Publications by authors named "Guillaume Mourey"

19 Publications

  • Page 1 of 1

Severe thrombophilia in a factor V-deficient patient homozygous for the Ala2086Asp mutation (FV Besançon).

J Thromb Haemost 2021 Feb 19. Epub 2021 Feb 19.

C2VN, INSERM, INRA, Aix Marseille University, Marseille, France.

Background: Coagulation factor V (FV), present in plasma and platelets, has both pro- and anticoagulant functions.

Objective: We investigated an FV-deficient patient (FV:C 3%, FV:Ag 4%) paradoxically presenting with recurrent venous thrombosis (11 events) instead of bleeding.

Methods/results: Thrombophilia screening revealed only heterozygosity for the F2 20210G>A mutation. Although thrombin generation in the patient's platelet-poor plasma was suggestive of a hypocoagulable state, thrombin generation in the patient's platelet-rich plasma (PRP) was higher than in control PRP and extremely resistant to activated protein C (APC). This was partially attributable to the complete abolition of the APC-cofactor activity of FV and a marked reduction of plasma tissue factor pathway inhibitor antigen and activity. The patient was homozygous for a novel missense mutation (Ala2086Asp, FV ) that favors a "closed conformation" of the C2 domain, predicting impaired binding of FV(a) to phospholipids. Recombinant FV was hardly secreted, indicating that this mutation is responsible for the patient's FV deficiency. Model system experiments performed using highly diluted plasma as a source of FV showed that, compared with normal FVa, FVa has slightly (≤1.5-fold) unfavorable kinetic parameters (K , V ) of prothrombin activation, but also a lower rate of APC-catalyzed inactivation in the presence of protein S.

Conclusions: FV induces a hypercoagulable state via quantitative (markedly decreased FV level) and qualitative (phospholipid-binding defect) effects that affect anticoagulant pathways (anticoagulant activities of FV, FVa inactivation, tissue factor pathway inhibitor α level) more strongly than the prothrombinase activity of FVa. A possible specific role of platelet FV cannot be excluded.
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http://dx.doi.org/10.1111/jth.15274DOI Listing
February 2021

Comparison of different activators of coagulation by turbidity analysis of hereditary dysfibrinogenemia and controls.

Blood Coagul Fibrinolysis 2021 03;32(2):108-114

Faculty of Medicine.

Turbidity analysis is widely used as a quantitative technique in hereditary dysfibrinogenemia. We aimed to compare several coagulation triggers in hereditary dysfibrinogenemia and control plasmas. We included 20 patients with hereditary dysfibrinogenemia, 19 with hotspot mutations Aα Arg35His (n = 9), Aα Arg35Cys (n = 2), γ Arg301His (n = 6), γ Arg301Cys (n = 2), and one with Aα Phe27Tyr, and a commercial pooled normal plasma. Fibrin polymerization was activated by bovine or human thrombin or tissue factor (TF), in the presence or absence of tissue type plasminogen activator. The lag time (min), slope (mOD/s), maximum absorbance (MaxAbs, mOD), and area under the curve (AUCp, OD s) were calculated from the fibrin polymerization curves and the time for 50% clot degradation (T50, min), AUCf (OD s) and the overall fibrinolytic potential from fibrinolysis curves. The lag time was significantly shorter and AUC increased in Aα Arg35His patients with bovine thrombin as compared with human thrombin. The MaxAbs and AUCp were significantly higher in γArg301His patients with bovine thrombin compared with human thrombin. Fibrin polymerization parameters of patients' samples were closer to those of control when assessed with TF compared with both human and bovine thrombin. T50 and overall fibrinolytic potential were similar in all samples regardless of the coagulation trigger used, however, with TF the AUCf of Aα Arg35His and γ Arg301His groups were significantly decreased compared with control. Bovine and human thrombin cannot be used equally for studying fibrin polymerization in hotspot hereditary dysfibrinogenemia or control plasmas.
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http://dx.doi.org/10.1097/MBC.0000000000001000DOI 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

Processing methods and storage duration impact extracellular vesicle counts in red blood cell units.

Blood Adv 2020 11;4(21):5527-5539

University Bourgogne Franche-Comté, INSERM, Etablissement Français du sang Bourgogne Franche Comté, Unité Mixte de Recherche 1098, Interactions Hôte-Greffon-Tumeur, Ingénierie Cellulaire et Génique, Besançon, France.

Extracellular vesicles (EVs) are active components of red blood cell (RBC) concentrates and may be associated with beneficial and adverse effects of transfusion. Elucidating controllable factors associated with EV release in RBC products is thus important to better manage the quality and properties of RBC units. Erythrocyte-derived EVs (EEVs) and platelet-derived EVs (PEVs) were counted in 1226 RBC units (administered to 280 patients) using a standardized cytometry-based method. EV size and CD47 and annexin V expression were also measured. The effects of donor characteristics, processing methods, and storage duration on EV counts were analyzed by using standard comparison tests, and analysis of covariance was used to determine factors independently associated with EV counts. PEV as well as EEV counts were higher in whole-blood-filtered RBC units compared with RBC-filtered units; PEV counts were associated with filter type (higher with filters associated with higher residual platelets), and CD47 expression was higher on EEVs in RBC units stored longer. Multivariate analysis showed that EEV counts were strongly associated with filter type (P < .0001), preparation, and storage time (+25.4 EEV/µL per day [P = .01] and +42.4 EEV/µL per day [P < .0001], respectively). The only independent factor associated with PEV counts was the residual platelet count in the unit (+67.1 PEV/µL; P < .0001). Overall, processing methods have an impact on EV counts and characteristics, leading to large variations in EV quantities transfused into patients. RBC unit processing methods might be standardized to control the EV content of RBC units if any impacts on patient outcomes can be confirmed. The IMIB (Impact of Microparticles in Blood) study is ancillary to the French ABLE (Age of Transfused Blood in Critically Ill Adults) trial (ISRCTN44878718).
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http://dx.doi.org/10.1182/bloodadvances.2020001658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656935PMC
November 2020

Assessment of shear-dependent kinetics of primary haemostasis with a microfluidic acoustic biosensor.

IEEE Trans Biomed Eng 2020 Oct 15;PP. Epub 2020 Oct 15.

Primary haemostasis is a complex dynamic process, which involves in-flow interactions between platelets and sub-endothelial matrix at the area of the damaged vessel wall. It results in a first haemostatic plug, which stops bleeding, before coagulation ensues and consolidates it. The diagnosis of primary haemostasis defect would benefit from evaluation of the whole sequence of mechanisms involved in platelet plug formation. This work proposes a new approach that is based on characterization of the shear-dependent kinetics that enables the evaluation of the early stages of primary haemostasis. We used a label-free method with a quartz crystal microbalance (QCM) biosensor to measure the platelet deposits over time onto covalently immobilized type I fibrillar collagen. We defined three metrics: total frequency shift, lag time, and growth rate. The measurement was completed at four predefined shear rates prevailing in small vessels (500, 770, 1000 and 1500s-1) during five minutes of perfusion with anticoagulated normal whole blood. The rate of the frequency shift over the first five minutes was strongly influenced by shear rate conditions, presenting a maximum around 770s-1, and varying by a factor larger than three in the studied shear rate range. To validate the biosensor signal, the total frequency shift was compared to results obtained by atomic force microscopy (AFM) on final platelet deposits. The results show that shear-dependent kinetics assays is promising as an advanced method for screening of primary haemostasis.
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http://dx.doi.org/10.1109/TBME.2020.3031542DOI Listing
October 2020

Elevated D-dimers and lack of anticoagulation predict PE in severe COVID-19 patients.

Eur Respir J 2020 10 22;56(4). Epub 2020 Oct 22.

Dept of Cardiology, University Hospital, Besançon, France.

Background: Coronavirus disease 2019 (COVID-19) may predispose to venous thromboembolism. We determined factors independently associated with computed tomography pulmonary angiography (CTPA)-confirmed pulmonary embolism (PE) in hospitalised severe COVID-19 patients.

Methods: Among all (n=349) patients hospitalised for COVID-19 in a university hospital in a French region with a high rate of COVID-19, we analysed patients who underwent CTPA for clinical signs of severe disease (oxygen saturation measured by pulse oximetry ≤93% or breathing rate ≥30 breaths·min) or rapid clinical worsening. Multivariable analysis was performed using Firth penalised maximum likelihood estimates.

Results: 162 (46.4%) patients underwent CTPA (mean±sd age 65.6±13.0 years; 67.3% male (95% CI 59.5-75.5%). PE was diagnosed in 44 (27.2%) patients. Most PEs were segmental and the rate of PE-related right ventricular dysfunction was 15.9%. By multivariable analysis, the only two significant predictors of CTPA-confirmed PE were D-dimer level and the lack of any anticoagulant therapy (OR 4.0 (95% CI 2.4-6.7) per additional quartile and OR 4.5 (95% CI 1.1-7.4), respectively). Receiver operating characteristic curve analysis identified a D-dimer cut-off value of 2590 ng·mL to best predict occurrence of PE (area under the curve 0.88, p<0.001, sensitivity 83.3%, specificity 83.8%). D-dimer level >2590 ng·mL was associated with a 17-fold increase in the adjusted risk of PE.

Conclusion: Elevated D-dimers (>2590 ng·mL) and absence of anticoagulant therapy predict PE in hospitalised COVID-19 patients with clinical signs of severity. These data strengthen the evidence base in favour of systematic anticoagulation, and suggest wider use of D-dimer guided CTPA to screen for PE in acutely ill hospitalised patients with COVID-19.
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http://dx.doi.org/10.1183/13993003.01811-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487272PMC
October 2020

Antiplatelet Antibodies Do Not Predict the Response to Intravenous Immunoglobulins during Immune Thrombocytopenia.

J Clin Med 2020 Jun 25;9(6). Epub 2020 Jun 25.

Service de Médecine Interne et Immunologie Clinique, Centre de Référence Constitutif des Cytopénies Auto-immunes de l'adulte, Centre Hospitalo-Universitaire Dijon Bourgogne, Université de Bourgogne Franche Comté, 21000 Dijon, France.

Immune thrombocytopenia (ITP) is a rare autoimmune disease due to autoantibodies targeting platelet glycoproteins (GP). The mechanism of platelet destruction could differ depending on the specificity of antiplatelet antibodies: anti-GPIIb/IIIa antibodies lead to phagocytosis by splenic macrophages, in a Fcγ receptor (FcγR)-dependent manner while anti-GPIb/IX antibodies induce platelet desialylation leading to their destruction by hepatocytes after binding to the Ashwell-Morell receptor, in a FcγR-independent manner. Considering the FcγR-dependent mechanism of action of intravenous immunoglobulins (IVIg), we assumed that the response to IVIg could be less efficient in the presence of anti-GPIb/IX antibodies. We conducted a multicentric, retrospective study including all adult ITP patients treated with IVIg who had antiplatelet antibodies detected between January 2013 and October 2017. Among the 609 identified, 69 patients were included: 17 had anti-GPIb/IX antibodies and 33 had anti-GPIIb/IIIa antibodies. The response to IVIg was not different between the patients with or without anti-GPIb/IX (88.2% vs. 73.1%). The response to IVIg was better in the case of newly diagnosed ITP (odds ratio (OR) = 5.4 (1.2-24.7)) and in presence of anti-GPIIb/IIIa (OR = 4.82 (1.08-21.5)), while secondary ITP had a poor response (OR = 0.1 (0.02-0.64)). In clinical practice, the determination of antiplatelet antibodies is therefore of little value to predict the response to IVIg.
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http://dx.doi.org/10.3390/jcm9061998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357034PMC
June 2020

Identification and expression of a novel heterozygous frameshift mutation in FGA accounting for congenital hypofibrinogenemia in carriers of severe hemophilia A.

Thromb Res 2020 09 28;193:5-8. Epub 2020 May 28.

Department of Genetic Medicine and Development, University of Geneva Faculty of Medicine, Switzerland; iGE3, Institute of Genetics and Genomics in Geneva, Geneva, Switzerland. Electronic address:

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http://dx.doi.org/10.1016/j.thromres.2020.05.040DOI Listing
September 2020

In vitro quality of amotosalen-UVA pathogen-inactivated mini-pool plasma prepared from whole blood stored overnight.

Vox Sang 2018 Oct 6;113(7):622-631. Epub 2018 Aug 6.

Université de Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, FMTS, Strasbourg, France.

Background And Objectives: Small batch-pooled (mini-pool) whole blood (WB)-derived plasma could be an alternative cost-effective source of therapeutic plasma (TP), but carries an increased risk of transfusion-transmitted infection due to exposure of the recipient to several donors. This risk can be mitigated by inactivation of pathogens susceptible to the amotosalen-UVA (AUVA)-treatment. We evaluated the conservation of coagulation factors in AUVA-plasma prepared from WB stored overnight under routine operating conditions, to determine its therapeutic efficacy. Thrombin generation (TG) by the AUVA-plasma was used to provide an integrated measure of the hemostatic capacity.

Materials And Methods: WB-donations (~450 ml) stored overnight were processed to prepare five leucocyte-depleted plasma mini-pools (1300 ml), which were divided into two parts and treated with AUVA. Each mini-pool yielded six AUVA-plasma units (200 ml) which were frozen (-25°C) within 19 h of WB-collection. Their hemostatic quality was evaluated before and after treatment for up to 12 months of storage.

Results: Immediately after AUVA-treatment, the regulatory criteria for FVIII activity and fibrinogen content were met. As compared to untreated plasma there was a reduction in fibrinogen (14%), FV (9%), FVII (25%) and FVIII (32%). However, TG was similar in treated and untreated plasma at all-time-points.

Conclusions: Frozen WB-derived AUVA-plasma prepared from mini-pools within 19 h of WB-collection met the quality standards required for TP and retained hemostatic capacity for up to 12 months. This product could provide a cost-effective convenient substitute for apheresis plasma.
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http://dx.doi.org/10.1111/vox.12697DOI Listing
October 2018

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.

CERESS, Aix Marseille University, Marseille, 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

Circulating levels of 3-hydroxymyristate, a direct quantification of endotoxaemia in noninfected cirrhotic patients.

Liver Int 2019 01 30;39(1):106-114. Epub 2018 Jul 30.

Service d'Hépatologie, CHU Jean Minjoz, Besançon, France.

Background & Aims: The quantification of lipopolysaccharide (LPS) in biological fluids is challenging. We aimed to measure plasma LPS concentration using a new method of direct quantification of 3-hydroxymyristate (3-HM), a lipid component of LPS, and to evaluate correlations between 3-HM and markers of liver function, endothelial activation, portal hypertension and enterocyte damage.

Methods: Plasma from 90 noninfected cirrhotic patients (30 Child-Pugh [CP]-A, 30 CP-B, 30 CP-C) was prospectively collected. The concentration of 3-HM was determined by high-performance liquid chromatography coupled with mass spectrometry.

Results: 3-HM levels were higher in CP-C patients (CP-A/CP-B/CP-C: 68/70/103 ng/mL, P = 0.005). Patients with severe acute alcoholic hepatitis (n = 16; 113 vs 74 ng/mL, P = 0.012), diabetic patients (n = 22; 99 vs 70 ng/mL, P = 0.028) and those not receiving beta blockers (n = 44; 98 vs 72 ng/mL, P = 0.034) had higher levels of 3-HM. We observed a trend towards higher baseline levels of 3-HM in patients with hepatic encephalopathy (n = 7; 144 vs 76 ng/mL, P = 0.45) or SIRS (n = 10; 106 vs 75 ng/mL, P = 0.114). In multivariate analysis, high levels of 3-HM were associated with CP (OR = 4.39; 95%CI = 1.79-10.76) or MELD (OR = 8.24; 95%CI = 3.19-21.32) scores. Patients dying from liver insufficiency (n = 6) during a 12-month follow-up had higher baseline levels of 3-HM (106 vs 75 ng/mL, P = 0.089).

Conclusions: In noninfected cirrhotic patients, 3-HM arises more frequently with impairment of liver function, heavy alcohol consumption, diabetic status, nonuse of beta blockers and a trend towards poorer outcome is also observed. The direct mass measurement of LPS using 3-HM appears reliable to detect transient endotoxaemia and promising to manage the follow-up of cirrhotic patients.
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http://dx.doi.org/10.1111/liv.13916DOI Listing
January 2019

Increased levels of circulating platelet-derived microparticles are associated with metastatic cutaneous melanoma.

Exp Dermatol 2017 10 9;26(10):961-963. Epub 2017 May 9.

INSERM UMR 1098, University of Bourgogne Franche Comté, Besançon, France.

We investigated the plasma levels of PMPs in patients with 45 stage III and 45 stage IV melanoma. PMPs were characterised by flow cytometry and their thrombogenic activity. We also investigated the link between PMPs circulating levels and tumor burden. The circulating levels of PMPs were significantly higher in stage IV (8500 μL ) than in patients with stage III (2041 μL ) melanoma (P=.0001). We calculated a highly specific (93.3%) and predictive (91.7%) cut-off value (5311 μL ) allowing the distinction between high-risk stage III and metastatic stage IV melanoma. The thrombogenic activity of PMPs was significantly higher in patients with stage IV melanoma (clotting time: 40.7 second vs 65 second, P=.0001). There was no significant association between the radiological tumoral syndrome and the plasma level of PMPs. Our data suggest the role of PMPs in metastatic progression of melanoma.
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http://dx.doi.org/10.1111/exd.13339DOI Listing
October 2017

How to quantify microparticles in RBCs? A validated flow cytometry method allows the detection of an increase in microparticles during storage.

Transfusion 2017 03 5;57(3):504-516. Epub 2017 Feb 5.

Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1098, Bourgogne Franche-Comté.

Background: The procoagulant and proinflammatory microparticles (MPs) released during storage of packed red blood cells (pRBCs) can potentially modify transfusion benefits. A robust method to quantify MPs in pRBCs is needed to evaluate their impact in clinical trials.

Study Design And Methods: The objective was to validate the preanalytic conditions required to prepare pRBC supernatant as well as a method to quantify and evaluate MP variations over 42 days of pRBC storage.A flow cytometry method with size-calibrated beads was developed and fully validated. Quantification of MPs in pRBCs (n = 109) was assessed during short-term (7 days) and long-term (42 days) storage at 4°C, during short-term storage (8 hours) at room temperature, and after 2 years frozen.

Results: Repeatability, reproducibility, and linearity of the quantification method were validated, and variations during conservation are presented. There was high variability in RBC (erythrocyte) MP (ERMP) and platelet MP (PMP) levels between RBC units, depending on the filter used for leukocyte reduction. During the 42 days of storage at 4°C, significant increases in ERMPs and PMPs occurred (from 58 to 138 ERMPs/µL from Day 2 to Day 42; p = 0.0002; and from 326 to 771 PMPs/µL from Day 2 to Day 42; p = 0.00026).

Conclusion: We use a robust method to confirm that ERMPs and PMPs are present to various degrees in pRBCs and that storage for 42 days significantly increases their generation. This method is robust enough to allow MP quantification in pRBCs and is adapted to evaluate the clinical impact of transfused MPs in prospective clinical trials.
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http://dx.doi.org/10.1111/trf.13989DOI Listing
March 2017

Development of a NanoBioAnalytical platform for "on-chip" qualification and quantification of platelet-derived microparticles.

Biosens Bioelectron 2017 Jul 29;93:250-259. Epub 2016 Aug 29.

FEMTO-ST Institute, UBFC, CNRS, ENSMM, UTBM, 15B Avenue des Montboucons, 25030 Besançon, France. Electronic address:

Blood microparticles (MPs) are small membrane vesicles (50-1000nm), derived from different cell types. They are known to play important roles in various biological processes and also recognized as potential biomarkers of various health disorders. Different methods are currently used for the detection and characterization of MPs, but none of these methods is capable to quantify and qualify total MPs at the same time, hence, there is a need to develop a new approach for simultaneous detection, characterization and quantification of microparticles. Here we show the potential of surface plasmon resonance (SPR) method coupled to atomic force microscopy (AFM) to quantify and qualify platelet-derived microparticles (PMPs), on the whole nano-to micro-meter scale. The different subpopulations of microparticles could be determined via their capture onto the surface using specific ligands. In order to verify the correlation between the capture level and the microparticles concentration in solution, two calibration standards were used: Virus-Like Particles (VLPs) and synthetic beads with a mean diameter of 53nm and 920nm respectively. The AFM analysis of the biochip surface allowed metrological analysis of captured PMPs and revealed that more than 95% of PMPs were smaller than 300nm. Our results suggest that our NanoBioAnalytical platform, combining SPR and AFM, is a suitable method for a sensitive, reproducible, label-free characterization and quantification of MPs over a wide concentration range (≈10 to 10 particles/mL; with a limit of detection (LOD) in the lowest ng/µL range) which matches with their typical concentrations in blood.
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http://dx.doi.org/10.1016/j.bios.2016.08.100DOI Listing
July 2017

The anti-inflammatory effects of platelet-derived microparticles in human plasmacytoid dendritic cells involve liver X receptor activation.

Haematologica 2016 Mar 3;101(3):e72-6. Epub 2015 Dec 3.

INSERM, UMR1098, Besançon EFS Bourgogne Franche-Comté, UMR1098, Besançon Université Bourgogne Franche-Comté, UMR1098, Besançon LabEX LipSTIC, ANR-11-LABX-0021, Besançon/Dijon CHRU Besançon, INSERM CIC1431, FHU INCREASE, France

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http://dx.doi.org/10.3324/haematol.2015.135459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4815731PMC
March 2016

Performance of two new automated assays for measuring von Willebrand activity: HemosIL AcuStar and Innovance.

Thromb Haemost 2014 Oct 7;112(4):825-30. Epub 2014 Aug 7.

Dr. Marc Trossaërt, Centre Régional de Traitement de l'Hémophilie, 1 Place Alexis RICORDEAU, Centre Hospitalier Universitaire, 44093 Nantes Cedex 1, France, Tel.: +33 2 40 08 74 68, Fax: +33 2 40 08 42 59, E-mail:

The ristocetin cofactor activity assay (VWF:RCo) is the reference method for assessing von Willebrand factor (VWF) activity but remains difficult to perform, and the coefficient of variation of the method is high (about 20-30%). This study evaluated and compared the performance for measuring the VWF activity of two newly commercialised assays [VWF:Ac Innovance (VWF:Ac) and VWF:RCo Acustar (VWF:RCo Acu)] with the reference VWF:RCo aggregation in 123 pathological plasma samples. The correlation and concordance between both new tests (VWF:RCo-Acu and VWF:Ac) and the reference VWF:RCo were good. The results of the VWF activity to VWF antigen ratio were also comparable whatever the method for the classification of VWF deficiency in all patients. Our results showed that both new tests could replace the "gold standard" VWF:RCo in aggregometry with several benefits: they are fully automated, easier and faster to perform, better adapted to emergency situations if necessary.
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http://dx.doi.org/10.1160/TH14-02-0108DOI Listing
October 2014

Increased levels of circulating microparticles are associated with increased procoagulant activity in patients with cutaneous malignant melanoma.

J Invest Dermatol 2014 Jan 28;134(1):176-182. Epub 2013 Jun 28.

Service de Dermatologie, Centre Hospitalier Universitaire Jean Minjoz, Besançon, France; Université de Franche Comté, EA3181, SFR FED4234, Besançon, France.

Microparticles (MPs) are known to be increased in various malignancies and are involved in tumor invasion, angiogenesis, coagulation, and metastasis. We investigated the plasma levels of annexin-V MPs (AV(+)MPs), platelet-derived MPs (PMPs), and endothelial-derived MPs (EMPs) in patients with melanoma (n=129) and in healthy controls (n=49). A functional coagulation test STA Procoag-PPL measuring the clotting time was performed on samples containing MPs to evaluate their procoagulant potential. The plasma levels of PMPs, EMPs, and AV(+)MPs were significantly higher, and the clotting time-PPL was significantly lower in melanoma patients than in healthy controls. The plasma levels of PMPs, EMPs, and AV(+)MPs were higher in stage IV than in the other stages of melanoma, but with no significant difference. In addition, we observed an inverse correlation between PMPs, AV(+)MPs, and clotting times. Our data suggest that MPs are involved in the progression of melanoma and may be associated to melanoma-associated thrombogenesis.
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http://dx.doi.org/10.1038/jid.2013.288DOI Listing
January 2014