Review14th International Congress on Antiphospholipid Antibodies Task Force Report on Obstetric Antiphospholipid Syndrome☆
Introduction
The Obstetric Task Force of the 14th International Congress on Antiphospholipid Antibodies met on the 18 September 2013 in Rio de Janeiro, Brazil. The Task Force was charge with reviewing obstetric diagnostics and treatments as they pertain to our current understanding of obstetric antiphospholipid syndrome (Ob APS). In preparation for the meeting, the Task Force chairman, Guilherme R. de Jesus, MD, and associate director, Ware Branch, MD, engaged internationally-known experts in the field to present critical, evidence-based updates on Ob APS. The three current criteria for Ob APS [1] were identified as key components of meeting, and members of the APS international community also felt that a review of the possible association of infertility and antiphospholipid antibodies (aPL) should be included. Drs. de Jesus and Branch also asked Jane Salmon, MD, an expert in the role of complement-mediated inflammation in reproductive failure in antiphospholipid syndrome (APS), to review this topic, especially as findings might point to new therapeutic targets. As a general guideline for each area of Ob APS, presenters and participants were asked to consider the following questions. Drs. de Jesus and Branch stressed a critical, evidence-based analysis of each area.
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What is our current understanding of association of the clinical feature with antiphospholipid antibodies and antiphospholipid syndrome, and what needs to be done to improve our understanding of the association?
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What is the current status of the treatment for each clinical feature of Ob APS, and what needs to be done to clarify the evidence for or against currently used treatments?
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Are there intriguing, new ideas regarding prevention or treatment of Ob APS, and how might these be studied?
Of course, underlying these questions is the larger issue of whether or not the current clinical criteria for Ob APS deserve modification.
The issue of testing for antiphospholipid antibodies came up several times, though it was not the mission of this Task Force to make specific comments or recommendations about such testing. There seems little doubt, however, that crystalizing the relationship between alleged clinical associations and antiphospholipid antibodies fundamentally depends upon improvements in antiphospholipid testing.
Registered attendees were encouraged to offer comments and criticisms during the meeting, though time was somewhat limited, and via email after the meeting. Not surprisingly, several participants voiced their opinions about the current status of the clinical associations with antiphospholipid antibodies and the treatments currently used or recommended. Given the frustrating and emotionally-charged nature of reproductive failure, it came as no surprise that strong opinions emerged. Dr. Nancy Agmon-Levin and her colleagues were enthusiastic participants in this aspect of the Task Force and have offered their unpublished survey results regarding the management of “non-criteria Ob APS” for consideration by the group. We have included an abbreviated version of their observations in the section covering recurrent early miscarriage. Thus, the summary of this Task Force's findings is presented in 5 sections: (1) Recurrent early miscarriage (< 10 weeks gestation), (2) fetal death (≥ 10 weeks gestation), (3) preeclampsia and placental insufficiency, (4) infertility, and (5) complement-mediated inflammation in pathogenesis of APS-related adverse obstetric outcomes.
Section snippets
Association of aPL and REM [summary prepared by Guilherme R. de Jesus, MD, and Cecilia Chighizola, MD, with comments of Nancy Agmon-Levin, MD, and colleagues included]
The main objective of this review was to analyze the association of REM (< 10 weeks gestation) with aPL, as listed in the revised Sapporo criteria [1].
Dr. de Jesus reviewed the rationale for the association of REM and aPL, based on in vitro and animal studies. Besides classical thrombotic mechanism of aPL, these antibodies have been associated to complement activation, reduction of annexin-V, and placental tissue damage, ultimately resulting in abortion [2], [3], [4]. APL also induce trophoblast
Association of aPL and fetal death [summary prepared by Laura Andreoli, MD, and Angela Tincani, MD]
The association between fetal death and aPL has been addressed by a recent article [70]. According to this comprehensive systematic review of the literature, fetal death was shown to be associated with LA in 4 case–control studies and 3 cohort studies, aCL in 7 case–control studies and 5 cohort studies, and aβ2GPI in 2 cohort studies. However, the authors of the systematic review note several limitations that suggest caution. Firstly, many studies included a small number of patients such that
Association of aPL and preeclampsia [summary prepared by Carlos A. Andrade, MD, DSc, and D. Ware Branch, MD]
The objective of this review of the literature was to assess the status of the association between aPL and the obstetric clinical criteria of preeclampsia (PreE) in a two-fold manner. First, the authors assessed previously published systematic reviews or meta-analysis about the mentioned association; then, it was analyzed whether or not an additional meta-analysis should or could be performed.
The authors found two systematic analyses of the association between aPL and PreE that were of credible
Association of aPL and infertility and treatment of patients with infertility and positive aPL [summary prepared by Cecilia Chighizola, MD,and Guilherme R. de Jesus, MD]
The hypothesis that aPL might interfere with the earlier stages of pregnancy was first formulated in the late 80s, when a report suggesting an association between aPL positivity and infertility was published [101]. Since then, based on the assumption that aPL may affect implantation by hindering uterine decidualization, aPL have been investigated as a potential cause of infertility. Even though infertility is not enlisted among obstetrical criteria manifestations of APS [1], many physicians do
The role of complement in pathogenesis of preeclampsia and placental insufficiency in patients with aPL [summary prepared by Jane Salmon, MD]
The complement system protects the host against invading organisms, initiates inflammation and enhances the removal of opsonized and injured cells. It provides an important link between the innate and adaptive immune systems. Experimental observations suggest that increased complement activation causes and/or perpetuates inflammation during pregnancy. Recent studies suggest a link between complement activation and pregnancy loss, growth restriction and preeclampsia. Excessive activation or
Conclusions [prepared by Guilherme R. de Jesus, MD, and D. Ware Branch, MD]
The Obstetric Task Force of the 14th International Congress on Antiphospholipid Antibodies has carefully and critically examined the evidence for both the quality of association of each of the current clinical obstetric criteria for APS and the quality of the evidence that treatment(s) provide benefit in terms of avoiding recurrent adverse obstetric outcomes. The results of our analysis for each clinical obstetric criterion are summarized in the respective sections above. We found that after
Take-home messages
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High quality studies investigating the association of antiphospholipid antibodies (aPL) with pregnancy morbidity present in current classification criteria are lacking.
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Treatment of obstetric events related to aPL are not supported by consistent findings from well-designed studies.
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Patients with infertility should not be investigated or treated for aPL in routine clinical practice.
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New pathogenic mechanisms of obstetric morbidity related to activation of complement by aPL may lead to different
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Dedicated to the memory of Silvia Pierangeli, PhD.