Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.6 (thromboplastin)
13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The in vitro effects of N-3-(1-benzyl-cycloheptyloxy)-propyl-N,N-dimethylammonium-hydrogenfumarate (bencyclan) on clotting, fibrinolytic and platelet function test were investigated by adding the drug to normal human plasma. An anticoagulant activity, mainly of an antithromboplastin nature (directed against later stages of intrinsic thromboplastin formation and against tissue thromboplastin), was observed, while thrombin phase was unaffected. No effect was found in the fibrinolytic system tested (euglobulin lysis, UK-activated fibrinolysis, "hanging clot" method). The drug, although capable of aggregating platelets by itself at very high concentrations, showed a striking inhibitory effect, over a wide range of concentrations, both on platelet aggregation induced by ADP, epinephrine or collagen and on platelet adhesiveness to glass or collagen. Clot retraction was also clearly inhibited. PF3 availability was influenced with a peculiar two-phase behaviour dose-dependently. High concentrations showed a promoting action, while the lower were obviously inhibitory. It is suggested that the effects on platelet function may be due to an influence of the drug on cell membrane.
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PMID:In vitro effects of bencyclan on coagulation, fibrinolysis and platelet function. 1 70

alpha(2)-Plasmin inhibitor (alpha(2)PI) is a recently characterized, fast-reacting plasmin inhibitor in human plasma that appears to play an important role in regulation of in vivo fibrinolysis. We report here a case of complete deficiency of alpha(2)PI in man. The patient, a 25-yr-old Japanese man, had a life-long severe bleeding tendency (hemarthrosis and excessive bleeding after trauma). The following tests were within normal limits: platelet count, bleeding time, thrombin time, prothrombin time, partial thromboplastin time, titers of known clotting factors, platelet glass bead retention, Factor VIII-related antigen, platelet aggregation by ADP, collagen and ristocetin, and clot retraction. Routine liver function tests were also normal. The only abnormal finding was that whole blood clot lysis was extemely rapid and was complete in 4-8 h. The concentration of plasma protease inhibitors, including alpha(2)-macro-globulin, antithrombin III, alpha(1)-antitrypsin, and C1INH, were all normal. The concentration of alpha(2)-PI in the patient's plasma, assayed by immunological methods, was <0.1 mg/100 ml (normal concentration, 6.1+/-0.88 mg/100 ml [mean+/-SE]) and functional assays showed a complete deficiency of alpha(2)PI. Addition of purified alpha(2)PI to the patient's whole blood completely corrected the accelerated fibrinolysis. The patient's parents, four siblings, and four other members of this family were asymptomatic, but the titers of alpha(2)PI in their plasmas were congruent with50% of normal pooled plasma. There were three consanguineous marriages in this family, and the alpha(2)PI deficiency appears to have been inherited as an autosomal recessive trait. We speculate that alpha(2)PI deficiency in this patient has led to uninhibited in vivo fibrinolysis that probably causes the severe hemorrhagic tendency. Thus, this study indicates the important role of alpha(2)PI in hemostasis.
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PMID:Congenital deficiency of alpha 2-plasmin inhibitor associated with severe hemorrhagic tendency. 15 96

The vessel wall contains powerful inhibitors of thrombogenesis. One substance, a proteoglycan, is a strong anticoagulant but has only a limited effect on platelet aggregation. It prolongs the thrombin clotting time and partial thromboplastin time, but only blocks platelet aggregation induced by thrombin. Another vessel wall constituent, a prostaglandin derivative (prostacyclin), is a potent inhibitor of platelet aggregation. It antagonizes platelet aggregation induced by a variety of agents including adenosine diphosphate, collagen, arachidonic acid and thrombin; however, its only effect on coagulation is through the inhibition of platelet factor-3 release. Proteoglycans and prostacyclin comlement each other's antithrombotic activities, and together serve to limit the hemostatic response of blood to vessel wall injury. Vessels devoid of the intima continue to produce prostacyclin. Prostacyclin produced by these vessels is probably more important than that produced by vessels with the intima in the prevention of thrombus deposition.
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PMID:Vascular substances that modulate blood-to-vessel interactions. 39 10

Platelets provide a procoagulant activity for the conversion of prothrombin to thrombin during normal hemostatis. This activity designated as platelet prothrombin-converting activity (PPCA) was monitored as rate of thrombin production in a two-stage assay using gel-filtered bovine platelets, factor Xa, and prothrombin. Expression of PPCA was not associated with ADP-induced release or platelet shape change but was associated with aggregation. Release of the contents of dense bodies, measured by release of 14C-5-hydroxytryptamine, was not required for expression of PPCA during platelet aggregation. During the PPCA assay, 5-hydroxytrypamine was released, but only after onset of thrombin production. Furthermore, the release of 5-hydroxytryptamine was retarded during the assay by the addition of 2 mM theophylline and 100 nM prostaglandin E1 without a comparable reduction in PPCA. In addition, 125I-factor-Xa was bound in greater amounts to platelets (aspirin-treated) after ADP-induced aggregation (without detectable release) than to unactivated control platelets. Finally, the PPCA of the ADP-activated platelets was saturated with respect to factors Xa and Va at less than 1 nM concentrations, indicating that the aggregation induced by ADP leads to the exposure of specific procoagulant sites by some process other than dense body secretion.
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PMID:The effect of aggregation and release on platelet prothrombin-converting activity. 46 34

Thrombus weight was used as a measure of the thrombus enhancing effect of drugs in 135 rats. The weight of thrombus formed in one hour, on a 20 x 0.5 mm platinum wire, inserted in the vena cava was taken as a measure of thrombosis. The change in thrombus weight which followed the injection of ellagic acid to activate the coagulation system, adenosine diphosphate to activate the platelets, and epsilon-aminocaproic acid to inhibit the fibrinolytic system, was measured. Pilot studies showed that the drug doses used brought about the appropriate changes in the factors named. The mean thrombus weight in 45 control animals was 1.93 mg. Ellagic acid increased it about five-fold, and epsilon-aminocaproic acid almost two-fold, while adenosine diphosphate reduced it by almost a half. Concurrent controls were used in each case. Clotting tests (whole blood clotting time, kaolin-activated whole blood clotting time, thrombin time, and partial thromboplastin time), performed at the end of the hour, showed no significant correlation with thrombus weight.
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PMID:Thrombus weight as a measure of hypercoagulability induced by drugs. 50 92

Ischemic optic neuropathy and retinal arterial occlusion are 2 forms of arterial occlusive disease affecting the eye. Reports in the literature suggest platelet hyperactivity in acute arterial occlusive diseases affecting other organ systems. Therefore, 14 patients with ischemic optic neuropathy and 17 patients with central or branch retinal artery occlusion were studied to determine whether platelets have a role in the pathogenesis of these vascular occlusive disorders. The results of the following investigations were no different in these patients compared with those in 18 control patients with non-vascular eye diseases: prothrombin times, partial thromboplastin times, plasma fibrinogen, factor V, factor VIII, platelet counts and threshold concentrations of ADP, epinephrine and collagen resulting in secondary platelet aggregation and serotonin release. In contrast, platelet coagulant activities concerned with the early stages of intrinsic coagulation were significantly increased in patients with retinal artery occlusion without hypertension or type IV hyperlipoproteinemia, but generally normal in patients with ischemic optic neuropathy and in patients with retinal artery occlusion associated with hypertension, type IV hyperlipoproteinemia, diabetes mellitus and generalized atherosclerosis. These results are consistent with a platelet contribution to retinal arterial occlusive disease in patients without other known contributing factors such as hypertension, serum lipid abnormalities, diabetes mellitus and generalized atherosclerosis and may have implications regarding prophylaxis.
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PMID:Platelet coagulant activities in arterial occlusive disease of the eye. 50 1

A comparison has been made of some effects of a semi-synthetic heparin analogue, A73025, and heparin upon platelet function. In several of the in vitro tests performed, such as their potentiating effects on ADP and adrenaline induced aggregation and their effects on the aggregation of washed platelets by activated factor X, heparin proved to be more potent than A73025. Following intravenous injection of twice the quantity of A73025, an equivalent anti-factor Xa activity was obtained, in the agreement with our previous studies. However, it was found that PRP containing heparin and A73025 with comparable anti-Factor Xa acitvity responded differently to the addition of thrombin, as A73025 barely inhibited thrombin induced aggregation. Similarly, A73025 had little effect on the dilute thrombin clotting time of plasma, following intravenous injection. Heparin and A73025 were neutralized to approximately the same degree by a crude PF4 preparation.
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PMID:Comparison of heparin and a semi-synthetic heparin analogue, A73025. II. Some effects on platelet function. 60 58

By means of CM-Sephadex column chromatography, Trimeresurus mucrosquamatus venom was separated into 20 fractions. Fraction XX had the marked anticoagulant action. This fraction was refractionated three times on Sephadex G-75, and a single peak was obtained. The patterns of microzone and disc electrophoresis also showed a single band. A single, symmetrical boundary with a value of 1.61 S was obtained by ultracentrifugation. It was a single peptide chain with a molecular weight of 11 700. The isoelectric point was higher than pH 10. The anticoagulant principle possessed phospholipase A activity and was calcium ion dependent. It did not possess proteolytic, tosyl-L-arginine methyl ester esterase, phosphodiesterase and alkaline phosphomonoesterase activities of the crude venom. The phospholipase A activity was heat-labile at pH 7.4, but was heat-stable at pH 5.6. The anticoagulant activity was more resistant to heat treatment as compared with phospholipase A activity. The anitoagulant action of the purified principle was competitively inhibited by platelet phospholid, tissue thromboplastin and cephalin, and was neutralized by antiserum. The anticoagulant principle inhibited platelet aggregation induced by ADP. It did not destroy fibrinogen, Factor X, prothrombin and thrombin; nor did it induce fibrinolysis nor interfere with the interaction between thrombin and fibrinogen. It is concluded that the anticoagulant action of this phospholipase A was due to the inhibition of the activations of Factors X and II through the inactivation of the procoagulant activity of phospholipids mediated partly by phospholipid-binding activity of this venom enzyme and partly by its enzymatic hydrolysis of phospholipids.
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PMID:Purification and characterization of the anticoagulant principle of Trimeresurus mucrosquamatus venom. 66 29

A lupus-type anticoagulant which causes strong inhibition of the partial thromboplastin time with kaolin (PTTK), the stypven time, and the thrombin generation tests has been investigated. All tests for platelet function were normal, as were all specific coagulation factor assays with the exception of a slightly reduced factor XI in this patient. A diethylaminoethyl-cellulose-immunoglobulin (DEAE-cellulose-IgG) fractionation of the patient's plasma produced two peaks containing inhibitory activity in the PTTK test. The first of these peaks had a cloudy appearance, suggesting the presence of immunoglobulin aggregates. Studies with IgG aggregates prepared from normal IgG and from the patient's IgG demonstrated that such aggregates were not the cause of inhibition. It was possible to neutralize the inhibitory activity of the purified IgG but not platelet-poor plasma (PPP) with a rabbit anti-IgG. The inhibition of the patient's PPP in the thrombin generation, the contact product, and the stypven time tests were corrected by the inclusion in the test system of platelets activated either by aggregation due to adenosine diphosphate (ADP) or formalin fixation and washing. These studies lend support to earlier findings that platelets interact at several sites in the coagulation cascade.
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PMID:Demonstration of a platelet bypass mechanism in the clotting system using an acquired anticoagulant. 73 36

Serial measurements of coagulation activity, platelet counts, and platelet aggregation were done in patients with full-thickness burns involving 25% or more of body surface area to detect specific changes that might correlate with the onset of septicemia. Mean and maximal values for prothrombin time, partial thromboplastin time, thrombin time, activities of factor V and factor VIII, and concentrations of fibrinogen and fibrinogen-related antigens observed in the presence of bacterial septicemia did not differ significantly from those observed in the absence of septicemia. Mean platelet counts were significantly less with sepsis, but values in individual subjects were not indicative of the presence of septicemia. By contrast, platelet aggregation in response to adenosine diphosphate, epinephrine, and collagen always became severely abnormal with the onset of septicemia but not in the absence of sepsis.
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PMID:Platelet aggregation as a sign of septicemia in thermal injury. A prospective study. 94 30


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