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M Samama

Publications and source records attributed to M Samama.

At least 145 records · Page 8Linked to original sources
PubMed1986

[The new heparins].

The new, so-called molecular weight heparins (mean MW : about 5,000 daltons) are less heterogeneous than the old, fractionated heparins (mean MW: about 15,000 daltons). Both types of preparations contain molecules with affinity for antithrombin III (AT III) and anticoagulant activity, as well as other molecules without affinity for AT III but which are thought to contribute to the antithrombotic activity of heparin. The anticoagulant effect of low molecular weight heparins (defined as their ability to prolong the activated cephalin time) in 3 to 4 times lower than that of standard heparin, but their activity against the activated factor X (Xa) is approximately the same. The half-life of the anti-Xa activity of low molecular weight heparins is twice that of standard heparin. The bioavailability of low molecular weight heparins administered subcutaneously is greater than 90%, as against less than 30% with standard heparin. Clinical trails have shown that one single subcutaneous injection of low molecular weight heparin 2 hours before an operation, then every 24 hours reduces the incidence of isotopic venous thrombosis in general surgery at least as much as 2 daily injections of calcium heparinate 5000 I.U. Low molecular weight heparins are virtually devoid of the pro-platelet aggregation activity exhibited by standard heparin.

Blood Coagulation↗
PubMed1986

A new case of high-molecular-weight kininogen inherited deficiency.

A preoperative hemostasis study discovered a prolonged activated partial thromboplastin time in a 23-year-old Portuguese Caucasian woman without personal or past family history of hemorrhage or thrombosis. This was corrected by pooled plasma that excluded circulating anticoagulant. Activated partial thromboplastin time was prolonged whatever the activator, particularly ellagic acid, and was not corrected by prolonged kaolin incubation. Levels of factors VIII and XII were normal; factor XI and prekallikrein levels were either moderately low or normal according to activators and defective reagents used. High-molecular-weight kininogen (HMWK) level assessed by coagulation and immunological method was virtually nil. Fibrinolysis activity was normal before and after venous occlusion. The programmed operation was performed without any particular preparation and no complication arose. Family investigation found heterozygous HMWK deficiency in the proposita's father and three of her siblings.

Adult↗
PubMed1986

[Protein C].

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Blood Coagulation↗
PubMed1986

Relationship between biological activity and concentration of a low-molecular-weight heparin (PK 10169) and unfractionated heparin after intravenous and subcutaneous administration.

The pharmacokinetics of unfractionated heparin and the low-molecular-weight (LMW) heparin PK 10169 after intravenous and subcutaneous injection were compared by crossover study in 8 healthy volunteers. The heparin concentrations in plasma were measured by a competitive binding assay, and anti-IIa and anti-Xa activities were also assayed. Unfractionated heparin was cleared after intravenous administration with a half-life of 35 min irrespective of assay method. However, the concentration of PK 10169 declined with the longer half-life of 60 min, and its anti-IIa and anti-Xa activities had half-lives of 40 and 275 min, respectively. Some of this anti-Xa activity may be mediated by a compound released by PK 10169 rather than by the LMW heparin itself. The bioavailability of PK 10169 was 3-fold greater than that of unfractionated heparin, due to more effective absorption after subcutaneous administration.

Adult↗
PubMed1986

Partial reversal of low molecular weight heparin (PK 10169) anti-Xa activity by protamine sulfate: in vitro and in vivo study during cardiac surgery with extracorporeal circulation.

Neutralization of a low molecular weight (LMW) heparin fraction by protamine sulfate was evaluated in vitro and in vivo. Anti-Xa and anti-IIa activities were measured by amidolytic and coagulation methods (activated partial thromboplastin time, APTT). Fifteen patients (4 males and 11 females) underwent surgery with extracorporeal circulation. In vitro, anti-Xa and anti-IIa activities and APTT of unfractionated heparin were neutralized with a protamine/heparin (P/H) gravimetric ratio of 1.6, 1.33 and about 2, respectively. Anti-IIa activity and APTT induced by PK 10169 were completely corrected at a P/H ratio of 1 and 2, respectively, while anti-Xa activity was incompletely neutralized at a ratio of 5. In vivo, in 9 patients who did not receive intravenous protamine sulfate, a good correlation was found between doses of PK 10169 infused, anti-IIa plasma level and blood loss. In 3 patients who were treated prophylactically with protamine, bleeding was normal or only slightly increased. In 3 patients who received protamine because of hemorrhage, mean anti-Xa and anti-IIa were 2.3 and 0.54 U before and 1.32-0.06 U after neutralization. Bleeding was stopped by a second dose of protamine in 1 patient, but blood loss was abnormal in the other patients. However, a correlation between bleeding and anti-Xa or anti-IIa activities was not clearly evident.

Adolescent↗
PubMed1986

[Tissue plasminogen activator (t-PA) in myocardial infarction. Biological aspects].

A group of 37 patients with myocardial infarction less than 6 hours old was given 5,000 IU of heparin and 0.75 mg/kg of tissue plasminogen activator (rt-PA) (Group A, N = 18) or placebo (Group B, N = 19) intravenously over 90 minutes in a double blind study. Blood sampling was performed before, during and after treatment. The plasma rt-PA concentrations (micrograms/ml) of Group A were as follows: (Table: see text) The concentrations of plasminogen and antiplasmin have decreased significantly as did the fibrinogen level: a concentration of 1 g/l was observed in 7 cases during rt-PA therapy, lasting for 4 to 8 hours after the end of the infusion of rt-PA in 3 cases. The increase of FDP during rt-PA (m = 551 and 222 micrograms/ml at the 60th and 90th minutes) was relatively moderate considering the average level of defibrination (61%). No significant biological changes were observed in Group B. These results support those of our in vitro trials: at comparable thrombolytic activities, the reduction of plasma fibrinogen is less with rt-PA than with streptokinase (SK) or urokinase (UK). However, at concentrations 1 microgram/ml, rt-PA causes almost complete defibrination.

Double-Blind Method↗
PubMed1986

[Low molecular weight heparins].

Heparin is a heterogeneous component consisting of anionic polysaccharides chains of variable molecular weight ranging from 3 000 to 40 000 daltons. It is by potentiating antithrombin III (AT III) a natural inhibitor of coagulation, that heparin exerts its anticoagulant effect. Actually, it has been demonstrated that only 30% of the molecule in commercial heparin preparations are capable of binding to AT III: moreover, several procedures were used to prepare low molecular weight heparin fractions or fragments. These preparations were lacking in ability to prolong the clotting time (APTT) and to inhibit thrombin, but were capable of potentiating the inhibition of factor Xa. The hypothesis that low molecular weight heparins may exhibit antithrombotic effect by inhibition the coagulation cascade system at the initial stages is very attractive. Moreover, on animal models, heparin fractions with molecular weight less than 3 000 had limited ability to prevent experimental thrombosis despite good anti-Xa activity. Thus, the anti-Xa activity did not alone reflect the antithrombotic effect. Experimental studies have shown less bleeding with low molecular weight heparins compared to standard heparin. Some data have suggested other properties of low molecular weight heparins such as enhancement of fibrinolysis and a slighter effect on platelets. The risk of thrombocytopenia induced heparin could be reduced by the use of low molecular weight heparins. The pharmacokinetics of low molecular weight heparins have been studied in human subjects. A higher bioavailability and a longer duration of action were reported compared to heparin. Preliminary clinical trials have shown that one daily injection is sufficient to protect against post-operative thrombosis.

Animals↗
PubMed1986

Thrombocytopenia in venocclusive disease after bone marrow transplantation or chemotherapy.

Hepatic venocclusive disease (VOD) is a frequent complication of bone marrow transplantation (BMT). Analysis of 13 cases observed during a 3-year period in our BMT center shows that VOD is associated with a constant peripheral thrombocytopenia and refractoriness to platelet transfusion. These signs appear in the very early stage of VOD, five to ten days before the classical signs, painful hepatomegaly and sudden weight gain. Analysis of platelet consumption, frequency of platelet transfusion and platelet recovery, and examination of known causes of peripheral thrombocytopenia (mainly allo- and autoimmunization, disseminated intravascular coagulation [DIC] and splenomegaly) lead to the conclusions that this association is not coincidental. The exact mechanism of platelet consumption in VOD is unknown.

Bone Marrow Transplantation↗
PubMed1986

[Thrombolytic treatment in the acute phase of myocardial infarction. Evaluation in 1986].

Fibrinolytic therapy is effective in reducing the extent of myocardial infarction by lysing intracoronary clots. An overview of twelve trials of prolonged intravenous infusion of SK showed a highly significant reduction in short term mortality. Intra coronary SK infusion achieved reperfusion of the coronary artery in 60 to 90 p. 100 of patients and improvement of left ventricular function was reported. Mortality was also significantly reduced at 6 months. The frequency of bleeding was relatively low and ventricular arrhythmias were not a serious problem. High dose brief duration intravenous SK therapy achieved reperfusion of the occluded coronary artery in 44 to 60 p. 100 of patients. Left ventricular function was also improved. An Italian multicentre trial has shown a significant decrease in the overall hospital mortality of a randomized population. There is no evidence that UK was more effective than SK. New fibrinolytic agents (T-PA, acylated SK-plasminogen activator), with more fibrin specific activity, were successful in inducing coronary thrombolysis in patients with acute myocardial infarction. The rate of reocclusion was about 20 p. 100 and additional stabilising procedure (percutaneous transluminal coronary angioplasty) was necessary in many patients.

Fibrinolytic Agents↗
PubMed1986

Comparison of antithrombotic activity of two heparin fragments PK 10169 (mol. wt. 5,000) and EMT 680 (mol. wt. 2,500) and unfractionated heparin in a rabbit experimental thrombosis model: relative importance of systemic anti-Xa and anti-IIa activities.

Two fragments obtained by chemical depolymerization of heparin from porcine mucosal origin PK 10169 (mol. wt. 5,000) and EMT 680 (mol. wt. 2,500) were compared to the original heparin in a rabbit experimental thrombosis model. Thrombosis was induced either by human serum or by bovine Xa. Various doses of heparins (6 animals per dose and per inducer) were injected in order to find the lowest systemic levels of anti-Xa and anti-IIa activities able to inhibit venous-induced thrombogenesis. The systemic activities associated with an inhibition of 50% of the generated thrombi were as follows: 0.17 +/- 0.02 anti-Xa and 0.16 +/- 0.03 anti-IIa units obtained after injection of 97 micrograms/kg (14 anti-Xa and anti-IIa units/kg) of unfractionated heparin, 0.28 +/- 0.04 anti-Xa and 0.14 +/- 0.03 anti-IIa units obtained after injection of 250 micrograms/kg (15 anti-Xa and 7.5 anti-IIa units/kg of PK 10169, and 2.6 +/- 0.2 anti-Xa and 0.06 +/- 0.01 anti-IIa units obtained after injection of 5000 micrograms/kg (260 anti-Xa and 5 anti-IIa units/kg) of EMT 680. These results suggest that the presence of an anti-IIa activity associated with the anti-Xa activity strongly increases the thrombogenesis inhibition in the serum and Xa-induced thrombosis for the heparin fragments of low and very low molecular weight used in this study.

Animals↗