Differential AT III-response to oral and parenteral administration of 17 beta-estradiol.
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Administration, Oral↗
Biomedical subjects
M Samama
Publications and source records attributed to M Samama.
Familial and constitutional bleeding disorder due to platelet cyclo-oxygenase deficiency.
Three family members from two successive generations had a bleeding tendency. Their template bleeding time was prolonged and platelet aggregation induced by ADP and adrenaline showed no second wave; collagen at low to moderate concentrations failed to aggregate and release ATP, whereas higher amounts aggregated and released. Aggregation and release due to thrombin, ristocetin, and synthetic epoxy derivatives (U 44069 and U 46619) were normal. Arachidonate (AA) was inactive, and was not converted either in thromboxane (TX) A2 activity evaluated on the rabbit aorta strip, nor in TXB2 evaluated by radioimmunoassay and by radiochromatography. The parallel impairment of TXB2 and PGE2 formation by the patient's platelets are compatible with a platelet cyclo-oxygenase deficiency. This study suggests that transmission is autosomal dominant, and confirms that cyclo-oxygenase is not needed for aggregation and ATP release by high amounts of collagen.
Adolescent↗
Study of platelet aggregation induced by platelet activating factor (PAF) after administration of ticlopidine or aspirin.
Platelet aggregation induced by platelet activating factor (PAF) was studied in 95 subjects: 39 controls, 23 patients receiving aspirin and 33 receiving ticlopidine. Potentiation of aggregation by concentrations of adrenaline unable to induce aggregation when used alone was also assessed. The 33 patients treated with ticlopidine showed a highly significant fall of platelet aggregation (p less than 0.001) at the three concentrations of PAF used. The 23 subjects receiving aspirin showed a diminution of platelet aggregation induced by PAF due to inhibition of ADP release. In these last two groups, adrenaline often potentiated platelet aggregation. However, this phenomenon was absent in subjects having taken aspirin in the hours before blood was drawn. This study demonstrates ticlopidine's inhibitory action on PAF-induced aggregation and confirms ticlopidine's role in reducing platelet aggregation by ADP, which has previously been demonstrated.
Adult↗
Molar antithrombin concentration in normal human plasma.
Crude, commercial thrombin preparations and purified bovine thrombin were incubated with normal human reference plasma and the amount of thrombin inactivated was calculated. 1 ml of human plasma inactivated 140-193 NIH U of the various crude thrombin preparations. In the presence of heparin, a lower thrombin-inactivating capacity of plasma was confirmed using crude thrombin, but this phenomenon was less pronounced with the purified thrombin preparation. The molar concentration of the purified bovine thrombin was determined by active site titration. Comparing with protein concentration (A280), this preparation was 92% pure. 1 ml of human plasma inactivated 2.57 mumol of thrombin in the absence of heparin, and 2.50 mumol with heparin. Assuming 1:1 stoichiometry in the thrombin-antithrombin reaction, these results suggest that the concentration of antithrombin in the pooled reference plasma is approximately 2.57 mumol/l or 0.15 g/l.
Animals↗
[Pharmacology of anti-platelet agents].
A new class of drugs has appeared alongside classical anti-thrombotic agents such as heparin and oral anticoagulants, characterised by their ability to modify the behaviour of platelets: "anti-platelet" agents. This article reviews the platelet actions, pharmacokinetics, conditions of use and side effects of the four chief agents available: acetylsalicylic acid (ASA), sulfinpyrazone, dipyridamole and ticlopidine. The mode of action of the first of them is that best studied. ASA opposes the conversion of arachidonic acid to prostaglandins and thromboxane, by the irreversible acetylation of cyclo-oxygenase. Nevertheless, major therapeutic trials involving ASA have yielded only poor results. There are at least two possible explanations for this state of affairs: --aggregation may occur even when thromboxane is blocked, in particular in response to thrombin; --ASA has been used at doses also capable of inhibiting the formation by the vascular wall of an anti-aggregant prostaglandin, PGI2. Current efforts by pharmacologists which should result in better adapted and hence more effective anti-thrombotic methods, are essentially concerned with the following points: --to understand why sulfinpyrazone, which in principle has the same mode of action as ASA, seems sometimes more active and sometimes less active than the latter according to whether coronary or cerebrovascular accidents are involved; --to propose a rational prescription programme for ASA, in such a way that it inhibits only little, and for as short a time as possible, the production of PGI2 (e.g. 200 mg every three days): --to perfect more active combinations; --synthesis of new substances, e.g. thromboxane synthetase inhibitors, or stable analogues of PGI2. The reasons which suggest that such substances could be used more beneficially in man are expanded.
Animals↗
[Heparin treatment of thromboembolic complications].
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Aged↗
[Long-term antithrombotic treatment in coronary disease].
The respective roles of thrombosis and spasm in the pathogenesis of coronary disease is a subject of current discussion. Critical study of trials of long-term secondary prevention of myocardial infarction carried out between 1967 and 1982 have failed to yield any definitive conclusion as to the value of oral anticoagulants, aspirin, sulfinpyrazone or dipyridamole. However oral anticoagulants should be prescribed in the long-term, in the absence of any contra-indication, in cases of myocardial infarction complicated by ventricular ectasia, arrhythmias or cardiac failure with cardiomegaly. The use of better methods in secondary prevention trials would be desirable. Primary prevention of myocardial infarction using drugs raises difficult problems, in particular economic.
4-Hydroxycoumarins↗
[Determination of the factor VIII ristocetin cofactor (Willebrand factor) using a semi-quantitative slide test. Preliminary results].
The assay of factor VIII, co-factor of Ristocetin (VIIIR:Co) is a relatively delicate procedure which is presently reserved to specialized laboratories. It requires the use of an aggregometer and a long and difficult preparation of human platelets. In parallel with this classical method, we have used a new, rapid, semi-quantitative slide test whose advantages are: simple technique and rapid answer (2 minutes), small volume of plasma required for the test (50 microliters) and the possibility of using citrated or heparinized plasma taken form a venous or capillary blood sample. Using this test, we have assayed factor VIII co-factor of ristocetin: in 31 hospitalized adults patients with no previous history of bleeding and no disturbance of haemostasis and in 18 patients with Willebrand's factor deficiency in comparison with the standard technique using aggregometry (Allain's method); - in 28 normal neonates, in comparison with the VIIIR:Ag factor assay (Laurell's technique), only because of the small sample volume available; - in 17 patients with various disease associated with an abnormality of the VIII complex in comparison with the assay of VIIIR:Ag and VIIIC. The results obtained in the normal adults show a satisfactory correlation between the two methods. The mean level of factor VIII:Co is 100 +/- 10 per cent (M +/- SD) with the semi-quantitative slide test and 109 +/- 20 per cent (M +/- SD) with the method taken as the reference. The correlation is also satisfactory for patients with a deficit of Willebrand's factor. The test performed on the neonates gives a mean value of 101 +/- 37 per cent (M +/- SD) with good correlation between the factor VIIIR:Ag and the factor VIIIR:Co.
Adult↗
[4 cases of acquired Willebrand factor deficiency associated with monoclonal dysglobulinemia].
Acquired von Willebrand syndrome is reported in four patients with monoclonal IgG: benign gammapathy in three cases, multiple myeloma in one case; to our knowledge, this last association has not been previously reported. Coagulation abnormalities included a borderline bleeding time, a low platelet retention on glass beads, decreased levels of factor VIII coagulant activity (VIII: C), factor VIII related-antigen (VIII R: Ag) and ristocetin induced agglutination cofactor (VIII R: RC). The late clinical onset, the negative family history and the immunological abnormality suggest an acquired von Willebrand syndrome. After cryoprecipitate infusion the patients did not show the expected rise and there was no secondary increment in factor VIII: C. Time-dependent inhibition of factor VIII R: RC and factor VIII: C was found in one case only and was associated with qualitative abnormality of factor VIII R: Ag demonstrated by crossed-immunoelectrophoresis. It was not possible to interpret this last test in the other cases, due to the very low level of factor VIII R: Ag. The factor VIII abnormalities might be related to the binding and/or destruction of factor VIII by a circulating antibody, or to the adsorption of this factor on the malignant lymphocytes.
Adult↗
[Cutaneous necrosis of the breast: a complication of oral anticoagulant treatment].
Cutaneous necrosis of the breast is a rare complication of oral antivitamin K drugs. It occurs shortly after instituting therapy with well-limited, irreversible skin necrosis developing rapidly. The scar is superficial and only involves the subcutaneous tissue; early and extensive surgery does not therefore seem to be justified. Normal scarring is the eventual spontaneous outcome but this is always a long process. Several arguments are advanced in favour of a toxic effect of the drug itself on the vascular walls of the vessels in the dermis.
Administration, Oral↗
[Thrombotic thrombopenic purpura associated with Hodgkin's disease].
We report the second case of Hodgkin's disease associated with thrombotic thrombocytopenic purpura (TTP). Although the two diseases coexisted originally, TTP was diagnosed alone at first. Because of the very rare occurrence of this association the diagnosis of TTP is discussed according to the accepted criteria and taking into account the haematological complications which can reveal or be observed in Hodgkin's disease. No evident relationship between the two diseases can be suggested. But immunologic disorders observed in the two cases suggests that their coexistence is not necessarily accidental. The evolution of these two diseases is particularly good.
Adult↗
[Demonstration of spontaneous platelet aggregation and research on circulating platelet aggregates: methodology, results and significance].
136 control subjects and 131 patients, consisting of 23 diabetics with severe retinopathy, 43 cases of valvular disease with or without a prosthesis and 65 patients who had a cerebral vascular accident, were systematically investigated for the presence of spontaneous platelet aggregation 31 controls and 108 patients were examined for reversible circulating platelet aggregates using the technique of Wu and Hoak. Frank spontaneous aggregation was observed in 6 of the 136 control subjects, 6 of the 21 patients without a valvular prosthesis and 2 of the 22 patients with such a valvular prosthesis and 2 of the 22 patients with such a prosthesis, only 1 of the 23 diabetics and 5 of the 65 patients with old or recent cerebral vascular accidents. The incidence of spontaneous aggregation seems to be directly related to certain operative conditions: the type of machine used, the number of platelets, and to the treatment administered, the Wu and Hoak test. No statistically significant correlation was demonstrated between spontaneous aggregation and the Wu and Hoak test. The exact clinical significance of the presence of spontaneous aggregation is still disputed. However, the examination for this abnormality should be routine as its presence can alter the interpretation of the results of aggregation induced by various aggregating agents.
Blood Platelets↗
Kinetics of the inhibition of plasmin in acidified human plasma.
Acid-treated human plasma is a competitive inhibitor of the hydrolysis of D-Val-Leu-Lys-Nan (S-2251) by plasmin. The rate of hydrolysis is decreased to 50% by 750 fold diluted acidified normal plasma and by 60 fold diluted acidified alpha 2-antiplasmin depleted plasma (alpha 2-antiplasmin concentration less than 2%). These findings suggest that alpha 2-antiplasmin is a contributary but not the main competitive inhibitor of acidified plasma. This interpretation is supported by the finding that alpha 2-antiplasmin depleted plasma reconstituted with purified alpha 2-antiplasmin inhibits the hydrolysis of S-2251 by plasmin at a 125 fold dilution following acidification and by the finding that in a purified system acid inactivated alpha 2-antiplasmin inhibits the hydrolysis of S-2251 by plasmin with a Ki of 25 nM. Thus, besides alpha 2-antiplasmin, other plasma proteins which are at least in part eliminated by the removal of alpha 2-antiplasmin from plasma by immunoadsorption appear to be competitive inhibitors for plasmin in acidified plasma. It is suggested that several competitive inhibitors for plasmin are present and/or generated in acidified plasma and that these inhibitors may at least in part be responsible for the variability in the results of measurements of plasminogen and/or plasmin in plasma following acidification.
Fibrinolysin↗
Interactions of anticoagulant insoluble modified polystyrene resins with plasmatic proteins.
In previous papers, we have described the preparation and heparin-like properties of insoluble modified polystyrene resins. We now report results about the interactions of several coagulation factors with some of these materials. Most of the non-activated factors are neither adsorbed nor modified, except factor V and prekallikrein. In contrast thrombin, antithrombin III and factor Xa adsorb on the surface of such insoluble polymers. Thrombin can be desorbed by addition of a polycationic compound. The inactivation of thrombin or factor Xa by antithrombin is catalysed by the presence in the mixture of these insoluble materials as it is with soluble heparin. The initial velocity of these reactions is second order for both types of catalysis-homogeneous or heterogeneous - as previously reported for soluble heparin. In the case of these insoluble materials, the inhibition of protease by antiprotease seems to be accelerated when complexes are formed between the polymer and the proteins.
Adsorption↗
The amidolytic activity of the SK-plasminogen complex is enhanced by a potentiator which is generated in the presence of vascular plasminogen activator--role of fibrin degradation products.
In the presence of an excess of streptokinase (SK) the amidolytic activity of the plasminogen-SK complex on chromogenic substrates is 12% lower in serum than in the corresponding plasma. However, in subjects in whom venous stasis lead to a shortening of the euglobulin lysis time to less than 60 min (high responders), the amidolytic activity of the plasminogen-SK complex in serum was 60% higher than in the corresponding plasma. Attempts to find alterations of the plasminogen molecule itself which would account for the enhanced activity in high responder serum were negative. No free plasmin was present and the plasminogens isolated from plasma and serum before and after venous stasis had the same amidolytic activity as gluplasminogen in the presence of an excess of SK. N-terminal analysis of these four plasminogens revealed in each instance glutamic acid. The enhancement of the amidolytic activity of the SK-plasminogen complex in serum of high responders (potentiator activity) could be reproduced by adding purified tissue plasminogen activator (TA) to native blood before clotting, but not if TA was added to plasma or to prestasis serum. Removal of fibrin degradation products from poststasis serum resulted in the disappearance of potentiator activity. These experiments suggest that fibrin degradation products, generated during clotting in the presence of vascular or tissular plasminogen activator act as a potentiator of the amidolytic activity of the plasminogen SK-complex.
Amides↗
Comparative study of the activity of high and low molecular weight urokinase in the presence of fibrin.
The fibrinolytic or thrombolytic activity of low molecular weight urokinase (LMW-UK) and high molecular weight urokinase (HMW-UK) is not significantly different when measured in a bovine fibrin plate method, in a circulating plasma system containing a 125I-labelled human fibrin clot, or on 125I-fibrin films in culture plates using normal or alpha 2-antiplasmin depleted human plasma. In a human fibrin plate method however HMW-UK was found to be more active than LMW-UK. In a purified system on human 125I-fibrin films the activation of native or modified human plasminogen by HMW-UK was also found to be more effective than by LMW-UK. Using a clot lysis test system we did not observed a different inhibition of LMW-UK and HMW-UK upon incubation in human plasma. This is in contrast with previous reports that HMW-UK is inhibited more rapidly in human plasma than LMW-UK. In a purified system the inhibition rate of LMW-UK and HMW-UK by alpha 2-antiplasmin is the same (rate constants at 25 degree C of 167 +/- 9 M-1s-1 and 171 +/- 5 M-1s-1 respectively). The clinical trials available at present used doses of urokinase which were in excess of those required to obtain a maximal fibrinolytic effect. This might explain why in these trials no difference was observed between the thrombolytic effect of LMW-UK and HMW-UK, while in vitro HMW-UK appeared to be more effective. However, one should always be careful to extrapolate in vitro observations as such to the in vivo situation encountered during thrombolytic therapy.
Animals↗
[Severe hypoproconvertinemia and extracorporeal circulation for mitral valve replacement].
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Adolescent↗