Publications by authors named "Dominique Desprez"

23 Publications

  • Page 1 of 1

Use of recombinant Von Willebrand factor during transcatheter aortic valve replacement in a patient with acquired von Willebrand syndrome.

Transfus Med 2021 Apr 24;31(2):142-144. Epub 2021 Feb 24.

Centre de Ressource et Compétence des Maladies Hémorragiques Constitutionnelles, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

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http://dx.doi.org/10.1111/tme.12765DOI Listing
April 2021

Efficacy and safety of a recombinant Von Willebrand Factor treatment in patients with inherited Von Willebrand Disease requiring surgical procedures.

Haemophilia 2021 Mar 6;27(2):270-276. Epub 2021 Feb 6.

Department of Haemostasis, Versailles Hospital, Versailles, France.

Introduction: Von Willebrand Disease is a common inherited haemorrhagic disorder due to a deficiency of Von Willebrand Factor (VWF). In case of surgical procedures in patients who are not responsive or have contraindications to desmopressin, replacement therapy with VWF concentrates is indicated. Until recently, only plasma-derived VWF concentrates were available. A new recombinant VWF (rVWF) concentrate that contains no Factor VIII (FVIII) but a high amount of high molecular weight VWF multimers has been available in France since 2018.

Aim: Describe real-world experience of using rVWF in surgical procedures.

Methods: Sixty-three surgeries for 55 patients were retrospectively analysed in 7 French haemostasis centres.

Results: During minor surgeries, the median (range) number of infusions was 1 (1-8) with a preoperative loading dose of 35 (19-56) rVWF IU/kg and a total median dose of 37.5 IU (12-288). During major surgeries, the median (range) number of infusions was only 3 (1-14) with a median preoperative loading dose of 36 IU (12-51) rVWF IU/kg, and a total median dose of 108 IU (22-340) rVWF IU/kg. The overall clinical efficacy was qualified as excellent/good in 61 of the procedures (97%), moderate in 1 (1.5%) and poor in 1 (1.5%). There was no accumulation of VWF or FVIII during postoperative monitoring. No thromboembolic events, anti-VWF antibodies or adverse events were reported.

Conclusion: This French 'real-world' experience shows that a few infusions and low doses of rVWF provided effective prevention of bleeding in major and minor surgeries in inherited VWD, with no clinically significant safety concerns.
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http://dx.doi.org/10.1111/hae.14242DOI Listing
March 2021

Effectiveness and safety of hFVIII/VWF concentrate (Voncento) in patients with inherited von Willebrand disease requiring surgical procedures: the OPALE multicentre observational study.

Blood Transfus 2021 Mar 27;19(2):152-157. Epub 2020 Nov 27.

Centre de Traitement de l'Hémophilie, CHU Hôtel-Dieu Nantes, Nantes, France.

Background: In patients with moderate to severe qualitative and quantitative von Willebrand disease (VWD), even minor surgical procedures can be associated with a risk of life-threatening bleeding. Treatment strategies vary according to the levels of von Willebrand factor (VWF) and Factor VIII (FVIII). The aim of this study was to evaluate the effectiveness and the safety of Voncento (CSL Behring, Marburg, Germany), a plasma-derived FVIII/VWF concentrate (ratio 1:2.4), during surgeries performed in patients with inherited VWD.

Materials And Methods: The OPALE study, a French multicentre observational study, was carried out from May 2016 to May 2019. It evaluated and analysed patients with inherited VWD (any type) requiring treatment with Voncento who underwent surgery.

Results: In total, 92 patients were enrolled, and 66 patients underwent 100 surgical procedures: 69 minor and 31 major surgeries conducted in 30 patients with type 1, 50 patients with type 2, and 20 patients with type 3 VWD. During minor surgeries, the median number of infusions was one (range: 1-9), the pre-operative loading dose was 41 IU VWF:RCo kg (range: 18-147), and the total dose was 63 (range: 18-594). During major surgeries, the number of infusions was 4 (range: 1-23), the pre-operative loading dose was 43 (range: 25-66) IU VWF: RCo kg, and the total dose was 155 (range: 40-575). The median FVIII:C levels ranged from 78 to 165 IU dL during 5 days after minor surgeries and from 86 and 167 IU dL during 11 days after major surgeries. VW:RCo levels ranged between 35 and 65 IU dL and between 34 and 76 IU dL after minor and major surgeries, respectively. The overall clinical effectiveness was qualified as "excellent" or "good" in 99% of patients. No thrombotic events related to Voncento were recorded.

Discussion: The present study suggests that Voncento is an effective and well-tolerated therapy for the peri-operative management of patients with all VWD types.
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http://dx.doi.org/10.2450/2020.0246-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925218PMC
March 2021

Gastrointestinal bleeding from angiodysplasia in von Willebrand disease: Improved diagnosis and outcome prediction using videocapsule on top of conventional endoscopy.

J Thromb Haemost 2021 02 29;19(2):380-386. Epub 2020 Nov 29.

Department of Hematology and Transfusion, CHU Lille, Institut d'Hématologie Transfusion, Lille, France.

Background: Despite a high prevalence of angiodysplasia, no specific guidelines are available for the modalities of endoscopic exploration of gastrointestinal (GI) bleeding in von Willebrand disease (VWD). Whether VWD patients could benefit from video capsule endoscopy (VCE) looking for angiodysplasia eligible to endoscopic treatment or at high risk of bleeding is unknown.

Objectives: To assess the diagnostic efficacy for angiodysplasia and the prognostic value of VCE on top of conventional endoscopy in VWD patients with GI bleeding.

Patients/methods: A survey was sent to the 30 centers of the French-network on inherited bleeding disorders to identify VWD patients referred for endoscopic exploration of GI bleeding from January 2015 to December 2017. Data obtained included patient characteristics, VWD phenotype/genotype, GI bleeding pattern, results of endoscopic investigations, and medical management applied including endoscopic therapy. We assessed by Kaplan-Meier analysis the recurrence-free survival after the first GI bleeding event according to endoscopic categorization and, in patients with angiodysplasia, to the presence of small-bowel localizations on VCE exploration.

Results: GI bleeding source localization was significantly improved when including VCE exploration (P < .01), even in patients without history of angiodysplasia (P < .05). Patients with angiodysplasia had more GI bleeding recurrences (P < .01). A lower recurrence-free survival was observed in patients with angiodysplasia (log-rank test, P = .02), and especially when lesions were located in the small bowel (log-rank test, P < .01), even after endoscopic treatment with argon plasma coagulation (log-rank test, P < .01).

Conclusion: VCE should be more systematically used in VWD patients with unexplained or recurrent GI bleeding looking for angiodysplasia eligible to endoscopic treatment or at high risk of relapse.
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http://dx.doi.org/10.1111/jth.15155DOI Listing
February 2021

COVID-19 in a pediatric patient with Glanzmann thrombasthenia.

Pediatr Blood Cancer 2020 10 15;67(10):e28662. Epub 2020 Aug 15.

Centre de Ressource et Compétence des Maladies Hémorragiques Constitutionnelles, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

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http://dx.doi.org/10.1002/pbc.28662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460953PMC
October 2020

Management of von Willebrand disease with a factor VIII-poor von Willebrand factor concentrate: Results from a prospective observational post-marketing study.

J Thromb Haemost 2020 08 25;18(8):1922-1933. Epub 2020 Jun 25.

Hemophilia Treatment Centre, University Hospital of Caen, Caen, France.

Background: A triple-secured plasma-derived von Willebrand factor (pdVWF) almost devoid of factor VIII (FVIII):WILFACTIN , was approved in France in 2003, and then in other countries for the treatment of patients with von Willebrand disease (VWD).

Objective: To investigate long-term safety and efficacy of the product in real-life over the first 5 post-approval years.

Patients/methods: This prospective, observational, national post-marketing study (PMS) enrolled patients of all ages and VWD types. Patients were observed for up to 3 years and treated for one or more occasions. Efficacy was assessed for each major event. Breakthrough bleeding rate 3 days post-infusion and annualized bleeding rate (ABR) were also evaluated for long-term prophylaxis.

Results: Overall, 155 of 174 patients enrolled from 31 centers were eligible for efficacy assessment. Most patients (76.8%) were severely affected (VWF:RCo ≤ 15 IU/dL). They were treated for 743 bleeds and 140 surgeries including childbirth. Efficacy outcomes were excellent/good for 98.2% of 56 major surgeries and 94.0% of 67 major bleeds. Approximately 75% of 49 major mucosal bleeds were effectively managed without FVIII co-administration. In 32 patients receiving prophylaxis, breakthrough bleeding occurred in 1.5% of infusions and median ABR was 1.0 for 20 patients treated ≥ 12 months. Excellent tolerability was confirmed with no safety concerns. No thrombotic events were observed.

Conclusions: Results from this PMS increase the clinical experience of a FVIII-poor pdVWF in patients of all ages and VWD types including those with thrombotic risk factors and emphasize that giving FVIII is not always mandatory to effectively treat patients with severe VWD.
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http://dx.doi.org/10.1111/jth.14928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496521PMC
August 2020

Gynecological and obstetric outcome in the French cohort of women with factor XIII deficiency.

Thromb Res 2020 07 21;191:22-25. Epub 2020 Apr 21.

Hospices Civils de Lyon, Unité Hémostase Clinique, Hôpital Louis Pradel, Hospices Civils de Lyon, Bron, France.

Introduction: Congenital factor XIII deficiency is a very rare bleeding disorder affecting 33 patients in France. Besides its role in fibrin clot stabilization, factor XIII is involved in placental attachment. Fetal miscarriages represent a frequent and concerning issue for these patients. The aim of the present study was to describe clinical characteristics of women presenting severe congenital FXIII deficiency in France, to focus on gynecological and obstetrical events, and to report the management of these rare situations.

Methods: We conducted a retrospective study in the French Hemophilia Comprehensive Care and Clinical Hemostasis Centers. Women between 15 and 65 years with factor XIII activity <10 IU dL were included. Biological, clinical and therapeutic events that occurred to these patients during their gynecological and obstetrical period were recorded.

Results: Among 31 centers, eleven patients were included. The median age at diagnosis was 1.5 years (range: 0-35), and at inclusion it was 30 years (range: 15-63). Fetal miscarriage was the primary manifestations in 2 (18%) patients, the remaining were diagnosed during hemorrhage. Menorrhagias were reported by 2 women (27%), 13 pregnancies were reported by 9 women including one abortion. Every pregnancy was conducted under factor XIII substitution, no hemorrhagic episode was reported. Four patients (36%) experienced at least one fetal miscarriage with a total amount of 30 miscarriages with 6 occurring during substitution.

Conclusion: Altogether, our data confirmed the high incidence of miscarriage in women with factor XIII deficiency. Good outcome of pregnancies required prophylaxis in accordance with international guidelines.
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http://dx.doi.org/10.1016/j.thromres.2020.04.010DOI Listing
July 2020

Real Life Population Pharmacokinetics Modelling of Eight Factors VIII in Patients with Severe Haemophilia A: Is It Always Relevant to Switch to an Extended Half-Life?

Pharmaceutics 2020 Apr 21;12(4). Epub 2020 Apr 21.

Department of Medical Pharmacology, University Hospital of Reims, EA3801, SFR Cap-Santé, University of Reims, 51100 Reims, France.

We retrospectively analysed the data files of 171 adults and 87 children/adolescents with severe haemophilia, except for 14 patients (moderate; minor) (1), to develop a global population pharmacokinetic (PK) model for eight factors VIII (FVIII) that could estimate individual PK parameters for targeting the desired level of FVIII activity (FVIII:C); and (2) to compare half-life (HL) in patients switching from a standard half-life (SHL) to an extended half-life (EHL) and evaluate the relevance of the switch. One-stage clotting assay for the measurement of FVIII activity (FVIII:C, IU/mL) was used for population PK modelling. The software, Monolix version 2019R1, was used for non-linear mixed-effects modelling. A linear two-compartment model best described FVIII:C. The estimated PK parameters (between-subject variability) were: 2640 mL (23.2%) for volume of central compartment (V1), 339 mL (46.8%) for volume of peripheral compartment (V2), 135 mL/h for Q (fixed random effect), and 204 mL/h (34.9%) for clearance (Cl). Weight, age, and categorical covariate EHL were found to influence Cl and only weight for V1. This model can be used for all of the FVIII cited in the study. Moreover, we demonstrated, in accordance with previous studies, that Elocta had longer half-life (EHL) than SHL (mean ratio: 1.48) as compared to Advate, Factane, Kogenate, Novoeight, and Refacto.
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http://dx.doi.org/10.3390/pharmaceutics12040380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238177PMC
April 2020

[Switching toward the use of recombinant factor VIII Fc fusion protein Study among 30 patients with severe hemophilia A].

Ann Biol Clin (Paris) 2020 02;78(1):35-46

Centre de ressource et de compétence, maladie hémorragique constitutionnelle, CHU Hautepierre, Strasbourg, France.

Only a few studies on real-world clinical use of recombinant factor VIII -fusionned with Fc (rFVIIIFc, efmoroctocog alpha) have been performed to date, with data on the annual bleeding rate (ABR), the prophylaxis regimen, and FVIII consumption. The aim of our study was to report the real-world clinical application of rFVIIIFc with additional elements, both biological and clinical. A prospective monocentric study has been conducted in the Haemophilia treatment center (HTC) of the Strasbourg university hospital among the severe haemophilia A patients. Thirty male patients were enrolled in the study. After injection of rFVIIIFc, the average time spent above 5%, 2% and 1% of FVIII was respectively almost 3, 4 and 5 days. The average half-life was 15.8 hours. A strong linear correlation between incremental recovery of rFVIIIFc and weight and between rFVIIIFc half-life and basal VWF:Ag level was observed. FVIII activity measurement for rFVIIIFc showed similar results than those previously published. In the follow-up, residual FVIII activity was on average the one of a mild haemophilia patient, corroborated by the results of endogenous thrombin potential of the thrombin generation assay. In clinical practice, rFVIIIFc was well tolerated and patients were mostly satisfied or indifferent of the switch. A single failure was however noticed. No FVIII inhibitor has been detected. Decrease in FVIII consumption was observed, with reduced or unchanged ABR. The switch was an actual success for almost all of the 30 patients, corroborated by satisfactory clinical and biological results.
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http://dx.doi.org/10.1684/abc.2020.1520DOI Listing
February 2020

Congenital factor XIII deficiency: comprehensive overview of the FranceCoag cohort.

Br J Haematol 2020 01 14;188(2):317-320. Epub 2019 Aug 14.

Hospices Civils de Lyon - Unite d'Hemostase Clinique, Hôpital Cardiologique Louis Pradel, Lyon, France.

This FranceCoag network study assessed 33 patients with congenital factor XIII (FXIII) deficiency presenting FXIII levels <10 iu/dl. Diagnosis was based on abnormal bleeding in 29 patients, a positive family history in 2, recurrent miscarriages in 1 and was fortuitous in 1. Eighteen patients (62·1%) presented life-threatening umbilical or intracranial haemorrhages (ICH). Seven of the 15 patients who experienced ICH were diagnosed but untreated, including 3 with secondary neurological sequelae. All pregnancies without prophylaxis (26/26) led to miscarriages versus 3/16 with prophylaxis. In patients exhibiting FXIII levels <10 iu/dl, prophylaxis could be discussed at diagnosis and at pregnancy. Further controlled prospective studies are needed.
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http://dx.doi.org/10.1111/bjh.16133DOI Listing
January 2020

Determinants of adherence and consequences of the transition from adolescence to adulthood among young people with severe haemophilia (TRANSHEMO): study protocol for a multicentric French national observational cross-sectional study.

BMJ Open 2018 07 25;8(7):e022409. Epub 2018 Jul 25.

Haemophilia Treatment Centre, Hospital Edouard Herriot, University Hospital of Lyon, Lyon, France.

Introduction: Severe haemophilia is a rare disease characterised by spontaneous bleeding from early childhood, which may lead to various complications, especially in joints. It is nowadays possible to avoid these complications thanks to substitutive therapies for which the issue of adherence is major. The transition from adolescence to adulthood in young people with severe haemophilia is a critical period as it is associated with a high risk of lack of adherence to healthcare, which might have serious consequences on daily activities and on quality of life.

Methods And Analysis: We present the protocol for a cross-sectional, observational, multicentric study to assess the differences between adolescents and young adults with severe haemophilia in France through the transition process, especially on adherence to healthcare. This study is based on a mixed methods design, with two complementary and consecutive phases, comparing data from a group of adolescents (aged 14-17 years) with those from a group of young adults (aged 20-29 years). The quantitative phase focuses on the determinants (medical, organisational, sociodemographic and social and psychosocial and behavioural factors) of adherence to healthcare (considered as a marker of the success of transition). The qualitative phase explores participants' views in more depth to explain and refine the results from the quantitative phase. Eligible patients are contacted by the various Haemophilia Treatment Centres participating in the French national registry FranceCoag.

Ethics And Dissemination: The study was approved by the French Ethics Committee and by the French National Agency for Medicines and Health Products Safety (number: 2016-A01034-47). Study findings will be disseminated to the scientific and medical community in peer-reviewed journals and presented at scientific meetings. Results will be popularised to be communicated via the French association for people with haemophilia to participants and to the general public.

Trial Registration Number: NCT02866526; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2018-022409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067371PMC
July 2018

Effects of transcutaneous aortic valve implantation on aortic valve disease-related hemostatic disorders involving von Willebrand factor.

Can J Cardiol 2015 Jun 24;31(6):738-43. Epub 2015 Jan 24.

Department of Cardiology, University Hospital of Strasbourg, Nouvel Hôpital Civil, Strasbourg, France.

Background: Aortic valve stenosis (AVS) can be complicated by bleeding associated with acquired type 2A von Willebrand syndrome. The association of AVS and gastrointestinal bleeding from angiodysplasia is defined as Heyde syndrome. We sought to evaluate the effect of transcutaneous aortic valve implantation (TAVI) on hemostasis disorders and to assess its effectiveness to treat Heyde syndrome.

Methods: We prospectively enrolled 49 consecutive patients with severe AVS addressed for TAVI at our institution. Biological hemostasis parameters involving von Willebrand factor (vWF) were assessed at baseline and 1 week after the procedure.

Results: At baseline, a significant link between vWF abnormalities and the severity of AVS was evidenced: mean aortic transvalvular gradient was negatively correlated with the levels of vWF antigen (vWF:Ag) (r = -0.29; P < 0.05), vWF ristocetin cofactor activity (r = -0.402; P = 0.006), and vWF collagen-binding activity (vWF:CB; r = -0.441; P = 0.005). One week after the procedure, a significant increase of vWF:Ag, vWF ristocetin cofactor activity, and vWF:CB was evidenced in the whole cohort (respectively, 3.32 vs. 2.29 IU/mL, P < 0.001; 2.98 vs. 1.86 IU/mL, P < 0.001; and 3.16 vs. 2.16 IU/mL, P < 0.001). Patients with pre-TAVI vWF abnormalities consistent with a type 2A vWF syndrome (ratio vWF:CB/vWF:Ag < 0.7) preferentially improved their vWF function with respect to patients with a normal ratio (relative increase of vWF:CB of 63.8% vs. 3.5%).

Conclusions: Hemostasis parameters involving vWF are improved after TAVI, especially in patients with pre-existing abnormalities consistent with acquired type 2A von Willebrand syndrome.
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http://dx.doi.org/10.1016/j.cjca.2015.01.012DOI Listing
June 2015

[Post-varicella cerebral thrombophlebitis with anti-protein S: report of a pediatric case].

Ann Biol Clin (Paris) 2012 Jan-Feb;70(1):99-103

Pôle de pédiatrie, Hôpital de Hautepierre, Strasbourg.

Purpura fulminans and venous thrombosis are rare complications of chickenpox. We report the case of a 6 year old with no history individuals who experienced cerebral thrombophlebitis, 3 weeks after varicella. MRI, performed at admission, has objectified longitudinal sinus thrombosis and a frontal parenchymal hematoma law. Meanwhile, a recent varicella seroconversion was demonstrated. The assessment of thrombophilia, meanwhile, has objectified a significant decrease in free protein S and activity, without associated DIC. Origin acquired this deficit was confirmed by the detection of antibodies (IgG and IgM) against the total protein S by ELISA. After evaluation of the benefit/risk only anticoagulation was initiated. The clinical and biological evolution was favorable, with rapid normalization of the S protein and decrease of anti-protein S. Many studies report the presence of anti-protein S in young children at the waning of chickenpox, without their exact frequency is determined. The decrease in protein S they cause leads to a transient hypercoagulable state may result in different clinical pictures. Cases of purpura fulminans seem more frequent when venous thrombosis isolated post chickenpox, sometimes atypical, appear rare.
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http://dx.doi.org/10.1684/abc.2011.0657DOI Listing
March 2012

[Anti-PF4 antibodies and thrombophlebitis in a child with cerebral venous thrombosis].

Ann Biol Clin (Paris) 2010 Nov-Dec;68(6):725-8

Laboratoire d'hématologie, Hôpital de Hautepierre, Strasbourg.

We report the case of a 13-year-old girl, with a cerebral venous thrombosis treated initially by heparin. In front of this early thrombocytopenia, in spite of the absence of preliminary treatment by heparin, the "heparin-dependent" anti-PF4 antibodies ELISA assay was realized and turned out to be strongly positive. In spite of the negativity of the specific functional tests, the heparinotherapy was substituted by a treatment by danaparoïd of sodium, allowing a clinico-biological improvement. Because of the low score of HIT imputability, we realized a specific antibodies anti-PF4 alone assay which was strongly positive. This specific positivity probably explains the positivity of the antibodies anti PF4 "heparin-dependent" assay. The originality of this case lies in the young age of the patient and in the probably pathogenic character of these unusual antibodies, in addition markers of an auto-immune disease.
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http://dx.doi.org/10.1684/abc.2010.0474DOI Listing
December 2011

Clinical characteristics and laboratory testing of patients with suspected HIT: a survey on current practice in 11 university hospitals in France.

Thromb Res 2010 Jun 23;125(6):e294-9. Epub 2010 Feb 23.

Laboratory of Hematology, Hôpital Cardiologique-Haut Lévêque, CHU Bordeaux, France.

Unlabelled: We undertook a survey of French university hospital hematological laboratories to ascertain the clinical characteristics of patients with suspected HIT, the laboratory tests performed, and the therapeutic strategy adopted in current practice.

Methods: A standardized medical records database for patients with suspected HIT was sent to 19 laboratories. During two months, all consecutive patients for whom a biological test was performed were included.

Results: 169 patients were included, 27 (16%) patients having a final diagnosis of HIT. At the time HIT was suspected, the heparin duration and the level of thrombocytopenia were similar in HIT- positive and HIT-negative groups. The use of unfractionated heparin, a therapeutic heparin dose regimen and the presence of thrombotic complications were significantly more frequent in HIT-positive patients. When the heparin dose regimen was taken into account, only thrombotic complications under a therapeutic dose regimen were significantly increased in HIT-positive patients. Eighty-six percent of patients presented at least one alternative diagnosis of thrombocytopenia without significant difference between the two groups. Laboratory tests were performed after a mean of 0.3days and mainly consisted of antigen assays. At the time HIT was suspected, heparin was stopped in 56 (33%) patients, being replaced mainly by danaparoid. Only three laboratories declared they usually received all the necessary clinical information to establish the likelihood of HIT.

Conclusion: In current practice in France, the clinical probability of HIT is rarely established, leading to systematic requests for laboratory HIT tests.
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http://dx.doi.org/10.1016/j.thromres.2010.02.003DOI Listing
June 2010

Procoagulant membrane microparticles correlate with the severity of pulmonary arterial hypertension.

Am J Respir Crit Care Med 2008 Mar 15;177(5):536-43. Epub 2007 Nov 15.

Hôpitaux Universitaires de Strasbourg, Fédération de Cardiologie, Strasbourg, France.

Rationale: Procoagulant microparticles constitute valuable hallmarks of cell damage. Microparticles also behave as cellular effectors.

Objectives: We hypothesized that the extent of the vascular cell damage measured by circulating microparticles could be related to the severity of pulmonary arterial hypertension (PAH).

Methods: Circulating biomarkers of vascular damage and cell activation were measured in blood samples from 20 patients with PAH. Samples were withdrawn from occluded pulmonary artery and jugular vein. Peripheral venous blood samples were obtained in 23 control subjects. The microparticle procoagulant abilities were quantified by functional prothrombinase and tissue factor assays and their cellular origin was determined.

Measurements And Main Results: Soluble vascular cellular adhesion molecule-1 and proinflammatory markers, such as monocyte chemoattractant protein-1 and highly specific C-reactive protein, were elevated in patients with PAH compared with control subjects. Microparticles bearing active tissue factor and CD105 (endoglin) were also elevated in patients with PAH compared with control subjects (29 +/- 13 vs. 16 +/- 6 fmol/L, P < 0.001, and 1.10 +/- 0.46 vs. 0.49 +/- 0.33 nmol/L phosphatidylserine equivalent, P < 0.001, respectively). A further increase in endothelium-derived CD105 microparticles was observed in pulmonary arterial blood compared with venous blood in patients with PAH (1.73 +/- 0.77, P = 0.038). Microparticles bearing active tissue factor were at a higher level in patients in functional class III and IV and who were walking fewer than 380 m with the six-minute-walk test.

Conclusions: Circulating markers of endothelium damage, proinflammatory markers, and cell stimulation estimated with circulating microparticles appear to be valuable tools in determining the severity of PAH.
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http://dx.doi.org/10.1164/rccm.200706-840OCDOI Listing
March 2008

Diagnostic and prognostic value of circulating D-Dimers in patients with acute aortic dissection.

Crit Care Med 2006 May;34(5):1358-64

Fédération of cardiologie, Service de chirurgie cardiaque, Hôpitaux Universitaires de Strasbourg, France.

Objective: We sought to determine whether assessing D-Dimer might be helpful for the management of acute aortic dissection (AAD).

Design: Single-center retrospective case-control study.

Setting: University Hospital of Strasbourg France.

Patients: Patients were 94 consecutive patients admitted to our institution with confirmed AAD and in whom D-Dimer test had been performed at presentation. These patients were matched with 94 controls presenting with clinical suspicion of dissection, which was later ruled out.

Interventions: Patient characteristics and clinical course were analyzed.

Measurements And Main Results: Ninety-three (99%) patients with AAD had elevated D-Dimer (>400 ng/mL) with a median D-Dimer value of 8610 ng/mL (interquartile range, 2982-20,000 ng/mL). Receiver operating characteristic curves analysis showed that D-Dimer, but not C-reactive protein, troponin, lactate dehydrogenase, or leukocyte count, was predictive of a diagnosis of AAD, with a sensitivity and specificity of 99% and 34%, respectively. D-Dimer concentration positively correlated with the anatomical extension of the dissection to the different segments of the aorta (R = .47, p < .0001). A positive relationship was observed between D-Dimer and in-hospital mortality rate among patients with AAD (p = .037). On multivariate analysis, the independent predictors of in-hospital mortality were the presence of pericardial effusion (odds ratio, 6.80; confidence interval, 1.87-27.60), D-Dimer >5200 ng/mL (odds ratio, 5.38; confidence interval, 1.27-30.87), and female gender (odds ratio, 4.96; confidence interval, 1.39-19.95).

Conclusions: D-Dimers are elevated in patients with AAD and provide valuable diagnostic and prognostic information. In patients with acute chest pain and elevated D-Dimer, a diagnosis of AAD should also be considered. D-Dimer might be a useful complementary tool to the current diagnostic work-up of patients with suspected AAD.
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http://dx.doi.org/10.1097/01.CCM.0000216686.72457.ECDOI Listing
May 2006

Circulating cell-derived microparticles in Crohn's disease.

Dig Dis Sci 2005 Mar;50(3):574-80

Service d'Hepato-Gastroentérologie, et d'Assistance Nutritive, Hôpital de Hautepierre, 67098 Strasbourg Cedex, France.

Procoagulant membrane microparticles can be released from activated or apoptotic cells in response to various environmental stimuli. The aim of this study was to investigate the presence of microparticles in Crohn's disease and to assess their variations after infliximab therapy. We compared the levels of circulating microparticles in 38 patients with Crohn's disease, 16 patients with ulcerative colitis, 7 patients with infectious colitis, and 17 control subjects. The evolution of microparticle levels was assessed after infliximab therapy in 13 patients with Crohn's disease. Circulating microparticle levels were elevated in patients with Crohn's disease (9.31+/-0.66 nmol/L phosphatidylserine equivalent [PS Eq]) or infectious colitis (10.71+/-0.92 nmol/L PS Eq) compared to patients with ulcerative colitis (5.75+/-0.59 nmol/L PS Eq) and control subjects (4.06+/-0.37 nmol/L PS Eq) (P = 0.001). Infliximab induced a significant diminution of the amounts of circulating microparticles, from 10.33+/-1.20 to 6.45+/-0.90 nmol/L PS Eq (P = 0.002). Generation of circulating microparticles occurs in Crohn's disease; infliximab induces significant diminution. Release of microparticles could be linked to the type of inflammatory response underlying Crohn's disease.
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http://dx.doi.org/10.1007/s10620-005-2477-0DOI Listing
March 2005

Circulating microparticles: a marker of procoagulant state in normal pregnancy and pregnancy complicated by preeclampsia or intrauterine growth restriction.

Thromb Haemost 2003 Mar;89(3):486-92

Service de Gynécologie-Obstétrique, Pr. B. Blanc, Centre Hospitalo'Universitaire de la Conception, Marseille, France.

In the present study, we explored the microparticles involved in the control of hemostatic equilibrium, i.e microparticles originating from platelet, endothelial cells and total MP defined as annexin V positive microparticles. Our aim was to analyze the level and procoagulant activity of these microparticles in normal pregnancy and pregnancies complicated with preeclampsia or isolated intrauterine growth restriction. We reported increased levels of platelet and endothelial microparticles in normal pregnancy compared to non pregnant healthy women. Number of annexin V microparticles was significantly increased together with their procoagulant activity. In pathological pregnancies, significant reduction in platelet microparticle number was found in preeclampsia. The procoagulant activity generated by the total annexin V MP was unchanged, suggesting that the microparticles remaining in the circulation were procoagulant. This study evidenced that microparticles constitute a cellular marker of a proinflammatory and procoagulant responses in normal pregnancy. In pregnancies with vascular complications, circulating MP with procoagulant potential may be part of the exacerbation of these responses.
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March 2003