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 effect of collagen on isolated platelets, platelet-rich plasma and whole blood has been studied. Collagen failed to generate factor XIa-like activity in mixtures of isolated platelets, collagen and Ca++. Moreover, collagen added to whole blood or platelet-rich plasma containing 125I-factor IX and Ca++, also failed to form cleaved (activated) factor IX. In preliminary studies, lysed endothelial cells were found to enhance the formation of factor Xa and thrombin and to induce cleavage of 125I-factor IX in normal plasma, factor XII and factor-XI-deficient plasma even in the presence of antibody to tissue factor.
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PMID:The role of endothelial cells and subendothelial components in the initiation of blood coagulation. 51 Oct 12

We have shown recently that the calcium-dependent phospholipid-binding protein annexin V (placental anticoagulant protein I) can be used to study the exposure of anionic phospholipid after platelet activation. In this study we have further examined the mechanism of this process. Collagen-induced exposure of annexin V binding sites correlated directly with increased ability to support activity of the reconstituted prothrombinase complex. The potency of annexin V as an inhibitor of platelet prothrombinase was the same as its Kd for platelets. Prior incubation of platelets with 5'-p-fluorosulfonylbenzoyladenosine or p-chloromercuribenzenesulfonate had no significant effect on annexin V binding. Similarly, inhibition of platelet cyclic endoperoxide synthesis by acetylsalicylic acid or indomethacin did not inhibit annexin V binding. Staurosporine inhibited collagen-induced, but not A23187-induced, annexin V binding. Agents that increase intraplatelet cyclic nucleotides partially inhibited collagen-induced annexin V binding. Thus, collagen-induced exposure of anionic phospholipid appears to depend primarily on increases in intraplatelet free calcium and may be independent of ADP- or endoperoxide-mediated pathways. Binding sites for annexin V on microparticles derived from collagen-stimulated platelets were demonstrated by flow cytometry and gel filtration. In addition, prior incubation of platelets with 100 nM annexin V inhibited factor Va binding to both platelets and platelet-derived microparticles. These results support the concept that the procoagulant effect of platelets and platelet-derived microparticles is mediated by calcium-induced exposure of anionic phospholipids.
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PMID:Collagen-induced exposure of anionic phospholipid in platelets and platelet-derived microparticles. 166 6

This study explores the effects on some hematological parameters of a low-dose aspirin regimen (50 mg/day) versus a conventional aspirin treatment with reported antithrombotic efficacy (324 mg/day), in patients with acute myocardial infarction. Fifteen patients were randomized into 3 equal groups receiving 50 mg or 324 mg aspirin or placebo, daily for 21 days. Compared with placebo, bleeding time was significantly and similarly prolonged with both aspirin doses (+ 71 +/- 22% and + 69 +/- 20%, mean +/- S.D.). Aspirin 50 mg/day suppressed arachidonate-induced platelet aggregation and secondary phase aggregation after ADP and adrenaline. Collagen aggregation was inhibited by 44 +/- 15%. In no case were differences in the antiplatelet effects of the two doses observed. The effects of 50 mg/day persisted without attenuation during the observation period. Platelet thromboxane B2 generation during arachidonate-induced aggregation was inhibited by 95 +/- 2 and 99 +/- 1% compared to placebo group after 50 and 324 mg/day, respectively (P between doses less than 0.05). No change was observed with any treatment in coagulation time, prothrombin time or plasma thromboplastin time. Thus, in patients with acute myocardial infarction, the antiplatelet effects of aspirin 50 mg/day are stable over time and superimposable on those of 324 mg/day. The antithrombotic efficacy of aspirin 50 mg/day remains to be tested clinically.
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PMID:Equal antiplatelet effects of aspirin 50 or 324 mg/day in patients after acute myocardial infarction. 408 90

Exposure of phospholipids at the outer surface of activated and control platelets was studied by incubation with a mixture of phospholipase A2 from Naja naja and bee venom, solely or in combination with sphingomyelinase from Staphylococcus aureus, using conditions under which cell lysis remained below 10%. Incubation with phospholipase A2 alone revealed a markedly increased susceptibility of the phospholipids in platelets activated by a mixture of collagen plus thrombin, by the SH-oxidizing compound diamide, or by calcium ionophore A23187, as compared to control platelets or platelets activated separately by collagen or thrombin. Collagen plus thrombin, diamide, and ionophore treated platelets revealed an increased exposure of phosphatidylserine at the outer surface accompanied by a decreased exposure of sphingomyelin, as could be concluded from incubations with a combination of phospholipase A2 and sphingomyelinase. These alterations were much less apparent in platelets activated either by thrombin or by collagen alone. The increased exposure of phosphatidylserine in activated platelets is accompanied by an increased ability of the platelets to enhance the conversion of prothrombin to thrombin by coagulation factor Xa, in the presence of factor Va and calcium. It is concluded that the altered orientation of the phospholipids in the plasma membrane of platelets activated by collagen plus thrombin, by diamide, or by calcium ionophore, is the result of a transbilayer movement. Moreover, the increased exposure of phosphatidylserine in platelets stimulated by the combined action of collagen and thrombin might be of considerable importance for the hemostatic process.
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PMID:Changes in membrane phospholipid distribution during platelet activation. 641 5

The relationship between platelet release and fibrinopeptide A cleavage from fibrinogen to form fibrin I in vitro was examined in blood allowed to clot undisturbed or with gentle agitation. In undisturbed or agitated blood platelet release and fibrin I formation occurred simultaneously. When hirudin was added to undisturbed blood it prevented platelet release as well as fibrin I formation. In contrast, hirudin added to agitated blood had little effect on platelet release despite complete inhibition of fibrin I formation. Collagen added to either undisturbed or agitated blood increased platelet release and then fibrin I formation, and ADP added to undisturbed blood caused an initial burst of platelet release followed by slight acceleration of fibrinopeptide A cleavage. Prostaglandin E1 and theophylline prevented platelet release in both undisturbed and agitated blood, but did not affect fibrin I formation. The results with inhibitors in agitated blood suggest that fibrin I formation and platelet release can occur independently in the presence of the increased interactions induced by agitation. Addition of thrombin or tissue thromboplastin to undisturbed blood accelerated fibrin I formation with little effect on platelet release. Finally, initial thrombin formation in undisturbed blood appeared to be associated with the platelet surface. These relationships suggest that thrombin formation via the intrinsic system leads to thrombin generation on the platelet surface and simultaneous platelet release and fibrin I formation, while thrombin generated via tissue thromboplastin leads to thrombin formation in the plasma and fibrin I formation preceding platelet release. Activation by interaction of blood with collagen causes initial acceleration of platelet release and later acceleration of fibrin I formation.
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PMID:Fibrinopeptide A cleavage and platelet release in whole blood in vitro. Effects of stimuli, inhibitors, and agitation. 645 36

Extracts of adult Ancylostoma ceylanicum prolonged the prothrombin time (PT) and partial thromboplastin time with kaolin ( PPTK ) of both human and dog plasmas in vitro. Excretory/secretory (E/S) products of these worms had similar effects while larval extract prolonged the PTTK only. Thus, the anticoagulant activities of this parasite are dependent upon the stage of the worm's life cycle. Collagen- and ADP-induced platelet aggregation were inhibited by adult and larval extracts. When the peripheral blood and bleeding times of dogs with varying worm burdens were examined, the only abnormality was shortening of the PTTK in the most heavily infected animals. Homogenates of dog small bowel subjacent to adult hookworms prolonged the PT of dog plasma and electron microscopical examination of this tissue revealed aggregation of platelets in blood venules without fibrin deposition. Thus, this study provides evidence that the anticoagulant properties of hookworms may have biological significance in infected animals.
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PMID:The anticoagulant effects of the hookworm, ancylostoma ceylanicum: observations on human and dog blood in vitro and infected dogs in vivo. 674 May 54

In order to understand some of the haemostatic mechanisms in rats for the interpretation of toxicological data, basic haemostatic parameters with a special emphasis on platelet functions were first measured in vitro. The results of reactions of rat platelets to many aggregating agents suggest that only ADP may be a consistently significant aggregator. The search for physiologic aggregators revealed ADP to be available from erythrocytes. Adhesion reaction also required ADP. Collagen was not considered to be essential for either reaction. Aggregation and adhesion were probably both reversible in flowing blood, while irreversible thrombi were formed in blood at rest ex vivo. Blood coagulation parameters determined revealed that the intrinsic pathway may be more important than the extrinsic one. The rate of intrinsic coagulation reaction was rapid, and plasma coagulation appeared to be of primary importance while the influence of platelet aggregation was minor. A simple model of rat haemostatic mechanism is proposed based on these results. Additionally, to define the relative contribution of platelets versus other cellular and plasma coagulation in vivo, rats were administered antiplatelet drugs (ticlopidine, suprofen and clopidogrel) and an anticoagulant (warfarin) intraperitoneally. Bleeding times (BTs) were significantly increased in all treated groups. ADP-induced platelet aggregations were significantly depressed by the administration of the three antiplatelet drugs, while kaolon-activated partial thromboplastin time and prothrombin time were greatly increased in the warfarin-treated rats. The increase in BT may be due to the inhibition of platelet activity or blood coagulation defect in rats given antiplatelet drugs or warfarin, respectively. These results suggest that platelets play a key role in haemostasis in the rat. Two possible explanations of the disparity between in vitro and in vivo results may be that functional tests used here are not adequate to cover the properties of rat platelets or that mechanisms leading to the formation of platelet thrombi in rats are ADP-dependent adhesion and ADP-induced aggregation.
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PMID:Characteristics of rat platelets and relative contributions of platelets and blood coagulation to haemostasis. 1071 61

In a new 2-stage assay of platelet procoagulant activity (PCA), we first subjected gel-filtered platelets to adhesion on collagen (as a model of primary hemostasis) or plasma clots (as a model of preformed thrombus) for 30 minutes, and then the adherent platelets were supplemented with pooled, reptilase-treated, diluted plasma. Defibrinated plasma provided coagulation factors for assembly on platelet membranes without uncontrolled binding of thrombin to fibrin(ogen). Platelet adhesion to both surfaces showed modest individual variation, which increased at platelet densities that allowed aggregation. However, adhesion-induced PCA varied individually and surface-independently >3-fold, suggesting a uniform platelet procoagulant mechanism. Permanently adhered platelets showed markedly enhanced PCA when compared with the platelet pool in suspension, even after strong activation. The rate of thrombin generation induced by clot-adherent platelets was markedly faster than on collagen-adherent platelets during the initial phase of coagulation, whereas collagen-induced PCA proceeded slowly, strongly promoted by tissue thromboplastin. Therefore at 10 minutes, after adjustment for adhered platelets, collagen supported soluble thrombin formation as much as 5 times that of the thrombin-retaining clots. Activation of platelets by their firm adhesion was accompanied by formation of microparticles, representing about one third of the total soluble PCA. Collagen-adhered platelets provide soluble thrombin and microparticles, whereas the preformed clot serves to localize and accelerate hemostasis at the injury site, with the contribution of retained thrombin and microparticles.
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PMID:Procoagulant activity on platelets adhered to collagen or plasma clot. 1130 82

Traditionally known as a haemostatic agent, alum shows a paradoxical effect of increased prothrombin and partial thromboplastin times. This study investigated the in vivo effect of alum on platelet aggregation and bleeding time in rabbits. The collagen-induced platelet aggregation of platelet-rich plasma samples from 14 healthy rabbits was measured turbidometrically using a platelet aggregometer, before and 1 hour after intravenous injection of alum. Collagen-induced platelet aggregation was significantly reduced after alum injection. Bleeding time from an ear puncture in 8 rabbits was also significantly prolonged after intravenous alum injection. These results suggest that the use of alum as an oral antiplatelet drug could be explored further, taking into account possible side-effects especially in renal compromised patients.
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PMID:In vivo antiplatelet effect of intravenous alum in rabbits. 1660 65

Rivaroxaban (BAY 59-7939) is an oral, direct factor Xa inhibitor in advanced development. This study was undertaken to investigate its effects on thrombin generation. In this placebo-controlled, randomized, crossover study, 12 healthy subjects received rivaroxaban (single 5- or 30-mg dose) or placebo. Thrombin generation was investigated by measuring the endogenous thrombin potential and prothrombinase-induced clotting time. Maximal effect of rivaroxaban was observed 2 hours after drug administration: prothrombinase-induced clotting time was prolonged 1.8 and 2.3 times baseline after rivaroxaban 5 and 30 mg, respectively. Collagen-induced endogenous thrombin potential was reduced by approximately 80% and approximately 90% compared with baseline after rivaroxaban 5 and 30 mg, respectively, and tissue factor-induced endogenous thrombin potential was reduced by approximately 40% (5 mg) and approximately 65% (30 mg), respectively. Thrombin generation remained inhibited for 24 hours. There was a close correlation between plasma concentration of rivaroxaban and prolongation of prothrombinase-induced clotting time and reduction in endogenous thrombin potential. Rivaroxaban strongly inhibits platelet-induced thrombin generation, after activation of either platelets or the coagulation pathway, even in the presence of minimal factor Xa inhibition in plasma.
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PMID:Effects of the oral, direct factor xa inhibitor rivaroxaban on platelet-induced thrombin generation and prothrombinase activity. 1787 38


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