syndrome and its relation to the antiphospholipid antibody profile

Lupus ◽

10.1177/0961203319852155 ◽

2019 ◽

Vol 28 (7) ◽

pp. 868-877 ◽

Cited By ~ 2

Author(s):

A Högdén ◽

A Antovic ◽

E Berg ◽

K Bremme ◽

R Chaireti

Keyword(s):

Birth Weight ◽

Antiphospholipid Syndrome ◽

Pregnancy Outcomes ◽

University Hospital ◽

Obstetric Outcomes ◽

Antiphospholipid Antibody ◽

Primary Antiphospholipid Syndrome ◽

Antibody Positivity ◽

Obstetric Antiphospholipid Syndrome ◽

Antibody Profile

Introduction: Previous studies suggested different obstetric outcomes between patients with thrombotic or obstetric antiphospholipid syndrome, but the data are inconclusive. Aims: To investigate obstetric outcomes and their relation to the antiphospholipid antibody profile in primary thrombotic or obstetric antiphospholipid syndrome patients and compare those to a control population. Materials and methods: A retrospective single-centre study on a cohort of 30 pregnant women with primary antiphospholipid syndrome treated at Karolinska University Hospital Solna, Sweden between 2000 and 2016. The pregnancy outcomes were compared to the outcomes of all pregnancies in Stockholm County during the same period. Results: Preeclampsia ( p < 0.001), low birth weight at delivery ( p = 0.001), Apgar < 7 at 5 minutes ( p < 0.001) and small infants ( p < 0.001) were more common in antiphospholipid syndrome patients compared to controls. Obstetric antiphospholipid syndrome patients had a higher incidence of small infants ( p = 0.023), lower birth weight ( p = 0.013) and infants born with complications ( p=0.004) compared to thrombotic antiphospholipid syndrome. Mothers with triple antibody positivity had a higher incidence of preeclampsia ( p = 0.03), preterm delivery ( p = 0.011), small infants ( p=0.002) and infants born with complications ( p = 0.012). Conclusions: Patients with primary antiphospholipid syndrome, especially those with obstetric antiphospholipid syndrome and triple antibody positivity, are at higher risk for adverse pregnancy outcomes, even under antithrombotic treatment. More frequent antenatal controls in high-risk patients can further improve outcomes.

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COVID-19: Uncertainties from Conception to Birth

Revista Brasileira de Ginecologia e Obstetrícia / RBGO Gynecology and Obstetrics ◽

10.1055/s-0040-1721856 ◽

2021 ◽

Vol 43 (01) ◽

pp. 054-060

Author(s):

Bruno Ramalho de Carvalho ◽

Karina de Sá Adami ◽

Walusa Assad Gonçalves-Ferri ◽

Marise Samama ◽

Rui Alberto Ferriani ◽

...

Keyword(s):

Pregnant Women ◽

Present Article ◽

Vertical Transmission ◽

Scientific Information ◽

Obstetric Outcomes ◽

Reproductive Events ◽

The Impact ◽

Initial Impressions ◽

Quality Evidence

AbstractScientific information on the impact of the new coronavirus (SARS-CoV-2) on the health of pregnant women, fetuses and newborns is considered of limited confidence, lacking good-quality evidence, and drawing biased conclusions. As a matter of fact, the initial impressions that the evolution of COVID-19 was no different between pregnant and non-pregnant women, and that SARS-CoV-2 was not vertically transmitted, are confronted by the documentation of worsening of the disease during pregnancy, poor obstetric outcomes, and the possibility of vertical transmission. The present article aims to compile the data available on the association of COVID-19 and reproductive events, from conception to birth.

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Does incomplete obstetric antiphospholipid syndrome really exist?

Medicina Clínica (English Edition) ◽

10.1016/j.medcle.2020.12.018 ◽

2021 ◽

Vol 156 (10) ◽

pp. 515-519

Author(s):

Jaume Alijotas-Reig

Keyword(s):

Antiphospholipid Syndrome ◽

Obstetric Antiphospholipid Syndrome

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AB1240 C4B BINDING PROTEIN AND WARFARIN IN THE ANTIPHOSPHOLIPID SYNDROME

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5606 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1911.2-1911

Author(s):

G. Grosso ◽

K. Sandholm ◽

I. Gunnarsson ◽

A. Zickert ◽

A. Vikerfors ◽

...

Keyword(s):

Antiphospholipid Syndrome ◽

Mediation Analysis ◽

Binding Protein ◽

Protein A ◽

Protein S ◽

Protein Isoforms ◽

Type I ◽

Complement Inhibitor ◽

Warfarin Treatment ◽

The Impact

Background:Complement plays a role in the Antiphospholipid Syndrome (APS). C4b Binding Protein (C4BP) is a complement inhibitor with anticoagulant function (1). It belongs to the same protein family as β2GPI, the main antigen in APS. Its main isoform is bound to protein S in the circulation. Levels of both protein S and C4BP are known to be reduced by warfarin treatment (2) as well as by aPL, directly and indirectly.Objectives:To investigate the levels of C4BP in primary (p) and secondary (s) APS, also considering warfarin treatment.Methods:The total amount of C4BP (C4BPt) was measured by using magnetic carboxylated microspheres which were coupled with a monoclonal antibody against the α-chain of human-C4BP to capture the antigen. To detect C4BPt the same antibody was used, biotinylated. The binding of biotinylated antibodies was detected by streptavidin-phycoerythrin and data were collected using a MAGPIX Multiplex Reader. Using independent t-test, we compared C4BP in 118 SLE patients with repeated positivity for Antiphospholipid antibodies (aPL) (39/118 on warfarin), 291 aPL negative SLE patients (16/291 on warfarin), 67 pAPS (33/67 on warfarin), and 322 controls (none on warfarin). We then performed an interaction and a mediation analysis (3) in the SLE group to study the impact of warfarin on C4BP levels: since warfarin is mostly prescribed to aPL+ patients, it is considered a mediator in the reducing effect of aPL on C4BP. Therefore we compared individuals exposed and non-exposed to the presence of aPL with or without the mediator warfarin and calculated the percentage of reduction in C4BP that could be attributed to aPL or warfarin.Results:Overall C4BP is 20% reduced in aPL+ patients (fig 1), independently of SLE, past thrombotic events and nephritis. Warfarin treated patients have lower levels of C4BP (fig 2). According to mediation analysis 11% of C4BP reduction is due to aPL and 9% to warfarin.Figure 1.C4BP in different subgroups (67 pAPS, 118 SLEaPL+, 291 SLEaPL-, 322 controls)Figure 2.C4BP in 67 pAPS patients, 33/67 on warfarinConclusion:Both aPL and warfarin decrease levels of C4BP, a complement and coagulation regulator. Reduction of this complement inhibitor could contribute to complement activation and thrombosis in APS. Our results raise new questions regarding the effects of warfarin treatment on complement and coagulation in APS.References:[1]Dahlbäck B. C4b-binding protein: a forgotten factor in thrombosis and hemostasis. Seminars in thrombosis and hemostasis 2011; 37(4): 355.[2]Zöller B, García de Frutos P, Dahlbäck B. Evaluation of the relationship between protein S and C4b-binding protein isoforms in hereditary protein S deficiency demonstrating type I and type III deficiencies to be phenotypic variants of the same genetic disease. Blood 1995; 85(12): 3524.[3]Vanderweele TJ, Vansteelandt S. Conceptual issues concerning mediation, interventions and composition. Statistics and Its Interface 2009; 2(4): 457-68.Disclaimer:AV is employed at the Swedish Medical Products Agency, the views expressed in this paper are the personal views of the authors and not necessarily the views of the Governement AgencyAcknowledgments:Thanks to the Biostatistics Core Facility, Karolinska UniversityDisclosure of Interests:None declared

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Trisomy 18 Pregnancies: Is there an Increased Maternal Risk?

American Journal of Perinatology ◽

10.1055/s-0037-1603679 ◽

2017 ◽

Vol 34 (11) ◽

pp. 1054-1057

Author(s):

Kayli Senz ◽

Whitney Humphrey ◽

Vanessa Lee ◽

Aaron Caughey ◽

Sarah Dotters-Katz

Keyword(s):

International Classification Of Diseases ◽

Vital Statistics ◽

Trisomy 18 ◽

Trisomy 13 ◽

Obstetric Outcomes ◽

Maternal Risk ◽

Increased Risk ◽

Multiparous Women ◽

Classification Of Diseases ◽

The Impact

Objective Characterize the impact of a trisomy 18 (T18) fetus on maternal and obstetric outcomes in a cohort including T18-affected deliveries. Study Design Retrospective cohort study of singleton deliveries in California from 2005 to 2008 using linked vital statistics and the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9) data to compare deliveries affected by T18 to those without known aneuploidy. Outcomes of interest included gestational diabetes mellitus (GDM), preterm delivery (PTD), preeclampsia, cesarean delivery (CD), and intrauterine fetal demise (IUFD). The χ2 and paired t-tests were used to compare the outcomes. Multiple logistic regression was used to further characterize these risks and control potential confounders. Results Of 2,029,000 deliveries, 298 involved T18. Compared with unaffected deliveries, T18 was associated with GDM (10.7 vs. 6.5%, p = 0.003), PTD < 37 (40.6 vs. 9.9%, p < 0.001) and < 32 weeks (14.8 vs. 1.4%, p < 0.001), and cesarean section (56 vs. 30.2%, p < 0.001), but not preeclampsia. In adjusted analyses, T18 pregnancies were associated with an increased risk of PTD < 37 and < 32 weeks (adjusted odds ratio [AOR]: 5.48, 95% confidence interval [CI]: 4.29, 6.99; AOR: 10.4, 95% CI: 7.26, 14.8), and an increased odd of CD for primiparous and multiparous women (AOR: 2.41, 95% CI: 1.48, 3.91; AOR: 5.42, 95% CI: 3.90, 7.53). Risk of GDM did not persist. Conclusion Unlike trisomy 13 (T13), pregnancies complicated by fetal T18 did not appear to result in an increased risk of preeclampsia. However, there is an increased risk of a range of other obstetric complications.

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