Publications by authors named "Sylvie Bouvier"

23 Publications

  • Page 1 of 1

Early ADAMTS13 testing associates with pre-eclampsia occurrence in antiphospholipid syndrome.

Thromb Res 2021 Apr 27;203:101-109. Epub 2021 Apr 27.

Department of Gynaecology and Obstetrics, First Moscow State Medical University (Sechenov University), Russian Federation; Department of Haematology, CHU Nîmes, Univ Montpellier, Nîmes, France; Faculty of Pharmaceutical and Biological Sciences, Montpellier University, Montpellier, France; UA 011 INSERM- Université de Montpellier, Institut Desbrest d'Epidémiologie et de Santé Publique, Montpellier, France. Electronic address:

Introduction: Women with obstetric antiphospholipid syndrome (oAPS) still develop placental diseases, mainly pre-eclampsia (PEcl), which diagnosis is associated with reduced ADAMTS13 levels. Testing ADAMTS13 in newly pregnant oAPS may provide evidence for risk stratification.

Materials And Methods: We retrospectively investigated the prognostic value of ADAMTS13 activity, antigen and antibodies on stored plasma samples obtained prior to beginning low-molecular weight heparin-low dose aspirin treatment in 513 oAPS women.

Results: Some women had evidences of early positive ADAMTS13 antibodies and low ADAMTS13 activity:antigen ratio, suggestive of ADAMTS13 dysfunction. Women with a subsequent PEcl had higher ADAMTS13 antibodies (p < 0.0001), and lower ADAMTS13 activity and activity:antigen ratios (p < 0.0001). In multivariate analysis, these markers were significant risk factors for PEcl and for the most devastating PEcl subgroups (early-onset PEcl, severe PEcl, PEcl with no living child after 28 days). ADAMTS13-related markers showed acceptable discrimination power to predict clinical events, particularly for ADAMTS13 activity:antigen ratio in predicting PEcl cases with no living child after 28 days (AUC: 0.844 (0.712-0.974), p < 0.0001), with excellent negative predictive value (0.990).

Conclusions: The characterization of ADAMTS13 in newly pregnant women with oAPS depicts the risk of PEcl occurrence. ADAMTS13 might help identify pregnant women with oAPS not requiring escalating treatment strategies to prevent PEcl.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.thromres.2021.04.021DOI Listing
April 2021

NETosis Markers in Pregnancy: Effects Differ According to Histone Subtypes.

Thromb Haemost 2021 Jan 10. Epub 2021 Jan 10.

Department of Haematology, University Hospital, Nîmes, France.

NETosis is an innate immune response occurring after infection or inflammation: activated neutrophils expel decondensed DNA in complex with histones into the extracellular environment in a controlled manner. It activates coagulation and fuels the risk of thrombosis. Human pregnancy is associated with a mild proinflammatory state characterized by circulatory neutrophil activation which is further increased in complicated pregnancies, placenta-mediated complications being associated with an increased thrombotic risk. This aberrant activation leads to an increased release of nucleosomes in the blood flow. The aim of our study was to initially quantify nucleosome-bound histones in normal pregnancy and in placenta-mediated complication counterpart. We analyzed the role of histones on extravillous trophoblast function. Circulating nucleosome-bound histones H3 (Nu.QH3.1, Nu.QH3PanCit, Nu.QH3K27me3) and H4 (Nu.QH4K16Ac) were increased in complicated pregnancies. In vitro using the extravillous cell line HTR-8/SVNeo, we observed that free recombinant H2B, H3, and H4 inhibited migration in wound healing assay, but only H3 also blocked invasion in Matrigel-coated Transwell experiments. H3 and H4 also induced apoptosis, whereas H2B did not. Finally, the negative effects of H3 on invasion and apoptosis could be restored with enoxaparin, a low-molecular-weight heparin (LMWH), but not with aspirin. Different circulating nucleosome-bound histones are increased in complicated pregnancy and this would affect migration, invasion, and induce apoptosis of extravillous trophoblasts. Histones might be part of the link between the risk of thrombosis and pregnancy complications, with an effect of LMWH on both.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0040-1722225DOI Listing
January 2021

Placenta-mediated complications: Nucleosomes and free DNA concentrations differ depending on subtypes.

J Thromb Haemost 2020 12 18;18(12):3371-3380. Epub 2020 Oct 18.

Department of Haematology, CHU Nimes, Univ Montpellier, Nîmes, France.

Background: Placenta-mediated pregnancy complications generate short- and long-term adverse medical outcomes for both the mother and the fetus. Nucleosomes and free DNA (fDNA) have been described in patients suffering from a wide range of inflammatory conditions.

Objective: The objective of our study was to compare nucleosomes and fDNA circulating levels during pregnancy and particularly in women developing a placenta-mediated complication according to the subtype (preeclampsia or intrauterine growth restriction) (NCT01736826).

Patients/methods: A total of 115 women were prospectively included in the study across three groups: 30 healthy non-pregnant women, 50 with normal pregnancy, and 35 with a complicated pregnancy. Blood samples were taken up to every 4 weeks for several women with normal pregnancy and nucleosomes and fDNA were quantified using enzyme-linked immunosorbent assay and quantitative polymerase chain reaction, respectively.

Results: We show that nucleosomes and fDNA concentrations significantly increase during normal pregnancy, with concentrations at delivery differing between the two groups. Interestingly, we show that concentrations differ according to the type of placenta-mediated complications, with higher levels in preeclampsia compared to intrauterine growth restriction.

Conclusions: These data suggest that nucleosomes and fDNA may be additional actors participating in placenta-mediated pregnancy complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jth.15105DOI Listing
December 2020

Discovery of Type 3 von Willebrand Disease in a Cohort of Patients with Suspected Hemophilia A in Côte d'Ivoire.

Mediterr J Hematol Infect Dis 2020 1;12(1):e2020019. Epub 2020 Mar 1.

Department of Hematology, Faculty of Pharmacy, Felix Houphouet Boigny University, Abidjan, Côte d'Ivoire.

Background: Type 3 von Willebrand disease (VWD) is the most severe form of VWD, characterized by a near-total absence of von Willebrand factor (vWF), leading to a massive deficiency in plasmatic factor VIII (FVIII). VWD may be confused with hemophilia A, sometimes leading to misdiagnosis. The purpose of this work was to finalize the biological diagnosis of patients with FVIII activity deficiency in Abidjan in order to guide the best type of management.

Methods: We conducted a cross-sectional descriptive study from June 2018 to April 2019. Forty-nine patients, all of whom had lower FVIII levels or had been referred for a bleeding disorder, were monitored in the clinical hematology service. The pro-coagulant activity of coagulation factors was performed in Abidjan. The assays for von Willebrand antigen and activity were performed at Nîmes University Hospital in France.

Results: The mean age of patients was 13.8 years (1 - 65) and 86% were Ivorian. FVIII deficiency was discovered during a biological checkup, circumcision or post-traumatic bleeding, in 33%, 31% and 29% respectively. The FVIII deficiency of patients was classified as severe (89.8%), moderate (8.2%) and mild (2%). Only one patient had a quantitative deficiency of von Willebrand factor (vWF: Ag <3%) with undetectable von Willebrand factor activity (vWF: Ac) and an FVIII level <1%.

Conclusions: Not all of the congenital deficiency of FVIII are represented by hemophilia A. It was crucial to assess the Willebrand factor of these patients followed in Côte d'Ivoire for whom hemophilia A had been suspected.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4084/MJHID.2020.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059751PMC
March 2020

The role of haemostasis in placenta-mediated complications.

Thromb Res 2019 Sep;181 Suppl 1:S10-S14

University of Montpellier, France; Department of Vascular Imaging and Vascular Medicine, Nîmes University Hospital, France.

Normal pregnancy is associated with an increasing state of activation of the haemostatic system. This activation state is excessive in women with placenta-mediated pregnancy complications (PMPCs), including preeclampsia (PE). Platelet activation plays a crucial pathophysiological role in PE. The very early activation of coagulation in the intervillous space is mandatory for placental growth and morphogenesis but its excesses and/or inadequate control may participate to the emergence of the trophoblastic phenotype of PE. Extracellular vesicles, of endothelial but also of trophoblastic origin, can favour key cellular reactions of preeclampsia, acting as proactive cofactors. The understanding of this intricate relationship between haemostasis activation and PMPCs may provide interesting keys for new pathophysiological therapeutic developments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0049-3848(19)30359-7DOI Listing
September 2019

Increased incidence of cancer in the follow-up of obstetric antiphospholipid syndrome within the NOH-APS cohort.

Haematologica 2020 31;105(2):490-497. Epub 2020 Jan 31.

UPRES EA2992 "Caractéristiques Féminines des Dysfonctions des Interfaces Vasculaires", University of Montpellier, Montpellier, France.

Malignancies can be associated with positive antiphospholipid antibodies but the incidence of cancer among women with the purely obstetric form of antiphospholipid syndrome (APS) is currently unknown. Our aim was to investigate the comparative incidence of cancers in women with a history of obstetric APS within a referral university hospital-based cohort (NOH-APS cohort). We performed a 17-year observational study of 1,592 non-thrombotic women with three consecutive spontaneous abortions before the 10 week of gestation or one fetal death at or beyond the 10 week of gestation. We compared the incidence of cancer diagnosis during follow-up among the cohort of women positive for antiphospholipid antibodies (n=517), the cohort of women carrying the rs6025 or rs1799963 polymorphism (n=279) and a cohort of women with negative thrombophilia screening results (n=796). The annualized rate of cancer was 0.300% (0.20%-0.44%) for women with obstetric APS and their cancer risk was substantially higher than that of women with negative thrombophilia screening [adjusted hazard ratio (aHR) 2.483; 95% confidence interval (CI) 1.27-4.85]. The computed standardized incidence ratio for women with obstetric APS was 2.89; 95% CI: 1.89-4.23. Among antiphospholipid antibodies, lupus anticoagulant was associated with incident cancers (aHR 2.608; 95% CI: 1.091-6.236). Our cohort study shows that the risk of cancer is substantially higher in women with a history of obstetric APS than in the general population, and in women with a similar initial clinical history but negative for antiphospholipid antibodies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3324/haematol.2018.213991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012495PMC
April 2021

Successful Pregnancy under Fibrinogen Substitution with Heparin and Aspirin in a Woman with Dysfibrinogenemia Revealed by Placental Abruption.

Thromb Haemost 2018 Nov 8;118(11):2006-2008. Epub 2018 Oct 8.

Department of Haematology, Nîmes University Hospital, University of Montpellier, Nîmes, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0038-1673615DOI Listing
November 2018

Clinical value of automated fibrin generation markers in patients with septic shock: a SepsiCoag ancillary study.

Br J Haematol 2018 11 11;183(4):636-647. Epub 2018 Sep 11.

Intensive Care Unit, CHU Nîmes, Univ Montpellier, France.

An ancillary analysis to the SepsiCoag multicentric prospective observational study on patients entering an intensive care unit with septic shock evaluated the prognostic potential of fibrin generation markers (FGMs) tested at inclusion in the study, on survival at day 30. After centralization of samples, three automated FGMs were compared: D-dimers (DDi), fibrin/fibrinogen degradation products (FDP) and fibrin monomers (FM). FM was the single FGM that was significantly higher in non-surviving patients, area under the receiver-operator characteristic curve (AUC ): 0·617, P < 0·0001. Significantly higher International Society on Thrombosis and Haemostasis Disseminated Intravascular Coagulation (ISTH DIC) scores were calculated in non-survivors using each of the three FGMs. A dose-effect relationship was observed between ISTH DIC scores and non-survival, with highest significance obtained using FM as the FGM. An overt DIC diagnosis using the ISTH DIC score calculated using FM was a predictor of non-survival at day 30, independently from overt DIC diagnosis based on scores calculated using FDP or DDi. The AUC values testing the ability of the ISTH DIC score to predict non-survival were 0·650, 0·624 and 0·602 using FM, DDi and FDP, respectively, as the FGM. In patients with septic shock, among the commercially-available automated assays, automated FM is the FGM best related with late prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bjh.15576DOI Listing
November 2018

Atypical monoblasts with micronuclei.

Blood 2017 10;130(17):1958

Nîmes University Hospital.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2017-07-795542DOI Listing
October 2017

Antiphospholipid antibodies are associated with positive screening for common mental disorders in women with previous pregnancy loss. The NOHA-PSY observational study.

World J Biol Psychiatry 2019 01 19;20(1):51-63. Epub 2017 Jun 19.

f Department of Internal Medicine , University Hospital , Nîmes , France.

Objectives: Case reports describe neuropsychiatric manifestations associated with antiphospholipid antibodies (aPlAbs). In patients sharing the same symptoms fulfilling the antiphospholipid syndrome (APS) clinical criteria, the prevalence of common mental disorders has, however, never been studied.

Methods: We observed women with three consecutive abortions before the 10th week of gestation or one foetal loss at or beyond the 10th week. We compared the prevalence of common psychiatric disorders detected through screening using the Mini International Neuropsychiatric Interview, 10 years after inclusion, in women with APS (n = 506), women negative for aPlAbs but carrying the F5rs6025 or F2rs1799963 thrombogenic polymorphism (n = 269), and women with negative thrombophilia screening results as controls (n = 764).

Results: Similar prevalence values were obtained for controls and women bearing one of the two thrombogenic polymorphisms. Women with APS more frequently had mood disorders (relative risk (RR) 1.57 (1.262-1.953), P = .0001) and anxiety (RR 1.645 (1.366-1.979), P < .0001). Within the APS group, lupus anticoagulant (LA) and anti-β2GP1 IgG, or triple positivity, were strong risk factors for mood disorders.

Conclusions: Women with obstetric APS have a higher risk of positive screening for common mental disorders than women without APS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15622975.2017.1333146DOI Listing
January 2019

Soluble CD146, an innovative and non-invasive biomarker of embryo selection for in vitro fertilization.

PLoS One 2017 14;12(3):e0173724. Epub 2017 Mar 14.

Aix Marseille Univ, Inserm U1076, Marseille, France.

Although progress was made in in vitro fertilization (IVF) techniques, the majority of embryos transferred fail to implant. Morphology embryo scoring is the standard procedure for most of IVF centres for choosing the best embryo, but remains limited since even the embryos classified as "top quality" may not implant. As it has been shown that i) CD146 is involved in embryo implantation and ii) membrane form is shed to generate soluble CD146 (sCD146), we propose that sCD146 in embryo supernatants may constitute a new biomarker of embryo selection. Immunocytochemical staining showed expression of CD146 in early embryo stages and sCD146 was detected by ELISA and Western-blot in embryo supernatants from D2. We retrospectively studied 126 couples who underwent IVF attempt. The embryo culture medium from each transferred embryo (n = 222) was collected for measurement of sCD146 by ELISA. Significantly higher sCD146 concentrations were present in embryo supernatants that did not implant (n = 185) as compared to those that successfully implanted (n = 37) (1310 +/- 1152 pg.mL-1 vs. 845+/- 1173 pg.mL-1, p = 0.024). Sensitivity analysis performed on single embryo transfers (n = 71) confirmed this association (p = 0.0054). The computed ROC curve established that the optimal sCD146 concentration for embryo implantation is under 1164 pg.mL-1 (sensitivity: 76%, specificity: 48%, PPV: 25% and NPV: 92%). Over this sCD146 threshold, the implantation rate was significantly lower (9% with sCD146 levels >1164 pg.ml-1 vs. 22% with sCD146 levels ≤ 1164 pg.mL-1, p = 0.01). Among the embryos preselected by morphologic scoring, sCD146 determination could allow a better selection of the embryo(s), thus improving the success of elective single embryo transfer. This study establishes the proof of concept for the use of sCD146 as a biomarker for IVF by excluding the embryo with the highest sCD146 level. A multicentre prospective study will now be necessary to further establish its use in clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0173724PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349662PMC
September 2017

Antiphospholid antibodies and the risk of pregnancy complications.

Thromb Res 2017 Mar;151 Suppl 1:S34-S37

Department of Gynaecology and Obstetrics, Nîmes, France.

Antiphospholipid antibodies (APLAbs) are generally considered as risk factors for foetal death, for premature birth ≤34weeks due to severe pre-eclampsia or severe placental insufficiency and for recurrent consecutive spontaneous abortions <10weeks. Among these three obstetrical morbidities, only the first one is however not regularly questioned. The coexistence of an inflammatory disease and/or of thrombotic manifestations increases the obstetrical risks. Among the three criteria APLAbs, i.e. lupus anticoagulant (LA), anticardiolipin (aCL) Abs, anti-β2 glycoprotein-I (aβ2GP1)Abs, LA seems the more widely associated to clinical risks, the clinical impact of aβ2GP1Abs is progressively defined and the pejorative impact of triple positivity is still discussed. High quality prospective multicentric epidemiological studies are still awaited. The identification of predictors of pregnancy outcome is necessary to streamline the design and use of new treatments acting on pathophysiological molecular targets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0049-3848(17)30064-6DOI Listing
March 2017

Obstetric antiphospholipid syndrome: early variations of angiogenic factors are associated with adverse outcomes.

Haematologica 2017 05 25;102(5):835-842. Epub 2017 Jan 25.

Department of Hematology, University Hospital, Nîmes, France

The prognostic value of angiogenic factors in newly pregnant women with obstetric antiphospholipid syndrome (oAPS) has not been documented. We observed 513 oAPS who experienced three consecutive spontaneous abortions before the 10 week of gestation or one fetal loss at or beyond the 10 week. We assessed the plasma concentrations of the proangiogenic factor placenta growth factor (PIGF) and of the antiangiogenic factor soluble fms-like tyrosine kinase-1 on the eve and on the 4 day of the low-molecular weight heparin-low-dose aspirin treatment. Placenta growth factor and fms-like tyrosine kinase-1 plasma concentrations showed marked increases. Treatment-associated variations of PIGF and of soluble fms-like tyrosine kinase-1 were antagonist risk factors for placenta-mediated complications (PMC) and for severe PMC, for fetal death, stillbirth and neonatal death. The ratio between PIGF increase and soluble fms-like tyrosine kinase-1 was a summary variable whose best cut-off values (1.944.10) had high negative predictive values for PMC (0.918) and may be used to help rule out the development of PMC in evolutive pregnancies after 19 completed weeks. The early variations of PIGF and soluble fms-like tyrosine kinase-1 concentrations in newly pregnant oAPS may help to detect patients at low risk of PMC. ().
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3324/haematol.2016.155184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5477602PMC
May 2017

Neuropsychiatric presentations of antiphospholipid antibodies.

Thromb Res 2015 Feb 9;135 Suppl 1:S56-9. Epub 2015 Feb 9.

Department of Haematology, University Hospital, Nîmes and University of Montpellier, France.

Antiphospholipid syndrome (APS) is a systemic disease which can affect the central nervous system (CNS) through thrombotic mechanisms prone to induce vascular damage: stroke or transient ischemic attack (TIA) on the arterial side, cerebral venous thrombosis on the venous side. Beside these academic syndromic manifestations, some nonvascular neurological manifestations of antiphospholipid antibodies (aPLAbs) are progressively emerging, being associated with a wide range of polymorphic neurological, psychological and psychiatric manifestations. Animal models and in vitro experimental data support an immune-mediated pathogenesis, with direct binding and effect of aPLAbs on neurons and glial cells which are thought to occur after a disruption or a permeability alteration of the blood-brain barrier (BBB). The magnitude of the association and cellular and molecular mechanisms involved need to be further elucidated. No standard treatment is available for nonvascular neuropsychiatric manifestations associated with positive aPLAbs and specific developments are warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0049-3848(15)50445-3DOI Listing
February 2015

Polymorphisms of human placental alkaline phosphatase are associated with in vitro fertilization success and recurrent pregnancy loss.

Am J Pathol 2014 Feb 2;184(2):362-8. Epub 2013 Dec 2.

Department of Haematology, University Hospital, and EA2992, University of Montpellier 1, Nîmes, France; Laboratory of Haematology, Faculty of Pharmaceutical and Biological Sciences, University of Montpellier 1, Montpellier, France.

Fertility is a quantitative, complex character governed by a considerable number of genes. Despite clinical and scientific advances, several cases of human infertility remain unexplained. In the present study, using a positional cloning approach in a mouse model of interspecific recombinant lines, a candidate gene, ALPP, encoding the placental alkaline phosphatase, was identified as being potentially involved in recurrent spontaneous abortion. We then analyzed patients for detecting putative associations between ALPP polymorphisms, in vitro fertilization failures, and miscarriages. ALPP was sequenced in 100 controls and 100 patients affected by recurrent spontaneous abortion, from the same ethnic background. The frequency of several alleles and allelic combinations were different between recurrent spontaneous abortion and control women. One polymorphism induced a coding substitution (Ile89Leu) that was associated with a decreased risk of abortion and in vitro fertilization failure. Thereafter, the population was increased by the analysis of 92 additional controls and 612 additional patients for the coding polymorphism Ile89Leu. We finally show, by functional analysis, that the 89Leu placental alkaline phosphatase has an enhanced alkaline phosphatase activity. This study suggests that ALPP genotyping could be a strong predictor of implantation success.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajpath.2013.10.024DOI Listing
February 2014

Comparative incidence of pregnancy outcomes in treated obstetric antiphospholipid syndrome: the NOH-APS observational study.

Blood 2014 Jan 7;123(3):404-13. Epub 2013 Nov 7.

Department of Hematology, University Hospital, Nîmes, France;

The incidence of pregnancy outcomes for women with the purely obstetric form of antiphospholipid syndrome (APS) treated with prophylactic low-molecular-weight heparin (LMWH) plus low-dose aspirin (LDA) has not been documented. We observed women without a history of thrombosis who had experienced 3 consecutive spontaneous abortions before the 10th week of gestation or 1 fetal loss at or beyond the 10th week. We compared the frequencies of complications during new pregnancies between treated women with APS (n = 513; LMWH + LDA) and women negative for antiphospholipid antibodies as controls (n = 791; no treatment). Among APS women, prior fetal loss was a risk factor for fetal loss, preeclampsia (PE), premature birth, and the occurrence of any placenta-mediated complication. Being positive for anticardiolipin immunoglobulin M antibodies was a risk factor for any placenta-mediated complication. Among women with a history of recurrent abortion, APS women were at a higher risk than other women of PE, placenta-mediated complications, and neonatal mortality. Among women with prior fetal loss, LMWH + LDA-treated APS women had lower pregnancy loss rates but higher PE rates than other women. Improved therapies, in particular better prophylaxis of late pregnancy complications, are urgently needed for obstetric APS and should be evaluated according to the type of pregnancy loss.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2013-08-522623DOI Listing
January 2014

Comparative incidence of pregnancy outcomes in thrombophilia-positive women from the NOH-APS observational study.

Blood 2014 Jan 7;123(3):414-21. Epub 2013 Nov 7.

Department of Hematology, University Hospital, Nîmes, France;

The incidence of pregnancy outcomes in women with constitutive thrombophilia is uncertain. We observed women with no history of thrombotic events (nonthrombotic), who had experienced 3 consecutive spontaneous abortions before the 10th week of gestation or 1 fetal death at or beyond the 10th week of gestation. We compared the frequencies of complications during a new pregnancy attempt among women carrying the F5 rs6025 or F2 rs1799963 polymorphism (n = 279; low-molecular-weight heparin [LMWH] treatment during pregnancy only in case of prior fetal death), and women with negative thrombophilia screening results as control women (n = 796; no treatment). Among women with prior recurrent abortions, thrombophilic women were at increased risk for fetal death. Among women with prior fetal death, thrombophilic women experienced less fetal death recurrences, less preterm births and preeclampsia, and more live births as they were treated with LMWH. In nonthrombotic F5 rs6025 or F2 rs1799963 heterozygous women with prior pregnancy loss, fetal loss may indicate a clinical subgroup in which future therapeutic randomized controlled trials testing the effect of LMWH prophylaxis are required in priority.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2013-09-525014DOI Listing
January 2014

Systemic mastocytosis.

Blood 2013 Feb;121(7):1071

Centre Hospitalier Universitaire de Nimes.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2012-10-462671DOI Listing
February 2013

Antiphospholipid syndrome: looking for a refocusing.

Thromb Res 2013 Jan;131 Suppl 1:S28-31

Department of Haematology, University Hospital, Nîmes and University of Montpellier, France.

The antiphospholipid syndrome (APS) is characterised by thrombotic or obstetric symptoms associated with persistent antiphospholipid antibodies (aPL). Despite an increasing standardisation of aPLs testing, which is prone to strong evolutions due to brilliant progresses in the understanding of APS pathophysiology, the specificity and sensitivity of the epidemiological associations between symptoms and aPLs are highly variable, with persistent strong equivocal evidences probably leading to over-diagnosis, particularly in the obstetrical presentations where consistent association studies are rare and levels of evidence limited. We propose to review the APS definition based on biological mechanisms, to abandon the clinical syndromes which are still molecularly unclassified like "unexplained recurrent pregnancy losses before week 10" and the aspecific markers like classic anticardiolipin antibodies, and finally to narrow APS criteria asa constructive promise for a determined move toward precision medicine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0049-3848(13)70016-1DOI Listing
January 2013

Comparative incidence of a first thrombotic event in purely obstetric antiphospholipid syndrome with pregnancy loss: the NOH-APS observational study.

Blood 2012 Mar 6;119(11):2624-32. Epub 2011 Dec 6.

Department of Hematology, University Hospital, Nîmes, France.

The incidence of thrombosis in the purely obstetric form of antiphospholipid syndrome is uncertain. We performed a 10-year observational study of 1592 nonthrombotic women who had experienced 3 consecutive spontaneous abortions before the 10th week of gestation or 1 fetal death at or beyond the 10th week of gestation. We compared the frequencies of thrombotic events among women positive for antiphospholipid Abs (n = 517), women carrying the F5 6025 or F2 rs1799963 polymorphism (n = 279), and women with negative thrombophilia screening results (n = 796). The annual rates of deep vein thrombosis (1.46%; range, 1.15%-1.82%), pulmonary embolism (0.43%; range, 0.26%-0.66%), superficial vein thrombosis (0.44%; range, 0.28%-0.68%), and cerebrovascular events (0.32%; range, 0.18%-0.53%) were significantly higher in aPLAbs women than in the other groups despite low-dose aspirin primary prophylaxis. Women carrying 1 of the 2 polymorphisms did not experience more thrombotic events than women who screened negative for thrombophilia. Lupus anticoagulant was a risk factor for unprovoked proximal and distal deep and superficial vein thrombosis and women in the upper quartile of lupus anticoagulant activity had the highest risk. Despite data suggesting that aPLAbs may induce pregnancy loss through nonthrombotic mechanisms, women with purely obstetric antiphospholipid syndrome are at risk for thrombotic complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2011-09-381913DOI Listing
March 2012