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Biomedical subjects

M M Samama

Publications and source records attributed to M M Samama.

At least 127 records · Page 7Linked to original sources
PubMed1995

[Association of dysfibrinogenemia and thrombosis. Apropos of a family (Fibrinogen Melun) and review of the literature].

We report a family with history of deep and superficial venous thrombosis. A large number of siblings had numerous episodes of deep venous thrombosis and less frequently arterial thrombosis. The most frequent site was lower limb. Dysfibrinogenaemia seems to play an essential role in predisposition to thromboembolism in this family, other known aetiologies having been excluded. Genetic studies of fibrinogen gene show a point mutation in the gamma chain (364 Asp-Val), the site close to gamma 363 one of the sites involved in fibrin monomers polymerisation, although fibrinogen polymerisation is normal. Review of the 250 families with dysfibrinogenaemia published up to now shows that the prevalence of dysfibrinogenaemia in patients with a history of thromboembolism is about 0.7%, and that thrombosis is observed in about 10% of cases of dysfibrinogenaemia. Abortion risk seems to be increased in women with dysfibrinogenaemia. In contrast thromboembolism risk does not seem to be higher during pregnancy, but may be increased after delivery. The main mechanisms which have been proposed to explain thromboembolism observed in dysfibrinogenaemia are: resistance of the clot to thrombolysis; defective thrombin binding; enhanced platelet aggregation; increased blood viscosity, alteration of clot architecture. This family study together with the previously reported cases supports the hypothesis that there is a link between thrombosis and dysfibrinogenaemia in a small number of patients.

Female↗
PubMed1995

[Study of hemostasis in patients with a recent thromboembolic complication].

The clinical history of well-documented personal or familial episodes of thromboembolism with systematic construction of a genealogical tree orients the diagnosis of hereditary or acquired thrombophilia. The presence of favorable medical or surgical conditions for pulmonary embolism (surgical operation, prolonged bed rest, oral contraception, pregnancy, etc) are commonly observed in thrombophilia. Young age, under 40, at the time of the first episode, the recurrent nature of thromboses and a positive family history are three criteria in favour of the diagnosis of hereditary thrombophilia. Laboratory tests should be performed, if possible anticoagulant therapy, or taking into account its effect on the results, heparin reducing the antithrombin level and the oral anticoagulants those of proteins C and S and affecting the "classical" test of resistance to activated protein C. This abnormality is observed in nearly 20% of patients with previous thromboembolism in familial thrombophilia whereas it is twice less common in deficits of antithrombin, protein C and protein S. The other more or less acknowledged causes, alteration of plasminogen, dysfibrinogenaemia, homocysteinaemia, particular blood diseases, indicating systematic association of a full blood count with blood clotting tests, are much more rare. Of the acquired thrombophilias, the commonest is the presence of circulating anticoagulant and/or anticardiolipine antibodies, these two conditions also requiring systematic investigation. Biological examinations for determining the cause of unexpected pulmonary embolism is essential but should not delay instauring treatment. It should be associated with a familial enquiry if the patient has a hereditary thrombophilia. Interpretation of the results should obey the rule of the 3 cs: is the biological abnormality the cause, a coincidence or the consequence of the affection?

Adult↗
PubMed1994

A randomized, double-masked study on the treatment of retinal vein occlusion with troxerutin.

Hemorheologic factors probably play a role in the pathogenesis and prognosis of retinal vein occlusion. Accordingly, we designed a prospective, randomized, double-masked study to evaluate the effect of troxerutin, a rheologic drug, on retinal vein occlusion. Fifty-three patients were included, 27 with central retinal vein occlusion and 26 with branch retinal vein occlusion. They were randomly assigned for treatment with either troxerutin or a placebo. All subjects were similar in age, gender, associated diseases, hemorheologic values, and clinical severity of the retinal vein occlusion. At the end of follow-up, members of the troxerutin-treated group, as compared with the placebo group, showed significant improvement in visual acuity (P = .03), macular threshold (P = .01), retinal circulation times (P = .04), and macular edema (P = .05). Furthermore, they had diminished progression of ischemia (P = .05) and decreased red blood cell aggregability (P = .006) when compared with the controls. These encouraging preliminary results obtained with a rheologic treatment attest to the pathogenic role of blood viscosity in retinal vein occlusion and suggest that a large-scale randomized study should be conducted.

Adult↗
PubMed1994

Plasma TFPI activity after intravenous injection of pentasaccharide (PS) and unfractionated heparin in rabbits.

Tissue Factor Pathway Inhibitor (TFPI), is known, to be released in plasma after injection of intravenous or subcutaneous injection of heparin or low molecular weight heparin (1,2). Addition of protamine or polybrene in plasma can neutralize anticoagulant effects of heparin in vitro but not completely ex vivo in patients treated with heparin (3). It was believed for many years that this post-heparin anticoagulant effect was due to another activity released by heparin. More recently it has been shown that post-heparin anticoagulant effect could be inhibited by anti-TFPI antibodies (4). Since we have shown in a previous work (5), that in healthy volunteers, pharmacokinetics of TFPI were more closely related to anti IIa activity than anti Xa activity we hypothesized that fragments with anti-IIa activity may be required for this release, possibly from vascular wall. In order to determine if a very low molecular weight glycosaminoglycan can release TFPI in plasma, in the present study, we compared plasma TFPI amidolytic activity after intravenous injection in rabbits of pentasaccharide (PS), a synthetic fragment of very low molecular weight and with a strong and exclusive anti Xa activity, and unfractionated heparin (UFH).

Animals↗
PubMed1994

Elevated erythrocyte aggregation in patients with central retinal vein occlusion and without conventional risk factors.

BACKGROUND: Retinal venous circulation is characterized by the combination of a low flow state and a high vascular resistance, which would make it particularly dependent on blood viscosity. Erythrocyte aggregation is the chief determinant of blood viscosity at low shear rates. Recent studies have demonstrated increased erythrocyte aggregation in many systemic vascular disorders and also in retinal vein occlusion. METHODS: To assess the possible role of abnormal hemorheologic findings in the pathogenesis of central retinal vein occlusion (CRVO), the authors retrospectively studied erythrocyte aggregation and hematocrit and fibrinogen levels in 33 patients with CRVO and without any known risk factors (diabetes, hypertension, smoking, hyperlipidemia, cardiovascular disease, glaucoma). Erythrocyte aggregation was assessed with a light back-scattering method. Results were compared with those of a group of 33 age- and sex-matched controls. RESULTS: Eleven (33%) of the 33 patients with CRVO had abnormal hemorheologic findings. Erythrocyte aggregation was highly significantly increased in the CRVO group when compared with the control group (P < 0.0001), as was the hematocrit level (P < 0.05). In addition, the proportion of patients with abnormal blood rheologic tests was greater (50%) in the subgroup of patients who initially had nonischemic CRVO that worsened into an ischemic CRVO during the follow-up. CONCLUSION: These data suggest that abnormal hemorheologic findings could affect the pathogenesis of CRVO, and perhaps be predictive of an aggravation. The latter hypothesis needs to be confirmed in a larger, prospective study.

Adult↗
PubMed1994

Red blood cell aggregability in patients with a history of leg vein thrombosis: influence of post-thrombotic treatment.

Reversible aggregation of red blood cells (RBC) plays an important role in determining blood flow properties, and it is this aggregation which increases blood viscosity at low shear rates. The structure and sites of venous thrombi, as well as the fact that stasis is a major predisposing factor in venous thrombosis, suggest a strong association between vein thrombosis, slow blood flow and increased blood viscosity. RBC aggregation and disaggregation were measured (SEFAM erythroaggregameter, France) in 54 patients with a history of unexplained leg vein thrombosis. Results were compared to those of controls classified according to age. Increased RBC aggregability was observed in 41% of the patients, and the mean values indicated a significant elevation of RBC aggregability in patients when compared with controls (P < 0.05). Subgroups were compared to study the influence of thrombus recurrence and thrombosis type (deep versus superficial vein thrombosis) on the aggregation parameters. No significant difference was found between these subgroups. The use of compression stockings and veinotropic drugs tended to reduce the abnormalities in RBC aggregability (P < 0.05). An increase in RBC aggregability and in the shear resistance of RBC aggregates, by predisposing to circulatory stasis, is likely to contribute to the evolution and complications of leg vein thrombosis.

Adult↗
PubMed1994

An animal model for the evaluation of graft thrombosis in the acute phase on carbon-lined PTFE prosthesis.

Forty-five carbon-lined (CL) and 45 standard (ST) 4 mm internal diameter polytetra-fluoroethylene (PTFE) grafts were implanted as aortic interposition in 90 rabbits. A pilot study of 20 animals: 10 CL and 10 ST grafts were used to develop microsurgical techniques, then 60 grafts were placed in 60 New Zealand rabbits with lower morbidity. The two hours graft patency (Doppler and angiographic studies) showed better patency rate in CL group (93% versus 80%). In 10 animals, platelet accumulation was investigated in vivo using gammacamera imaging after injection of autologous platelets labeled with Indium111. In vitro, radioactivity counting of the explanted midgraft sections at 2 hours revealed 6 times greater activity in ST grafts (6.60 +/- 1.98 x 10(3) platelets/mm2 versus 0.82 +/- 0.25 x 10(3) platelets/mm2; p < 0.05). Light microscopy found platelet and fibrin deposition (PFD) in nearly all ST grafts whereas PFD were found in only 13% of the CL grafts corresponding to those thrombosed (chi 2: 61.117, p < 0.001). Carbon-lining decreases platelet accumulation on PTFE grafts in the acute phase of a new experimental model.

Angiography↗
PubMed1994

Expression of a paternal history of premature myocardial infarction on fibrinogen, factor VIIC and PAI-1 in European offspring--the EARS study. European Atherosclerosis Research Study Group.

To assess the role of genetic and environmental factors in the predisposition to atherosclerosis, 682 students whose father had suffered a myocardial infarction before the age of 55 ("cases") and 1312 controls matched for age and sex, were recruited from 14 Universities in Europe. Fibrinogen, factor VIIc and PAI-1 were compared between cases and controls across European regions. Fibrinogen and factor VIIc were positively correlated with BMI, smoking and contraception. PAI-1 was positively and independently correlated with BMI and waist-to-hip ratio, and negatively with contraception. Factor VIIc and PAI-1 were correlated with cholesterol and triglycerides, and fibrinogen was weakly correlated with LDL-cholesterol. After adjustment for covariates and lipids, fibrinogen level was significantly higher in male cases than in controls (2.38 vs 2.29, p < 0.01). No such difference was found in females (2.59 vs 2.57 - NS). There was no significant case/control difference for factor VIIc and PAI-1. These results support the hypothesis that fibrinogen is a transmissible risk factor of coronary artery disease in males. No such evidence was provided for factor VIIc and PAI-1.

Adolescent↗
PubMed1993

Haemostatic variables and menopausal status: influence of hormone replacement therapy.

Large cohort studies have shown that postmenopausal estrogen use was associated with a reduction in the risk of coronary heart disease. This putative beneficial effect of hormone replacement therapy (HRT) may be partly mediated through changes in clotting factors and fibrinolytic system. We have measured haemostatic variables in 293 consecutive healthy women aged 45-54 years who attended a health check-up centre in Paris (IPC). Premenopausal women taking hormonal therapy were excluded (n = 34). Most women using HRT were given 17-beta estradiol in combination with progestin. Mean levels (m +/- sd) of plasma fibrinogen, factor VII coagulant activity and plasminogen activator inhibitor (PAI) were significantly higher in postmenopausal women not taking HRT (n = 99) than in premenopausal women (n = 139) within the same decade (319 +/- 52 mg/dl vs 304 +/- 60 mg/dl, 107 +/- 17% vs 96 +/- 16%, 9.73 +/- 5.71 U/ml vs 7.61 +/- 4.36 U/ml respectively). Allowance for main cardiovascular risk factors made no substantial differences to the results, although the effect of the menopause on fibrinogen was no longer significant. HRT (n = 21) significantly reversed the menopause-related changes in factor VII (94 +/- 15%), even after adjustment for confounding factors. The same trend in both fibrinogen (294 +/- 46 mg/dl) and PAI (8.22 +/- 5.51 U/ml) was observed. Similar results were found in women using oral or percutaneous estrogen. Our findings suggest that 17-beta estradiol in combination with progestins may protect against an increased thrombotic tendency in postmenopausal women. Randomized clinical trials are urgently needed for a better understanding of HRT effect on atherothrombotic process.

Coronary Disease↗
PubMed1993

Normalization of markers of coagulation activation with a purified protein C concentrate in adults with homozygous protein C deficiency.

Homozygous or double heterozygous protein-C deficiency can present at birth with purpura fulminans or later in life with venous thrombosis. Two homozygous patients who had previously sustained thrombotic episodes were investigated at a time when they were asymptomatic and not receiving antithrombotic therapy. The plasma levels of protein-C antigen and activity in both individuals were approximately 20% of normal. We administered a highly purified plasma-derived protein C concentrate to these individuals and monitored levels of several markers of in vivo coagulation activation. Assays for protein-C activation (activated protein C and protein C activation peptide) showed a sustained increase from reduced baseline levels, whereas thrombin generation (as measured by prothrombin fragment F1 + 2) gradually decreased over about 24 hours into the normal range. These investigations provide direct evidence that protein C is converted to activated protein C in vivo, and that the protein-C anticoagulant pathway is a tonically active mechanism in the regulation of hemostatic system activation in humans.

Adult↗
PubMed1993

Factor Xa inhibition: correlation between the plasma levels of anti-Xa activity and occurrence of thrombosis and haemorrhage.

A multicentre, double-blind, randomised trial was conducted to compare the efficacy of a low-molecular-weight (LMW) heparin, Logiparin, with that of an unfractionated (UF) heparin in the prophylactic treatment of thrombosis in patients undergoing general surgery. A total of 1,290 patients were randomised to receive a single daily dose of Logiparin (2,500 IU: 431 patients; 3,500 IU: 430 patients) or UF heparin (2 x 5,000 IU: 429 patients). The incidence of the main end point, deep venous thrombosis, was found to be significantly different between the groups (p = 0.03), whereas the incidence of severe haemorrhage was not (p = 0.05). The plasma anti-Xa activity was found to be correlated with body weight, but correlated only very weakly with antithrombotic activity (p = 0.045) after adjustment in a stepwise multivariate analysis, and did not significantly correlate with the incidence of haemorrhage. Logiparin at 3,500 IU and UF heparin showed similar efficacy. Although a correlation between plasma anti-Xa activity and body weight was observed, there is not sufficient evidence to recommend the adjustment of the Logiparin dose on patient's weight for prophylaxis in general surgery patients.

Body Weight↗
PubMed1993

Genetic variation at the beta-fibrinogen locus in relation to plasma fibrinogen concentrations and risk of myocardial infarction. The ECTIM Study.

Increased plasma fibrinogen concentration is a major cardiovascular risk factor. Conflicting results on genetic variations in plasma fibrinogen levels have been reported. Furthermore, whether fibrinogen genotype is associated with the risk of ischemic heart disease has not been studied so far. An HaeIII restriction fragment length polymorphism of the beta-fibrinogen gene was used in a case-control study to investigate the genetic variation at this locus in relation to plasma fibrinogen concentrations and the risk of myocardial infarction (MI). Five hundred thirty-three male patients aged 27-66 years and 648 control subjects were recruited from four World Health Organization MONICA centers in Northern Ireland and in France. The absence of the HaeIII cutting site (H2 allele) was associated with a significant rise in fibrinogen concentrations in both patients and control subjects. The effect of the HaeIII polymorphism on plasma fibrinogen levels did not significantly differ between centers. Fibrinogen levels were higher in smokers than in nonsmokers. The difference between the two groups was larger in subjects with the genotype H2H2 than in those with either genotype H1H1 or H1H2, regardless of the case-control status. However, there was no significant interaction between smoking status and genotype in their effects on variance in fibrinogen levels, whereas fibrinogen levels. HaeIII genotype accounted for approximately 1% of the total variance in fibrinogen levels, whereas smoking and age together explained 7% and 5% in control subjects and patients, respectively. The frequency of the H2 allele was 0.21 in control subjects and 0.19 in patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Low molecular weight heparin in prevention of perioperative thrombosis.

OBJECTIVE: To determine whether prophylactic treatment with low molecular weight heparin reduces the incidence of thrombosis in patients who have had general or orthopaedic surgery. DESIGN: Meta-analysis of results from 52 randomised, controlled clinical studies (29 in general surgery and 23 in orthopaedic surgery) in which low molecular weight heparin was compared with placebo, dextran, or unfractionated heparin. SUBJECTS: Patients who had had general or orthopaedic surgery. INTERVENTION: Once daily injection of a low molecular weight heparin compared with placebo, dextran, or unfractionated heparin. MAIN OUTCOME MEASURES: Incidence of deep venous thrombosis, pulmonary embolism, major haemorrhages, and death. RESULTS: The results confirm that low molecular weight heparins are more efficacious for the prophylactic treatment of deep venous thrombosis than placebo (common odds ratio 0.31, 95% confidence interval 0.22 to 0.43; p < 0.001) and dextran (0.44, 0.30 to 0.65; p < 0.001). The results suggest that low molecular weight heparins are also more efficacious than unfractionated heparin (0.85, 0.74 to 0.97; p = 0.02), with no significant difference in the incidence of major haemorrhages (1.06, 0.93 to 1.20; p = 0.62). CONCLUSIONS: Low molecular weight heparins seem to have a higher benefit to risk ratio than unfractionated heparin in preventing perioperative thrombosis. However, it remains to be shown in a suitably powered clinical trial whether low molecular weight heparin reduces the risk of fatal pulmonary embolism compared with heparin.

Blood Loss, Surgical↗
PubMed1992

A comparative study of recombinant hirudin and standard heparin in the Wessler model.

The in vitro anticoagulant activity of recombinant desulphated hirudin (HBW 023) and its antithrombotic activity in a rabbit venous stasis model were assessed in comparison to unfractionated heparin (UH). The specific activity of r-hirudin in rabbit plasma is similar to that of unfractionated heparin on a weight basis when using the whole blood clotting time or APTT, while it was five times more potent according to the thrombin clotting time (TCT). Forty-eight (6x8) anaesthetized New Zealand male rabbits were randomized to receive HBW 023 (12.5, 25, 50, 100, 200, 400 micrograms.kg-1), standard heparin (90 micrograms.kg-1) or placebo. Five minutes after administration of the drug, the experimental thrombosis was induced by an injection of glass activated overnight human serum into the marginal vein of the ear and ligation of the jugular vein (Wessler model). The jugular vein was removed after 10 min stasis and examined by a researcher unaware of the treatment administered. In the Wessler stasis model the fresh thrombus weight and a score as well as the circulating level of r-hirudin using a chromogenic substrate assay were used to determine the inhibitory effect of the drug. Highly significant inverse correlations were found between fresh thrombus weight and the injected doses as well as r-hirudin plasma levels. The ID50 which was the dose of the drug that induced a complete inhibition of thrombosis in 50% of the dose group tests was about 200 micrograms.kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗