Publications by authors named "Manon Lejeune"

6 Publications

  • Page 1 of 1

Extracorporeal Membrane Oxygenation Induces Early Alterations in Coagulation and Fibrinolysis Profiles in COVID-19 Patients with Acute Respiratory Distress Syndrome.

Thromb Haemost 2021 Aug 15;121(8):1031-1042. Epub 2021 Jun 15.

Sorbonne Université, INSERM UMRS_1166, Institute of Cardiometabolism And Nutrition, Paris, France.

Hemostatic changes induced by extracorporeal membrane oxygenation (ECMO) support have been yet poorly documented in coronavirus-19 (COVID-19) patients who have a baseline complex hypercoagulable state. In this prospective monocentric study of patients with severe acute respiratory distress syndrome (ARDS) rescued by ECMO, we performed longitudinal measurements of coagulation and fibrinolysis markers throughout the course of ECMO support in 20 COVID-19 and 10 non-COVID-19 patients. Blood was sampled before and then 24 hours, 7, and 14 days after ECMO implantation. Clinical outcomes were prospectively assessed until discharge from the intensive care unit or death. The median age of participants was 47 (35-56) years, with a median body mass index of 30 (27-35) kg/m, and a Sepsis-related Organ Failure Assessment score of 12 (8-16). Baseline levels of von Willebrand factor, fibrinogen, factor VIII, prothrombin F1 + 2, thrombin-antithrombin, D-dimer, and plasminogen activator inhibitor-1 (PAI-1) were elevated in both COVID-19 and non-COVID-19 ARDS patients, indicating that endothelial activation, endogenous thrombin generation, and fibrinolysis shutdown occur in all ARDS patients before ECMO implantation. From baseline to day 7, thrombin generation (prothrombin F1 + 2,  < 0.01) and fibrin formation markers (fibrin monomers,  < 0.001) significantly increased, further resulting in significant decreases in platelet count ( < 0.0001) and fibrinogen level ( < 0.001). PAI-1 levels significantly decreased from baseline to day 7 ( < 0.0001) in all ARDS patients. These changes were more marked in COVID-19 patients, resulting in 14 nonfatal and 3 fatal bleeding. Additional studies are warranted to determine whether monitoring of thrombin generation and fibrinolysis markers might help to early predict bleeding complications in COVID-19 patients supported by ECMO.
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http://dx.doi.org/10.1055/a-1529-2257DOI Listing
August 2021

Utility of a mainstreamed genetic testing pathway in breast and ovarian cancer patients during the COVID-19 pandemic.

Eur J Med Genet 2020 Dec 10;63(12):104098. Epub 2020 Nov 10.

UF d'Oncogénétique, Département de Génétique et Institut Universitaire de Cancérologie, Groupe Hospitalier Pitié-Salpêtrière, AP-HP.Sorbonne Université, 47-83 Boulevard de l'Hôpital, F-75013 Paris, France; Sorbonne Université, INSERM, Unité Mixte de Recherche Scientifique 938 et SIRIC CURAMUS, Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancer, 184 rue du Faubourg Saint-Antoine, F-75012 Paris, France.

Introduction: Mainstreamed genetic testing (MGT) obviates the need for a cancer genetics consultation, since trained oncologists (O) and gynaecologists (G) provide counseling, prescribe testing and deliver results. We report results from our MGT program and emphasize its utility during the COVID-19 lockdown, when cancer genetics clinics had suspended their activity.

Methods: An MGT pathway for breast and ovarian cancer (BC/OC) patients was established in Jan-2018 between the Assistance Publique - Hôpitaux de Paris.Sorbonne Université Cancer Genetics team and the Oncology/Gynecology departments at one teaching and two regional hospitals. Trained O + G evaluated patients with the Manchester Scoring System. A 12-point threshold was recommended for testing. Next-generation sequencing of BRCA1, BRCA2, PALB2, RAD51C and RAD51D was performed. Results were delivered to the patient by O/G. Pathogenic variants (PV) carriers were referred to the genetics clinic. Results are reported for the 2nd-Jan-2018 to 1st-June-2020 period. That includes the eight-week COVID-19 lockdown and three-week de-confinement phase 1.

Results: Results were available for 231/234 patients. Twenty-eight (12.1%) carried a PV. Of the 27 patients tested during the COVID-19 period, three carried a PV, two in BRCA1 and one in RAD51C. The clinical impact was immediate for the two BRCA1 BC cases undergoing neo-adjuvant chemotherapy, since double mastectomy and salpingo-oophorectomy will now be performed using two-step strategies.

Conclusions: MGT guaranteed care continuity in BC/OC patients during the critical phases of the COVID-19 pandemic, with immediate implications for PV carriers. More broadly, we report for the first time the successful implementation of MGT in France.
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http://dx.doi.org/10.1016/j.ejmg.2020.104098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654320PMC
December 2020

Systemic Inflammatory Response Syndrome Is a Major Contributor to COVID-19-Associated Coagulopathy: Insights From a Prospective, Single-Center Cohort Study.

Circulation 2020 08 17;142(6):611-614. Epub 2020 Jun 17.

Medical Intensive Care Unit (P.M., G.H., J.C., C.D., M.P.D.C., A.N., N.B., M.S., C.E.L., A.C.), Department of Hematology (M.L., I.M.-T., C.F.), and Cardiothoracic Surgery Department (G.L.), Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, France. Sorbonne Université, INSERM UMRS_1166, Institute of Cardiometabolism and Nutrition, Paris, France (G.H., G.L., M.S., C.E.L., A.C., C.F.).

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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.048925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418760PMC
August 2020

Are Patients with Active Cancer and Those with History of Cancer Carrying the Same Risks of Recurrent VTE and Bleeding While on Anticoagulants?

Cancers (Basel) 2020 Apr 9;12(4). Epub 2020 Apr 9.

Global Thrombosis Strategy, Medical Affairs, Leo Pharma A/S, 2750 Ballerup, Denmark.

Direct oral anticoagulants (DOAC) are now recommended for the treatment of cancer-associated thrombosis (CAT) based on the results of dedicated trials demonstrating that DOAC are non-inferior to low molecular weight heparins in preventing recurrent venous thromboembolism (VTE) in this population. The definition of "cancer patient" differs substantially among studies. Whether patients with active cancer and those with a history of cancer (HOC) carry the same risks of recurrent VTE and bleeding remains unclear. Few studies reported data on the efficacy and safety of anticoagulants according to active cancer or HOC categories. While in subgroup analyses of EINSTEIN and HOKUSAI the rates of recurrent VTE and bleeding did not differ between these categories, results from a subgroup analysis of AMPLIFY, from HOKUSAI-Cancer, and from the COMMAND cohort suggest that HOC patients might have a lower bleeding risk than active cancer patients. Whether the inclusion of HOC patients in CAT studies might introduce some bias by decreasing the rates of both recurrent VTE and bleeding remains an unanswered issue since no dedicated prospective study addressed this question. A strict definition of active cancer should be used in further trials.
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http://dx.doi.org/10.3390/cancers12040917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226070PMC
April 2020

Antiplatelet Agents for Cancer Prevention: Current Evidences and Continuing Controversies.

Cancers (Basel) 2019 Oct 24;11(11). Epub 2019 Oct 24.

Department of Haematology, Saint-Antoine Hospital, Assistance Publique Hôpitaux de Paris, F-75012 Paris, France.

Over the past two decades, aspirin has emerged as a promising chemoprotective agent to prevent colorectal cancer (CRC). In 2016, the mounting evidence supporting its chemoprotective effect, from both basic science and clinical research, led the US Preventive Services Task Force to recommend regular use of low-dose aspirin in some subgroups of patients for whom the benefits are deemed to outweigh the risks. In contrast, data on the chemoprotective effect of aspirin against other cancers are less clear and remain controversial. Most data come from secondary analyses of cardiovascular prevention trials, with only a limited number reporting cancer outcomes as a prespecified endpoint, and overall unclear findings. Moreover, the potential chemoprotective effect of aspirin against other cancers has been recently questioned with the publication of 3 long-awaited trials of aspirin in the primary prevention of cardiovascular diseases reporting no benefit of aspirin on overall cancer incidence and cancer-related mortality. Data on the chemoprotective effects of other antiplatelet agents remain scarce and inconclusive, and further research to examine their benefit are warranted. In this narrative review, we summarize current clinical evidence and continuing controversies on the potential chemoprotective properties of antiplatelet agents against cancer.
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http://dx.doi.org/10.3390/cancers11111639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895806PMC
October 2019

Beta-1,4-galactosyltransferase 2 c.909C>T gene variant is predictive of on-clopidogrel platelet reactivity.

Pharmacogenomics 2018 08 18;19(12):937-945. Epub 2018 Jul 18.

AP-HP, Department of Clinical chemistry, Hôpital Européen Georges Pompidou, Paris, France.

CYP2C19 genotype influences clopidogrel response but only accounts for a small part of the variability in platelet reactivity. Recently, exome sequencing identified a variant of the gene encoding B4GALT2 as a potential candidate implicated in on-treatment platelet reactivity. Carriers of the B4GALT2 c.909C>T variant have lower platelet reactivity indicating that B4GALT2 could influence clopidogrel sensitivity and could expose to the risk of bleeding events. We undertook this observational retrospective study to determine if B4GALT2 c.909C>T influences P2RY12-specific vasodilator-stimulated phosphoprotein phosphorylation and agonist-induced platelet aggregation in a nonselected cohort of 174 patients under clopidogrel-based antiplatelet therapy. Our results indicate that in individuals under dual antiplatelet therapy, B4GALT2 c.909C>T might be an independent genetic predictor of on-treatment platelet reactivity.
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http://dx.doi.org/10.2217/pgs-2018-0057DOI Listing
August 2018
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