Publications by authors named "Ygal Benhamou"

55 Publications

Bilateral deep vein thrombosis: Time to screen for occult cancer?

Vasc Med 2021 Sep 17:1358863X211034919. Epub 2021 Sep 17.

Department of Internal Medicine, Rouen University Hospital, Rouen, France.

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http://dx.doi.org/10.1177/1358863X211034919DOI Listing
September 2021

Efficacy and safety of TNF-α antagonists and tocilizumab in Takayasu arteritis: Multicenter retrospective study of 209 patients.

Rheumatology (Oxford) 2021 Aug 7. Epub 2021 Aug 7.

Service de Médecine Interne et Immunologie Clinique Groupe Hospitalier UNEOS Metz-Vantoux, France.

Objective: To assess safety and efficacy of TNF-α antagonists and tocilizumab in patients with Takayasu arteritis (TAK).

Methods And Results: Two-hundred nine patients with TAK [median age of 29 years [7-62], and 186 (89%) females] were included. They received either TNF-α antagonists [n = 132 (63%) with 172 lines; infliximab (n = 109), adalimumab (n = 45), golimumab (n = 8), certolizumab (n = 6) and etanercept (n = 5)], or tocilizumab [n = 77 (37%) with 121 lines; intravenous and subcutaneous in 95 and 26 cases, respectively]. A complete response at 6 months was evidenced in 101/152 (66%) on TNF-α antagonists and 75/107 (70%) on tocilizumab, respectively. Age ≥ 30 years [OR = 2.09 [1.09; 3.99]] was associated with complete response, whereas vascular signs [0.26 [0.1; 0.65]], baseline prednisone ≥ 20 mg/day [0.51 [0.28; 0.93]] were negatively associated with the complete response to TNF-α antagonists or tocilizumab. During a median follow-up of 36 months, 103 relapses were noted. Supra-aortic branches and thoracic aorta involvements [HR 2.44 (1.06; 5.65) and 3.66 (1.18; 11.4), respectively], and systemic signs at baseline [HR 2.01 (1.30; 3.11)] were significantly associated with relapse. The cumulative incidence of treatment discontinuation and relapse were similar in TNFα antagonists and tocilizumab. Fifty-eight (20%) adverse effects occurred on biological-targeted therapies of whom 37 (21%) and 21 (17%), (p= 0.4) on TNF-α antagonists and tocilizumab, respectively.

Conclusion: This large multicentre study shows high efficacy of biological-targeted treatments in refractory TAK. Efficacy, relapse and drug retention rate were equivalent with TNF-α antagonists and tocilizumab.
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http://dx.doi.org/10.1093/rheumatology/keab635DOI Listing
August 2021

Triaging acute pulmonary embolism for home treatment by Hestia or simplified PESI criteria: the HOME-PE randomized trial.

Eur Heart J 2021 08;42(33):3146-3157

F-CRIN, INNOVTE, Saint-Etienne, France.

Aims: The aim of this study is to compare the Hestia rule vs. the simplified Pulmonary Embolism Severity Index (sPESI) for triaging patients with acute pulmonary embolism (PE) for home treatment.

Methods And Results: Normotensive patients with PE of 26 hospitals from France, Belgium, the Netherlands, and Switzerland were randomized to either triaging with Hestia or sPESI. They were designated for home treatment if the triaging tool was negative and if the physician-in-charge, taking into account the patient's opinion, did not consider that hospitalization was required. The main outcomes were the 30-day composite of recurrent venous thrombo-embolism, major bleeding or all-cause death (non-inferiority analysis with 2.5% absolute risk difference as margin), and the rate of patients discharged home within 24 h after randomization (NCT02811237). From January 2017 through July 2019, 1975 patients were included. In the per-protocol population, the primary outcome occurred in 3.82% (34/891) in the Hestia arm and 3.57% (32/896) in the sPESI arm (P = 0.004 for non-inferiority). In the intention-to-treat population, 38.4% of the Hestia patients (378/984) were treated at home vs. 36.6% (361/986) of the sPESI patients (P = 0.41 for superiority), with a 30-day composite outcome rate of 1.33% (5/375) and 1.11% (4/359), respectively. No recurrent or fatal PE occurred in either home treatment arm.

Conclusions: For triaging PE patients, the strategy based on the Hestia rule and the strategy based on sPESI had similar safety and effectiveness. With either tool complemented by the overruling of the physician-in-charge, more than a third of patients were treated at home with a low incidence of complications.
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http://dx.doi.org/10.1093/eurheartj/ehab373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408662PMC
August 2021

Adipose tissue-derived stromal vascular fraction for treating hands of patients with systemic sclerosis: a multicentre randomized trial.

Rheumatology (Oxford) 2021 Jul 23. Epub 2021 Jul 23.

Vascular Research Center Marseille, INSERM, INRA, Aix-Marseille University, MARSEILLE, FRANCE.

Objective: To assess the superiority of adipose tissue-derived stromal vascular fraction (AD-SVF) injection into the fingers vs placebo in reducing hand disability in systemic sclerosis (SSc) patients.

Methods: We performed a double-blind, multicentre, phase II trial from October 2015 to January 2018 in France. SSc patients with a Cochin Hand Function Scale (CHFS) ≥20/90 were randomized 1:1 to receive injection of AD-SVF or placebo. AD-SVF was obtained using the automated processing Celution®800/CRS system. The placebo was lactated Ringer's solution. The primary efficacy end point was the change of the CHFS score from baseline to 3 months. Secondary efficacy endpoints included the CHFS score at 6 months, hands function, vasculopathy, hands pain, skin fibrosis, sensitivity of the finger' pulps, Scleroderma Health Assessment Questionnaire, patients and physician satisfaction and the safety.

Results: 40 patients were randomized. The AD-SVF and placebo groups were comparable for age, sex ratio, disease duration, skin fibrosis of the hands and main cause of hand disability. After 3 month-follow-up, hand function significantly improved in both groups with no between-group difference of CHFS (mean change of -9.2 ± 12.2 in the AD-SVF group vs -7.6 ± 13.2 in the placebo group). At 6 months, hand function improved in both groups.

Conclusion: This study showed an improvement of hand function in both groups other time, with no superiority of the AD-SVF. Considering the limits of this trial, studies on a larger population of patients with homogeneous phenotype and hand handicap, should be encouraged to accurately assess the benefit of AD-SVF therapy.

Trial Registration: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02558543. Registered on September 24, 2015.
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http://dx.doi.org/10.1093/rheumatology/keab584DOI Listing
July 2021

Eculizumab in gemcitabine-induced thrombotic microangiopathy: experience of the French thrombotic microangiopathies reference centre.

BMC Nephrol 2021 07 21;22(1):267. Epub 2021 Jul 21.

Medical Intensive Care Unit, Rouen University Hospital, 37 boulevard Gambetta, 76031, Rouen Cedex, France.

Background: Gemcitabine is a broadly prescribed chemotherapy, the use of which can be limited by renal adverse events, including thrombotic microangiopathy (TMA).

Methods: This study evaluated the efficacy of eculizumab, a monoclonal antibody targeting the terminal complement pathway, in patients with gemcitabine-induced TMA (G-TMA). We conducted an observational, retrospective, multicenter study in 5 French centres, between 2011 and 2016.

Results: Twelve patients with a G-TMA treated by eculizumab were included. The main characteristics were acute renal failure (100%), including stage 3 acute kidney injury (AKI, 58%) and renal replacement therapy (17%), hypertension (92%) and diffuse oedema (83%). Eculizumab was started after a median of 15 days (range 4-44) following TMA diagnosis. A median of 4 injections of eculizumab was performed (range 2-22). Complete hematological remission was achieved in 10 patients (83%) and blood transfusion significantly decreased after only one injection of eculizumab (median of 3 packed red blood cells (range 0-10) before treatment vs 0 (range 0-1) after one injection, P < 0.001). Two patients recovered completely renal function (17%), and 8 achieved a partial remission (67%). Compared to a control group of G-TMA without use of eculizumab, renal outcome was more favourable. At the end of the follow up, median eGFR was 45 vs 33 ml/min/1.73m respectively in the eculizumab group and in the control group.

Conclusions: These results suggest that eculizumab is efficient on haemolysis and reduces transfusion requirement in G-TMA. Moreover, eculizumab may improve renal function recovery.
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http://dx.doi.org/10.1186/s12882-021-02470-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293501PMC
July 2021

Hypercoagulability Evaluation in Antiphospholipid Syndrome without Anticoagulation Treatment with Thrombin Generation Assay: A Preliminary Study.

J Clin Med 2021 Jun 21;10(12). Epub 2021 Jun 21.

Vascular Hemostasis Unit, Rouen University Hospital, Normandie University, UNIROUEN, INSERM U1096, F 76000 Rouen, France.

Antiphospholipid syndrome (APS) is associated with thrombotic events (tAPS) and/or obstetrical morbidity (oAPS), with persisting antiphospholipid antibodies (aPL). Despite an update of aPL in 2006, several patients had typical clinical events without the classical biological criteria. The aim of our study was to evaluate the hypercoagulability state with both thrombin generation (TG) profiles and activated protein C resistance (aPCR) in different types of APS.

Methods: We retrospectively included 41 patients with Sydney criteria classification (tAPS, oAPS) and no clinical manifestation of APS with persistent aPL (biological APS). A thrombin generation assay was performed with a Fluoroskan Ascent fluorometer in platelet-poor plasma (PPP). Activated protein C resistance was measured as a ratio: ETP/ETP × 100.

Results: Thrombotic APS and oAPS had an increase of global thrombin generation (ETP = 808 nM.min (756-853) vs. 1265 nM.min (956-1741) and 1863 nM.min (1434-2080), respectively) (Peak = 78 nM (74-86) vs. 153 nM (109-215) and 254 nM.min (232-289), respectively). Biological APS had only a lag time increase (T = 4.89 ± 1.65 min vs. 13.6 ± 3.9 min). An increased aPCR was observed in tAPS (52.7 ± 16.4%), oAPS (64.1 ± 14.6%) as compared to the control group (27.2 ± 13.8%).

Conclusion: Our data suggest an increase of thrombin generation in thrombotic and obstetrical APS and no hypercoagulable states in patients with biological APS. The study of a prospective and a larger controlled cohort could determine the TGA useful for APS monitoring and could confirm an aPCR evaluation in PPP.
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http://dx.doi.org/10.3390/jcm10122728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234883PMC
June 2021

Acute Ischemic Stroke Revealing ChAdOx1 nCov-19 Vaccine-Induced Immune Thrombotic Thrombocytopenia: Impact on Recanalization Strategy.

J Stroke Cerebrovasc Dis 2021 Sep 24;30(9):105942. Epub 2021 Jun 24.

Department of Neurology, Rouen University Hospital, Rouen F-76000, France.

Vaccine-induced immune thrombotic thrombocytopenia is a rare syndrome following the ChAdOx1 nCov-19 or Ad26.COV2.S vaccine. Reported patients developed mainly venous thrombosis. We describe a case of a young healthy women suffering from acute ischemic stroke due to large vessel occlusion without cerebral venous thrombosis 8 days after vaccination and its consequences on recanalization strategy. Considering the thrombocytopenia, intravenous thrombolysis was contraindicated. She underwent mechanical thrombectomy with complete recanalization and dramatically improved clinically. Positive detection of anti-PF4-heparin-antibodies confirmed vaccine-induced immune thrombotic thrombocytopenia diagnosis. In case of acute ischemic stroke after recent ChAdOx1 nCov-19 or Ad26.COV2.S vaccine, platelet count should be systematically checked before giving thrombolysis, and direct mechanical thrombectomy should be proposed in patients with large vessel occlusion.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105942DOI Listing
September 2021

Shiga Toxin-Associated Hemolytic Uremic Syndrome in Adults, France, 2009-2017.

Emerg Infect Dis 2021 ;27(7):1876-1885

We conducted a retrospective study on hemolytic uremic syndrome caused by Shiga toxin-producing Escherichia coli (STEC) in 96 adults enrolled in the cohort of the National Reference Center for Thrombotic Microangiopathies network in France during 2009-2017. Most infections were caused by STEC strains not belonging to the O157 or O104 serogroups. Thirty (31.3%) patients had multiple risk factors for thrombotic microangiopathy. In total, 61 (63.5%) patients required dialysis, 50 (52.1%) had a serious neurologic complication, 34 (35.4%) required mechanical ventilation, and 19 (19.8%) died during hospitalization. We used multivariate analysis to determine that the greatest risk factors for death were underlying immunodeficiency (hazard ratio 3.54) and severe neurologic events (hazard ratio 3.40). According to multivariate analysis and propensity score-matching, eculizumab treatment was not associated with survival. We found that underlying conditions, especially immunodeficiency, are strongly associated with decreased survival in adults who have hemolytic uremic syndrome caused by STEC.
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http://dx.doi.org/10.3201/eid2707.204638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237898PMC
July 2021

CATASTROPHIC ANTIPHOSPHOLIPID SYNDROME AND POSTERIOR OCULAR INVOLVEMENT: Case Series of 11 Patients and Literature Review.

Retina 2021 Nov;41(11):2332-2341

AP-HP, Cochin Hospital, Internal Medicine Department, Centre de Référence Maladies Auto-immunes et Systémiques Rares de l'Ile de France, AP-HP, Cochin Hospital, Paris, France.

Purpose: To describe the posterior ophthalmic manifestations of catastrophic antiphospholipid syndrome.

Methods: Retrospective case series of patients presenting with catastrophic antiphospholipid syndrome and posterior segment ocular manifestations. The main outcomes were the type of posterior segment manifestations at catastrophic antiphospholipid syndrome diagnosis, specifically retinal vascular occlusion, vasculitis, or choroidopathy, and the final best-corrected visual acuity.

Results: This study included 23 patients (11 cases treated by the authors and 12 published case reports); 21 (91%) of them female. Their median age at diagnosis was 28 years (range, 16-79 years). Ophthalmologic manifestations were usually bilateral (n = 19, 83%) and involved vascular occlusive retinopathy (n = 17, 74%), choroidopathy (n = 11, 48%), or retinal vasculitis (n = 1, 4%). Final best-corrected visual acuity was not significantly worse than the best-corrected visual acuity at diagnosis (P = 0.16). Retinal vascular occlusions were associated with poorer final visual acuity than choroidopathy (P = 0.002). After a median follow-up of 14 months (range, 2-132 months), nearly half the patients (n = 11, 48%) had permanent vision loss including best-corrected visual acuity of <20/400 for 4 patients.

Conclusion: Posterior ophthalmic manifestations of catastrophic antiphospholipid syndrome were mainly bilateral retinal vascular occlusion, which had the worst visual prognosis, followed by choroidopathy and retinal vasculitis. Permanent visual loss was common.
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http://dx.doi.org/10.1097/IAE.0000000000003185DOI Listing
November 2021

Identification of a novel genetic locus associated with immune mediated thrombotic thrombocytopenic purpura.

Haematologica 2021 Feb 18. Epub 2021 Feb 18.

Haemostasis Research Unit, UCL (London, UK); National Institute for Health Research Cardiometabolic Programme, UCLH/UCL Cardiovascular BRC (London, UK).

Not available.
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http://dx.doi.org/10.3324/haematol.2020.274639DOI Listing
February 2021

A regimen with caplacizumab, immunosuppression, and plasma exchange prevents unfavorable outcomes in immune-mediated TTP.

Blood 2021 02;137(6):733-742

Centre de Référence des Microangiopathies Thrombotiques, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.

The anti-von Willebrand factor nanobody caplacizumab was licensed for adults with immune-mediated thrombotic thrombocytopenic purpura (iTTP) based on prospective controlled trials. However, few data are available on postmarketing surveillance. We treated 90 iTTP patients with a compassionate frontline triplet regimen associating therapeutic plasma exchange (TPE), immunosuppression with corticosteroids and rituximab, and caplacizumab. Outcomes were compared with 180 historical patients treated with the standard frontline treatment (TPE and corticosteroids, with rituximab as salvage therapy). The primary outcome was a composite of refractoriness and death within 30 days since diagnosis. Key secondary outcomes were exacerbations, time to platelet count recovery, the number of TPE, and the volume of plasma required to achieve durable remission. The percentage of patients in the triplet regimen with the composite primary outcome was 2.2% vs 12.2% in historical patients (P = .01). One elderly patient in the triplet regimen died of pulmonary embolism. Patients from this cohort experienced less exacerbations (3.4% vs 44%, P < .01); they recovered durable platelet count 1.8 times faster than historical patients (95% confidence interval, 1.41-2.36; P < .01), with fewer TPE sessions and lower plasma volumes (P < .01 both). The number of days in hospital was 41% lower in the triplet regimen than in the historical cohort (13 vs 22 days; P < .01). Caplacizumab-related adverse events occurred in 46 patients (51%), including 13 major or clinically relevant nonmajor hemorrhagic events. Associating caplacizumab to TPE and immunosuppression, by addressing the 3 processes of iTTP pathophysiology, prevents unfavorable outcomes and alleviates the burden of care.
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http://dx.doi.org/10.1182/blood.2020008021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986049PMC
February 2021

Cardiac involvement in adult-onset Still's disease: Manifestations, treatments and outcomes in a retrospective study of 28 patients.

J Autoimmun 2021 01 15;116:102541. Epub 2020 Sep 15.

Department of Internal Medicine, Rouen University Hospital, 76000, Rouen, France; INSERM U 905, University of Rouen IFRMP, Institute for Biochemical Research, Rouen University Hospital, 76000, Rouen, France.

Objective: Adult-onset Still's disease (AOSD) is a rare inflammatory disease that may be life-threatening if complicated by cardiac problems. We performed a retrospective multicenter study to describe the manifestations, treatments and outcomes of cardiac involvement in AOSD.

Methods: We reviewed the medical databases of eight centers. All AOSD patients identified as fulfilling Yamagushi's or Fautrel's criteria were included in the study. Cardiac involvement, clinical manifestations, laboratory features, the course of the disease and treatments were evaluated.

Results: We included 96 AOSD patients in this study: 28 (29%) had documented cardiac involvement (AOSD + C group) and 68 (71%) had no cardiac involvement (control group). Cardiac complications were observed at diagnosis in 89% of cases. It were pericarditis (n = 17), tamponade (n = 5), myocarditis (n = 5) and non-infectious endocarditis (n = 1). Levels of leukocytes, neutrophils and C-reactive protein were significantly higher (p = 0.02, p = 0.02 and p = 0.002, respectively in the AOSD + C group than in the control group. Admission to intensive care, and the use of biotherapy were more frequent during follow-up in the AOSD + C group than the control group (p = 0.0001 and p = 0.03 respectively). Cardiac involvement was associated with refractory form in multivariate analyzed (p = 0.01). Corticosteroids were effective with or without methotrexate in 71% of patients but not in severe involvement as myocarditis or tamponade.

Conclusion: Cardiac complications are frequent, inaugural, can be life-threatening and predictive of a refractory course in patients with AOSD. Systematic cardiac screening should be proposed at diagnosis and biotherapy early use should be considered especially in myocarditis.
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http://dx.doi.org/10.1016/j.jaut.2020.102541DOI Listing
January 2021

Vasculitis associated with myelodysplastic syndrome and chronic myelomonocytic leukemia: French multicenter case-control study.

Semin Arthritis Rheum 2020 10 11;50(5):879-884. Epub 2020 Jul 11.

Department of Internal Medicine, Assistance Publique-Hôpitaux de Marseille, Hôpital La Timone, Marseille, France.

Introduction: Our objective was to evaluate characteristics, treatment and outcome of vasculitis associated with myelodysplastic syndrome (MDS) and chronic myelomonicytic leukemia (CMML) PATIENTS AND METHODS: Retrospective descriptive analysis of MDS/CMML-related vasculitis and comparison with MDS/CMML patients without dysimmune features.

Results: Seventy patients with vasculitis and MDS/CMML were included, with median age of 71.5 [21-90] years and male/female ratio of 2.3. Vasculitis was diagnosed prior to MDS/CMML in 31 patients (44%), and after in 20 patients. In comparison with MDS/CMML without autoimmune/inflammatory features, vasculitis with MDS/MPN showed no difference in MDS/CMML subtypes distribution nor International Prognostic Scoring System and CMML-specific prognostic (IPSS/CPSS) scores. Vasculitis subtypes included Giant cell arteritis in 24 patients (34%), Behçet's-like syndrome in 11 patients (20%) and polyarteritis nodosa in 6 patients (9%). Glucocorticoids (GCs) were used as first-line therapy for MDS/CMML vasculitis in 64/70 patients (91%) and 41 (59%) received combined immunosuppressive therapies during the follow-up. After a median follow-up of 33.2 months [1-162], 31 patients (44%) achieved sustained remission. At least one relapse occurred in 43 patients (61%). Relapse rates were higher in patients treated with conventional Disease Modifying Anti-Rheumatic Drug (DMARDs) (odds ratio 4.86 [95% CI 1.38 - 17.10]), but did not differ for biologics (odds ratio 0.59 [95% CI 0.11-3.20]) and azacytidine (odds ratio 1.44 [95% CI 0.21-9.76]) than under glucocorticoids. Overall survival in MDS/CMML vasculitis was not significantly different from MDS/CMML patients without autoimmune/inflammatory features (p = 0.5), but acute leukemia progression rates were decreased (log rank <0.05).

Conclusion: This study shows no correlation of vasculitis diagnoses with subtypes and severity of MDS/CMML, and no significant impact of vasculitis on overall survival. Whereas conventional DMARDs seem to be less effective, biologics or azacytidine therapy could be considered for even low-risk MDS/CMML vasculitis.
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http://dx.doi.org/10.1016/j.semarthrit.2020.07.002DOI Listing
October 2020

Understanding the Health Literacy in Patients With Thrombotic Thrombocytopenic Purpura.

Hemasphere 2020 Aug 11;4(4):e462. Epub 2020 Aug 11.

Centre de Référence des Microangiopathies Thrombotiques, AP-HP.6, Paris, France.

Following an acute thrombotic thrombocytopenic purpura (TTP) episode, patients are at risk for relapse, and a careful long-term follow-up is needed. Adherence to the follow-up by patients implies a good understanding of the disease. However, TTP literacy in patients is currently unknown. To explore the TTP literacy in patients and identify factors associated with poor disease understanding, a questionnaire was developed focusing on patient's characteristics, knowledge about TTP and patients' actions in an emergency. The questionnaire was presented to 120 TTP patients in remission from the French National Registry for Thrombotic Microangiopathies. TTP literacy was low in 24%, intermediate in 43% and high in 33% of the patients. Low TTP literacy was associated with older age and low education level. Among the knowledge gaps identified, few patients knew that plasma exchange in acute phase is mandatory and has to be done daily (39%), 47% of participants did not consider themselves at risk for relapse, and 30% of women did not know that pregnancy exposes them to a greater risk of relapse. Importantly, few patients responded about life-saving actions in an emergency. Hence, the design of educational material should pay special attention to the age and education level of the target population focusing on the events leading to TTP, the importance of the emergency treatment, controllable predisposing factors for TTP development and patient attitude in an emergency.
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http://dx.doi.org/10.1097/HS9.0000000000000462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430230PMC
August 2020

Obstetrical outcome and treatments in seronegative primary APS: data from European retrospective study.

RMD Open 2020 08;6(2)

Sorbonne Université, AP-HP, Hôpital Saint-Antoine, Service de Médecine Interne and Inflammation-Immunopathology-Biotherapy Department (DMU 3iD), Paris, France

Objective: To compare characteristics, pregnancies and treatments during pregnancies of seronegative and seropositive antiphospholipid syndrome (APS), to analyse factors associated with obstetrical outcome.

Patients And Methods: Inclusion criteria were: (1) thrombotic and/or obstetrical APS (Sydney criteria); (2) absence of conventional antiphospholipid antibodies (APL); (3) at least one persistent non-conventional APL among IgA anticardiolipin antibodies, IgA anti-B2GPI, anti-vimentin G/M, anti-annexin V G/M, anti-phosphatidylethanolamine G/M and anti-phosphatidylserine/prothrombin G/M antibodies. The exclusion criteria were: (1) systemic lupus erythematosus ( SLE) or SLE-like disease; and (2) other connective tissue disease.

Results: A total of 187 women (mean 33±5 years) with seronegative APS were included from 14 centres in Austria, Spain, Italy, Slovenia and France and compared with 285 patients with seropositive APS. Seronegative APS has more obstetrical rather than thrombotic phenotypes, with only 6% of venous thrombosis in comparison to seropositive APS. Cumulative incidence of adverse obstetrical events was similar in seronegative and seropositive APS patients, although higher rates of intrauterine deaths (15% vs 5%; p=0.03), of preeclampsia (7% vs 16%, p=0.048) and lower live birth term (36±3 vs 38±3 weeks of gestation; p=0.04) were noted in seropositive APS. The cumulative incidence of adverse obstetrical events was significantly improved in treated versus untreated seronegative APS (log rank<0.05), whereas there was no difference between patients who received aspirin or aspirin-low-molecular weighted heparin combination.

Conclusion: Several non-criteria APL can be detected in patients with clinical APS features without any conventional APL, with various rates. The detection of non-criteria APL and thus the diagnosis of seronegative APS could discuss the therapeutic management similar to seropositive APS, but well-designed controlled studies are necessary.
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http://dx.doi.org/10.1136/rmdopen-2020-001340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507995PMC
August 2020

Comparison of conventional immunosuppressive drugs versus anti-TNF-α agents in non-infectious non-anterior uveitis.

J Autoimmun 2020 09 23;113:102481. Epub 2020 Jun 23.

Ophthalmology Department, Hospital Charles Nicolle, Rouen, France; EA7510, UFR Santé, Rouen University, Rouen, France.

Objective: To compare the efficacy and safety of Disease-modifying antirheumatic drugs (DMARDs) and anti-TNF-α agents in patients with non-infectious non-anterior uveitis.

Methods: Single center retrospective study including adult patients with non-infectious intermediate, posterior or pan-uveitis. Outcomes were compared between patients treated with DMARDs or anti-TNF-α agents. The primary outcome was treatment failure or occurrence of serious adverse events. Treatment failure was determined by ophthalmologic criteria.

Results: Seventy-three patients were included, mostly female (52%). Among them, 39 were treated with DMARDs and 34 with anti-TNF-α agents. The main uveitis causes were idiopathic (30%), birdshot chorio-retinopathy (25%), sarcoidosis (16%) and Behçet's disease (14%). The primary outcome was observed in 56% of patients treated with anti-TNF-α agents versus 59% of patients treated with DMARDs (p = 0.82). Median time to observe the primary outcome was 16 months (anti-TNF-α group) versus 21 months (p = 0.52). There was no significant difference between the two groups in terms of treatment failure, corticosteroid sparing effect, visual acuity improvement or adverse events. Earlier control of ocular inflammation was achieved with anti-TNF-α agents than with DMARDs (p = 0.006). In relapsing patients, anti-TNF-α agents allowed better corticosteroid sparing (p = 0.06).

Conclusion: DMARDs could still be used as first-line therapy for non-infectious non-anterior uveitis after corticosteroid therapy. However, anti-TNF-α agents could be proposed as an alternative in cases of severe inflammation or initial high level of steroid dependency.
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http://dx.doi.org/10.1016/j.jaut.2020.102481DOI Listing
September 2020

Open ADAMTS13, induced by antibodies, is a biomarker for subclinical immune-mediated thrombotic thrombocytopenic purpura.

Blood 2020 07;136(3):353-361

Laboratory for Thrombosis Research, IRF Life Sciences, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium.

Recently, we showed that ADAMTS13 circulates in an open conformation during the acute phase of immune-mediated thrombotic thrombocytopenic purpura (iTTP). Although the cause of this conformational change remains elusive, ADAMTS13 is primarily closed in iTTP patients in remission with ADAMTS13 activity >50% and undetectable anti-ADAMTS13 autoantibodies, as well as after rituximab treatment, suggesting a role for anti-ADAMTS13 autoantibodies. Therefore, immunoglobulin G from 18 acute iTTP patients was purified and added to closed ADAMTS13 in healthy donor plasma. This resulted in open ADAMTS13 in 14 of 18 (78%) samples, proving that anti-ADAMTS13 autoantibodies can induce an open ADAMTS13 conformation. To further elucidate the conformation of ADAMTS13 in iTTP patients, we studied a novel iTTP patient cohort (n = 197) that also included plasma samples from iTTP patients in remission in whom ADAMTS13 activity was <50%. The open ADAMTS13 conformation was found during acute iTTP, as well as in patients in remission with ADAMTS13 activity <50% and in half of the patients with ADAMTS13 activity >50%, although free anti-ADAMTS13 autoantibodies were not always detected. Thus, open ADAMTS13 is a hallmark of acute iTTP, as well as a novel biomarker that can be used to detect subclinical iTTP in patients in remission. Finally, a long-term follow-up study in 1 iTTP patient showed that the open conformation precedes a substantial drop in ADAMTS13 activity. In conclusion, we have shown that anti-ADAMTS13 autoantibodies from iTTP patients induce an open ADAMTS13 conformation. Most importantly, an open ADAMTS13 conformation is a biomarker for subclinical iTTP and could become an important tool in TTP management.
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http://dx.doi.org/10.1182/blood.2019004221DOI Listing
July 2020

Giant-cell arteritis associated with myelodysplastic syndrome: French multicenter case control study and literature review.

Autoimmun Rev 2020 Feb 13;19(2):102446. Epub 2019 Dec 13.

Department of Internal Medicine, Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France Sorbonne Université, France; Sorbonne Universités, INSERM U938, Centre de Recherche Saint-Antoine (CRSA), Paris, France. Electronic address:

Introduction: Myelodysplastic syndromes (MDS) and MDS/myeloproliferative neoplasms (MDS/MPN) can be associated with giant cell arteritis (GCA). In this nationwide study by the "French Network of dysimmune disorders associated with hemopathies" (MINHEMON) the objective was to evaluate characteristics, treatment and outcome of GCA MDS-MDS/MPN.

Patients And Methods: Retrospective analysis of patients that presented a MDS or MDS/MPN associated with GCA. Treatment efficiency, relapse-free and overall survival of GCA MDS-MDS/MPN were compared to GCA alone.

Results: Twenty-one patients with GCA MDS-MDS/MPN were included with median age 76 [42-92], M/F ratio 2.5, 8 MDS with multilineage dysplasia (38%), 4 chronic myelomonocytic leukemia (19%), at low or intermediate risk according to IPPS and IPSS-R. The prevalence of headaches, jaw claudication and anterior ischemic optic neuropathy was significantly lower in patients with GCA MDS-MDS/MPN compared to idiopathic GCA (14.3%, 0% and 0% versus 30%, 25%, and 25%, respectively; p < .05). Other clinical and histology findings were similar. All GCA patients received steroid therapy as first-line treatment. Complete or partial response was observed in 14 GCA MDS-MDS/MPN patients (66.7%), of whom 6 (28.6%) received combined immunosuppressive therapies (versus 10% of idiopathic GCA; p = .07). Relapse incidence was similar in the two groups. Steroid dependence was more frequent among GCA MDS-MDS/MPN patients (12 (57%) versus 18 (22.5%); p < .05). Relapse-free and steroid-free survivals were significantly decreased in GCA MDS-MDS/MPN patients (log rank 0.002 and 0.049 respectively), but not overall survival.

Conclusion: Characteristics of GCA MDS-MDS/MPN seem different than idiopathic GCA, with a distinct clinical phenotype and poorer outcome with a higher risk of steroid dependence and relapse.
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http://dx.doi.org/10.1016/j.autrev.2019.102446DOI Listing
February 2020

Increased diagnostic accuracy of giant cell arteritis using three-dimensional fat-saturated contrast-enhanced vessel-wall magnetic resonance imaging at 3 T.

Eur Radiol 2020 Apr 6;30(4):1866-1875. Epub 2019 Dec 6.

Department of Neuroradiology, Foundation Adolphe de Rothschild Hospital, 29 rue Manin, 75019, Paris, France.

Objectives: To compare the diagnostic accuracy of 3D versus 2D contrast-enhanced vessel-wall (CE-VW) MRI of extracranial and intracranial arteries in the diagnosis of GCA.

Methods: This prospective two-center study was approved by a national research ethics board and enrolled participants from December 2014 to October 2017. A protocol including both a 2D and a 3D CE-VW MRI at 3 T was performed in all patients. Two neuroradiologists, blinded to clinical data, individually analyzed separately and in random order 2D and 3D sequences in the axial plane only or with reformatting. The primary judgment criterion was the presence of GCA-related inflammatory changes of extracranial arteries. Secondary judgment criteria included inflammatory changes of intracranial arteries and the presence of artifacts. A McNemar's test was used to compare 2D to 3D CE-VW MRIs.

Results: Seventy-nine participants were included in the study (42 men and 37 women, mean age 75 (± 9.5 years)). Fifty-one had a final diagnosis of GCA. Reformatted 3D CE-VW was significantly more sensitive than axial-only 3D CE-VW or 2D CE-VW when showing inflammatory change of extracranial arteries: 41/51(80%) versus 37/51 (73%) (p = 0.046) and 35/50 (70%) (p = 0.03). Reformatted 3D CE-VW was significantly more specific than 2D CE-VW: 27/27 (100%) versus 22/26 (85%) (p = 0.04). 3D CE-VW showed higher sensitivity than 2D CE-VW when detecting inflammatory changes of intracranial arteries: 10/51(20%) versus 4/50(8%), p = 0.01. Interobserver agreement was excellent for both 2D and 3D CE-VW MRI: κ = 0.84 and 0.82 respectively.

Conclusions: 3D CE-VW MRI supported more accurate diagnoses of GCA than 2D CE-VW.

Key Points: • 3D contrast-enhanced vessel-wall magnetic resonance imaging is a high accuracy, non-invasive diagnostic tool used to diagnose giant cell arteritis. • 3D contrast-enhanced vessel-wall imaging is feasible for clinicians to complete within a relatively short time, allowing immediate assessment of extra and intracranial arteries. • 3D contrast-enhanced vessel-wall magnetic resonance imaging might be considered a diagnostic tool when intracranial manifestation of GCA is suspected.
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http://dx.doi.org/10.1007/s00330-019-06536-7DOI Listing
April 2020

Safety of Primary Thromboprophylaxis Using Apixaban in Ambulatory Cancer Patients with Intracranial Metastatic Disease or Primary Brain Tumors.

Thromb Haemost 2019 11 10;119(11):1886-1887. Epub 2019 Oct 10.

Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.

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http://dx.doi.org/10.1055/s-0039-1695769DOI Listing
November 2019

Immune thrombotic thrombocytopenic purpura in older patients: prognosis and long-term survival.

Blood 2019 12;134(24):2209-2217

Service d'Hématologie, AP-HP.6, Paris, France; and.

Older age is associated with increased mortality in immune thrombotic thrombocytopenic purpura (iTTP). Yet, data are scarce regarding iTTP occurring among older patients. To assess clinical features and long-term impact of iTTP on mortality in older patients (>60 years old), characteristics and prognoses of adult iTTP patients enrolled in the French Reference Center for Thrombotic Microangiopathies registry between 2000 and 2016 were described according to age (<60 years old or ≥60 years old). Long-term mortality of iTTP older survivors was compared with that of non-iTTP geriatric subjects. Comparing, respectively, older iTTP patients (N = 71) with younger patients (N = 340), time from hospital admission to diagnosis was longer (P < .0001); at diagnosis, delirium (P = .034), behavior impairment (P = .045), renal involvement (P < .0001), and elevated troponin level (P = .025) were more important whereas cytopenias were less profound (platelet count, 22 × 103/mm3 [9-57] vs 13 × 103/mm3 [9-21], respectively [P = .002]; hemoglobin level, 9 g/dL [8-11] vs 8 g/dL [7-10], respectively [P = .0007]). Short- and mid-term mortalities were higher (P < .0001) and increased for every 10 years of age range. Age ≥60 years, cardiac involvement, increased plasma creatinine level, and total plasma exchange volume were independently associated with 1-month mortality. Compared with a non-iTTP geriatric population, older survivors showed an increased long-term mortality (hazard ratio = 3.44; P < .001). In conclusion, older iTTP patients have atypical neurological presentation delaying the diagnosis. Age negatively impacts short-term but also long-term mortality.
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http://dx.doi.org/10.1182/blood.2019000748DOI Listing
December 2019

Caplacizumab: a change in the paradigm of thrombotic thrombocytopenic purpura treatment.

Expert Opin Biol Ther 2019 11 5;19(11):1127-1134. Epub 2019 Aug 5.

French Reference Center for Thrombotic Microangiopathies, Hôpital Saint Antoine, Assistance Publique -Hôpitaux de Paris , Paris , France.

Immune thrombotic thrombocytopenic purpura (iTTP) is an immune-mediated deficiency in von Willebrand factor-cleaving protease ADAMTS13 allowing unrestrained adhesion of von Willebrand factor multimers to platelets and microthrombosis. Caplacizumab, an anti-von Willebrand factor humanized, bivalent single-domain nanobody preventing its binding to the platelet has been investigated and approved for use in the treatment of iTTP. The purpose of this article is to summarize the available clinical data on the efficacy and safety of caplacizumab in iTTP and to provide our opinion on the place of caplacizumab in current treatment regimens. Caplacizumab is a new drug with a complementary mechanism of action with respect to the standard available therapeutics. It demonstrated efficacy in clinical trials through a faster platelet count normalization and protection of patients from exacerbations and refractoriness. Caplacizumab is well tolerated with minor bleeds as the most important side effect. The efficacy of caplacizumab now needs to be assessed in real-life but definitely, this drug opens hope for a significant improvement in iTTP prognosis at the very early, critical step of the disease.
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http://dx.doi.org/10.1080/14712598.2019.1650908DOI Listing
November 2019

Large-vessel vasculitis diagnosed between 50 and 60 years: Case-control study based on 183 cases and 183 controls aged over 60 years.

Autoimmun Rev 2019 Jul 4;18(7):714-720. Epub 2019 May 4.

Department of Internal Medicine, Hôpital Lariboisière, Paris, France.

Background: Age at onset of large-vessel vasculitis (LVV) is commonly used to distinguish giant cell arteritis (GCA) and Takayasu arteritis (TA). However, LVV between age 50 and 60 years may be difficult to classify.

Methods: We conducted a retrospective study including LVV aged between 50 and 60 years at onset (LVV, cases) and compared them to LVV aged over 60 years (LVV, controls). LVV was defined histologically and/or morphologically. Controls fulfilled ACR 1990 criteria for GCA or presented isolated aortitis.

Results: We included 183 LVV and 183 gender-matched LVV. LVV had more frequent peripheral limb manifestations (23 vs. 5%), and less frequent cephalic (73 vs. 90%) and ocular signs (17 vs. 27%) than LVV. Compared to LVV, CT angiography and PET/CT scan were more frequently abnormal in LVV (74 vs. 38%, and 90 vs. 72%, respectively), with aorta being more frequently involved (78 vs. 47%). By multivariate analysis, absence of cephalic symptoms, presence of peripheral limb ischemia and aorta involvement, and increased CRP level were significantly associated with LVV presentation compared to LVV. At last follow-up, compared to LVV, LVV received significantly more lines of treatment (2 vs. 1), more frequent biologics (12 vs. 3%), had more surgery (10 vs. 0%), and had higher prednisone dose (8.8 vs. 6.5 mg/d) at last follow-up, CONCLUSION: LVV onset between 50 and 60 years identifies a subset of patients with more frequent aorta and peripheral vascular involvement and more refractory disease compared to patients with LVV onset after 60.
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http://dx.doi.org/10.1016/j.autrev.2019.05.008DOI Listing
July 2019

Hydroxychloroquine reverses the prothrombotic state in a mouse model of antiphospholipid syndrome: Role of reduced inflammation and endothelial dysfunction.

PLoS One 2019 14;14(3):e0212614. Epub 2019 Mar 14.

Rouen University Hospital, Department of Internal Medicine, Rouen, France.

Antiphospholipid antibodies (aPL) promote endothelial dysfunction, inflammation and procoagulant state. We investigated the effect of hydroxychloroquine (HCQ) on prothrombotic state and endothelial function in mice and in human aortic endothelial cells (HAEC). Human aPL were injected to C57BL/6 mice treated or not with HCQ. Vascular endothelial function and eNOS were assessed in isolated mesenteric arteries. Thrombosis was assessed both in vitro by measuring thrombin generation time (TGT) and tissue factor (TF) expression and in vivo by the measurement of the time to occlusion in carotid and the total thrombosis area in mesenteric arteries. TGT, TF, and VCAM1 expression were evaluated in HAEC. aPL increased VCAM-1 expression and reduced endothelium dependent relaxation to acetylcholine. In parallel, aPL shortened the time to occlusion and extended thrombus area in mice. This was associated with an overexpression of TF and an increased TGT in mice and in HAEC. HCQ reduced clot formation as well as TGT, and improved endothelial-dependent relaxations. Finally, HCQ increased the p-eNOS/eNOS ratio. This study provides new evidence that HCQ improves procoagulant status and vascular function in APS by modulating eNOS, leading to an improvement in the production of NO.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0212614PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6417644PMC
November 2019

Preemptive rituximab prevents long-term relapses in immune-mediated thrombotic thrombocytopenic purpura.

Blood 2018 11 10;132(20):2143-2153. Epub 2018 Sep 10.

Centre de Référence des Microangiopathies Thrombotiques, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France.

Preemptive rituximab infusions prevent relapses in immune thrombotic thrombocytopenic purpura (iTTP) by maintaining normal ADAMTS13 activity. However, the long-term outcome of these patients and the potential adverse events of this strategy need to be determined. We report the long-term outcome of 92 patients with iTTP in clinical remission who received preemptive rituximab after identification of severe ADAMTS13 deficiency (activity <10%) during the follow-up. Thirty-seven patients had >1 iTTP episode, and the median cumulative relapse incidence before preemptive rituximab was 0.33 episode per year (interquartile range [IQR], 0.23-0.66). After preemptive rituximab, the median cumulative relapse incidence in the whole population decreased to 0 episodes per year (IQR, 0-1.32; < .001). After preemptive rituximab, ADAMTS13 activity recovery was sustained in 34 patients (37%) during a follow-up of 31.5 months (IQR, 18-65), and severe ADAMTS13 deficiency recurred in 45 patients (49%) after the initial improvement. ADAMTS13 activity usually improved with additional courses of preemptive rituximab. In 13 patients (14%), ADAMTS13 activity remained undetectable after the first rituximab course, but retreatment was efficient in 6 of 10 cases. In total, 14 patients (15%) clinically relapsed, and 19 patients (20.7%) experienced benign adverse effects. Preemptive rituximab treatment was associated with a change in ADAMTS13 conformation in respondent patients. Finally, in the group of 23 historical patients with iTTP and persistently undetectable ADAMTS13 activity, 74% clinically relapsed after a 7-year follow-up (IQR, 5-11). In conclusion, persistently undetectable ADAMTS13 activity in iTTP during remission is associated with a higher relapse rate. Preemptive rituximab reduces clinical relapses by maintaining a detectable ADAMTS13 activity with an advantageous risk-benefit balance.
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http://dx.doi.org/10.1182/blood-2018-04-840090DOI Listing
November 2018

Overall survival and mortality risk factors in Takayasu's arteritis: A multicenter study of 318 patients.

J Autoimmun 2019 01 17;96:35-39. Epub 2018 Aug 17.

Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, Inflammation-Immunopathology-Biotherapy Department (DHU i2B), F-75005, Paris, France; INSERM, UMR_S 959, F-75013, Paris, France; CNRS, FRE3632, F-75005, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, F-75013, Paris, France; Centre de Référence des Maladies Auto-Immunes et Systémiques Rares, Centre de Référence des Maladies Auto-Inflammatoires et de l'Amylose, France. Electronic address:

Objective: To report the long term mortality in Takayasu arteritis (TA) and to identify prognosis factors.

Methods: We analyzed the causes of death and the factors associated with mortality in a cohort of 318 patients [median age at diagnosis was 36 [25-47] years and 276 (86%) patients were women] fulfilling American College of Rheumatology and/or Ishikawa criteria of TA. A prognostic score for death and vascular complications was elaborated based on a multivariate model.

Results: Among 318 TA patients, 16 (5%) died after a median [IQR] follow-up of 6.1 [2.8-13.0] years. The median age at death was 38 [25-47] years with 88% of women. Main causes of death included mesenteric ischemia (n = 4, 25%) and aortic aneurysm rupture (n = 4, 25%). The mortality rate at 5 and 10 years was of 1.9% and 3.9%, respectively. Caucasians (p = 0.049) and smokers (p = 0.002) TA patients were more likely to die. There was an increased mortality in TA (SMR with 95% confidence interval, 2.73 [1.69-4.22]) as compared to age and sex matched healthy controls. We defined high risk patients for death and vascular complications according to the presence of two of the following factors (i.e a progressive clinical course, thoracic aorta involvement and/or retinopathy). In the high risk TA group, the 5-year incidence of death and vascular complication was 48.5% compared to 21.6% (p = 0.001) in those with low risk.

Conclusion: The overall mortality in our Takayasu cohort was 5% after a median follow-up of 6.1 years. We identified specific characteristics that distinguish TA patients at highest risk for death and vascular complications.
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http://dx.doi.org/10.1016/j.jaut.2018.08.001DOI Listing
January 2019

Development of a thrombin generation test in cultured endothelial cells: Evaluation of the prothrombotic effects of antiphospholipid antibodies.

Thromb Res 2018 09 17;169:87-92. Epub 2018 Jul 17.

Normandie Univ, UNIROUEN, INSERM U1096, Rouen University Hospital, Vascular Hemostasis Unit, F 76000 Rouen, France. Electronic address:

Introduction: Circulating antiphospholipid antibodies (APL) induce vascular injury and endothelial dysfunction, which are associated with thrombotic events and/or fetal loss. We developed a model in which calibrated automated thrombin generation (CAT) is carried out in wells lined with cultured endothelial cells. Then we investigated how far b2GP1 antibodies provoked thrombin generation (TG) enhancing effects in these cells and/or in blood platelets.

Materials And Methods: Thrombin generation induced by different concentrations of tissue factor and different levels of endothelial aortic cell confluence was investigated by calibrated automated thrombogram. Endothelial cells were incubated with the purified anti-β2glycoprotein I antibodies of patients with antiphospholipid syndrome (APS). Platelet free plasma and platelet rich plasma were used to study thrombin generation in endothelial cells and platelet reactivity, respectively.

Results: Endothelial cell confluence was negatively correlated with thrombin generation which was dependent on the concentration of APL incubated. Activation of endothelial cells with APL significantly increased thrombin generation triggered by PFP. Triggering by PRP increased thrombinogram parameters. Moreover, anti-β2glycoprotein I antibodies incubated with platelet significantly amplified thrombin formation in PRP and induced platelet activation without tissue factor.

Conclusion: In this in vitro study, we demonstrate the feasibility of using thrombin generation test in cultured endothelial cells and suggest the need to realize adjustments to standardize results. The mechanism of prothrombotic states in APS requires endothelial dysfunction and platelet activation. The quantification of thrombin formation shows that APL incubation induces endothelial injury in cultured cells amplified by platelets.
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http://dx.doi.org/10.1016/j.thromres.2018.07.021DOI Listing
September 2018

[Cancer and venous thromboembolism recurrence: The keys for an optimal management].

Bull Cancer 2018 May 12;105(5):508-516. Epub 2018 Mar 12.

AP-HP, université Paris 7, hôpital Louis-Mourier, service de médecine interne, 178, rue des Renouillers, 92700 Colombes, France.

Low-molecular-weight heparins (LMWH) are to date the standard for 3-to-6-month treatment of cancer-associated thrombosis (CAT) as they are consistently recommended by international clinical practice guidelines. Despite the high risk of VTE recurrence and death in patients with cancer and the favorable benefit-risk profile of LMWH demonstrated in randomized-control studies, the implementation of treatment guidelines remains insufficient in the clinical practice. A systematic review of observational studies, registries and surveys reveals that approximately only 50% of patients with CAT are treated according to practice guidelines while both physicians and patients may be accountable for this situation. Based on the few available published data, we have observed differences between guidelines and clinical practice and we have identified factors influencing patient's management with the perspective to improve adherence to clinical practice guidelines in patients with CAT. Improving the implementation of clinical practice guidelines requires a better knowledge of physician and patient-related factors that influence therapeutic decisions. A global approach of patients with CAT is warranted to optimize the therapeutic management of cancer-associated VTE.
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http://dx.doi.org/10.1016/j.bulcan.2017.12.006DOI Listing
May 2018

Direct oral anticoagulant use in patients with thrombophilia, antiphospholipid syndrome or venous thrombosis of unusual sites: A narrative review.

Blood Rev 2018 07 20;32(4):272-279. Epub 2018 Apr 20.

University of Occidentale Brittany, EA 3878 GETBO, Brest, France; Department of Internal Medicine and Pneumology, Hospital de la Cavale Blanche, Brest, France.

Direct oral anticoagulants (DOACs) are indicated in the treatment and prevention of venous thromboembolism (VTE). However, the use of DOACs in unusual VTE, including cerebral venous thrombosis (CVT) and splanchnic venous thrombosis (SVT), and in patients with biological thrombophilia including minor thrombophilia (Factor V Leiden and prothrombin G20210A), major innate thrombophilia (protein C and S deficiency, and antithrombin) and major acquired thrombophilia (antiphospholipid syndrome [APS]), remains controversial due to the paucity of available data. There are some reports of DOACs use in the initial treatment or long-term maintenance of patients with either CVT or SVT, but their efficacy remains unclear. The efficacy of DOACs may be suitable in patients with biological minor or major thrombophilia. The use of DOACs for the long-term maintenance of patients with APS is more contentious. Randomized clinical trials, which are currently underway, should offer definitive insight into the efficacy and safety profiles of DOACs in these patient populations.
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http://dx.doi.org/10.1016/j.blre.2018.01.002DOI Listing
July 2018

Dosing issues with non-vitamin K antagonist oral anticoagulants for the treatment of non-valvular atrial fibrillation: Why we should not underdose our patients.

Arch Cardiovasc Dis 2018 Feb 2;111(2):85-94. Epub 2017 Oct 2.

Department of cardiology, Henri Mondor hospital, AP-HP, Créteil, France.

Non-vitamin K antagonist oral anticoagulants (NOACs) - dabigatran, rivaroxaban, apixaban and edoxaban - are well established in terms of preventing stroke or systemic embolism in patients with non-valvular atrial fibrillation and high thromboembolism risk. When prescribed incorrectly, NOACs are associated with an increased risk of ischaemic events and bleeding. Current NOAC labels explicitly address dose adjustments according to age, body weight, renal function and concomitant treatment with P-glycoprotein inhibitors. The required dose adjustments vary significantly from molecule to molecule, thereby creating a complex dose adjustment environment. Furthermore, recommendations support assessment of individual risk using thromboembolic and bleeding risk scores. Evidence-based medicine also provides data about specific patient profiles. In particular, some patients who are at higher risk of bleeding, such as patients on polymedication, are often at higher risk of stroke. More and more patients are being treated with NOACs. The question of appropriate dosing has become important, as studies are starting to show that reduced doses are being prescribed at very high rates. Although these data have not been evaluated in light of individual risk assessments, in everyday practice, physicians are often more concerned about drug-related bleeding than about the spontaneous evolution of the disease (stroke/systemic embolism), leading to high rates of prescription of inadequately low doses. Recent results have shown that only certain risk criteria justify dose reduction. Thus, the right dose needs to be prescribed for the right patient in order to obtain, in real-life practice, the benefits of NOACs that have been demonstrated in randomized clinical trials.
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http://dx.doi.org/10.1016/j.acvd.2017.04.008DOI Listing
February 2018
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