PubMed Health⌕ Search

Biomedical subjects

Ludovic Drouet

Publications and source records attributed to Ludovic Drouet.

At least 37 records · Page 2Linked to original sources
PubMed2003

Comparison of effects on markers of blood cell activation of enoxaparin, dalteparin, and unfractionated heparin in patients with unstable angina pectoris or non-ST-segment elevation acute myocardial infarction (the ARMADA study).

The low-molecular-weight heparins (LMWHs) enoxaparin and dalteparin have shown superior and equivalent efficacy, respectively, over unfractionated heparin (UFH) in patients with unstable angina pectoris (UAP) or non-ST-segment elevation myocardial infarction (NSTEMI). This study aimed to identify markers of blood cell activation that are independent predictors of outcomes at 1 month and to compare the effects of enoxaparin, dalteparin, and UFH on any such markers. In this multicenter, prospective, open-label study, 141 patients with UAP or NSTEMI were randomized to treatment for 48 to 120 hours with enoxaparin (n = 46), dalteparin (n = 48), or UFH (n = 47). Blood samples were taken at the time of randomization and after > or =48 hours of treatment but before catheterization. Multivariate analysis identified increased plasma levels of von Willebrand factor (vWF) and decreased platelet levels of glycoprotein Ib/IX complexes as independent predictors of 1-month adverse outcome (a composite of death, myocardial infarction, and recurrent ischemia). vWF release was strongly related to and may have been released by inflammation as measured by C-reactive protein. Both LMWHs reduced the release of vWF in plasma (as well as C-reactive protein) compared with UFH. Enoxaparin had a more favorable effect on glycoprotein Ib/IX complexes than either dalteparin or UFH. The incidence of the composite clinical efficacy end point was: 13% (enoxaparin), 19% (dalteparin), and 28% (UFH). vWF and its receptor glycoprotein Ib/IX play a key role in acute coronary syndromes. vWF is linked to inflammation and, like glycoprotein Ib/IX, is affected more favorably by the LWMHs than by UFH.

Angina, Unstable↗
PubMed2003

[New and future antithrombotic agents in thrombo-embolic venous disease].

Two new classes of anticoagulants in development at the present time [anti-factor Xa and anti-factor IIa (direct antithrombin) agents] should change our future strategies for prevention and treatment of venous thromboembolic events. Among the anti-factor Xa, the pentasaccharides are initiating their clinical use. Fondaparinux, the synthetic form of the natural pentasaccharide is active in prevention and treatment of venous thromboembolic and coronary thrombotic events. A modified form (idraparinux) whose pharmacokinetics allows one administration only once a week should have the same type of efficacy. Among direct antithrombin agents, hirudin and derivatives have been developed in the past decade burt are not routinely used. Synthetic direct antithrombins allowing oral route are currently developed: Exanta with the most advanced development, is active in prevention and treatment of venous thromboembolic and coronary thrombotic events. It could allow (if confirmed by clinical trials) a complete oral treatment of deep vein thrombosis without any biological monitoring. Exanta is also active in the prevention of arterial thromboembolic events on atrial fibrillation. Other molecular forms of synthetic per os direct antithrombin are also in development. But molecules aimed at other targets are also tested: the most advanced are those antagonizing the initial phase of tissue factor activation of factor VII but other strategies are being tested such as stimulation of fibrinolysis.

Antithrombins↗
PubMed2003

Reduced thrombus cohesion in an ex vivo human model of arterial thrombosis induced by clopidogrel treatment: kinetics of the effect and influence of single and double loading-dose regimens.

OBJECTIVE: To compare the effects of clopidogrel on ex vivo thrombogenesis with those on ADP-dependent platelet aggregation, and to compare single and double loading-dose regimens. METHODS AND RESULTS: Step 1: Volunteers (n=12) received clopidogrel 75 mg/day for 8 days. ADP-induced platelet aggregation was measured in platelet-rich plasma (PRP). Thrombogenesis was measured in an ex vivo model. Clopidogrel produced rapid platelet inhibition, increasing up to day 5. Maximal intensity of platelet aggregation correlated with density of platelet thrombus, surface of collagen covered by platelets and thrombus cross-sectional surface (p<0.001). Step 2: On day 1, volunteers (n=60) randomly received clopidogrel 75 mg, a single 300-mg loading dose or two 300-mg loading doses separated by a 12-h interval. On day 2, all volunteers received clopidogrel 75 mg. Both loading dose regimens enhanced platelet inhibition at all time points (p<0.03 vs. clopidogrel 75 mg). After 3 h, the antiplatelet effect of a loading dose was substantial, and the mean decrease in dense thrombus surface was greater in the loading-dose groups than in the 75 mg group (p=0.041 for the single loading dose). Ex vivo, there were no significant differences between loading-dose groups. CONCLUSIONS: Clopidogrel reduces arterial thrombus cohesion by an effect that correlates with inhibition of ADP-induced platelet aggregation. A single 300-mg loading dose provides a rapid onset of such an antithrombotic effect, which was more significant at 24 h with the double loading dose.

Adult↗
PubMed2003

Soluble CD14 and aortic stiffness in a population-based study.

OBJECTIVE: Soluble CD14 (sCD14), an effective mediator for the activation of monocytes by bacterial endotoxin is involved in the release of substances able to modify the characteristics of the arterial wall. The aim of this study was to investigate, in humans, the relationship of sCD14 with aortic stiffness and to analyse the influence of arterial structure and endothelial function on this relationship. DESIGN: Cross-sectional population-based study. PARTICIPANTS: One thousand and fifteen subjects randomly selected from the polling lists, were recruited by the Toulouse MONICA centre between 1995 and 1997. METHODS: Carotid-femoral pulse wave velocity (PWV) and blood pressure (BP) were measured in the supine position. Common carotid intima-media thickness (IMT) and the presence of plaques were assessed by ultrasonography. sCD14 was measured using an immunoenzymatic method. RESULTS: The results concern the 891 subjects with complete data for all the variables. In the bivariate analyses, PWV (P < 0.001), systolic BP (P < 0.05), pulse pressure (PP) (P < 0.01), IMT (P < 0.001), the number of plaques (P < 0.05) and von Willebrand factor activity (vWFa) (P < 0.001) were positively associated with sCD14, whereas no significant relationship was observed between sCD14 and diastolic BP. After adjustment for age and sex, no significant relationship remained between IMT, the number of plaques, SBP, PP and sCD14. A significant and positive relationship was observed between sCD14 and PWV (trend P < 0.05) after adjustment for numerous confounders. CONCLUSION: This population-based study yields first evidence that sCD14 is associated with aortic stiffness independently of age, BP and atherosclerosis in humans.

Adult↗
PubMed2003

In vivo pig models of venous thrombosis mimicking human disease.

Most animal models of venous thrombosis involve acute thrombosis with hypercoagulability in small rodents. To better replicate human disease, we developed two models in the pig, a species similar to humans in size and in vascular and coagulation reactivity. One model involves de-endothelialisation with 50% or 80% stenosis and the other replacement of a venous segment by a Gore-Tex vascular prosthesis. Both models were tested with and without acute induced hypercoagulability (thromboplastin infusion). Thrombi obtained without thromboplastin infusion were composed of a multilayered platelet and a fibrin meshwork structure similar to that usually found in humans. With thromboplastin infusion, the thrombi were homogeneous fibrin structures imprisoning red blood cells. The high incidence of thrombosis obtained with the 80% stenosis model would be useful for studying anticoagulant treatments, whereas the low incidence with 50% stenosis would be useful for evaluating procoagulant effects of conditions or treatments. These new models shed further light on the development of venous thrombi under conditions similar to those seen in humans and may prove useful for investigating anticoagulant and procoagulant effects.

Animals↗
PubMed2003

[Treatment and prevention of venous thromboembolic events: present and future antithrombotic agents].

Two new classes of anticoagulants are actually developed which would change in the near future our strategies for the prevention and the treatment of venous thromboembolic events. These two classes are the anti-factor Xa and anti-factor IIa (direct antithrombin) agents. Among the anti factor Xa, the pentasaccharides are initiating their clinical use. Fondaparinux is a synthetic form of the natural pentasaccharide, its pharmacokinetics allows one s.c. administration/24 hours. It is active in prevention and treatment of venous thromboembolic and coronary thrombotic events. A modified form (idraparinux) whose pharmacokinetics allows one administration only once a week should have the same type of efficacy. Among direct antithrombin agents, hirudin and derivatives have been developed in the past decade with a limited use due to several drawback. More recently synthetic direct antithrombins modified to allow oral route have been developed, the most advanced in development, melagatran, is active in the prevention and treatment of venous thromboembolic and coronary thrombotic events. It could allow (if confirmed by clinical trials) a complete oral treatment of deep vein thrombosis without any biological monitoring. Melagatran is also active in the prevention of arterial thromboembolic events on atrial fibrillation. But other molecular forms of synthetic orally active direct antithrombin are also in development. Besides these important changes in our therapeutics which should appear in a near future, molecules aimed at other target are also tested: the most advanced are those antagonizing the initial phase of tissue factor activation of factor VII but other strategies are being tested such as stimulation of fibrinolysis. These new drugs at our disposal to treat venous thromboembolism should modify completely our handling of the patients. But additionally the numerous clinical trials necessary to prove the efficacy of the drugs, modify our understanding in the implication of the coagulation and in the physiopathogeny of thrombotic events.

Administration, Oral↗
PubMed2002

Erythropoietin and granulocyte colony-stimulating factor increase plasminogen activator inhibitor-1 release in HUVEC culture.

UNLABELLED: Recombinant human erythropoietin (rHuEPO) is considered to be a mitogenic and chemotactic agent in cultured endothelial cells (ECs). The effect of recombinant granulocyte-macrophage (rGM-CSF) and granulocyte (rG-CSF) colony-stimulating factors on the proliferation of human umbilical vein endothelial cells (HUVECs) has been controversial. METHODS: HUVEC proliferation and the release of endothelial markers in HUVEC culture stimulated by rHuEPO, rGM-CSF and G-CSF were measured. RESULTS: We found the dose-dependent stimulating effect of rHuEPO and rGM-CSF on HUVEC proliferation, but we did not achieve this with rG-CSF. rHuEPO like rG-CSF was an effective agent in stimulating the plasminogen activator inhibitor (PAI)-1 release from HUVECs to a cultured medium, while rGM-CSF failed. CONCLUSION: We suggest that rHuEPO showed prothrombotic changes in HUVEC culture. Our results support the idea of suspected rHuEPO direct prothrombotic role in haemodialysed patients treated with rHuEPO.

Biomarkers↗
PubMed2002

Soluble intercellular adhesion molecule-1 is associated with carotid and femoral atherosclerosis but not with intima-media thickness in a population-based sample.

Since inflammatory mechanisms seem to be involved in different stages of atherosclerosis, we analysed a random population-based sample of 972 subjects to assess the relationships between soluble intercellular adhesion molecule-1 (sICAM-1), subclinical peripheral atherosclerosis and intima-media thickness (IMT). B-mode ultrasonography was used to assess the presence of carotid (common and internal) and femoral atherosclerotic plaques and to measure common carotid IMT (avoiding plaque sites). Mean sICAM-1 level was 287.4 (standard deviation: 102.8) and 255.2 (83.5) ng/ml, respectively, in subjects with and without carotid plaques (P<0.0001). It equalled 286.7 (101.1) and 249.7 (79.7) ng/ml, respectively, in subjects with and without femoral plaques (P<0.0001). Subjects beyond the 90th percentile of common carotid IMT had higher sICAM-1 levels than those below, but this was not significant (P=0.08). Multiple logistic regression analyses adjusted for age, gender and other cardiovascular risk factors showed that sICAM-1 was independently associated with the risk of having at least one carotid plaque (adjusted odds ratio for a 10 ng/ml increase in sICAM-1: OR=1.03, 95% confidence interval: [1.02-1.05]) and with the risk of having at least one femoral plaque (adjusted OR=1.04 [1.02-1.06]). On the other hand, no significant relationship was found in multivariate analysis between sICAM-1 and common carotid IMT.

Adult↗
PubMed2002

Dissociation between fibrinogen and fibrin interaction with platelets in patients with different subtypes of Glanzmann's thrombasthenia: studies in an ex vivo perfusion chamber model.

To explore the possible role of a residual or variant alphaIIbbeta3 integrin (alphaIIbbeta3) in thrombogenesis, we used a new ex vivo perfusion chamber model to examine blood from patients with different subtypes of Glanzmann's thrombasthenia (GT). Non-anticoagulated blood was perfused through capillaries coated with type III collagen for 4.5 min (shear rate: 1600/s). Platelet deposition was quantified as platelet adhesion and mean thrombus size volume; fibrin and von Willebrand Factor (VWF) were specifically revealed by immunohistochemistry. In two patients with variant and in one patient with type II GT, platelet adhesion was maximal and we observed an unexpected formation of thrombi that were smaller than normal in size. These thrombi were surrounded by a thick meshwork that displayed a strong staining for fibrin and VWF. In two patients with heterozygous GT, platelet adhesion and thrombogenesis were normal. In two patients with type I GT, there was no thrombus formation, although platelet adhesion was also maximal. These data suggest the existence of a substitute pathway for thrombogenesis mediated by fibrin and possibly alphaIIbbeta3 (alphaIIbbeta3 at a reduced level, as in type II, and/or abnormal) as this fibrin network was not observed in type I GT with no alphaIIbbeta3. These interactions might facilitate haemostasis and even lead to thrombosis under certain favourable conditions. Furthermore, these data might have pharmacological relevance to the development of anti-alphaIIbbeta3 antithrombotic agents.

Blood Platelets↗
PubMed2002

Association between a genomic polymorphism within the CD14 locus and septic shock susceptibility and mortality rate.

OBJECTIVE: Genetic differences in immune responses may affect susceptibility to and outcome of septic shock. CD14 seems to be an important part of the innate immune system, initiating antimicrobial response. We evaluated the frequency of a recently discovered CD14 promoter gene polymorphism (C to T transition at base pair -159) among patients with septic shock compared with those in a control group. DESIGN: Multiple-center study. SETTING: Hospital research department. PATIENTS: Ninety consecutive white patients with septic shock were included. The control group consisted of 122 age- and gender-matched white subjects. INTERVENTIONS: In both groups, the C-159T CD14 promoter genetic polymorphism was determined by using polymerase chain reaction and subsequent Hae III restriction enzyme digestion of the polymerase chain reaction products. MEASUREMENTS AND MAIN RESULTS: The C-159T polymorphism and the TT genotype were significantly overrepresented among septic shock patients compared with controls. Within the septic shock group, the mortality of patients with TT genotype (71%) was significantly higher than in patients with other genotypes (48%; Pearson chi-square, p =.008). In a multiple logistic regression model, the TT genotype was independently associated with an increased relative risk of death (odds ratio, 5.30; 95% confidence interval, 1.20-22.50, p =.02). CONCLUSIONS: The C-159T polymorphism affects susceptibility to septic shock and seems to be a new genetic risk factor for death.

Female↗
PubMed2002

Atherothrombosis as a systemic disease.

Atherothrombosis is a generalized disease process that affects large- and medium-diameter arteries throughout the arterial tree. The trigger of the ischaemic clinical events is the complication of a disrupted atherosclerotic plaque by the formation of a platelet-rich thrombus. These thrombotic events are not always clinically manifest; in most cases, the thrombotic reaction remains parietal but contributes to plaque growth by infiltration of the thrombus by smooth muscle cells. In addition, the evolution of the thrombotic reaction destroys the microvasculature of the downstream tissue by subclinical platelet thrombi. Less often, the resulting thrombus leads to partial or total occlusion of the affected artery with subsequent ischaemic clinical manifestations such as ischaemic stroke, unstable angina and Q-wave or non-Q-wave myocardial infarction. The proportion of ischaemic arterial events that is due to atherothrombosis varies according to the vascular bed in which the event occurs, from a near-total dependency for the lower limbs (intermittent claudication) to less than 50% for cerebrovascular events (ischaemic stroke). Occurrence of an arterial ischaemic event due to atherothrombosis implies that other arterial territories may already be affected by a similar pathological process, even if still clinically silent. Treatment of atherothrombotic patients should include the management of cardiovascular risk factors (which aims at the prevention of incidence, evolution and instability of the plaques) and antiplatelet treatment for the prevention of thrombotic complications. Secondary prevention of an ischaemic event in the index territory will provide primary prevention for other arterial territories that are still clinically silent. The aims of antiplatelet therapy are first to prevent the occurrence of acute ischaemic events through inhibition of platelet thrombus formation and second to protect distal tissues through inhibition of microembolization. Due to the systemic nature of the disease, antiplatelet therapy that has shown a proven consistent benefit across all arterial beds is mandatory for optimal prevention of ischaemic events in atherothrombotic patients.

Female↗
PubMed2002

Prevalence of insulin resistance syndrome in southwestern France and its relationship with inflammatory and hemostatic markers.

OBJECTIVE: To assess the prevalence and relationships of insulin resistance syndrome (IRS) with inflammatory and hemostatic markers in a representative sample of the population of Southwestern France aged 35-64 years. RESEARCH DESIGN AND METHODS: In this cross-sectional study, data were collected from 597 men and 556 women and were assessed regarding BMI, blood pressure, total and HDL cholesterol levels, triglyceride level, glucose level, plasma insulin level, white blood cell count, fibrinogen level, factor VII level, von Willebrand factor, C-reactive protein level, soluble intercellular adhesion molecule, soluble vascular cell adhesion molecule-1, and soluble CD(14). Insulin resistance was defined by homeostasis model assessment > or =3.8. RESULTS: Prevalence of IRS was higher in men than in women (23 vs. 12%, respectively; P < 0.001) and increased with age in both sexes (9, 24, and 34% for age groups 35-44, 45-54, and 55-64 years, respectively, for men and 4, 10, and 21% for women). After adjusting for age, alcohol consumption, tobacco smoking, and also for menopause in women, subjects (men and women) with IRS had significantly higher white blood cell count, factor VII levels, coagulating factor VII levels, and C-reactive protein levels than the other subjects. In men, further increases in soluble intercellular adhesion molecule and soluble vascular cell adhesion molecule-1 were noted, whereas in women, the differences were borderline significant. Conversely, no differences were found in fibrinogen, von Willebrand factor, and soluble CD(14) in both sexes. CONCLUSIONS: IRS is relatively common in residents of Southwestern France and is related to a deleterious increase in hemostatic and inflammatory parameters.

Adult↗
PubMedDate not supplied

Management of intracranial hemorrhage in patients with mechanical circulatory support: a role for low-molecular-weight heparins?

Patients on mechanical circulatory support are at high risk of bleeding, particularly intracranial hemorrhage (ICH). The management of ICH in patients needing anticoagulation and antiplatelet therapies remains a challenge. We report our initial experience of ICH management with low-molecular-weight heparin in patients with mechanical circulatory support, without bleeding or thromboembolic complications.

Aged↗
PubMedDate not supplied

Low molecular weight heparin for the prevention of deep venous thrombosis: a suitable monitoring in elderly patients?

Monitoring of anti-Xa activity (aXa) levels is not routinely required in patients receiving enoxaparine at prophylactic dosages, since aXa is supposed to stay below the manufacturer's recommended range in patients treated for venous thrombosis (0.5-1 IU/ml). In order to aXa in elderly subjects receiving prophylactic enoxaparin, 68 consecutive patients (mean age 82.5 +/- 10.7 years) hospitalized in a medical department receiving 4000 IU enoxaparin daily subcutaneously for the prevention of venous thromboembolic disease were studied. After the first injection of enoxaparin, the aXa of 57.4% patients was superior to 0.5 IU/ml while 69.4% had an aXa higher than 0.5 after 8.4 +/- 1.2 days. A negative relationship between aXa and body weight and a trend towards a positive correlation between aXa and age but not with creatinine clearance were noted. Our findings question the opportunity to monitor aXa in elderly patients receiving 4000 IU enoxaparin as antithrombotic prophylaxis.

Age Factors↗
PubMedDate not supplied

[Is fibrinogen a predictor or a marker of the risk of cardiovascular events?].

Most cardiovascular events result from a thrombotic complication of an atherosclerotic lesion. Inflammation plays a central role in both the pathogenesis of atherosclerosis and the progression of its complications (especially plaque rupture). Fibrinogen, on the one hand a marker of inflammation and on the other a major determinant in thrombosis and haemorrheology, plays a central role in atherosclerosis and its thrombotic complications. The clinical data are in agreement with epidemiological data, and show that increased plasma fibrinogen levels (compared with values in paired controls) are predictive of the risk of cardiovascular events - both primary cardiovascular events in the general population and recurrence in patients. Determining the plasma fibrinogen level in terms of genetic predisposition and environmental factors provides a good example of the interrelationship between genes and the environment. It must be recognised that a minimal increase in the fibrinogen level (within the plasma reference values) is an indicator of a significantly increased risk. This shows why epidemiological data are not useful for determining cardiovascular risk in individual patients in daily clinical practice (with the exception of the very high levels that are infrequently observed).

Amino Acid Sequence↗