Publications (8)42.7 Total impact
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Article: Recurrent acute coronary syndromes are associated with increased shear induced platelet aggregation. A case-control study.
International journal of cardiology 12/2011; 155(2):313-4. · 7.08 Impact Factor -
Article: Microparticle-linked tissue factor activity and increased thrombin activity play a potential role in fibrinolysis failure in ST-segment elevation myocardial infarction.
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ABSTRACT: Fibrinolysis for acute ST-segment elevation MI achieves early recanalisation of the infarct artery in approximately 60% of cases. The aim of the study was to determine whether failure to achieve recanalisation was associated with differences in haemostasis biomarkers compared to patients with successful fibrinolysis. Fourty-three patients were prospectively enrolled in a case-control study. All patients had received tenecteplase (TNK-tPA) together with aspirin (500 mg) and heparin (5,000 IU). Emergency angiography within 90 minutes of bolus TNK-tPA identified 13 TIMI 0-2 patients (cases) and 30 TIMI 3 patients (controls). Blood samples were collected before angiography to determine tissue factor activity associated with microparticles (TF-MP); soluble platelet glycoprotein V (sGPV) and thrombin-antithrombin complexes (TAT) as markers of thrombin generation; tissue plasminogen activator (endogenous tPA+ TNK-tPA), plasminogen activator inhibitor (PAI-1) and plasmin-antiplasmin complexes (PAP) as markers of plasmin generation. The baseline characteristics of the two patients' groups were similar with respect to sex, age, and risks factors. Cases differed from controls by higher TF-MP levels (1.9 [1-13] vs. 1 [0.6-1.3] pM), sGPV (67 [51-126] vs. (48 [39-72] ng/ml), p = 0.039 and TAT (10 [4-37.5] vs. 4 [2.9-7.2] ng/ml), p = 0.035. TAT correlated with TF-MP (r = 0.51, p = 0.0064) and sGPV (r = 0.51, p = 0.0018). No significant difference was observed in tPA or PAI-1 levels. PAP were lower in cases (18.83 [14.83-40.43] mug/ml) than in controls (35.83 [27.9-43.94] mug/ml), p = 0.045. In conclusion, fibrinolysis failure in AMI is characterised by a higher procoagulant state associated with TF-MP and a lower plasmin generation.Thrombosis and Haemostasis 05/2009; 101(4):734-40. · 5.04 Impact Factor -
Article: Leukocyte activation: the link between inflammation and coagulation during heatstroke. A study of patients during the 2003 heat wave in Paris.
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ABSTRACT: The mechanisms linking severe inflammation and coagulation during heatstroke are poorly understood. Here, we examined the roles of the tissue factor pathway, leukocyte activation, and mediators of innate immunity in patients admitted to an intensive care unit for heatstroke during an intense heat wave in Paris. Retrospective observational study. Intensive care unit of a university medical center. Eighteen critically ill severe patients with heatstroke were enrolled in the study and 14 age-matched patients with severe sepsis as controls. None. High circulating levels of some inflammation and stress mediators (interleukin-6, -8, C5a, interleukin-1 receptor antagonist, heat shock protein 60 and 70) were observed. Blood leukocyte activation was shown by beta2 integrin up-regulation, L-selectin down-regulation, and strong production of reactive oxygen species and interleukin-8 ex vivo. High levels of circulating promatrix metalloproteinase-9 were detected in all the patients studied, and its active form was present in two patients. Overt disseminated intravascular coagulation according to the International Society of Thrombosis and Hemostasis score was present in five patients. Whole-blood tissue factor was present in all the patients and part of this activity was associated with microparticles in five patients. The degrees of inflammation and disseminated intravascular coagulation are correlated with clinical severity. These results suggest that neutrophil activation plays a key role in the acute activation of coagulation observed during severe heatstroke, despite a rapid and sustained antiinflammatory response. The comparison with a group of patients with severe sepsis suggests some common mechanisms, but more intense responses during heatstroke.Critical care medicine 09/2008; 36(8):2288-95. · 6.37 Impact Factor -
Article: Hypercoagulability after partial liver resection.
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ABSTRACT: One concern of living donor liver transplantation remains the risk of morbidity and/or mortality for the donors, including the risk of postoperative thrombosis. We studied the coagulation changes after partial liver resection in l2 living donors and eight patients with non-malignant hepatic tumors (controls) and searched for potential predictive markers of thrombotic complications. Thrombosis (pulmonary embolism and portal vein thrombosis) developed in two donors and two controls. In donors and controls, we observed an early postoperative decrease in coagulation inhibitors protein C and antithrombin together with an increase in factor VIII and von Willebrand factor, which both persisted when prothrombin time had returned to normal. Dysregulation in the haemostatic system was confirmed by increased prothrombotic markers, with a 10- to 30-fold increase in thrombin-antithrombin complexes and moderate increase(1.5- to 2.0-fold) in sP-Selectin. No difference between donors and controls was observed and the data were pooled for comparison of patients with (n = 4) versus without (n = 16) thrombosis. Thrombin-antithrombin complexes were significantly higher in the thrombosis group, on day 1 (28.8 vs. 13.5 microg/l, p = 0.027) and day 2 (52.3 vs. 9.3 microg/l, p = 0.013). sP-selectin was also significantly higher in the thrombosis group on day 2 (103 vs. 53 ng/ml, p = 0.044) and day 4 (116 vs. 58 ng/ml, p = 0.026) after surgery. Our study indicates that improvement of thromboprophylaxis in partial liver resection is needed. It also suggests that thrombin-antithrombin complexes and sP-selectin could serve as early biological predictors of thrombotic complications in the post-operative period.Thrombosis and Haemostasis 01/2008; 98(6):1252-6. · 5.04 Impact Factor -
Article: Prothrombotic markers and early spontaneous recanalization in ST-segment elevation myocardial infarction.
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ABSTRACT: We tested the hypothesis that selected prothrombotic biomarkers might be associated with early spontaneous coronary recanalization in patients with ST-segment elevation acute myocardial infarction (STEMI). We prospectively enrolled 123 patients with STEMI including 53 patients with spontaneous coronary recanalization (cases) and 70 patients with persistent occlusion (controls) at the time of emergent coronary angiography and before angioplasty. All had received aspirin and heparin. Blood samples were collected immediately before angioplasty to measure soluble P-selectin, circulating microparticles originating from platelets (PMPs), granulocytes (GMPs), endothelial cells (EMPs); tissue factor-associated MP (TF-MP); soluble platelet glycoprotein V (sGPV) and prothrombin F1 + 2; tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI-1) and plasmin-antiplasmin (PAP). A sub-group of 70 patients (35 cases, 35 controls) was available for flow cytometry analysis of platelet P-selectin and activated GPIIb-IIIa. Baseline clinical characteristics did not differ between groups except for more frequent hypertension and dyslipidemia in controls. Platelet activation markers and PMP did not differ between the two groups. Controls had higher numbers of EMPs and GMPs compared to cases, but the difference was no longer significant when corrected for risk factors. Controls differed from cases by higher plasma levels of sGPV [64 (47-84) ng/ml vs. 53 (44-63) ng/ml] and PAP [114(65-225) ng/ml vs. 88 (51-147) ng/ml]. The difference persisted after adjustment for risks factors (p = 0.031 and 0.037, respectively). Persistent occlusion of the infarct related artery is associated with some markers related to higher thrombin (sGPV) and plasmin (PAP) production but is not associated with markers of platelet activation.Thrombosis and Haemostasis 09/2007; 98(2):420-6. · 5.04 Impact Factor -
Article: Thrombin interaction with platelet membrane glycoprotein Ib alpha.
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ABSTRACT: The interaction of thrombin with platelet glycoprotein Ibalpha (GPIb alpha) is required for optimal platelet activation. The crystal structures of platelet GPIb alpha bound to thrombin reported by Dumas et al. and Celikel et al. both reveal the simultaneous interaction of GPIb alpha with thrombin exosites I and II but differ markedly regarding how the two proteins interact. The possible consequences on thrombus formation of thrombin interacting with GPIb alpha are discussed in light of these new data.Trends in Molecular Medicine 12/2003; 9(11):461-4. · 10.35 Impact Factor -
Article: Hemostasis imbalance in experimental hypertension.
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ABSTRACT: The rat model of chronic intoxication by N(G) -nitro-L-arginine methyl ester (L-NAME) induces severe systemic arterial hypertension and progressive ischemic lesions in the central nervous system and kidneys. We investigated the possible molecular basis of these thrombotic events. Administration of L-NAME increased plasma markers of thrombin generation, thrombin-antithrombin complexes, and soluble glycoprotein V, measured by specific ELISA. Thrombin generation in vivo was associated with ex vivo platelet desensitization to adenosine 5'-diphosphate and collagen-induced aggregation. In the aortic layers and renal arterioles, tissue factor mRNA (semi-quantitative RT-PCR) and activity (coagulation assay) were increased. In contrast, tissue factor activity was not modified in glomeruli. In parallel, an impairment of the fibrinolytic system was demonstrated by an increase in plasma levels and arterial secretion of plasminogen activator inhibitor-1. In the arterial wall, plasminogen activator inhibtor-1 mRNA was significantly increased. Moreover, antifibrinolytic activity, studied by fibrin reverse zymography, was increased whereas all tissue-plasminogen activator activity secreted by the hypertensive arterial wall was detected as complexes with its specific inhibitor. In animals treated with the angiotensin-converting enzyme (ACE) inhibitor Zofenil, all of these parameters remained at control levels. These results indicate that chronic blockade of nitric oxide production in rats results in enhancement of blood markers of thrombin generation associated with tissue factor induction and impairment of fibrinolysis in the vascular wall, which may contribute to the thrombotic complications associated with hypertension.Molecular Medicine 05/2002; 8(4):169-78. · 3.76 Impact Factor -
Article: Thrombin interaction with platelet membrane glycoprotein Ibα
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ABSTRACT: The interaction of thrombin with platelet glycoprotein Ibα (GPIbα) is required for optimal platelet activation. The crystal structures of platelet GPIbα bound to thrombin reported by Dumas et al. and Celikel et al. both reveal the simultaneous interaction of GPIbα with thrombin exosites I and II but differ markedly regarding how the two proteins interact. The possible consequences on thrombus formation of thrombin interacting with GPIbα are discussed in light of these new data.Trends in Molecular Medicine.
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Institutions
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2007–2009
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Hôpital "Bichat - Claude-Bernard" – Hôpitaux Universitaires Paris Nord Val de Seine
Paris, Ile-de-France, France
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