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Biomedical subjects

M M Samama

Publications and source records attributed to M M Samama.

At least 91 records · Page 5Linked to original sources
PubMed1996

[Prevention of venous thromboembolic disease].

The prevention of post-operative venous thromboembolic accidents is well documented. This is in contrast to prophylaxis in medical patients. In surgical patients, prophylaxis should take into consideration the risk associated with the operation and the patient's risk factors. Low molecular weight heparins (LMWH) are frequently used since they more convenient and at least as efficiacious or somewhat superior to subcutaneous administration of unfractionated heparin (UH). Gradued compression stockings are recommended for low or moderate risk of thrombosis. Their use in combination with LMWH is limited to high risk patients. Oral anticoagulants are mainly used when long term prophylaxis starting with LMWH administration is required. Several meta-analysis and consensus conferences in France, Europe or North-America have provided recommendations, the comparison of which shows a great homogeneity. It is generally accepted that the recommendations made for surgical patients may be extrapolated to medical patients. The medical situations associated with an increased risk of thrombosis which are well documented are cancer, myocardial infarction, cardiac insufficiency, ischemic cerebro-vascular accidents with paralysis of lower limb(s), acute respiratory insufficiency in patients admitted to intensive care unit, prolonged immobilisation in elderly invalid patients and paralysis of the limbs due to spinal trauma. Prophylactic treatment in medical patients is still empirical. The use of LMWH in these patients is related to results obtained when unfractionated heparin is used and in rare controlled clinical trials where LMWH were compared to UH.

Abdomen↗
PubMed1996

Treatment with LMWHs inhibits factor VIIa generation during in vitro coagulation of whole blood.

The role of factor VII and activated factor VII (VIIa) is considered to be crucial in the coagulation process. The efficacy of low molecular weight heparins (LMWHs) in the prevention and treatment of thromboembolic episodes has been established in numerous controlled therapeutic trials. However, the mechanisms of their antithrombotic action are still disputed. Heparins exert their anticoagulant effect by enhancing ATIII inhibitory action on factor Xa and thrombin, which results in decreased factor X activation, prothrombinase formation, prothrombin activation and thrombin generation. Moreover, it is clearly established that both kinds of heparins (unfractionated heparin and LMWHs) induce the release of tissue factor pathway inhibitor (TFPI). Therefore, they are involved indirectly in tissue factor (TF)/factor VIIa complex inhibition by the TFPI/factor Xa complex. Factor VII activation is an essential step in the process of blood coagulation and it plays an important role in thrombogenesis. A method for the measurement of factor VIIa has been recently developed. A study on the effects of antithrombotic drugs, as heparins, on factor VIIa generation might allow to better understand the mechanisms that regulate its activation. We investigated ex vivo the effect of treatment with LMWHs on factor VIIa generation during in vitro coagulation of whole blood in order to clarify if LMWHs interfere with factor VIIa generation.

Adult↗
PubMed1996

Prognostic factors for retinal vein occlusion: prospective study of 175 cases.

BACKGROUND: The prognosis of retinal vein occlusion is highly unpredictable because nonischemic types may convert into ischemic types within the first months. This study was designed to identify epidemiologic characteristics of the different types of retinal vein occlusion, their visual outcome, and their prognostic factors. METHODS: The authors analyzed prospectively the data from patients who have had retinal vein occlusion with complete medical and biologic examination, including fluorescein angiography, and a 1-year follow-up. RESULTS: One hundred seventy-five retinal vein occlusion eyes consisted of 120 central retinal vein occlusions (CRVO), 7 hemicentral occlusions, and 48 branch occlusions. In initially nonischemic CRVO eyes, retinal ischemia developed in 54%. The study of prognostic factors in the CRVO group showed that older age, male sex, and the number of risk factors (systemic vascular risk factors and glaucoma) were correlated with a poor visual outcome and with the development of retinal ischemia, as well as baseline visual acuity, initial extent of retinal ischemia, and rheologic findings (hematocrit, fibrinogen, and erythrocyte aggregation levels). Logistic regression underlined the prognostic role of sex, the number of risk factors, erythrocyte aggregation, and initial clinical features. Persistent macular edema was shown to be associated with hyperlipidemia and cardiovascular history, and inversely correlated to glaucoma. CONCLUSION: Because clinical characteristics of CRVO may worsen, the authors' results provide a basis to predict visual outcome by taking into account epidemiologic and rheologic findings. A careful follow-up of these patients is recommended.

Adult↗
PubMed1996

A fatal low-molecular-weight heparin-associated thrombocytopenia after hip surgery: possible usefulness of PF4-heparin ELISA test.

In 37 patients undergoing total hip replacement, a prophylactic treatment by a low-molecular-weight heparin (LMWH) was conducted for 2 weeks. They belonged to a group of 499 patients included in a multicenter clinically controlled trial comparing two LMWHs. Blood was collected 1 day before surgery (D-1) and at D+1 or D+2 and D+5 or D+6 as well as D+10 through D+14 after surgery for determinations of platelets counts and anti-Xa. Bilateral venography was performed between D+10 and D+14. A fatal heparin-associated-thrombocytopenia (HAT) occurred on D+9 in one patient and was associated with a positive platelet aggregation test. This finding was confirmed with a recent ELISA test which evidenced a high concentration of PF4-heparin dependent antibodies 72 h before the detection of thrombocytopenia. This led us to study retrospectively PF4-heparin ELISA results by testing the plasma samples of 36 other surgical patients treated under the same conditions and during the same period (four measurements per patient). Among these patients, seven had a venous thrombotic event as a treatment failure. Although some authors claimed that some post-operative thromboses may be facilitated by the presence of heparin-dependent antibodies associated with or without thrombocytopenia, no thrombocytopenia and no positive PF4-heparin ELISA test was observed in this group. Out of the 144 tests performed in these 36 patients for the detection of PF4-heparin complexes dependent antibodies, 15 results were borderline in ten patients and three results in two patients were positive. No relation was evidenced between a positive ELISA test and the occurrence of venous thrombosis. This study points out the possible usefulness of the PF4-heparin ELISA test for HAT-antibodies detection. A daily platelet count in a postoperative patient under heparin therapy, showing thrombocytopenia associated with the detection of heparin-dependent antibodies could allow an earlier and more reliable diagnosis of HAT.

Aged↗
PubMed1996

Diagnosis and clinical characteristics of inherited activated protein C resistance.

The diagnostic strategies and clinical characteristics of thrombophilia associated with heterozygous or homozygous factor V Leiden mutation have been determined according to the literature and to a personal study in 51 families. Factor V mutation was present in the 51 propositi and in 84 out of 125 family members (81 heterozygous, 3 homozygous). Venous thrombosis was observed in all the propositi, in 17 of the 84 family members with the mutation and in 6 of the 41 with a normal APC resistance test and no mutation. An associated protein C or protein S deficiency was present in 5 families (10%). The most frequent clinical manifestations were superficial or deep vein thrombosis and/or pulmonary embolism, but also thrombosis at an unusual site (cerebral, mesenteric or central retinal vein). A causal relationship is frequently difficult to demonstrate. A precipitating factor was observed in 84% of cases and a recurrent thrombotic episode occurred in 50% of propositi. The risk of thrombosis associated with pregnancy was high in the post-partum period, especially in homozygous women. In the 28 homozygous subjects, markers of coagulation activation were frequently elevated in untreated patients. Finally, the efficacy of anticoagulant treatment is suggested but the long period often observed between treatment interruption and a recurrence does not militate in favour of long term treatment.

Anticoagulants↗
PubMed1996

Levels of factor VIIc associated with decreased tissue factor pathway inhibitor and increased plasminogen activator inhibitor-1 in dyslipidemias.

Tissue factor pathway inhibitor (TFPI), a kunitztype inhibitor of the extrinsic coagulation pathway, factor VII coagulant (FVIIc), FVIIa, and the fibrinolytic factors plasminogen activator inhibitor-1 (PA1-1) and tissue plasminogen activator (TPA) have been studied in various hyperlipidemias. Compared with a normal lipidic group, mean TFPI activity was 70% higher (P < .001) and 36% higher (P < .001) in type IIa and IIb hyperlipidemias, respectively, and was lower by 13% in type IV hyperlipidemia (P = .05). TFPI was correlated with LDL cholesterol (P < .001), total cholesterol (P < .001), HDL cholesterol (P < .01), apolipoproteins (apo) AI (P < .001) and B (P < .001) and lipoprotein a (P < .01). TFPI was negatively correlated with the triglyceride level (P < .05); the correlation was dependent on LDL cholesterol and HDL cholesterol levels, which were decreased in type IV hyperlipidemia. FVIIc activity (P < .001) was increased by 30% in both type IV and type IIb hyperlipidemia and was correlated with triglyceride levels. FVIIa was not significantly increased in any group compared with control group. FVIIc was correlated with triglyceride level (P < .001), while FVIIa was not. Interestingly, FVIIa was correlated with FVIIc (r = .5, P < .001) in the control group as well as in the hyperlipidemic groups (r = .32, P < .01). These results favor the hypothesis that higher FVIIc concentrations in hyperlipidemic patients are likely due to enhancement of synthesis of FVII and that a part of this FVII circulates in an activated chemical form. Compared with the control group, PAI-1 activity was twofold higher (P < .08) in type IIa hyperlipidemia, threefold higher (P < .001) in type IIb hyperlipidemia, and fourfold higher in type IV hyperlipidemia (P < .001). PAI-1 activity correlated with triglyceride levels (P < .001), apoB levels (P < .001) and total cholesterol levels (P < .05). These correlations were dependent on apoB and probably reflect the correlation between PAI-1 and VLDL. In contrast, TPA level was normal in the different hyperlipidemias. No correlation was found between TFPI, FVIIc, and PAI-1. Variation of TFPI activity appears to be related to the variations of its main lipoprotein carriers: LDL, HDL, and Lp (a). The association in hypertriglycemic patients of hypercoagulability (increased FVIIc and decreased TFPI) and hypofibrinolysis (increased PAI-1) may explain thrombosis predisposition of some of these patients. However, it would be interesting to study the increased levels of endothelium-derived TFPI in plasma induced by the injection of heparin.

Adult↗
PubMed1996

Coagulation studies, factor V Leiden, and anticardiolipin antibodies in 40 cases of cerebral venous thrombosis.

BACKGROUND AND PURPOSE: Cerebral venous thrombosis (CVT) is an infrequent condition with a large variety of causes. However, in 20% to 35% of cases, no cause is found. We studied coagulation parameters, including activated protein C resistance associated with factor V gene mutation (factor V Leiden) and anticardiolipin antibodies, in a large series of patients with CVT with or without identified cause or risk factor. METHODS: Forty patients (30 women and 10 men) aged 19 to 71 years (mean age, 36.2 years) with CVT diagnosed by angiography and/or MRI were studied 1 to 18 years after thrombosis. No known cause was found in 10 idiopathic cases. Coagulation studies included the following tests: fibrinogen, antithrombin, protein C, protein S, plasminogen, anticardiolipin antibodies, activated protein C resistance, and factor V Leiden. RESULTS: Six cases of thrombophilia (15%) were found: 1 protein C deficiency, 1 protein S deficiency, and 4 activated protein C resistance with heterozygous factor V Leiden mutation (10%). Only 1 case (protein S deficiency) was found in the group of 10 patients with idiopathic CVT. In the other 5, there was another cause or risk factor. Three patients (8%) had increased anticardiolipin antibodies: 1 with systemic lupus and 2 with primary antiphospholipid syndrome; 2 of these 3 patients also had factor V Leiden mutation. CONCLUSIONS: Although present in a number of CVT cases, acquired (anticardiolipin) or congenital varieties of thrombophilia (factor V Leiden being the most frequent) are almost invariably associated with other predisposing factors. This suggests that (1) these abnormalities should be looked for in patients with CVT, whether a cause is found or not, and (2) their presence should not deter the search for other potential causes. The detection of such abnormalities has major practical consequences on the long-term management of patients to prevent further thrombotic episodes.

Adult↗
PubMed1996

New data on the pharmacology of heparin and low molecular weight heparins.

Studies on the pharmacological and pharmacodynamic properties of heparins are complicated by the heterogeneity of heparin preparations. It is important to consider the molecular weight distribution, which may differ from one preparation to another. Molecules with a molecular weight ranging from about 2000 to 5000D are abundant in low molecular weight heparins (LMWHs), while they are present at a very low concentration in standard heparin. The clinical relevance of this difference is not fully understood. Recent work from our laboratory demonstrates that factor VII activation to factor VIIa in vitro is significantly inhibited by heparins. This is another aspect of some importance in understanding the mechanism of action of heparins. The bioavailability and plasma clearance of anti-Xa activity are well documented. In contrast, clear results regarding the bioavailability of anti-IIa activity are still missing. Recent data indicate that the anti-Xa activity of different molecules of heparin does not increase in parallel with the molecular weight of the heparin chain. In contrast, the anti-IIa activity of different molecules of heparin increases in parallel with the molecular weight. This could explain why activated partial-thromboplastin time is less prolonged with LMWHs than with standard heparin. There is growing evidence that anti-Xa activity contributes to the antithrombotic effect of heparins, although it is generally accepted that anti-IIa activity plays a major role. There have been 3 important findings from recent work on the pharmacology of heparins: i) heparin at a very low dose has thrombopoietic activity; ii) in hip surgery, the incidence of heparin-induced thrombocytopenia is significantly lower in patients receiving subcutaneous LMWHs for 2 weeks compared with patients receiving unfractionated heparin; and iii) the risk of osteoporosis with long term treatment with LMWHs seems lower than with standard heparin.

Animals↗
PubMed1996

[Osteoporosis induced either by unfractionated heparin or by low molecular weight heparin].

Since the first suggestion of heparin-induced osteoporosis in 1963, a large body of work has been published. The mechanism can be explained by the effect of heparin as a cofactor for physiological stimulators of osteoclasts. Low-molecular weight heparins are an interesting alternative to non-fractionate heparin as the risk is reduced with an equivalent anticoagulation activity. Prevention is based on screening for patients at risk, preferential use of low-molecular weight heparins, early switch to anti-vitamin K and vitamin and calcium supplementation in pregnant women an elderly subjects. Curative treatment combines vitamin-calcium supplementation with inhibitors of bone resorption.

Aged↗
PubMed1996

[Low molecular weight heparin in unstable angina].

Encouraging results have been reported with non fractionated heparin in the acute treatment of unstable angina. Recent therapeutic trials have shown that some low molecular weight heparins, associated with aspirin, and prescribed in the long term after the hospital phase, have a significant beneficial effect on the frequency of clinical events. A phenomenon of reactivation with a notable increase in clinical events has clearly been demonstrated in the period following withdrawal of heparin. Data comparing non fractionated and low molecular weight heparins are scarce at present. A major question remains: the choice of therapeutic strategy after the acute phase, pharmacological or early revascularisation? Clinical trials taking pharmaco-economic aspects into consideration are required.

Angina, Unstable↗
PubMed1996

[Biological monitoring and prevention of complications from antithrombotic agents].

Antithrombotic agents are widely prescribed in cardiovascular diseases. It is essential to understand the conditions of biological monitoring and the potential complications of these drugs. Treatment with unfractionated heparin and vitamin-K antagonists requires strict biological follow-up, the rules of which must be respected to avoid therapeutic failure or bleeding complications. Biological monitoring of low molecular weight heparins is extremely simple and that of antiplatelet agents is unnecessary. Regular patient follow-up, both clinical and biological, the respecting of contra-indications and recommendations of usage, and special attention to the problem of drug interaction, should result in better efficacy and tolerance of antithrombotic therapy.

Adult↗
PubMed1995

[New antithrombotic agents].

The wide range of compounds currently being developed is the result of the continuing need for validated new antithrombotic agents. The prevention and treatment of venous thrombosis is predominated by anticoagulants: low molecular weight heparins, and potentially new antithrombin agents including hirudin. The effectiveness of new antiplatelet agents, and particularly c7E3 and integrelin, confirms the hypothesis concerning the role played by platelets in thrombogenesis in coronary arteries. But, due to the proaggregating effect of thrombin, anticoagulants could also have an important role in preventing arterial clots, either when given alone or in combination. Finally, the development of antithrombin and anti-platelet-glycoprotein IIb IIIa given orally is one of the major objectives of current research. Until the ideal antithrombotic agent is discovered, multiple-drug regimens combining anticoagulants and/or antiplatelet agents could be proposed in patients with a very high risk of thrombosis. Such regimens must taken into account the increased risk of bleeding and be adapted on the basis of careful laboratory surveillance.

Factor Xa Inhibitors↗