Publications by authors named "Isabelle Martin-Toutain"

14 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 Jun 15. 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
June 2021

Antiphospholipid antibodies and thrombotic events in COVID-19 patients hospitalized in medicine ward.

Autoimmun Rev 2021 Feb 13;20(2):102729. Epub 2020 Dec 13.

Sorbonne Universités, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Centre National de Référence Maladies AUtoimmunes et systémiques rares Maladies Autoinflammatoires Rares et des Myopathies Inflamatoires, F-75013 Paris, France. Electronic address:

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http://dx.doi.org/10.1016/j.autrev.2020.102729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834187PMC
February 2021

Heparin-induced thrombocytopenia in COVID-19 patients with severe acute respiratory distress syndrome requiring extracorporeal membrane oxygenation: two case reports.

J Artif Organs 2021 Jun 12;24(2):277-281. Epub 2020 Aug 12.

Sorbonne Université, INSERM, UMRS_1166-ICAN, Institute of Cardiometabolism and Nutrition, F-75013, Paris, France.

Veno-venous (VV) extracorporeal membrane oxygenation (ECMO) is increasingly used in Coronavirus disease-19 (COVID-19) patients with the most severe forms of acute respiratory distress syndrome (ARDS). Its use is associated with a significant hemostatic challenge, especially in COVID- 19 patients who have been demonstrated to otherwise present a COVID-19-associated coagulopathy. The systematic use of unfractionated heparin therapy to prevent circuit thrombosis is warranted during ECMO support. The clinical presentation and management of heparin-induced thrombocytopenia, which is a rare but life-threatening complication of heparin therapy, has not been described in those patients yet. We report herein two cases of laboratory-confirmed HIT in COVID-19 patients with severe ARDS admitted to our intensive care unit for VV-ECMO support and the successful use of argatroban as an alternative therapy. We also provide a brief literature review of best evidence for managing such patients. The diagnosis and management of HIT is particularly challenging in COVID-19 patients receiving ECMO support. An increased awareness is warranted in those patients who already present a procoagulant state leading to higher rates of thrombotic events which can confuse the issues. Argatroban seems to be an appropriate and safe therapeutic option in COVID-19 patients with HIT while on VV-ECMO.
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http://dx.doi.org/10.1007/s10047-020-01203-xDOI Listing
June 2021

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

Reduced Rivaroxaban Dose Versus Dual Antiplatelet Therapy After Left Atrial Appendage Closure: ADRIFT a Randomized Pilot Study.

Circ Cardiovasc Interv 2020 07 17;13(7):e008481. Epub 2020 Jul 17.

Sorbonne Université, ACTION Study Group (Allies in Cardiovascular Trials, Initiatives and Organized Networks), INSERM UMRS1166, ICAN, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France (G.D., J.S., N.B., A.C., N.H., D.B., G.M.).

Background: Percutaneous left atrial appendage closure (LAAC) exposes to the risk of device thrombosis in patients with atrial fibrillation who frequently have a contraindication to full anticoagulation. Thereby, dual antiplatelet therapy (DAPT) is usually preferred. No randomized study has evaluated nonvitamin K antagonist oral anticoagulant after LAAC, and we decided to evaluate the efficacy and safety of reduced doses of rivaroxaban after LAAC.

Methods: ADRIFT (Assessment of Dual Antiplatelet Therapy Versus Rivaroxaban in Atrial Fibrillation Patients Treated With Left Atrial Appendage Closure) is a multicenter, phase IIb study, which randomized 105 patients after successful LAAC to either rivaroxaban 10 mg (R, n=37), rivaroxaban 15 mg (R, n=35), or DAPT with aspirin 75 mg and clopidogrel 75 mg (n=33). The primary end point was thrombin generation (prothrombin fragments 1+2) measured 2 to 4 hours after drug intake, 10 days after treatment initiation. Thrombin-antithrombin complex, D-dimers, rivaroxaban concentrations were also measured at 10 days and 3 months. Clinical end points were evaluated at 3-month follow-up.

Results: The primary end point was reduced with R (179 pmol/L [interquartile range (IQR), 129-273], <0.0001) and R (163 pmol/L [IQR, 112-231], <0.0001) as compared with DAPT (322 pmol/L [IQR, 218-528]). We observed no significant reduction of the primary end point between R and R while rivaroxaban concentrations increased significantly from 184 ng/mL (IQR, 127-290) with R to 274 ng/mL (IQR, 192-377) with R, <0.0001. Thrombin-antithrombin complex and D-dimers were numerically lower with both rivaroxaban doses than with DAPT. These findings were all confirmed at 3 months. The clinical end points were not different between groups. A device thrombosis was noted in 2 patients assigned to DAPT.

Conclusions: Thrombin generation measured after LAAC was lower in patients treated by reduced rivaroxaban doses than DAPT, supporting an alternative to the antithrombotic regimens currently used after LAAC and deserves further evaluation in larger studies. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03273322.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.119.008481DOI Listing
July 2020

Perioperative management of a patient with Glanzmann thrombasthenia undergoing a coronary artery bypass graft surgery: a case report.

Blood Coagul Fibrinolysis 2018 Apr;29(3):327-329

Department of Biological Hematology.

: We report herein the successful perioperative management of a 57-year-old man with a type I Glanzmann thrombasthenia undergoing coronary artery bypass graft surgery and right carotid endarterectomy. The patient suffered from several lesions in the three major coronary arteries and in the right carotid necessitating surgery. Prophylactic human leukocyte antigen (HLA)-matched platelets transfusions were continuous administrated before, and through the immediate perioperative period. Posttransfusion platelet recovery was monitored using flow cytometry to determine the percentage of circulating platelet expressing CD61 (β3). No bleeding complications occurred during and following the procedure. The patient did not develop HLA antibodies or αIIbβ3 antibodies. Thrombophilia screening revealed a heterozygous G20210A prothrombin gene mutation. The patient also suffered from an atrial fibrillation, necessitating anticoagulation therapy. During the hospital stay, a treatment with vitamin K antagonists for stroke prevention was initiated. The patient was discharged 8 days following surgery, and no further complications occurred during the 6 months follow-up.
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http://dx.doi.org/10.1097/MBC.0000000000000719DOI Listing
April 2018

[Evaluation of the automated coagulation analyser Sysmex(®) CS-5100 (Siemens)].

Ann Biol Clin (Paris) 2015 Jul-Aug;73(4):413-9

UF d'hémostase, Service d'hématologie biologique, Hôpital de la Pitié-Salpêtrière-CFX, Paris, France.

The Sysmex® CS-5100 is a fully automated multiparameter hemostasis analyzer equipped with a photo-optical clot detection unit, a cap-piercing system and a pre-analytical check screens for interfering substances such as bilirubin, lipids and haemolysis (HIL system). It is designed to perform coagulation tests as well as coagulometric, chromogenic and immunologic assays. The aim of the present study was to evaluate its performance. The intra-assay and inter-assay coefficients of variation (CV) were below 6% for most parameters both in the normal and in the pathological range (exceptions: intra-assay for severe factor VIII deficiency (CV = 7.4%) and for vWFRco (CV = 7.3% and 7.7%); and inter-assay for anti-Xa activity (CV = 8.8%) and vWFRco (9.3% and 11.1%). The measured lower limits of linearity for factor VIII and factor V were satisfactory. No sample or reagent carryover was detected in the conditions of the study. Our results demonstrated that using the Sysmex® CS-5100 analyzer, routine coagulation testing can be performed with satisfactory precision. This automate has the advantage of being connectable to an automation chain.
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http://dx.doi.org/10.1684/abc.2015.1054DOI Listing
June 2016

Thrombophilia Associated with Anti-DFS70 Autoantibodies.

PLoS One 2015 23;10(9):e0138671. Epub 2015 Sep 23.

Département d'Immunologie, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France; INSERM U1135, Centre d'Immunologie et des Maladies Infectieuses (CIMI), Paris, France.

Context: Anti-DFS70 antibodies are the most frequent antinuclear antibodies (ANA) found in healthy individuals. We assessed the clinical significance of the presence of anti-DFS70 antibodies.

Methods: We defined a group of patients (n = 421) with anti-DFS70 antibodies and a group of patients (n = 63) with a history of idiopathic arterial and/or venous thrombotic disease and/or obstetric complication (i.e. ≥ 3 miscarriages, fetal death or premature birth with eclampsia). Anti-DFS70 antibodies prevalence was also assessed in a cohort of 300 healthy blood donors.

Results: The prevalence of thrombotic disease and/or obstetric complication in the 421 patients with anti-DFS70 antibodies was 13.1% (n = 55) and the prevalence of connective tissue disease was 19% (n = 80). Among the 63 patients with a history of thrombosis and/or obstetric complications, 7 (11.1%) had anti-DFS70 antibodies and among the latter, 5 had no common thrombophilic factor. In contrast, the prevalence of anti-DFS70 antibodies was of 3.0% (9 out of 300) in healthy donors. Finally, the Activated Partial Thromboplastin Time (aPTT) ratio of patients with a history of thrombosis and anti-DFS70 antibodies was lower than the aPTT ratio of other patients, suggesting that thrombotic patients with anti-DFS70 antibodies may have a hypercoagulable state.

Conclusion: We described here for the first time an immune procoagulant state involving anti-DFS70 antibodies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0138671PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4580612PMC
June 2016

[Evaluation of the automated coagulation analyzer Sysmex(®) CS-2100i (Siemens)].

Ann Biol Clin (Paris) 2011 Nov-Dec;69(6):699-704

Groupe hospitalier Pitié-Salpêtrière, service d'hématologie biologique, Paris, France.

The Sysmex(®) CS-2100i is a fully automated multiparameter hemostasis analyzer equipped with a photo-optical clot detection unit, a cap-piercing system and a pre-analytical check screens for interfering substances such as bilirubin, lipids and haemolysis (HIL system). It is designed to perform coagulation tests as well as chromogenic and immunologic assays. The aim of the present study was to evaluate its performance. The tests performed were routine coagulation (prothrombin time, activated partial thromboplastin time, fibrinogen, factor VIII and factor V), chromogenic (antithrombin) and immunologic assays (D-Dimer). The intra-assay and inter-assay coefficients of variation (CV) were below 5% for most parameters both in the normal and in the pathological range (exceptions: intra-assay CV = 5.65% for the fibrinogen in the low range of concentrations; and inter-assay CV = 6% for clotting factor). The measured lower limits of linearity for factor VIII and factor V were satisfactory. No sample or reagent carryover was detected in the conditions of the study. Our results demonstrated that using the CS-2100i analyzer, routine coagulation testing can be performed with satisfactory precision.
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http://dx.doi.org/10.1684/abc.2011.0624DOI Listing
February 2012

Rituximab failure in a patient with monoclonal gammopathy of undetermined significance (MGUS)-associated acquired von Willebrand syndrome.

Thromb Haemost 2008 Apr;99(4):782-3

Service de Médecine Interne, Hôpital Henri Mondor, 52 Av. du Maréchal de Lattre de Tassigny, 94010 Créteil cedex, France.

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http://dx.doi.org/10.1160/TH07-07-0456DOI Listing
April 2008

Predictive factors for thrombosis and major bleeding in an observational study in 181 patients with heparin-induced thrombocytopenia treated with lepirudin.

Blood 2006 Sep 11;108(5):1492-6. Epub 2006 May 11.

Institut National de la Santé et de la Recherche Médicale (Inserm) Centre d'Investigation Clinique Epidémiologique 3 (CIC E3), Service d'Urgence et de Réanimation Médicales Hôpital Bellevue, Saint-Etienne, France.

The antithrombotic efficacy of lepirudin in patients with heparin-induced thrombocytopenia (HIT) is compromised by an increased risk for bleeding. A retrospective observational analysis in 181 patients (median age, 67 years) with confirmed HIT treated in routine practice with lepirudin was performed to identify predictive factors for thrombotic and bleeding complications. Lepirudin was administered at a mean (+/- SD) dose of 0.06 +/- 0.04 mg/kg/h (compared with a recommended initial dose of 0.15 mg/kg/h). Mean activated partial thromboplastin time was greater than 1.5 times baseline value in 99.4% of patients. Median treatment duration was 7.7 days. Until discharge from the hospital, 13.8% and 20.4% of patients experienced a thrombotic or a major bleeding event, respectively. On multivariate analysis, mean lepirudin dose was not a significant predictive factor for thrombosis. In contrast, mean lepirudin dose greater than 0.07 mg/kg/h, long duration of lepirudin treatment, and moderate to severe renal impairment were significant positive factors for major bleeding. Overall, these results suggest that the recommended dose of lepirudin in patients with HIT is too high; the use of reduced doses may be safer with regard to bleeding risk and does not compromise antithrombotic efficacy.
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http://dx.doi.org/10.1182/blood-2006-02-001057DOI Listing
September 2006