Publications by authors named "Jérôme Duchemin"

18 Publications

  • Page 1 of 1

Placental growth factor level in plasma predicts COVID-19 severity and in-hospital mortality.

J Thromb Haemost 2021 Apr 8. Epub 2021 Apr 8.

Université de Paris, PARCC, INSERM, F-75015, Paris, France.

Background: Coronavirus disease 2019 (COVID-19) is a respiratory disease associated with vascular inflammation and endothelial injury.

Objectives: Correlate circulating angiogenic markers VEGF-A, PlGF and FGF-2 to in-hospital mortality in COVID-19 adult patients.

Methods: Consecutive ambulatory and hospitalized patients with COVID-19 infection were enrolled. VEGF-A, PlGF and FGF-2 were measured in each patient ≤48 h following admission.

Results: Study enrolled 237 patients with suspected COVID-19: 208 patients had a positive diagnostic for COVID-19 of whom 23 were mild outpatients and 185 patients hospitalized after admission. Levels of VEGF-A, PlGF and FGF-2 significantly increase with the severity of the disease (p<0.001). Using a logistic regression model we found a significant association between the increase of FGF-2 or PlGF and mortality (OR 1.11, 95% CI [1.07-1.16], p<0.001 for FGF-2 and OR 1.07 95% CI [1.04-1.10], p<0.001 for PlGF) while no association were found for VEGF-A levels. ROC curve analysis was performed and we identified PlGF above 30 pg/mL as the best predictor of in-hospital mortality in COVID-19 patients. Survival analysis for PlGF confirmed its interest for in-hospital mortality prediction, by using a Kaplan-Meier survival curves (p=0.001) and a Cox proportional hazard model adjusted to age, body mass index, D-dimer and CRP (3.23 95% CI [1.29-8.11], p=0.001).

Conclusion: Angiogenic factor PlGF is a relevant predictive factor for in-hospital mortality in COVID-19 patients. More than a biomarker, we hypothesize that PlGF blocking strategies could be a new interesting therapeutic approach in COVID-19.
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http://dx.doi.org/10.1111/jth.15339DOI Listing
April 2021

Metabolomic analyses of COVID-19 patients unravel stage-dependent and prognostic biomarkers.

Cell Death Dis 2021 03 11;12(3):258. Epub 2021 Mar 11.

Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, 94800, Villejuif, France.

The circulating metabolome provides a snapshot of the physiological state of the organism responding to pathogenic challenges. Here we report alterations in the plasma metabolome reflecting the clinical presentation of COVID-19 patients with mild (ambulatory) diseases, moderate disease (radiologically confirmed pneumonitis, hospitalization and oxygen therapy), and critical disease (in intensive care). This analysis revealed major disease- and stage-associated shifts in the metabolome, meaning that at least 77 metabolites including amino acids, lipids, polyamines and sugars, as well as their derivatives, were altered in critical COVID-19 patient's plasma as compared to mild COVID-19 patients. Among a uniformly moderate cohort of patients who received tocilizumab, only 10 metabolites were different among individuals with a favorable evolution as compared to those who required transfer into the intensive care unit. The elevation of one single metabolite, anthranilic acid, had a poor prognostic value, correlating with the maintenance of high interleukin-10 and -18 levels. Given that products of the kynurenine pathway including anthranilic acid have immunosuppressive properties, we speculate on the therapeutic utility to inhibit the rate-limiting enzymes of this pathway including indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase.
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http://dx.doi.org/10.1038/s41419-021-03540-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948172PMC
March 2021

Circulating Von Willebrand factor and high molecular weight multimers as markers of endothelial injury predict COVID-19 in-hospital mortality.

Angiogenesis 2021 Jan 15. Epub 2021 Jan 15.

Université de Paris, Innovative Therapies in Haemostasis, INSERM, 75006 Paris, France, Hematology Department and Biosurgical Research Lab (Carpentier Foundation), Assistance Publique Hôpitaux de Paris. Centre-Université de Paris (APHP.CUP), 20 rue Leblanc, 75015, Paris, France.

Background: Coronavirus disease 2019 (COVID-19) is a respiratory disease associated with endotheliitis and microthrombosis.

Objectives: To correlate endothelial dysfunction to in-hospital mortality in a bi-centric cohort of COVID-19 adult patients.

Methods: Consecutive ambulatory and hospitalized patients with laboratory-confirmed COVID-19 were enrolled. A panel of endothelial biomarkers and von Willebrand factor (VWF) multimers were measured in each patient ≤ 48 h following admission.

Results: Study enrolled 208 COVID-19 patients of whom 23 were mild outpatients and 189 patients hospitalized after admission. Most of endothelial biomarkers tested were found increased in the 89 critical patients transferred to intensive care unit. However, only von Willebrand factor antigen (VWF:Ag) scaled according to clinical severity, with levels significantly higher in critical patients (median 507%, IQR 428-596) compared to non-critical patients (288%, 230-350, p < 0.0001) or COVID-19 outpatients (144%, 133-198, p = 0.007). Moreover, VWF high molecular weight multimers (HMWM) were significantly higher in critical patients (median ratio 1.18, IQR 0.86-1.09) compared to non-critical patients (0.96, 1.04-1.39, p < 0.001). Among all endothelial biomarkers measured, ROC curve analysis identified a VWF:Ag cut-off of 423% as the best predictor for in-hospital mortality. The accuracy of VWF:Ag was further confirmed in a Kaplan-Meier estimator analysis and a Cox proportional Hazard model adjusted on age, BMI, C-reactive protein and D-dimer levels.

Conclusion: VWF:Ag is a relevant predictive factor for in-hospital mortality in COVID-19 patients. More than a biomarker, we hypothesize that VWF, including excess of HMWM forms, drives microthrombosis in COVID-19.
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http://dx.doi.org/10.1007/s10456-020-09762-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809553PMC
January 2021

Pharmacodynamics of eftrenonacog-alfa (rFIX-Fc) in severe hemophilia B patients: A real-life study.

Eur J Pharmacol 2021 Jan 27;891:173764. Epub 2020 Nov 27.

Service D'Hématologie Biologique, AP-HP.Centre-Université de Paris, Hôpital Cochin, F-75014, Paris, France; Université de Paris, Innovative Therapies in Haemostasis, INSERM UMR-S1140, F-75006, Paris, France. Electronic address:

Eftrenonacog-alfa is a recombinant factor IX-Fc fusion protein increasingly prescribed in hemophilia B patients. We aimed to assess its pharmacodynamics (PD) in real-life setting via FIX activity measurement and thrombin generation assay (TGA). Sixty samples from 15 severe hemophilia B treated patients were collected at different time points. FIX activity was measured using product-specific one-stage clotting assay (reference method) and two chromogenic assays (CSA) (Biophen FIX and Rox FIX). TGA was triggered with 1 pM tissue factor. Five parameters were analyzed: lag time (LT), time to peak (TTP), peak height (PH), endogenous thrombin potential (ETP), and velocity. PD models were built to characterize their relationships with FIX activity, using mixed effects models. Mean trough FIX level was estimated at 4.64 (±1.50) IU/dl with a recovery at 0.78 (±0.16) IU/dl per 1 IU/kg injected dose. FIX activity ranged between 1 and 86 IU/dl with 21.5 IU/dl median value. Biophen FIX and Rox FIX allowed reliable measurements except in samples with FIX <20 IU/dl in which values were underestimated (delta >30%). PD models revealed that velocity was the most sensitive TGA parameter to FIX activity followed by PH, ETP, TTP and finally LT. Following FIX activity peak after eftrenonacog-alfa injection, velocity decreased first, followed by PH then ETP. Both CSA failed to accurately measure FIX in severe hemophilia B patients receiving eftrenonacog-alfa throughout the measuring range. TGA could be an additional valuable tool to evaluate hemostasis balance in treated patients.
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http://dx.doi.org/10.1016/j.ejphar.2020.173764DOI Listing
January 2021

Comparative Analysis of a French Prospective Series of 144 Patients with Heparin-Induced Thrombocytopenia (FRIGTIH) and the Literature.

Thromb Haemost 2020 Jul 22;120(7):1096-1107. Epub 2020 Jun 22.

EA 7501, GICC, Université de Tours, Tours, France.

Background:  Heparin-induced thrombocytopenia (HIT) is a rare complication of heparin treatments, and only a few large patient cohorts have been reported. In this study, biological and clinical data from 144 French patients with HIT were analyzed in comparison with the literature.

Methods:  The diagnosis of HIT was confirmed in all patients by an immunoassay combined with serotonin release assay. In the literature, only cohorts of at least 20 HIT patients published from 1992 were selected for a comparative analysis.

Results:  Two-thirds of patients were hospitalized in surgery and most were treated with unfractionated heparin (83.2% vs. 16.8% with low molecular weight heparin only). Thrombotic events in 54 patients (39.7%) were mainly venous (41/54). However, arterial thrombosis was more frequent after cardiac surgery (13.2% vs. 2.4% in other surgeries,  = 0.042) with a shorter recovery time (median = 3 vs. 5 days,  < 0.001). The mortality rate was lower in our series than in the 22 selected published studies (median = 6.3% vs. 15.9%). Three genetic polymorphisms were also studied and homozygous subjects FcγRIIA RR were more frequent in patients with thrombosis (37.8 vs. 18.2% in those without thrombosis,  = 0.03).

Conclusion:  This study shows that the mortality rate due to HIT has recently decreased in France, possibly due to earlier diagnosis and improved medical care. It also confirms the strong association between polymorphism FcγRIIA H131R and thrombosis in HIT.
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http://dx.doi.org/10.1055/s-0040-1712957DOI Listing
July 2020

Potential usefulness of activated charcoal (DOAC remove®) for dRVVT testing in patients receiving Direct Oral AntiCoagulants.

Thromb Res 2019 Dec 5;184:86-91. Epub 2019 Nov 5.

Service d'Hématologie Biologique, CHU Pontchaillou, Rennes, France; University of Rennes 1, CIC-Inserm1414, Rennes, France.

Introduction: Lupus Anticoagulant testing using dilute Russell Viper Venom Time (dRVVT) is challenging in patients receiving Direct Oral AntiCoagulants (DOAC) due to potential false positive results. In a multicenter study, we evaluated the in vitro removal of DOAC by activated charcoal (DOAC remove®), allowing reliable dRVVT testing.

Materials And Methods: Patient samples were analyzed before and after treatment with DOAC remove®: 49 apixaban, 48 rivaroxaban, 24 dabigatran and 30 none. DOAC plasma concentrations were measured using anti-Xa or diluted thrombin time assays. In a subset of 28 samples, DOAC concentrations were also measured using HPLC-MS/MS following treatment with DOAC remove®. DRVVT was performed using STA-Staclot dRVVT Screen®/Confirm® (Stago) or LAC-Screening®/Confirmation® (Siemens).

Results: Baseline median [min-max] concentrations were 94 [<20-479] for apixaban, 107 [<20-501] for rivaroxaban and 135 ng/mL [<20-792] for dabigatran; dRVVT screen ratio/confirm ratio was positive in 47, 90 and 42% of apixaban, rivaroxaban and dabigatran samples. Treatment with DOAC remove® did not affect dRVVT results in non-DOAC patients while it resulted in DOAC concentrations <20 ng/mL in 82, 98 and 100% of samples, respectively. Concentrations were <5 ng/mL with HPLC-MS/MS in 5 out of 10, 8 out of 10 and 7 out of 8 samples, respectively. DOAC remove® corrected DOAC interference with dRVVT assays in 76, 85 and 95% of the patients, respectively.

Conclusion: For dRVVT testing in DOAC patients, we suggest the use of DOAC remove® for every rivaroxaban sample, whereas it might only be used in positive apixaban and dabigatran samples. A residual DOAC interference cannot be ruled out in case of persisting dRVVT positive results after treatment with DOAC remove®.
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http://dx.doi.org/10.1016/j.thromres.2019.11.001DOI Listing
December 2019

Effect of rivaroxaban and dabigatran on platelet functions: in vitro study.

Thromb Res 2019 Nov 22;183:159-162. Epub 2019 Oct 22.

Université de Paris, U1140 Innovative Therapies in Haemostasis, INSERM, F-75006 Paris, France; Service d'Hematologie Biologique, AP-HP, Georges Pompidou European Hospital, F-75015 Paris, France.

Introduction: Clinical benefit-risk balance of direct oral anticoagulants (DOAC) in atherothrombosis prevention differs between anti-Xa and anti-IIa drugs and their specific effect on platelet functions remains controversial. We hence investigated rivaroxaban and dabigatran effect on platelets in identical experimental conditions.

Materials And Methods: Blood of fifteen healthy volunteers was spiked with DOAC which plasma concentrations were measured by specific anti-Xa or anti-IIa assays. Light transmission aggregometry measured in platelet-rich plasma used low doses of agonists: 0.5 mM arachidonic acid, 2.5 μM ADP, 0.5 μM epinephrine, 0.8 μg/ml collagen, 7.5 μM TRAP-6 and 0.5 pM tissue factor in the presence of H-Gly-Pro-Arg-Pro-OH to prevent fibrin polymerization. Platelet adhesion on collagen fibres was evaluated in whole blood under flow. Same experiments were reproduced in the presence of aspirin.

Results: Median [95% CI] plasma concentrations were of 28 [23-36], 128 [119-144] and 321 [293-361] ng/ml for rivaroxaban and 39 [34-45], 171 [166-193] and 353 [349-382] ng/ml for dabigatran. DOAC did not modify platelet aggregation or adhesion on collagen fibres at any tested concentrations. However, they delayed platelet aggregation secondary to coagulation activation with a more potent effect with dabigatran (p < 0.001). Aspirin did not modify DOAC effect.

Conclusion: Efficacy of combining DOAC and aspirin in atherothrombosis prevention would not stem from a direct antiplatelet effect of the formers but to their additive inhibitory effect on platelet aggregation secondary to coagulation activation. This effect differs according to DOAC molecules and may also result from the pleiotropic roles of the different coagulation factors targeted by DOAC.
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http://dx.doi.org/10.1016/j.thromres.2019.10.007DOI Listing
November 2019

Lupus anticoagulant diagnosis in patients receiving direct oral FXa inhibitors at trough levels: A real-life study.

Int J Lab Hematol 2019 Dec 5;41(6):738-744. Epub 2019 Sep 5.

Service d'Hématologie Biologique, AP-HP, Cochin Hospital, Paris, France.

Introduction: Direct oral factor Xa inhibitors (xabans) induce false positive results for lupus anticoagulant (LA) diagnosis. Consequently, it is suggested not to perform LA testing in xabans patients although it may be useful in selected patients. In this monocentric study, we evaluated xabans impact at trough levels (ie, just before the next intake) on LA diagnosis in treated patients using dilute Russell viper venom time (dRVVT) and two LA sensitive activated partial thromboplastin time (aPTT).

Methods: Sixty patients receiving rivaroxaban (30) or apixaban (30) were included. Plasma concentrations were measured using specific anti-Xa assays. LA testing was performed using one dRVVT (LAC-Screening /Confirm ; Siemens) and two LA sensitive aPTT-based assays (Hemosil Silica Clotting Time (SCT) Screen/Confirm; Werfen and Dade Actin Factor Sensitivity FSL/FS (Actin F); Siemens).

Results: Median [min-max] concentrations were 23 [<18-68] for rivaroxaban and 42 ng/mL [19-99] for apixaban. dRVVT was positive in 93% of rivaroxaban and 40% of apixaban samples. SCT was positive in 40 and 30% and Actin F in 17 and 20% of samples respectively. Xabans affected more significantly dRVVT than aPTT-based assays (P < .001) with less false positive results with apixaban than with rivaroxaban samples irrespective of the assay used.

Conclusion: lupus anticoagulant diagnosis in rivaroxaban and apixaban samples drawn at trough levels remains questionable whenever positive results are obtained. If LA testing in apixaban samples might be useful to rule-out LA using dRVVT and/or aPTT-based assays, the wide majority of rivaroxaban samples would give false positive results.
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http://dx.doi.org/10.1111/ijlh.13101DOI Listing
December 2019

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

Increased thrombin generation measured in the presence of thrombomodulin in women with early pregnancy loss.

Fertil Steril 2011 Apr 3;95(5):1813-5.e1. Epub 2010 Dec 3.

Department of Internal Medicine and Chest Diseases, Brest University Hospital, La Cavale Blanche Hospital, Brest, France.

Compared with 537 parous controls with no history of pregnancy loss, a lower thrombomodulin-related inhibition of the endogenous thrombin potential was measured in 264 cases with previous unexplained pregnancy loss, especially when losses occurred between 9 and 12 weeks of gestation. Adjusting age, protein S, factor VIII, factor V Leiden, and prothrombin G20210A did not change the results.
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http://dx.doi.org/10.1016/j.fertnstert.2010.11.019DOI Listing
April 2011

Increased circulating procoagulant activity and thrombin generation in patients with myeloproliferative neoplasms.

Thromb Res 2010 Sep 24;126(3):238-42. Epub 2010 Jul 24.

CHU Brest, Laboratoire d'Hématologie, Hôpital La Cavale Blanche, INSERM, U613, Université de Brest, UFR Médecine et Sciences de la Santé, Brest, France.

Microparticles (MPs) are membrane fragments ranging in size from 0.1 to 1 microm, and are considered as biomarkers reflecting prothrombotic state in many clinical diseases. The clinical course of myeloproliferative neoplasms (MPN) being frequently complicated by thrombotic events, we determined the MPs activity, i.e. circulating procoagulant activity (CPA), in polycythemia vera (PV) and essential thrombocythemia (ET) patients. To evaluate the influence of MPs on the coagulation, a thrombin generation test was realized in the absence and presence of thrombomodulin (TM). Compared with controls, patients had a higher CPA (24.0+/-9.0 vs 10.6+/-4.4 nM, p<0.001), which was associated with a lower inhibition of the thrombin generation in the presence of TM (20.1+/-9.5% vs 28.4+/-11.8%, p<0.001), compatible with a low sensitivity to TM. This sensitivity was influenced by the JAK2V617F mutational status, homozygous patients presenting the lowest inhibition rate of the thrombin generation. Filtration through a 0.22 microm membrane increased the sensitivity to TM in plasma, suggesting an influence of MPs in the "TM-resistance" observed in patients. Moreover, MPN patients receiving antiplatelet and/or cytoreductive therapies, our study suggests that CPA might be influenced by cytoreductive therapy. In conclusion, our data evidence in MPN patients the occurrence of an acquired "TM-resistance" partly determined by circulating microparticles. This TM-resistance might contribute to the hypercoagulable state observed in MPN patients, but the predictive value of the "TM-resistance" for thrombosis had not been evaluated.
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http://dx.doi.org/10.1016/j.thromres.2010.06.025DOI Listing
September 2010

Influence of coagulation factors and tissue factor concentration on the thrombin generation test in plasma.

Thromb Haemost 2008 Apr;99(4):767-73

Service d'Hématologie biologique, Hôpital La Cavale Blanche, Bd Tanguy Prigent, 29609 Brest Cedex, France.

The thrombin generation test is used to study coagulation in patients with haemorrhagic diseases or with high thrombotic risk. To our knowledge, this is the first study investigating the relative influence of coagulation factors on thrombin generation in plasma. The aim was to investigate the influence of coagulant factors, anticoagulant factors, and tissue factor (TF) on three parameters: endogenous thrombin potential (ETP), peak thrombin concentration, and lag time for the appearance of thrombin. At a low TF concentration, all factors except factor XI influenced thrombin generation. At a high TF concentration, only the factors of the extrinsic pathway exerted an influence. ETP and peak thrombin were linearly correlated to factor II concentration. Factor V and factor VII effects increased hyperbolically with factor concentration. The influence of factor X on thrombin generation depended on TF concentration. In the absence of factor VIII and factor IX, ETP fell to 60-70% of the normal when peak thrombin fell to 25-30% of the normal. Fibrinogen concentration influenced ETP and peak thrombin and decreasing fibrinogen levels shortened the lag time. As expected, decreasing antithrombin concentration caused dramatic increases in thrombin generation. Protein S prolonged the lag time, especially at a low TF concentration. No effect of protein C was observed, likely due to the absence of thrombomodulin. The thrombin generation test was more sensitive to factor deficiencies at low than at high TF concentration. ETP was not the most critical parameter for studying coagulation factor deficiencies. Instead, peak thrombin was the most sensitive parameter.
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http://dx.doi.org/10.1160/TH07-09-0581DOI Listing
April 2008

Thrombin generation in first-degree relatives of patients with venous thromboembolism who have factor V Leiden. A pilot study.

Thromb Haemost 2008 Jan;99(1):223-8

G.E.T.B.O. (Groupe d'Etude de la Thrombose de Bretagne Occidentale), EA 3878, Department of Internal Medicine and Chest Diseases, University Hospital of Brest, Brest, France.

The thrombin generation test appears to be a highly sensitive and specific test in the detection of thrombophilia in patients with venous thromboembolism. We aimed to determine the accuracy of the thrombin generation test to detect factor V Leiden and/or other prothrombotic states in first-degree relatives of patients with venous thromboembolism and factor V Leiden. Sixty-two first-degree relatives of 21 index cases were tested for factor V Leiden, the G20210A prothrombin gene mutation and thrombin generation. Information about oestrogen therapy and previous VTE was also collected. The normalized Thrombomodulin sensitivity ratio (n-TMsr) was defined as the ratio of endogenous thrombin potential determined in the presence and absence of thrombomodulin which was normalized against the same ratio determined in normal control plasma. The mean n-TMsr was 1.37 (+/- 0.33) in the 45 relatives with one or more prothrombotic state (factor V Leiden, G20210A prothrombin mutation, oestrogen therapy or hormonal therapy) and 1.02 (+/- 0.34) in the 17 relatives without prothrombotic state (p = 0.001). The positive predictive value was 90.3 (95%CI, 73.1-97.4). In relatives with an abnormal n-TMsr, the adjusted odds ratio for having a prothrombotic state was 8.3 (95%CI, 1.9-36.9) and the adjusted odds ratio for having the factor V Leiden was 14.3 (95%CI, 2.9-71.2). An abnormal thrombin generation test appears highly predictive for having factor V Leiden and/or other prothrombotic states in first-degree relatives of patients with venous thromboembolism and factor V Leiden.
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http://dx.doi.org/10.1160/TH07-08-0515DOI Listing
January 2008

Correlations between carotid IMT, factor VIII activity level and metabolic disturbances: a cardio-vascular risk factor in the HIV positive persons.

Curr HIV Res 2007 May;5(3):361-4

Brest University Hospital, Brest, France.

In the HIV infection, the short time-scale between the HIV-induced cardiovascular events and the onset of antiretroviral therapy elicits a thrombophilic co-factor that worsens the induced atherosclerosis. We compared the factor VIII plasma activity, previously implicated in arterial and venous thrombosis, with a surrogate marker of atherosclerosis, the carotid intima-media thickness, and with the usual atherosclerosis risk factors in 154 HIV infected outpatients. The FVIII plasma activity is significantly associated with the carotid intima-media thickness and, strongly, with blood glucose and triglycerides levels. A raised FVIII plasma activity is an important feature of the metabolic syndrome and a putative co-factor of HAART induced cardiovascular events. Thus the prevention of the HAART-induced cardio-vascular events should probably not be exclusively focused on atherosclerosis but likewise on the thrombus formation process.
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http://dx.doi.org/10.2174/157016207780636498DOI Listing
May 2007

Acquired thrombopathia related to montelukast therapy.

Thromb Haemost 2004 Jun;91(6):1247-8

Service d'Hématologie biologique, Hôpital La Cavale Blanche, Bd Tanguy Prigent, 29609 Brest Cedex, France.

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June 2004

Insertion of chromosome 11 in chromosome 4 resulting in a 5'MLL-3'AF4 fusion gene in a case of adult acute lymphoblastic leukemia.

Cancer Genet Cytogenet 2003 Aug;145(1):74-7

Service de Cytogénétique, Cytologie et Biologie de la Reproduction, CHU Morvan, Brest, France.

We report on a 69-year-old woman with B-lineage acute lymphoblastic leukemia. Cytogenetic studies at diagnosis with R banding showed an insertion, ins(4;11)(q21;q13q23). Fluorescence in situ hybridization (FISH) with whole chromosome painting probes confirmed the insertion of chromosome 11 material into chromosome 4. FISH using the MLL probe showed the translocation of the 5' end of MLL into chromosome 4. Since the 5'MLL-3'AF4 fusion transcript was detected by a reverse transcriptase polymerase chain reaction, we concluded that the insertion of part of chromosome 11 split the AF4 gene in two, resulting in the presence of the 5'MLL-3'AF4 fusion gene on the der(4) instead of the der(11), as commonly observed. Our findings stress the value of combining banding cytogenetics with FISH and molecular techniques to better assess rearrangements in leukemia.
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http://dx.doi.org/10.1016/s0165-4608(03)00029-3DOI Listing
August 2003