Publications by authors named "Hubert Galinat"

22 Publications

  • Page 1 of 1

Vitamin K antagonist has a higher impact than heparin in preventing circuit clotting in chronic haemodialysis patients.

Clin Kidney J 2020 Aug 10;13(4):647-653. Epub 2019 Oct 10.

Haematology Laboratory, University Hospital La Cavale Blanche, Université de Bretagne Occidentale, Brest, France.

Background: In dialysis sessions, some data suggest that decreasing or even avoiding additional anticoagulation by heparin is possible among patients already treated with oral anticoagulation. However, the required dose of heparin may actually depend on the pre-dialysis international normalized ratio (INR), which varies from one session to another. The aim of our study was to determine the respective role of INR and heparin dosing in the risk of circuit clotting during chronic haemodialysis.

Methods: From early 2012 to July 2016, we analysed the totality of dialysis sessions performed at Brest University Hospital among haemodialysis patients treated by vitamin K antagonists (VKA). We established a prediction of circuit clotting on the basis of a simplified score obtained by combining INR and heparin dosing.

Results: In total, 7184 dialysis sessions among chronic haemodialysis patients under VKA were identified, including 233 with clotting events. The mean INR without clotting events was 2.5 versus 1.8 with clotting events (P). Frequencies of circuit clotting were different according to INR group (INR <2.0, INR 2.0-3.0, INR >3.0; P). The protective role of VKA was higher than heparin, as shown by discriminant factor analysis (P. Our study established a predictive model of thrombosis risk of dialysis circuits in patients treated by VKA for a given heparin dose and a given INR. This model shows a marginal contribution of heparin to protect against the risk of thrombosis compared with VKA. Moreover, heparin would not appear to be necessary for patients with an INR >2.2.
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http://dx.doi.org/10.1093/ckj/sfz131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467595PMC
August 2020

Physiological characteristics associated with increased resistance to decompression sickness in male and female rats.

J Appl Physiol (1985) 2020 09 23;129(3):612-625. Epub 2020 Jul 23.

University of Brest, ORPHY, IBSAM, Brest, France.

Decompression sickness (DCS) is a complex and poorly understood systemic disease with wide interindividual resistance variability. We selectively bred rats with a threefold greater resistance to DCS than standard ones. To investigate possible physiological mechanisms underlying the resistance to DCS, including sex-related differences in these mechanisms, 15 males and 15 females resistant to DCS were compared with aged-matched standard Wistar males ( = 15) and females ( = 15). None of these individuals had been previously exposed to hyperbaric treatment. Comparison of the allelic frequencies of single nucleotide polymorphisms (SNPs) showed a difference of one SNP located on the X chromosome. Compared with nonresistant rats, the neutrophil-to-lymphocyte ratio and the plasmatic activity of coagulation factor X were significantly higher in DCS-resistant individuals regardless of their sex. The maximal relaxation elicited by sodium nitroprusside was lower in DCS-resistant individuals regardless of their sex. Males but not females resistant to DCS exhibited higher neutrophil and lymphocyte counts and higher prothrombin time but lower mitochondrial basal O consumption and citrate synthase activity. Principal components analysis showed that two principal components discriminate the DCS-resistant males but not females from the nonresistant ones. These components were loaded with activated partial thromboplastin time, monocyte-to-lymphocyte ratio, prothrombin time, factor X, and fibrinogen for PC1 and red blood cells count and neutrophils count for PC2. In conclusion, the mechanisms that drive the resistance to DCS appear different between males and females; lower coagulation tendency and enhanced inflammatory response to decompression stress might be key for resistance in males. The involvement of these physiological adaptations in resistance to DCS must now be confirmed. By selective breeding of individuals resistant to decompression sickness (DCS) we previously obtained a rat model of inherited resistance to this pathology. Comparison of these individuals with nonresistant animals revealed differences in leukocyte counts, coagulation, and mitochondrial and vascular functions, but not resistance to oxidative stress. This study also reveals sex-related differences in the physiological changes associated with DCS resistance. A principal components analysis of our data allowed us to discriminate DCS-resistant males from standard ones, but not females. These differences represent possible mechanisms driving resistance to DCS. Although still far from the diver, this opens a pathway to future adaptation of personalized decompression procedures for "DCS-prone" individuals.
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http://dx.doi.org/10.1152/japplphysiol.00324.2020DOI Listing
September 2020

Antiphospholipid autoantibody detection is important in all patients with systemic autoimmune diseases.

J Autoimmun 2020 12 18;115:102524. Epub 2020 Jul 18.

Laboratory of Immunology and Immunotherapy, CHRU Morvan, Brest, France; UMR1227, Lymphocytes B et Autoimmunité, Université de Brest, INSERM, CHU de Brest, Brest, France. Electronic address:

Antiphospholipid (aPL) autoantibodies are uncommon in systemic autoimmune diseases (SADs). However, the European PRECISESADS study provides the opportunity to better characterize this rare association. The study was composed of 1818 patients with SADs including 453 with systemic lupus erythematosus (SLE), 359 with rheumatoid arthritis (RA), 385 with systemic sclerosis (SSc), 367 with Sjögren's syndrome (SjS), 94 with mixed connective tissue disease (MCTD), and 160 with undifferentiated connective tissue disease (UCTD). Assays used for aPL determination include the lupus anticoagulant (LAC) analysis using the dilute Russell's viper venom time (dRVVT) assay plus anti-cardiolipin (aCL) and anti-aβ2GPI autoantibodies of IgG and IgM isotype. Information regarding clinical and biological characteristics of SAD patients was available. Among SAD patients, the prevalence of aPL differs significantly between two groups: SLE (57.6%) and non-SLE SADs (13.7%, p < 10). Next, association between aPL plus thrombosis and miscarriage were observed in both SLE and non-SLE patients. Thrombosis was best predicted in SLE patients by dRVVT (OR = 6.1; IC95:3.5-10.3) and miscarriage by aCL±β2GPI IgG (OR = 2.5; IC95:1.2-5.2); while in non-SLE SADs the best predictors were aCL±β2GPI IgG for thrombosis (OR = 6.6; IC95:2.4-18.4) and aCL±β2GPI IgM for miscarriage (OR = 2.9; IC95:1.2-6.8). In the case of multiple positivity of aPL, the risk for thrombosis and miscarriage was increased. Central nervous system involvement characterized the SLE patients, in contrast to pulmonary and skin fibrosis, valve lesions, hypertension, elevated creatinemia, C4 fraction reduction, platelet reduction and inflammation that characterized the non-SLE SAD patients. Anti-PL determination remains important in SADs patients and should not be restricted to only SLE patients.
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http://dx.doi.org/10.1016/j.jaut.2020.102524DOI Listing
December 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

Factor VIII and IX assays for post-infusion monitoring in hemophilia patients: Guidelines from the French BIMHO group (GFHT).

Eur J Haematol 2020 Aug 27;105(2):103-115. Epub 2020 May 27.

Service d'Hématologie Hémostase, Hospices Civils de Lyon, Bron, France.

Replacement therapy with plasma-derived or recombinant FVIII and FIX (pdFVIII/pdFIX or rFVIII/rFIX) concentrates is the standard of treatment in patients with haemophilia A and B, respectively. Measurement of factor VIII (FVIII:C) or factor IX (FIX:C) levels can be done by one-stage clotting assay (OSA) or chromogenic substrate assay (CSA). The French study group on the Biology of Hemorrhagic Diseases (a collaborative group of the GFHT and MHEMO network) presents a literature review and proposals for the monitoring of FVIII:C and FIX:C levels in treated haemophilia A and B patients, respectively. The use of CSA is recommended for the monitoring of patients treated with pdFVIII or rFVIII including extended half-life (EHL) rFVIII. Except for rFVIII-Fc, great caution is required when measuring FVIII:C levels by OSA in patients substituted by EHL-rFVIII. The OSA is recommended for the monitoring of patients treated with pdFIX or rFIX. Large discordances in the FIX:C levels measured for extended half-life rFIX (EHL-rFIX), depending on the method and reagents used, must lead to great attention when OSA is used for measuring FIX:C levels in patients substituted by EHL-rFIX. Data of most of recent studies, obtained with spiked plasmas, deserve to be confirmed in plasma samples of treated patients.
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http://dx.doi.org/10.1111/ejh.13423DOI Listing
August 2020

Multicentre pharmacokinetic evaluation of rFVIII-Fc (efmoroctocog alfa) in a real life and comparison with non-extended half-life FVIII concentrates.

Haemophilia 2020 Mar 27;26(2):282-289. Epub 2020 Feb 27.

Laboratoire d'Hémostase Hémobiologie, CHU de Lille, Lille, France.

The use of enhanced half-life (EHL) FVIII has improved the quality of prophylaxis in haemophilia A, but with a benefit that may vary from one patient to another. We analysed the pharmacokinetic data obtained with efmoroctocog alfa (rFVIII-Fc) in 114 patients and, in 47 cases, compared them to those previously measured with non-EHL FVIII. The in vivo recovery (IVR) of rFVIII-Fc measured with one stage clotting assay (OSA) and chromogenic assay (CSA) was 2.2 and 2.8 IU/mL per IU/kg, respectively. The median half-life (T ) of rFVIII-Fc was 14.5 hours whatever the FVIII:C assay used, but variable and correlated with preinfusion VWF:Ag levels (r = .76). Both IVR and T were lower in patients under 12 years old (2.4 IU/mL per IU/kg and 11.1 hours, respectively; CSA). PK study of rFVIII-Fc vs non-EHL FVIII showed a T ratio of 1.4 in favour of rFVIII-Fc, regardless of the patient's age. However the relative increase in T with rFVIII-Fc was lower than 30% in one-third of patients evaluated, particularly when the previous FVIII administered was a BHK-derived product. This study therefore suggests that analysis of individual PK profile in response to a specific FVIII concentrate is potentially useful before a switch in haemophilia A patients.
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http://dx.doi.org/10.1111/hae.13946DOI Listing
March 2020

Detection of intrinsic pathway factor deficiency associated with bleeding risk by kaolin-based aPTT.

Int J Lab Hematol 2020 06 6;42(3):e107-e109. Epub 2020 Jan 6.

CHRU Brest, Service d'Hématologie Biologique, Brest, France.

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http://dx.doi.org/10.1111/ijlh.13149DOI Listing
June 2020

New considerations on pathways involved in acute traumatic coagulopathy: the thrombin generation paradox.

World J Emerg Surg 2019 12;14:57. Epub 2019 Dec 12.

1ORPHY Laboratory EA4324, Université de Bretagne Occidentale, Brest, France.

Abstract:

Background: An acute traumatic coagulopathy (ATC) is observed in about one third of severely traumatized patients. This early, specific, and endogenous disorder is triggered by the association of trauma and hemorrhage. The early phase of this condition is characterized by the expression of a bleeding phenotype leading to hemorrhagic shock and the late phase by a prothrombotic profile leading to multiple organ failure. The physiopathology of this phenomenon is still poorly understood. Hypotheses of disseminated intravascular coagulation, activated protein C-mediated fibrinolysis, fibrinogen consumption, and platelet functional impairment were developed by previous authors and continue to be debated. The objective of this study was to observe general hemostasis disorders in case of ATC to confront these hypotheses.

Method: Four groups of 15 rats were compared: C, control; T, trauma; H, hemorrhage; and TH, trauma and hemorrhage. Blood samples were drawn at baseline and 90 min. Thrombin generation tests, platelet aggregometry, and standard hemostasis tests were performed.

Results: Significant differences were observed between the baseline and TH groups for aPTT (17.9 ± 0.8 s vs 24.3 ± 1.4 s, < 0.001, mean ± SEM), MAP (79.7 ± 1.3 mmHg vs 43.8 ± 1.3 mmHg, < 0.001, mean ± SEM), and hemoglobin (16.5 ± 0.1 g/dL vs 14.1 ± 0.3 g/dL, < 0.001, mean ± SEM), indicating the presence of an hemorrhagic shock due to ATC. Compared to all other groups, coagulation factor activities were decreased in the TH group, but endogenous thrombin potential was (paradoxically) higher than in group C (312 ± 17 nM/min vs. 228 ± 23 nM/min; = 0.016; mean ± SEM). We also observed a subtle decrease in platelet count and function in case of ATC and retrieved an inversed linear relationship between fibrinogen concentration and aPTT (intercept, 26.53 ± 3.16; coefficient, - 3.40 ± 1.26; adjusted : 0.1878; = 0.0123).

Conclusions: The clinical-biological profile that we observed, combining normal thrombin generation, fibrinogen depletion, and a hemorrhagic phenotype, reinforced the hypothesis of activated protein C mediated-fibrinolysis. The key role of fibrinogen, but not of the platelets, was confirmed in this study. The paradoxical preservation of thrombin generation suggests a protective mechanism mediated by rhabdomyolysis in case of major trauma. Based on these results, we propose a new conception concerning the pathophysiology of ATC.
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http://dx.doi.org/10.1186/s13017-019-0276-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909491PMC
July 2020

A very potent factor V inhibitor interferes with the levels of all coagulation factors and causes a fatal hemorrhagic syndrome.

Eur J Haematol 2019 Aug 28;103(2):137-139. Epub 2019 May 28.

CHRU Brest - Laboratoire d'Hématologie, Brest, France.

We report a very high factor V inhibitor affecting the measurement of all coagulation factors besides fibrinogen, all these factors being dramatically decreased. This inhibitor could be linked to antibiotic use. The patient died of massive hemorrhage before a plasma exchange could be initiated.
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http://dx.doi.org/10.1111/ejh.13249DOI Listing
August 2019

[Factor VIII assays in treated hemophilia A patients].

Ann Biol Clin (Paris) 2019 02;77(1):53-65

CHU Lille, Institut d'hématologie-transfusion, Inserm U1011, Lille, France.

Replacement therapy with plasma-derived or recombinant FVIII (pdFVIII or rFVIII) concentrates is the standard of treatment in patients with hemophilia A. The reference method used for measuring factor VIII (FVIII:C) levels in patients treated by FVIII concentrates is the chromogenic substrate assay (CSA). However, the one-stage clotting assay (OSA) is predominantly used in current clinical practice, but this method depends on the activated partial thromboplastin time (APTT) reagent and the coagulation analyzer used, and wide variations in the measurements of FVIII recovery have been reported with some factor concentrates. The French study group on the biology of hemorrhagic diseases (a collaborative group of the GFHT and MHEMO network) presents a review of the literature and proposals for the monitoring of FVIII:C levels in treated hemophilia A patients. The use of CSA calibrated with a plasma reference tested against the current FVIII WHO (World Health Organization) International Standard is recommended for the monitoring of patients treated with pdFVIII or rFVIII including extended half-life (EHL) rFVIII. OSA are adequate for the monitoring of patients treated with pdFVIII or with most of rFVIII concentrates. However, preliminary comparison with CSA is mandatory before measuring FVIII:C by OSA in patients treated by Refacto AF. For rFVIII-EHL, OSA are only acceptable for Elocta®. Great caution is therefore required when measuring FVIII:C levels by OSA in patients substituted by other EHL-rFVIII. Indeed, most of recent studies reported data obtained with spiked plasmas, which deserve to be confirmed on plasma samples collected in treated patients.
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http://dx.doi.org/10.1684/abc.2019.1413DOI Listing
February 2019

[Factor IX assays in treated hemophilia B patients].

Ann Biol Clin (Paris) 2019 02;77(1):41-52

Service d'hématologie hémostase, Hospices civils de Lyon, Bron, France.

Replacement therapy with plasma-derived or recombinant FIX (pdFIX or rFIX) concentrates is the standard of treatment in patients with hemophilia B. The method predominantly used for measuring factor IX (FIX:C) levels is the one-stage clotting assay (OSA) but this method depends on the activated partial thromboplastin time (APTT) reagent and the coagulation analyzer used, and wide variations in the measurements of FIX recovery have been reported with some factor concentrates. The French study group on the biology of hemorrhagic diseases (a collaborative group of the GFHT and MHEMO network), presents a review of the literature and proposals for the monitoring of FIX:C levels in treated hemophilia B patients. The use of OSA calibrated with a plasma reference tested against the current FIX WHO International Standard is recommended for the monitoring of patients treated with pdFIX or rFIX. Chromogenic substrate assays (CSA) are adequate for the monitoring of patients treated with Rixubis, but data available for Benefix are currently too limited. For extended half-life rFIX (EHL-rFIX), large discordances in the FIX:C levels measured were evidenced, depending on the method and reagents used. Great attention is therefore required for measuring FIX:C levels by OSA in patients substituted by EHL-rFIX. Commercial kits for CSA are not equivalent, and although potentially useful, they are not validated for all EHL-rFIX. Most of recent studies reported data obtained with spiked plasmas, which deserve to be confirmed on plasma samples collected in treated patients.
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http://dx.doi.org/10.1684/abc.2019.1414DOI Listing
February 2019

Statin exposure and thrombosis risk in patients with myeloproliferative neoplasms.

Thromb Res 2018 07 16;167:57-59. Epub 2018 May 16.

EA 3878 (GETBO), Brest University, 29200 Brest, France; Oncology and Hematology Institute, Hôpital Morvan, 29609 Brest Cedex, France.

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http://dx.doi.org/10.1016/j.thromres.2018.05.014DOI Listing
July 2018

Comparison of four methods to assess high-on platelet reactivity under P2Y12 receptor inhibitor.

Platelets 2018 May 26;29(3):257-264. Epub 2018 Mar 26.

a Service d'hématologie Biologique, CHRU de Brest , Brest , France.

P2Y12 receptor inhibitors are antiplatelet agents commonly prescribed in the treatment of coronary artery disease. Their efficacy can be limited by high on-treatment platelet reactivity (HPR), which can be evaluated by different biological assays. Most commonly, HPR is evaluated by flow cytometric vasodilator-stimulated phosphoprotein-phosphorylation (VASP-P) assay, which can be time consuming. To evaluate the potential interest of novel technologies, we compared four different assays. Ninety patients receiving P2Y12 inhibitors were included. Four technologies were evaluated: the current standard test measuring VASP-P by flow cytometry, the historical reference test based on light transmittance aggregation (LTA), and two relatively novel techniques: whole blood multiple electrode aggregometry (MEA) and platelet function analyzer (PFA), which are less time consuming. The three latter tests were compared with the VASP-P assay as a reference using receiver operating characteristics (ROC) analysis: LTA has an excellent comparability with the VASP test (ROC AUC > 0.9); the other two tests (multiplate and PFA) have only satisfactory comparability (ROC AUC around 0.7) and therefore may not replace the VASP "gold standard" test, if importance is attached to a quantitative assessment of the substitution parameter of VASP. Nevertheless, if a binary approach of the anti-aggregation result is sought, then one can conclude that the three tests are equivalent since Cohen's kappa coefficients are very close for the three tests (k = 0.548 for LTA; k = 0.554 for MEA; k = 0.570 for PFA/P2Y), and a similar proportion of patients are misclassified (15% for LTA, 14% for MEA, and 13.6% for PFA). Discriminant factor analysis using all the parameters provided by each test did not improve the diagnostic performance of MEA or PFA. In conclusion, only LTA shows a good comparability to the VASP assay using ROC curve analysis, probably because misclassified patients have results close to the cutoff values. All three tests have moderate agreement regarding the classification of patients as responders to P2Y12 inhibition.
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http://dx.doi.org/10.1080/09537104.2018.1453058DOI Listing
May 2018

Decreased turnover aspirin resistance by bidaily aspirin intake and efficient cytoreduction in myeloproliferative neoplasms.

Platelets 2018 Nov 1;29(7):723-728. Epub 2017 Nov 1.

a Service d'Hématologie Biologique , CHU de Brest , Brest , France.

Essential thrombocythemia (ET) and polycythemia vera (PV) are myeloproliferative neoplasms (MPN) with an increased risk of arterial and venous thrombosis. Aspirin is recommended to reduce this risk, but resistance to antiplatelet therapy seems to hamper its efficacy in some patients. We have previously shown that multiple electrode aggregometry (MEA) was a valuable tool to assess aspirin resistance in MPN. In this study, MEA was used to assess the reduction in aspirin resistance after bi-daily (BID) aspirin intake or cytoreduction. Fifty one MPN patients (31 ET and 20 PV) receiving 75 mg aspirin once daily (OD) or BID, with or without cytoreductive treatment, were analyzed. Aspirin resistance was assessed using whole blood MEA (Multiplate®, Roche Diagnostics, Meylan, France). In all patients, global aspirin resistance consisted mainly of turnover resistance (TOR). 94% of patients with OD aspirin intake and without cytoreduction displayed biological aspirin resistance. By switching to a BID aspirin regimen, the proportion of resistant patients reduced to 47%. Cytoreduction also contributed to reduce aspirin resistance in a similar way (50% of aspirin resistant patients). Combining cytoreduction and BID aspirin regimen was the most efficient way to reduce aspirin resistance yielding to 12% resistant patients. Moreover, a nonlinear correlation was observed between TOR and naive platelet counts regardless of aspirin regimen. Last, mutational status did not seem to affect TOR. This study confirmed that BID aspirin is biologically more effective than OD aspirin in reduction of aspirin resistance. The latter was achieved through a reduction in TOR which was also decreased by cytoreductive therapy.
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http://dx.doi.org/10.1080/09537104.2017.1361018DOI Listing
November 2018

Administration of direct oral anticoagulants in patients with myeloproliferative neoplasms.

Int J Hematol 2017 Oct 16;106(4):517-521. Epub 2017 Jun 16.

INSERM EA-3878, GETBO (Groupe d'étude de la thrombose en Bretagne occidentale), CHRU de Brest, Brest, France.

Direct oral anticoagulants (DOACs) have been approved to treat and prevent thrombotic events. However, they are not yet labeled for use in patients with active cancers. Myeloproliferative neoplasms (MPNs) are clonal chronic disorders with a high incidence of thrombotic events, for which low-dose aspirin (LDA) is the standard drug treatment. We analyzed efficacy and safety of DOACs prescription in patients treated for MPNs. An MPN database, the OBENE registry, was established at our institution. We collected biological and clinical data from diagnosis to last follow-up for every patient included in this study. Thrombotic and hemorrhagic events and hematologic evolutions were categorized as major events in the database. Of the 760 MPN patients in the OBENE registry, 25 (3.3%) were treated with a DOAC. Median follow-up duration was 2.1 years (0.12-4.3 years). The reasons for prescribing DOACs were atrial fibrillation and thrombotic events for 13 and 12 patients, respectively. We only observed one thrombotic event (4%) and three major hemorrhagic events (12%). A case-control study did not detect a significant difference in thrombotic or hemorrhagic events in patients treated with LDA and DOACs. These preliminary results suggest that DOACs may be highly efficient and safe for use in MPN patients.
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http://dx.doi.org/10.1007/s12185-017-2282-5DOI Listing
October 2017

Venous gas emboli are involved in post-dive macro, but not microvascular dysfunction.

Eur J Appl Physiol 2017 Feb 21;117(2):335-344. Epub 2017 Jan 21.

ORPHY Laboratory, UBO, 6 avenue Le Gorgeu, 29200, Brest, France.

Purpose: Previous studies have shown vascular dysfunction of main conductance arteries and microvessels after diving. We aim to evaluate the impact of bubble formation on vascular function and haemostasis. To achieve this, we used a vibration preconditioning to influence bubble levels without changing any other parameters linked to the dive.

Methods: Twentty-six divers were randomly assigned to one of three groups: (1) the "vibrations-dive" group (VD; n = 9) was exposed to a whole-body vibration session 30 min prior the dive; (2) the "diving" group (D; n = 9) served as a control for the effect of the diving protocol; (3) The "vibration" protocol (V; n = 8) allowed us to assess the effect of vibrations without diving. Macro- and microvascular function was assessed for each subject before and after the dive, subsequently. Bubble grades were monitored with Doppler according to the Spencer grading system. Blood was taken before and after the protocol to assess any change of platelets or endothelial function.

Results: Bubble formation was lower in the VD than the diving group. The other measured parameters remained unchanged after the "vibration" protocol alone. Diving alone induced macrovascular dysfunction, and increased PMP and thrombin generation. Those parameters were no longer changed in the VD group. Conversely, a microvascular dysfunction persists despite a significant decrease of circulating bubbles.

Conclusions: Finally, the results of this study suggest that macro- but not microvascular impairment results at least partly from bubbles, possibly related to platelet activation and generation of pro-coagulant microparticles.
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http://dx.doi.org/10.1007/s00421-017-3537-9DOI Listing
February 2017

Thrombin Generation Measurements in Patients Scheduled for Laparoscopic Bariatric Surgery.

Obes Surg 2017 08;27(8):2015-2021

University of Bretagne Occidentale (UBO), EA 3878 (GETBO), 22 Avenue Camille Desmoulins, CS 93837-29238, Brest, France.

Purpose: Obese patients are known to be in an in vitro hypercoagulable state relative to normal-weight patients. Our study aimed to identify markers of enhanced coagulability (endogenous thrombin potential (ETP)) in morbidly obese patients using the thrombin generation (TG) test.

Materials And Methods: All patients scheduled for laparoscopic bariatric surgery (LBS) between September 1, 2014 and January 31, 2016 were eligible for our prospective study. We used logistic regression to compute the odds ratio (OR) across ETP quartile distributions to evaluate the risk of enhanced TG.

Results: We studied 102 patients, 77.5% were female, mean age was 41.2 ± 12.1 years, and mean BMI was 45.5 ± 7.0 k/m. Total cholesterol and fibrinogen levels were found to be independent risk factors for patients in the 4th quartile distribution of the ETP distribution (OR (95% CI)) 2.6 (1.2 to 5.4) (P = 0.01) and 2.2 (1.1 to 4.5 (P = 0.03). Patients in the 4th quartile of the ETP distribution had a lower ETP 1 month after surgery (157 (144-196) vs. 120 (98-140); P < 0.001) in parallel with a trend toward lower total cholesterol levels (5.0 ± 0.9 vs. 4.4 ± 1.0; P = 0.06). Fibrinogen levels were stable (4.5 ± 1.0 vs. 4.4 ± 0.9); P = 0.7).

Conclusions: Our study highlights the role of total cholesterol and blood inflammatory marker levels in enhancing ETP in morbidly obese patients. Further studies are necessary to confirm the decreased ETP following LBS with the expected reduced inflammatory marker and total cholesterol levels.
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http://dx.doi.org/10.1007/s11695-017-2545-5DOI Listing
August 2017

Reduction of coagulability state one year after bariatric surgery.

Surg Obes Relat Dis 2017 Feb 1;13(2):327-333. Epub 2016 Oct 1.

University of Bretagne Occidentale (UBO), EA 3878 (GETBO), Brest, France; Department of Internal Medicine, La Cavale Blanche University Hospital, Brest, France; INSERM, CIC1412 (FC, KL), La Cavale Blanche University Hospital, Brest, France.

Background: Obese patients are in a hypercoagulable state relative to normal-weight patients. Low-grade inflammation may be a key factor for this condition.

Objectives: Our study aimed to compare the coagulability state of morbidly obese patients before and 1 year after bariatric surgery (BS) using the Thrombin Generation (TG) test, a validated method to assess coagulation in vitro.

Setting: University hospital.

Methods: All patients undergoing BS between September 1, 2014 and April 30, 2015 were eligible for this prospective study (n = 42). Two distinct reagents were used for TG initiation based on the tissue factor concentration (Reagents LOW and HIGH). The main outcomes were endogenous thrombin potential (ETP) and peak height of TG. The rate of follow-up after one year was 97%.

Results: One year after surgery, %weight loss was 32.5±8.4%; CRP decreased from 9.0 (3.7-12.9) to 1.1 (0.3-2.8) mg/mL (P<.001) and fibrinogen from 4.2±.8 to 3.5±.8 g/L (P<.001). The ETP (%) decreased from (108.0 (95.0-117.0) to 78.0 (71.0-98.0) (P<.001) (LOW reagent) and from 113.0 (103.0-134.0) to 96.0 (86.0-107.0) (P<.001) (HIGH reagent). Peak height (%) decreased from (117.0 (92.0-139.0) to 82.0 (70.0-111.0) (P = .003) (LOW reagent) and from 106.0 (96.0-118.0) to 97.0 (87.8-105.2) (P = .003) (HIGH reagent).

Conclusion: Our study shows a significant reduction in TG potential one year after BS in morbidly obese patients. Reduction of low grade inflammation may be one of the underlying mechanisms.
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http://dx.doi.org/10.1016/j.soard.2016.09.030DOI Listing
February 2017

Multiple Electrode Aggregometry is an adequate method for aspirin response testing in myeloproliferative neoplasms and differentiates the mechanisms of aspirin resistance.

Thromb Res 2016 Jun 14;142:26-32. Epub 2016 Apr 14.

Service d'Hématologie Biologique, CHRU de Brest, France.

Introduction: In myeloproliferative neoplasms (MPN), aspirin reduces the thrombotic risk. Nevertheless, aspirin resistance may be due to excessive platelet production ("turnover" resistance). Aspirin resistance can also result from a lack of effect of aspirin; this second component is called "intrinsic resistance". Two biological tests are considered reference methods for the assessment of aspirin resistance: TXB2 assay and Light Transmittance Aggregometry (LTA) with arachidonic acid.

Materials & Methods: We have compared a third method, the Multiple Electrode Aggregometry (MEA), performed with arachidonic acid on the Multiplate® analyzer, with both reference methods. Thirty-six patients with MPN were assessed for aspirin resistance with all three techniques. 30 patients devoid of MPN were used as controls.

Results: The three methods were statistically equivalent: LTA and TXB2 were comparable methods (ROC curve AUC=0.844>0.7; LTA cutoff=67%). At this threshold, LTA had a sensitivity of 73% and a specificity of 96%. MEA (without added aspirin) and TXB2 were also comparable (ROC curve AUC=0.782; MEA cutoff=31U), but at this threshold, 11 patients (30%) were falsely positive with MEA. Last, MEA and LTA were comparable (ROC curve AUC=0.888; MEA cutoff=56U), with a sensitivity of 90% and a specificity of 84.6%. Besides, MEA gave an insight into the mechanism of aspirin resistance (turnover and/or intrinsic).

Conclusion: MEA is both rapid and reliable as compared to reference methods. Clinical correlation with risk of re-thrombosis should definitively validate this method and the best cutoff value.
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http://dx.doi.org/10.1016/j.thromres.2016.04.006DOI Listing
June 2016

[Campylobacter fetus endocarditis: a case report].

Ann Biol Clin (Paris) 2013 Jul-Aug;71(4):465-7

Hôpital d'instruction des armées, Clermont Tonnerre, Brest, France.

Campylobacter are known to be a cause of enteritidic infections but Campylobacter fetus is more often a cause of systemic infections, mainly in fragilized patients. We report a C. fetus endocarditis. The prognosis seemstobe improved by a prolonged betalactam antibiotic treatment.
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http://dx.doi.org/10.1684/abc.2013.0862DOI Listing
November 2013

Biological determinants of bleeding in patients with heterozygous factor XI deficiency.

Br J Haematol 2012 Jan 21;156(2):245-51. Epub 2011 Nov 21.

Centre Hospitalier Régional Universitaire de Brest, Haematology Laboratory, Brest , France.

Bleeding risk is not predictable in patients with factor XI (FXI; F11) deficiency. In this prospective study, our objectives were to determine the biological determinants for bleeding risk in patients with heterozygous FXI deficiency. Patients were classified as either bleeding patients or non-bleeding patients by calculating the bleeding score (BS) described for von Willebrand disease. Primary haemostasis, thrombin generation, thromboelastometry, procoagulant proteins, inhibitors, fibrinolysis, and F11 gene mutations were compared between bleeding and non-bleeding patients. Thirty-nine patients were included. BS significantly correlated with clinical assessment (P=0·001), and a score over 3 discriminated between bleeding (n=15) and non-bleeding (n=24) patients (P=0·034). Despite normal values, von Willebrand factor (VWF) and thrombomodulin (TM) plasma levels were significantly lower in bleeding patients than non-bleeding patients [ristocetin cofactor activity (VWF:RCo)=80·6±29·7 iu/dl and 101·8±29·5iu/dl respectively, P=0·043; and VWF antigen (VWF:Ag)=84·0±28·0 iu/dl and 106·3±36·1 iu/dl respectively, P=0·035; and TM=17·7±11·7ng/ml and 23·6±9·7ng/ml respectively, P=0·043]. When considering BS as a continuous variable, only VWF:RCo remained significant (P=0·042), which accounted for 11% of the variability in BS.
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http://dx.doi.org/10.1111/j.1365-2141.2011.08945.xDOI Listing
January 2012