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Article: The Risk of Thrombosis Around Pregnancy: Where Do We Stand?

Gris, Jean-Christophe / Guillotin, Florence / Chéa, Mathias / Bourguignon, Chloé / Bouvier, Sylvie

2022 Volume 9, Page(s) 901869

Abstract: Pregnancy and puerperium increase the relative risk of venous thromboembolism (VTE) and the absolute risk remains low, around 1 per 1,000, with induced mortality of around 1 per 100,000. Analysis of large databases has helped specify the modes of ... ...

Abstract	Pregnancy and puerperium increase the relative risk of venous thromboembolism (VTE) and the absolute risk remains low, around 1 per 1,000, with induced mortality of around 1 per 100,000. Analysis of large databases has helped specify the modes of presentation and risk factors (RF) whose impact is greater after than before childbirth, since VTE during pregnancy and post-partum obey different RFs. The evolution of the population concerned (mostly women over 35, obese, of multi-ethnicity undergoing medically assisted reproduction) affects the frequency of these RFs. Pulmonary embolism (PE) is over-represented after childbirth, but 30% of PE in pregnancy occurs without any RFs. Recommendations for prevention, mainly from expert groups, are heterogeneous and often discordant. Low molecular weight heparins (LMWH) are the mainstay of pharmacological thromboprophylaxis, in a field where randomized controlled studies are definitely lacking. VTE risk assessment in pregnancy must be systematic and repetitive. Risk assessment methods and scores are beginning to emerge to guide thromboprophylaxis and should be used more systematically. In the future, analyzing observational data from huge, nationwide registries and prospective cluster clinical trials may bring to light clinically relevant outcomes likely to feed comprehensive guidelines.
Language	English
Publishing date	2022-05-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2781496-8
ISSN	2297-055X
ISSN	2297-055X
DOI	10.3389/fcvm.2022.901869
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Article ; Online: Antiphospholipid Antibodies in Pregnancy: Maternal and Neonatal Implications.

Gris, Jean-Christophe / Guillotin, Florence / Chéa, Mathias / Bourguignon, Chloé / Nouvellon, Éva / Bouvier, Sylvie

Seminars in thrombosis and hemostasis

2022 Volume 49, Issue 4, Page(s) 337–347

Abstract: Antiphospholipid antibodies (aPL Abs) have long been associated with the occurrence of certain specific pregnancy morbidities, affecting both mother and fetus. Antithrombotic-based prophylactic regimens are the standard of care. Their intensity is ... ...

Abstract	Antiphospholipid antibodies (aPL Abs) have long been associated with the occurrence of certain specific pregnancy morbidities, affecting both mother and fetus. Antithrombotic-based prophylactic regimens are the standard of care. Their intensity is modulated by the thrombotic history and has greatly improved the prognosis related to spontaneous morbidity. Observational studies show that this treatment is still associated with the persistence of excess of late-pregnancy placental diseases, calling for new or complementary developments, yet to be validated. Rigorous prospective multicentric validation of clinical and laboratory parameters capable of identifying those women and fetuses at a risk of pejorative evolution, thus early prognosis, is a priority issue. These will make it possible to develop customized treatments and test them. Furthermore, there are still concerns, particularly neurodevelopmental ones, about children born to aPL Ab-positive mothers, and clarification based on regular, more systematic evaluations is required. Even after pregnancy, women with a pure obstetrical antiphospholipid syndrome are at a greater risk of venous and arterial thrombosis over time, and prevention needs to be improved. These women also appear to develop more psychiatric and mood disorders. Central nervous system imaging using high-resolution techniques has shown subtle impairments in the white matter, associated with the most pathogenic aPL Abs and the clinical significance of this is under investigation. These mothers also seem to develop an excess of cancers. The systemic impact of aPL Abs is gradually being suspected, although this requires further evidence, and prevention should be envisaged.
MeSH term(s)	Child ; Infant, Newborn ; Female ; Humans ; Pregnancy ; Prospective Studies ; Risk Factors ; Placenta ; Antibodies, Antiphospholipid ; Antiphospholipid Syndrome ; Thrombosis/complications
Chemical Substances	Antibodies, Antiphospholipid
Language	English
Publishing date	2022-09-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	196901-8
ISSN	1098-9064 ; 0094-6176
ISSN (online)	1098-9064
ISSN	0094-6176
DOI	10.1055/s-0042-1756193
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Article ; Online: New erythrocyte parameters derived from the Coulter principle relate with red blood cell properties-A pilot study in diabetes mellitus.

Bourguignon, Chloé / Ansel, Clémentine / Gineys, Jean-Philippe / Schuldiner, Sophie / Isèbe, Damien / Geitner, Michael / Taraconat, Pierre / Gris, Jean-Christophe

PloS one

2023 Volume 18, Issue 10, Page(s) e0293356

Abstract: In routine hematological instruments, blood cells are counted and sized by monitoring the impedance signals induced during their passage through a Coulter orifice. However, only signals associated with centered paths in the aperture are considered for ... ...

Abstract	In routine hematological instruments, blood cells are counted and sized by monitoring the impedance signals induced during their passage through a Coulter orifice. However, only signals associated with centered paths in the aperture are considered for analysis, while the rejected measurements, caused by near-wall trajectories, can provide additional information on red blood cells (RBC), as recent publications suggest. To assess usefulness of two new parameters in describing alterations in RBC properties, we performed a pilot study to compare blood samples from patients with diabetes mellitus (DM), frequent pathological condition associated with impairment in RBC deformability, versus controls. A total of 345 blood samples were analyzed: 225 in the DM group and 120 in the control group. A diagram of [Formula: see text] and [Formula: see text], the two new parameters derived from the analysis of impedancemetry pulses, was used to compare distribution of RBC subpopulations between groups. To discriminate RBC from DM and control individuals, based on our multiparametric analysis, we built a score from variables derived from [Formula: see text] matrix which showed good performances: area under the receiving operating characteristic curve 0.948 (0.920-0.970), p<0.0001; best discriminating value: negative predictive value 94.7%, positive predictive value was 78.4%. These results seem promising to approach RBC alterations in routine laboratory practice. The related potential clinically relevant outcomes remain to be investigated.
MeSH term(s)	Humans ; Pilot Projects ; Erythrocytes/pathology ; Diabetes Mellitus/pathology ; Erythrocyte Deformability ; Erythrocyte Indices
Language	English
Publishing date	2023-10-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0293356
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Article: Antiphospholipid Antibodies in Pregnancy: Maternal and Neonatal Implications

Gris, Jean-Christophe / Guillotin, Florence / Chéa, Mathias / Bourguignon, Chloé / Nouvellon, Éva / Bouvier, Sylvie

Seminars in Thrombosis and Hemostasis

(Maternal and Neonatal Hemostasis)

2022 Volume 49, Issue 04, Page(s) 337–347

Series title	Maternal and Neonatal Hemostasis
Abstract	Antiphospholipid antibodies (aPL Abs) have long been associated with the occurrence of certain specific pregnancy morbidities, affecting both mother and fetus. Antithrombotic-based prophylactic regimens are the standard of care. Their intensity is modulated by the thrombotic history and has greatly improved the prognosis related to spontaneous morbidity. Observational studies show that this treatment is still associated with the persistence of excess of late-pregnancy placental diseases, calling for new or complementary developments, yet to be validated. Rigorous prospective multicentric validation of clinical and laboratory parameters capable of identifying those women and fetuses at a risk of pejorative evolution, thus early prognosis, is a priority issue. These will make it possible to develop customized treatments and test them. Furthermore, there are still concerns, particularly neurodevelopmental ones, about children born to aPL Ab-positive mothers, and clarification based on regular, more systematic evaluations is required. Even after pregnancy, women with a pure obstetrical antiphospholipid syndrome are at a greater risk of venous and arterial thrombosis over time, and prevention needs to be improved. These women also appear to develop more psychiatric and mood disorders. Central nervous system imaging using high-resolution techniques has shown subtle impairments in the white matter, associated with the most pathogenic aPL Abs and the clinical significance of this is under investigation. These mothers also seem to develop an excess of cancers. The systemic impact of aPL Abs is gradually being suspected, although this requires further evidence, and prevention should be envisaged.
Keywords	antiphospholipid antibodies ; pregnancy ; placental disease ; mother ; neonate ; thrombosis ; psychiatric ; cancer
Language	English
Publishing date	2022-09-15
Publisher	Thieme Medical Publishers, Inc.
Publishing place	Stuttgart ; New York
Document type	Article
ZDB-ID	196901-8
ISSN	1098-9064 ; 0094-6176
ISSN (online)	1098-9064
ISSN	0094-6176
DOI	10.1055/s-0042-1756193
Database	Thieme publisher's database

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Article ; Online: Clonal haematopoiesis of indeterminate potential in patients with venous thromboembolism.

Guillotin, Florence / Mercier, Éric / Fortier, Mathieu / Bouvier, Sylvie / Jacquet, Quentin / Dallo, Marine / Chéa, Mathias / Bourguignon, Chloé / Cochery-Nouvellon, Éva / Perez-Martin, Antonia / Gris, Jean-Christophe

Journal of thrombosis and thrombolysis

2023 Volume 56, Issue 2, Page(s) 351–354

Abstract: Over the last decade, the concept of Clonal haematopoiesis of undetermined potential (CHIP) has emerged. Low frequency somatic mutations in hematopoietic cells can occur with age and might allow formation of clones in individuals with no characterized ... ...

Abstract	Over the last decade, the concept of Clonal haematopoiesis of undetermined potential (CHIP) has emerged. Low frequency somatic mutations in hematopoietic cells can occur with age and might allow formation of clones in individuals with no characterized haematological pathology. These CHIP mutations are associated with an increased risk of cancer or atherothrombosis, and their prevalence are more and more studied in pathologies with an inflammatory component. In our study, we analysed, by next generation sequencing, the prevalence of CHIP mutation in 94 patients with deep venous thrombosis (DVT), distinguishing two clinical phenotypes: provoked distal and non-provoked proximal DVTs. We show that there is no difference in CHIP prevalence between these two groups, nor with a matched-aged control group. The number of mutation per patients and the affected genes remain also the same between the three groups. Consequently and despite the relative small number of patients in each cohort, it seems that CHIP is not a strong concern in venous thromboembolism.
MeSH term(s)	Humans ; Venous Thromboembolism/etiology ; Clonal Hematopoiesis ; Risk Factors ; Venous Thrombosis/complications ; Neoplasms/complications ; Mutation
Language	English
Publishing date	2023-06-10
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1230645-9
ISSN	1573-742X ; 0929-5305
ISSN (online)	1573-742X
ISSN	0929-5305
DOI	10.1007/s11239-023-02836-4
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Article ; Online: Intimate partner violence as a risk factor for venous thromboembolism in women on combined oral contraceptives: An international matched case-control study.

Chéa, Mathias / Bourguignon, Chloé / Bouvier, Sylvie / Nouvellon, Eva / Laurent, Jeremy / Perez-Martin, Antonia / Mousty, Eve / Ripart, Sylvie / Nikolaeva, Mariya Gennadevna / Khizroeva, Jamilya / Bitsadze, Victoria / Makatsariya, Alexander / Gris, Jean-Christophe

European journal of internal medicine

2023 Volume 122, Page(s) 47–53

Abstract: Background: Intimate partner violence (IPV) targeting women is probably underestimated during a woman's lifetime. Venous thromboembolism (VTE) is a multifactorial disease associated with haemostasis-activating conditions. Minor injuries can trigger VTE.! ...

Abstract	Background: Intimate partner violence (IPV) targeting women is probably underestimated during a woman's lifetime. Venous thromboembolism (VTE) is a multifactorial disease associated with haemostasis-activating conditions. Minor injuries can trigger VTE. Objectives: We aimed to look for an association between VTE and IPV in women taking combined oral contraceptives (COCs) METHODS: We performed a multicentric, international, matched case-control study. Patients were women with a first VTE associated with COC intake. Controls were women taking COCs undergoing regular gynaecological check-ups. Patients and Controls were matched for country, age, length of COC intake and type (997 pairs). IPV was evaluated using the WAST self-administrated questionnaire. Results: IPV, defined as a WAST score value at least 5, was diagnosed in 33 Controls (3.3 %) and 109 patients (10.9 %), conditional odds ratio (OR): 3.586, 95 % confidence interval (2.404-5.549), p < 0.0001. After multivariate analysis, the adjusted OR was 3.720 (2.438-5.677), p < 0.0001. Sensitivity analysis using increasing WAST score thresholds confirmed the association. Conclusions: A first VTE in women taking COCs is associated with IPV. This association can have strong human consequences but also raises significant medical issues, for instance on the haemorrhagic risk of anticoagulant treatments in abused women. Pathophysiological studies are warranted.
MeSH term(s)	Female ; Humans ; Male ; Contraceptives, Oral, Combined/adverse effects ; Venous Thromboembolism/chemically induced ; Venous Thromboembolism/epidemiology ; Case-Control Studies ; Risk Factors ; Anticoagulants
Chemical Substances	Contraceptives, Oral, Combined ; Anticoagulants
Language	English
Publishing date	2023-12-21
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1038679-8
ISSN	1879-0828 ; 0953-6205
ISSN (online)	1879-0828
ISSN	0953-6205
DOI	10.1016/j.ejim.2023.12.016
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Article: Targeted therapy in eosinophilic chronic obstructive pulmonary disease.

Fieldes, Mathieu / Bourguignon, Chloé / Assou, Said / Nasri, Amel / Fort, Aurélie / Vachier, Isabelle / De Vos, John / Ahmed, Engi / Bourdin, Arnaud

ERJ open research

2021 Volume 7, Issue 2

Abstract: Chronic obstructive pulmonary disease (COPD) is a common and preventable airway disease causing significant worldwide mortality and morbidity. Lifetime exposure to tobacco smoking and environmental particles are the two major risk factors. Over recent ... ...

Abstract	Chronic obstructive pulmonary disease (COPD) is a common and preventable airway disease causing significant worldwide mortality and morbidity. Lifetime exposure to tobacco smoking and environmental particles are the two major risk factors. Over recent decades, COPD has become a growing public health problem with an increase in incidence. COPD is defined by airflow limitation due to airway inflammation and small airway remodelling coupled to parenchymal lung destruction. Most patients exhibit neutrophil-predominant airway inflammation combined with an increase in macrophages and CD8
Language	English
Publishing date	2021-04-12
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2827830-6
ISSN	2312-0541
ISSN	2312-0541
DOI	10.1183/23120541.00437-2020
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Article ; Online: Generation of four severe early-onset chronic obstructive pulmonary disease (COPD) patient-derived induced pluripotent stem cell lines from peripheral blood mononuclear cells.

Ahmed, Engi / Fieldes, Mathieu / Mianné, Joffrey / Bourguignon, Chloé / Nasri, Amel / Vachier, Isabelle / Assou, Said / Bourdin, Arnaud / De Vos, John

Stem cell research

2021 Volume 56, Page(s) 102550

Abstract: Evidence highlights the concept of multiple trajectories leading to COPD. Early-life events (i.e., in utero lung development) may influence the maximally attained lung function and increase the risk to develop COPD. Human pluripotent stem cells (hiPSC) ... ...

Abstract	Evidence highlights the concept of multiple trajectories leading to COPD. Early-life events (i.e., in utero lung development) may influence the maximally attained lung function and increase the risk to develop COPD. Human pluripotent stem cells (hiPSC) represent a unique opportunity to model lung development. We generated hiPSC lines from four highly characterized COPD patients with early onset and severe phenotype. Peripheral blood mononuclear cells (PBMCs) were reprogrammed using integration-free Sendai Virus. The cell lines had normal karyotype, expressed pluripotency hallmarks, and differentiated into the three primary germ layers. These lines offer a tool to study early-life origins of COPD.
MeSH term(s)	Cell Differentiation ; Cellular Reprogramming ; Humans ; Induced Pluripotent Stem Cells ; Leukocytes, Mononuclear ; Pulmonary Disease, Chronic Obstructive ; Sendai virus
Language	English
Publishing date	2021-09-27
Publishing country	England
Document type	Journal Article
ZDB-ID	2393143-7
ISSN	1876-7753 ; 1873-5061
ISSN (online)	1876-7753
ISSN	1873-5061
DOI	10.1016/j.scr.2021.102550
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Article ; Online: Differentiation of Human Induced Pluripotent Stem Cells from Patients with Severe COPD into Functional Airway Epithelium.

Ahmed, Engi / Fieldes, Mathieu / Bourguignon, Chloé / Mianné, Joffrey / Petit, Aurélie / Jory, Myriam / Cazevieille, Chantal / Boukhaddaoui, Hassan / Garnett, James P / Hirtz, Christophe / Massiera, Gladys / Vachier, Isabelle / Assou, Said / Bourdin, Arnaud / De Vos, John

Cells

2022 Volume 11, Issue 15

Abstract: Background: Chronic Obstructive Pulmonary Disease (COPD), a major cause of mortality and disability, is a complex disease with heterogeneous and ill-understood biological mechanisms. Human induced pluripotent stem cells (hiPSCs) are a promising tool to ... ...

Abstract	Background: Chronic Obstructive Pulmonary Disease (COPD), a major cause of mortality and disability, is a complex disease with heterogeneous and ill-understood biological mechanisms. Human induced pluripotent stem cells (hiPSCs) are a promising tool to model human disease, including the impact of genetic susceptibility. Methods: We developed a simple and reliable method for reprogramming peripheral blood mononuclear cells into hiPSCs and to differentiate them into air−liquid interface bronchial epithelium within 45 days. Importantly, this method does not involve any cell sorting step. We reprogrammed blood cells from one healthy control and three patients with very severe COPD. Results: The mean cell purity at the definitive endoderm and ventral anterior foregut endoderm (vAFE) stages was >80%, assessed by quantifying C-X-C Motif Chemokine Receptor 4/SRY-Box Transcription Factor 17 (CXCR4/SOX17) and NK2 Homeobox 1 (NKX2.1) expression, respectively. vAFE cells from all four hiPSC lines differentiated into bronchial epithelium in air−liquid interface conditions, with large zones covered by beating ciliated, basal, goblets, club cells and neuroendocrine cells, as found in vivo. The hiPSC-derived airway epithelium (iALI) from patients with very severe COPD and from the healthy control were undistinguishable. Conclusions: iALI bronchial epithelium is ready for better understanding lung disease pathogenesis and accelerating drug discovery.
MeSH term(s)	Epithelium/metabolism ; Humans ; Induced Pluripotent Stem Cells ; Leukocytes, Mononuclear/pathology ; Pulmonary Disease, Chronic Obstructive/metabolism ; Respiratory Mucosa/pathology
Language	English
Publishing date	2022-08-05
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11152422
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Article ; Online: Pregnancy after Combined Oral Contraceptive-Associated Venous Thromboembolism: An International Retrospective Study of Outcomes.

Gris, Jean-Christophe / Bourguignon, Chloé / Bouvier, Sylvie / Nouvellon, Eva / Laurent, Jeremy / Perez-Martin, Antonia / Mousty, Eve / Nikolaeva, Mariya / Khizroeva, Jamilya / Bitsadze, Victoria / Makatsariya, Alexander

Thrombosis and haemostasis

2022 Volume 122, Issue 10, Page(s) 1779–1793

Abstract: Background: Few data are available on thrombotic outcomes during pregnancy and puerperium occurring after an initial provoked venous thromboembolic (VTE) event.: Objectives: To describe thrombotic outcomes during pregnancy after a first combined ... ...

Abstract	Background: Few data are available on thrombotic outcomes during pregnancy and puerperium occurring after an initial provoked venous thromboembolic (VTE) event. Objectives: To describe thrombotic outcomes during pregnancy after a first combined oral contraceptive (COC)-associated VTE and the factors associated with recurrence. Methods: This was an international multicentric retrospective study on patients referred for thrombophilia screening from January 1, 2010 to January 1, 2021 following a first COC-associated VTE, including women with neither inherited thrombophilia nor antiphospholipid antibodies and focusing on those who had a subsequent pregnancy under the same thromboprophylaxis treatment. Thrombotic recurrences during pregnancy and puerperium as well as risk factors for recurrence were analyzed. Results: We included 2,145 pregnant women. A total of 88 thrombotic events, 58 antenatal and 29 postnatal, occurred, mostly during the first trimester of pregnancy and the first 2 weeks of puerperium. Incidence rates were 49.6 (37-62) per 1,000 patient-years during pregnancy and 118.7 (78-159) per 1,000 patient-years during puerperium. Focusing on pulmonary embolism, incidence rates were 1.68 (1-4) per 1,000 patient-years during pregnancy and 65.5 (35-97) per 1,000 patient-years during puerperium.Risk factors for antenatal recurrences were maternal hypercholesterolemia and birth of a very small-for-gestational-age neonate. A risk factor for postnatal recurrence was the incidence of preeclampsia. Conclusion: Our multicentric retrospective data show significant rates of VTE recurrence during pregnancy and puerperium in women with a previous VTE event associated with COC, despite a unique low-molecular-weight heparin-based thromboprophylaxis. These results may provide benchmarks and valuable information for designing future randomized controlled trials.
MeSH term(s)	Antibodies, Antiphospholipid ; Anticoagulants/adverse effects ; Contraceptives, Oral, Combined/adverse effects ; Female ; Heparin, Low-Molecular-Weight ; Humans ; Infant, Newborn ; Pregnancy ; Recurrence ; Retrospective Studies ; Risk Factors ; Thrombophilia/complications ; Thrombophilia/drug therapy ; Thrombosis/drug therapy ; Venous Thromboembolism/diagnosis ; Venous Thromboembolism/epidemiology ; Venous Thromboembolism/prevention & control
Chemical Substances	Antibodies, Antiphospholipid ; Anticoagulants ; Contraceptives, Oral, Combined ; Heparin, Low-Molecular-Weight
Language	English
Publishing date	2022-04-26
Publishing country	Germany
Document type	Journal Article
ZDB-ID	518294-3
ISSN	2567-689X ; 0340-6245
ISSN (online)	2567-689X
ISSN	0340-6245
DOI	10.1055/a-1835-8808
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