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Biomedical subjects

M M Samama

Publications and source records attributed to M M Samama.

158 records · Page 9Linked to original sources
PubMedDate not supplied

An epidemiologic study of risk factors for deep vein thrombosis in medical outpatients: the Sirius study.

BACKGROUND: Little information is available concerning risk factors for venous thromboembolism (VTE) in nonhospitalized patients. PARTICIPANTS AND METHODS: An epidemiologic case-control study of deep vein thrombosis (DVT) risk factors was conducted in 1272 outpatients by general practitioners. The case population (636 patients presenting with DVT) was paired with the control population (636 patients presenting with influenzal or rhinopharyngeal syndrome) according to sex and age. Deep vein thrombosis was to be documented by at least 1 objective test. Risk factors were classified into "intrinsic" ("permanent") and "triggering" ("transient") factors and were evidenced using univariate analysis. RESULTS: In the medical population, defined as patients who had not undergone surgery or application of a plaster cast to the lower extremities within the 3 weeks preceding inclusion (494 cases and 494 controls), intrinsic factors such as history of VTE, venous insufficiency, chronic heart failure, obesity, immobile standing position, history of more than 3 pregnancies, and triggering factors such as pregnancy, violent effort, or muscular trauma, deterioration of general condition, immobilization, long-distance travel, and infectious disease were significantly more frequent in the case patients than in the controls (odds ratio, >1; P<.05). In the overall population, additional risk factors were cancer, blood group A, plaster cast of the lower extremities, and surgery. In both populations, the number of risk factors per patient was greater in the case patients than in the controls. CONCLUSION: Several risk factors for DVT were identified in medical outpatients presenting with DVT, and their comprehension may improve appropriateness and efficiency of the different methods available for thromboprophylaxis. Arch Intern Med. 2000;160:3415-3420.

Adult↗
PubMedDate not supplied

Screening for inherited thrombotic disorders.

In order to determine a scheme for the screening of inherited thrombotic disorders, abnormalities considered as predisposing to thrombosis have been reviewed. Owing to the low prevalence of biological alterations, a selection of patients is required: documented venous thromboses, possibly at unusual sites (mesenteric vein, portal, cerebral veins), occurring before the age of 40 in patients with a positive family history of thromboses are relatively frequently associated with coagulation abnormalities. In addition, patients with skin necrosis at the initiation of oral anticoagulants, or with repeated superficial vein thrombosis or unexplained arterial occlusions at a young age might be included for screening. Tests have also to be selected. Some abnormalities, such as congenital deficiencies in antithrombin III, protein C and protein S, are recognized risk factors and have to be searched. Some others cannot be at present considered as definite risk factors (e.g., dysfibrinogenemias or deficiencies in factor XII), but their detection is easy by routine tests: prothrombin time, fibrinogen assay. Other abnormalities are recognized risk factors (or not) and need specific uncommon tests (e.g., study of fibrinolysis). Each time a biological abnormality is found, it is important to verify it is isolated since combined deficiencies have been observed and we should be able to answer the question whether the abnormality is the cause or the consequence of thrombosis, or a coincidence. Finally, in our experience, even in well selected patients, a coagulation disorder is detected in less than 30% of patients, so that new tests are needed to improve our knowledge in this field.

Antithrombin III Deficiency↗
PubMedDate not supplied

The role of abnormalities in the anticoagulant and fibrinolytic systems in retinal vascular occlusions.

The hemostatic mechanisms involve both an anticoagulant system to check the coagulation cascade and a fibrinolytic system to remove formed fibrin clots. Abnormalities of the hemostatic system or acquired abnormal hematological factors can produce a thrombophilic state which accounts for 15-28% of unexplained systemic vascular thrombosis in young patients. Similar abnormalities have recently been identified in some patients with retinal vascular occlusions. Screening of selected patients with retinal vascular occlusions may reveal additional ophthalmological patients with specific thrombotic syndromes.

Blood Coagulation Disorders↗
PubMedDate not supplied

Thrombolysis and adjunctive therapies in acute myocardial infarction.

Thrombolysis and percutaneous transluminal angioplasty represent the cornerstone of the pharmacologic treatment of and the interventional approach to patients with myocardial infarction (MI). They are very effective. However, they are hampered by some critical limitations. Therefore, alternatives to standard thrombolytic therapy have been developed. Platelet glycoprotein (GP) IIb/IIIa blockade is under investigation and seems very attractive. This review will focus on the use of GP IIb/IIIa antagonists and thrombin inhibitors as adjunctive therapies to the thrombolytic treatment of patients with acute MI.

Acute Disease↗
PubMedDate not supplied

Mechanisms for the antithrombotic activity in man of low molecular weight heparins (LMWHs).

Although LMWH have been widely used for several years, the mechanisms of their anti-thrombotic action are not well understood. This is due in part to the misconception that in vitro coagulation results can be extrapolated to the in vivo antithrombotic condition. Thus, the mode of action of heparins on thrombin generation in plasma after addition of increasing amounts of unfractionated heparin (UH) or LMWH has been investigated in several studies, but a distinction has to be made between the effects on the intrinsic and the extrinsic system. The same applies for experiments conducted with platelet-poor plasma (PPP) and platelet-rich plasma (PRP). These experiments show that inhibition of prothrombin activation in PPP is more pronounced in the intrinsic system than in the extrinsic system for both types of heparin. This inhibition has been attributed mainly to their antithrombin activity which reduces factor V and factor VIII activation and its related positive feedback on thrombin formation. The comparison of the effects of low doses of LMWH and UH in citrated PRP indicate that LMWH are more active than UH because they are more resistant to platelet neutralization by platelet factor 4. Moreover, in vitro study will neglect the role of pharmacokinetic parameters which are important determinants of the antithrombotic activity of heparins. Another important difference between in vitro and in vivo studies lies in the fact that sc injection of both heparins will release tissue factor pathway inhibitor (TFPI) in the blood. We have used native whole blood for in vitro and ex vivo experiments. This offers the advantage of studying heparin activity in the presence of platelets and calcium. In this condition the inhibition of pro-thrombin and factor VII activation during blood coagulation in a glass tube (intrinsic system) was judged by measuring residual prothrombin and factor VIIa in serum obtained 2 to 4 hours after clotting. At prophylactic doses, LMWHs in contrast to UH significantly inhibit prothrombin activation. Although thrombin inhibition seems essential for the antithrombotic activity of both heparins, reduction of thrombosis is a global effect to which "both anti-IIa and anti-Xa activity contribute but to a different exent" (C. Hemker et al.). It should be noted that the clearance half-life of anti-Xa activity is significantly longer than that of anti-IIa. The efficacy of a single daily injection of LMWH in the prophylaxis of thrombosis is not logical in light of the short half-life of anti-IIa activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMedDate not supplied

Vitamin K metabolism in a patient resistant to vitamin K antagonists.

We investigated various pharmacokinetic and pharmacodynamic parameters in a 63-year-old man, resistant to warfarin, fluindione, acenocoumarol and phenprocoumon. Daily doses of up to 30 mg of the long-acting phenprocoumon yielded a drug concentration of 85 mg/l (usual range 1-5 mg/l) but the international normalized ratio remained around 1. The plasma half-life of phenprocoumon was approximately 350 h (normal 120-150 h). Thus, the resistance was not due to malabsorption or to an accelerated metabolism of the drug. The level of vitamin K1 (1,202 ng/l) was insufficient to induce resistance. Decarboxyprothrombin concentrations were low, demonstrating that the gamma-carboxylation of the precursors of the vitamin K-dependent coagulation factors was not effectively reduced. The concentration of vitamin K epoxide, normally increased under oral anticoagulation, correlated to the vitamin K concentration (r2 = 0.77) but the quotient epoxide/vitamin K remained 4-fold lower than that of 22 warfarin-sensitive patients, suggesting an absence of blockade of the vitamin K reductase by phenprocoumon. This resistance to all the molecular forms of the vitamin K antagonists is most likely due to a reduced affinity of the drugs to a mutant vitamin K reductase.

Drug Resistance↗
PubMedDate not supplied

[Heparin-induced thrombocytopenia].

Heparin-induced thrombocytopenia is a threatening complication of heparin treatment. The physio-pathological mechanism is the production of antibodies, the most frequent target of which is the complex heparin-platelet factor 4. These antibodies may activate the coagulation and lead to venous or arterial thromboembolic manifestations. Clinical features as well as functional and immunological tests are used for the diagnosis. The treatment consists in discontinuing heparin administration and in setting up an alternative treatment for which two drugs are indicated in France: Orgaran and Refludan.

Antibody Formation↗
PubMedDate not supplied

[Follow-up of the treatment by direct thrombin inhibitors: activated partial thromboplastin time or ecarin clotting time].

The clinical use of the direct inhibitors of thrombin requires a reliable test to monitor the treatment and to predict the hemorragic risk. The activated partial thromboplastin time (APTT) is the most common test used to monitor treatment with unfractionated heparin. Thus APTT has been first chosen to follow patients treated with direct thrombin inhibitors, but studies have shown that it was probably not the most appropriate test. Indeed, APTT values were not well correlated with the dose administered and were dependent on the type of the thrombin inhibitor used and on the APTT reagent. The ecarin clotting time (ECT), which converts prothrombin into meizothrombin has been then tested and seemed to be a better test. In vitro studies have shown a good correlation between ECT and the different concentrations of thrombin inhibitors. Furthermore, the ECT in contrast to APTT is not sensitive to heparin or oral anticoagulant and interindividual variations are low with ECT. ECT which is a reliable test and is easy to perform seems to be a more appropriate test to monitor treatment with direct thrombin inhibitors but further studies are needed to validate its use in a clinical setting.

Animals↗
PubMedDate not supplied

[Venous thrombosis and cancer].

The incidence of newly diagnosed cancer is increased, among patients with idiopathic venous thromboembolic event (VTE), six to twelve months after the diagnosis. Among these cancers, the most common sites are colorectal, prostate, pancreas, lung and ovary cancers. However, no study has provided convincing evidence that a patient with idiopathic VTE should undergo an extensive search for underlying cancer. An hypercoagulable state is observed in cancer patients, as shown by abnormal "routine" blood tests found in up to 90% of these patients, as well as increased levels of specific markers of coagulation activation. Clinically, these abnormalities are expressed as thrombosis, hemorrhage or low grade or fulminant disseminated intravascular coagulation. The pathophysiology of this thrombophilic state is complex and due to interactions of tumor cells and their products with host cells. Cancer patients are thus at high risk of thrombosis and so far no biological test can predict the VTE. In special conditions, as surgery or during chemotherapy, prophylaxis with various forms of heparins or oral anticoagulant are recommended.

Administration, Oral↗
PubMedDate not supplied

[Influence of oral anticoagulant treatment on D-dimers levels].

The usefulness of D-dimers determination for the exclusion of deep vein thrombosis (DVT) has been extensively studied. The persistence of high levels of D-dimers has also been suggested as a marker of hypercoagulability in rare studies and might be used to identify patients at risk for recurrent DVT. We have studied the influence of oral anticoagulant treatment in 149 patients, 17 to 84 year-old, with a history of venous thromboembolism; 81 received oral anticoagulant treatment, 68 did not. Patients with known reasons for high level of D-dimers such as cancer were excluded. Thrombophilia was found in 84 patients. D-dimers measurements were performed by ELFA technique using Vidas (bioMérieux, France) analyzer. A significantly lower level of D-dimers was observed in patients under oral anticoagulant compared to patients without this treatment, 197 +/- 134 mug/L versus 399 +/- 239 mug/L, respectively (p < 0.001). A level upper the normal value (500 mug/L) was found in only 3 patients out of 81 receiving an oral anticoagulant treatment as compared with 21 of the 68 patients without treatment. This decrease of D-dimers in patients receiving oral anticoagulants was the same in the different age populations. There was no correlation between INR and D-dimers levels in this study. The clinician should be informed of the decrease of D-dimers in patients treated with anticoagulants. The decrease of D-dimers plasma level during oral anticoagulant treatment suggest that D-dimers concentration in plasma is an indirect marker of reduced clotting activity in vivo.

Administration, Oral↗