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)

In Japanese black cattle with large and long-existing hematomas, platelets was impaired in collagen aggregation function in vitro. There was no statistically significant difference from control animals in the tests of PT (prothrombin time) and PTT (partial thromboplastin time) for extrinsic and intrinsic blood coagulation system. Aside from impaired collagen aggregation function, platelets in the hematoma cattle showed the similar aggregation patterns as the normal cattle, when ADP, serotonin (5-HT), thrombin, arachidonic acid, epinephrine and ristocetin were used as agents for inducing aggregation. Decreased aggregation function as well as impaired collagen-induced release response in platelets suggested the hematoma cattle to be of storage pool disease (SPD). The impaired platelet was postulated to be a main cause of the large and long-existing hematomas. All of the hematoma cattle with impaired platelet functions had the eosinophils in peripheral blood of which granules were fewer and larger than normal ones. These large eosinophil granules were peroxidase positive and periodic acid Schiff (PAS) staining negative as typical eosinophil granules.
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PMID:Persistent hematomas in Japanese black cattle with impaired platelet aggregation function and large granule eosinophils. 183 Jul 60

In human filariasis, large numbers of blood-borne microfilariae circulate unimpeded through the blood stream. How intravascular filarial parasites avoid precipitating thrombosis has not been studied in detail. We hypothesized that extracts of Brugia malayi microfilariae would contain factors that inhibit activation of hemostatic mechanisms. Initial studies demonstrated an inhibitor specific for the intrinsic coagulation cascade. The addition of microfilarial extracts to human plasma prolonged the activated partial thromboplastin time in a dose-dependent fashion but did not prolong the prothrombin, thrombin, or Russell's viper venom times. Microfilarial extracts (0.1 mg/ml) completely inhibited activation of Hageman factor (factor XII, at 0.05 U/ml) as measured in an amidolytic assay. Hageman factor previously activated by ellagic acid (factor XIIa) retained full enzymatic activity in the presence of microfilarial extract (0.1 mg/ml). The presence of inhibitory activity in the culture medium of live parasites raises the possibility that microfilariae secrete an inhibitory protein into their local environment. Microfilarial extracts at a final concentration of 0.1 mg/ml also inhibited collagen- and adenosine diphosphate-induced platelet aggregation. Arachidonic acid-induced platelet aggregation was inhibited by microfilarial extracts at a final concentration of 0.6 mg/ml. These results suggest that microfilariae of Brugia malayi, a human filarial parasite, may avoid initiating thrombosis through inhibition of the intrinsic coagulation pathway and platelet aggregation.
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PMID:Inhibition of the activation of Hageman factor (factor XII) and of platelet aggregation by extracts of Brugia malayi microfilariae. 201 87

There are many factors influencing the growth of the fetus. Since these factors have complex interrelations, they are difficult to clarify. The authors studied the effects of blood coagulation and fibrinolysis on the growth of the fetus during pregnancy, especially from the 2nd trimester into the 3rd trimester. The subjects were 86 normal pregnant women, and the subjects of study were blood coagulation, fibrinolysis activity of the mother, and estimated fetal birth weight after the 28th (2nd trimester) and 36th weeks of gestation (3rd trimester) in each case. 1. Changes in blood coagulation activity and fibrinolysis varied from the 2nd trimester into the 3rd trimester. The percentage of cases showing lowered platelets was 68.6% of the total, and the percentages of cases with reduced platelet ADP, epinephrine, and collagen aggregation were 60.5%, 55.8%, and 51.2%, respectively. The percentages of cases showing shortened prothrombin time and activated partial thromboplastin time were 58.1% and 51.2% of the total, respectively. The percentage of cases with reduced fibrinogen was 24.4% of the total. The percentages of cases with reduced antithrombin III, plasminogen, and alpha 2-plasmin inhibitor activity were 66.3%, 55.8%, and 75.6% of the total, respectively. 2. The birth weight of babies in a group with shortened prothrombin time was 2,935.1 +/- 395.2g(n = 50, mean +/- SD), while that in a group with prolonged prothrombin time was 3,106.2 +/- 357.9g(n = 36). The estimated fetal birth weight gain from the 2nd trimester to the 3rd trimester was 1,431.6 +/- 296.5g in the former group and 1,644.5 +/- 390.5g in the latter group. The differences were significant (p less than 0.05, p less than 0.01). The birth weight of babies in a group with lowered antithrombin III activity was 2,960.1 +/- 341.3g(n = 57), and that in an acceleration group was 3,157.8 +/- 370.0g(n = 29). The estimated fetal weight gain from the 2nd trimester to the 3rd trimester was 1,477.7 +/- 281.9g in the former group and 1,637.1 +/- 390.6g in the latter group. The differences were significant (p less than 0.02, p less than 0.05). 3. The estimated fetal weight gain from the 2nd trimester to the 3rd trimester in the group showing prolongated prothrombin time and activated partial thromboplastin time in this period was significantly larger than in the group showing shortened prothrombin time and activated partial thromboplastin time (p less than 0.001). These results suggested that the changes in blood coagulation and fibrinolysis activity of mothers from the 2nd trimester to the 3rd trimester affected the growth of the fetus.
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PMID:[Blood coagulation and fibrinolysis activities during normal pregnancy and fetal growth--study based on estimated fetal body weight]. 191 80

We evaluated the effect of the RGD-containing peptide, echistatin, on thrombolysis time and acute reocclusion in a canine model of coronary thrombosis/thrombolysis. Occlusive thrombus formation was induced by electrical injury, via a stimulating electrode, to the endothelial surface of the circumflex coronary artery in the open-chest, anesthetized dog in the presence of a critical stenosis. Fifteen minutes after occlusive thrombus formation, dogs received either an intravenous infusion of vehicle (saline at 0.1 ml/min) or echistatin (15 micrograms/kg/min i.v.). Heparin was given as an initial bolus (100 U/kg i.v.) 15 min after thrombus formation and repeated at hourly intervals (50 U/kg). This dose of heparin increased activated partial thromboplastin time to 1.5- to 2.5- fold over control. Thrombolysis was induced with recombinant tissue-type plasminogen activator (tPA) at a total dose of 1 mg/kg, intravenously administered over 90 min with 10% given as an initial bolus. The vehicle-treated animals reperfused at 48 +/- 9 min with a reperfusion incidence of 60% (3/5). The echistatin-treated animals reperfused at 46 +/- 5 min with a reperfusion incidence of 100% (5/5). After stopping the tPA infusion, acute reocclusion occurred in 100% (3/3) of the vehicle-treated dogs and in only 20% (1/5) of the echistatin-treated dogs. Echistatin caused a greater than 5-fold increase in buccal mucosa bleeding time and almost completely inhibited ex vivo platelet aggregation to ADP, collagen, and U-46619. Residual thrombus wet weight, determined at the end of the experiment, was significantly lower for the echistatin group (2.1 +/- 0.2 mg) compared to the vehicle group (5.8 +/- 0.7 mg).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prevention of reocclusion following tissue type plasminogen activator-induced thrombolysis by the RGD-containing peptide, echistatin, in a canine model of coronary thrombosis. 194 98

In a double-blind study, we compared the postoperative (post-op) blood loss in 161 children undergoing open heart surgery with cardiopulmonary bypass whose immediate post-op transfusion requirements were met with either very fresh whole blood (VFWB), 24- to 48-hour-old whole blood or reconstituted whole blood (packed red blood cells, fresh frozen plasma [FFP], and platelets). Assignment to treatment groups was not strictly random but dependent, in part, on the ability of families to provide directed donors for fresh blood. The three patient groups were comparable with respect to patient age, pre-op coagulation profiles (bleeding time, prothrombin time, activated partial thromboplastin time, platelet count, fibrin split products, fibrinogen, and platelet aggregation tests) difficulty of operative procedures and time spent on CPB. Mean 24-hour post-op blood loss in milliliters per kilogram was 50.9 +/- 9.3 in the VFWB group, 44.8 +/- 6.0 in the 24- to 48-hour-old group, and 74.2 +/- 8.9 in the reconstituted group (p = .03). When blood loss was compared in the 93 children less than 2 years of age, mean blood loss was 52.3 +/- 10.8 in the VFWB group, 51.7 +/- 7.4 in the 24- to 48-hour-old group, and 96.2 +/- 10.7 in the reconstituted group (P = .001). For subjects who had received reconstituted blood, 30-minute and 3-hour post-op platelet aggregation responses to adenosine diphosphate (10 mumol/L) and 30-minute aggregation response to epinephrine (2.5 mumol/L) were more depressed than in the VFWB and 24- to 48-hour groups (P less than .001, P = .005, and P = .02). Comparison of other post-op coagulation tests could not explain the increased blood loss in the reconstituted group. We conclude that the transfusion of less than 48 hours old whole blood is associated with significantly less post-op blood loss than the transfusion of packed red blood cells, FFP, and platelets in children under 2 years old who underwent complex cardiac surgery. The blood losses associated with the transfusion of VFWB and 24- to 48-hour-old blood are comparable and may be, in part, due to better functioning platelets.
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PMID:Comparison of the hemostatic effects of fresh whole blood, stored whole blood, and components after open heart surgery in children. 199

Activation of human platelets considerably enhanced their ability to accelerate factor Va inactivation by activated protein C (APC). The anticoagulant activity of platelet suspensions was markedly dependent on the kind of agonist used to activate platelets. APC-catalyzed factor Va inactivation in free solution was characterized by an apparent second-order rate constant of 2 x 10(5) (mol/L)-1 (seconds)-1. Nonstimulated platelets (2.4 x 10(8)/mL) and platelets stimulated with adenosine diphosphate or adrenalin accelerated factor Va inactivation fourfold. Rates of factor Va inactivation were increased 11-fold by thrombin-stimulated platelets, 29-fold after platelet stimulation with the Ca(2+)-ionophore A23187. At low platelet concentrations (3 x 10(7)/mL) only background levels of anticoagulant activity were observed in platelet suspensions that were nonstimulated or stimulated with thrombin or collagen. However, when such reaction mixtures were stirred during the activation procedure, platelet anticoagulant activity was increased more than 10-fold. Independent of platelet stimulation and stirring conditions, exogenously added purified plasma protein S increased platelet-dependent factor Va inactivation approximately twofold. Addition of a neutralizing antiprotein S antibody had little effect on the anticoagulant activity of platelets. This indicates that, under the reaction conditions tested, platelet-released protein S did not contribute to factor Va inactivation. Approximately 25% of the anticoagulant activity of stimulated platelet suspensions appeared to be associated with microparticles that were released on platelet activation. Such microparticles may provide an important source of anticoagulant activity. A similar distribution of procoagulant, ie, prothrombinase, activity between platelets and microparticles was observed for the same platelet suspensions. Because platelet stimulation and stirring also had the same overall effects on the ability of platelets and platelet microparticles to promote prothrombin activation and factor Va inactivation, it appears likely that the generation of potential platelet anticoagulant and procoagulant activities is coupled to the same platelet stimulation reactions.
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PMID:Comparison of anticoagulant and procoagulant activities of stimulated platelets and platelet-derived microparticles. 204 66

To clarify the pathogenesis of antiphospholipid antibody (aPL) syndrome, the reactivities of anticardiolipin antibodies (aCL) in sera of patients with systemic lupus erythematosus (SLE) or other diseases to fresh, activated or destroyed blood cells were examined by the inhibition assay using an enzyme-linked immunosorbent assay. In addition, the effects of lupus anticoagulants (LA) in the patients' plasma and of immune complexes formed between LA and PL antigens on platelet aggregations were also determined. The IgG-aCL activity of patients' sera was markedly inhibited by pre-incubation with freeze-thawed blood cells, including erythrocytes (RBC), mononuclear cells (MNC) and platelets, but not fresh platelets or RBC. The aCL activity was slightly inhibited by fresh MNC, and was definitely inhibited by thrombin-activated platelets and polymorphonuclear cells (PMN) stimulated with phorbol 12-myristate 13-acetate (PMA). However, the activity was not inhibited by platelets stimulated with adenosine 5'-diphosphate (ADP; 10 microM). Twenty-two LA positive plasma and 17 LA negative plasma from patients similarly enhanced the aggregation of platelets which were obtained from healthy adults and stimulated with low concentrations of ADP (1 or 2 microM). However, such enhancement of platelet aggregation was not observed when high concentrations of ADP (5 microM) or collagen (2 micrograms/ml) were used as stimulators. In four of the 16 LA positive plasma examined, the mixture of plasma and phospholipid reagent for activated partial thromboplastin time induced platelet aggregations without the other stimulations, but the plasmas themselves did not induce such a reaction. The above results indicate that the aPL from patients do not react with intact blood cells in vitro, but they can react with activated or destroyed blood cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reactivities of antiphospholipid antibodies to blood cells and their effects on platelet aggregations in vitro. 212 28

Ten clinically healthy subjects (5 men and 5 women), 31 +/- 11 yrs of age, were studied at six timepoints (0800, 1200, 1600, 2000, 0000, 0400) distributed over a 1-week span. Circadian rhythms in platelet aggregation in response to adenosine diphosphate (ADP) and adrenalin (A), platelet adhesiveness measured as retention in a glass bead column, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen, Factor VIII activity and alpha-1-antitrypsin antigen showed circadian rhythms. The plasma concentrations of plasminogen, alpha-2-macroglobulin, and antithrombin III (AT III) antigen, Factor V and fibrinogen degradation products showed no circadian rhythm by ANOVA or cosinor analysis. The phase relations of the rhythms of different coagulation parameters are of interest in the physiology and pathobiology of the coagulation-fibrinolytic system. The extent of the circadian rhythm (range of change) described is not of a magnitude to lead to diagnostic problems in the clinical laboratory. The timing of these rhythms, however, may determine transient risk states for thromboembolic phenomena, including myocardial infarction and stroke. Several but not all coagulation parameters suggest a transient state of hypercoagulability during the morning hours. The recognition of these rhythmic, and thus in the time of the occurrence predictable temporary risk states for thromboembolic phenomena, may lead to timed treatment and/or effective prevention.
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PMID:Circadian variations in blood coagulation parameters, alpha-antitrypsin antigen and platelet aggregation and retention in clinically healthy subjects. 212 46

Proteins of the annexin/lipocortin family act as in vitro anticoagulants by binding to anionic phospholipid vesicles. In this study, we investigated whether annexin V (placental anticoagulant protein I) would bind to human platelets. Annexin V bound to unstimulated platelets in a reversible, calcium-dependent reaction with an apparent Kd of 7 nM and 5000-8000 sites/platelet. Additional binding sites could be induced by several platelet agonists in the following order of effectiveness: A23187 greater than collagen + thrombin greater than collagen greater than thrombin. However, neither ADP nor epinephrine induced additional binding sites. Three other proteins of the annexin family (annexins II, III, and IV) competed for annexin V platelets binding sites with the same relative potencies previously observed for binding to phospholipid vesicles. Phospholipid vesicles containing phosphatidylserine completely inhibited binding of annexin V to platelets. Annexin V completely blocked binding of 125I-factor Xa to thrombin-stimulated platelets. These results support the hypothesis that phosphatidylserine exposure occurs during platelet activation and may be necessary for assembly of the prothrombinase complex on platelet membranes.
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PMID:Binding of annexin V/placental anticoagulant protein I to platelets. Evidence for phosphatidylserine exposure in the procoagulant response of activated platelets. 214 74

The functional characterization of human platelet-released factor V and its activation by factor Xa and thrombin was studied by functional assessment of cofactor activity and Western blotting analyses of platelet releasates, obtained by stimulating washed suspensions of platelets with various agonists, including collagen, collagen with ADP, and the calcium ionophore A23187. Platelet factor V was released as a partially proteolyzed molecule that was bound to platelet microparticles, irrespective of the agonist used. Radiolabeled plasma factor V was not cleaved for up to 30 min following release when added to platelets prior to stimulation, suggesting that platelet factor V was stored in a partially proteolyzed form. Released platelet factor V possessed significant cofactor activity that was increased only 2-3-fold by either factor Xa or thrombin. The factor V subunits that expressed cofactor activity were isolated and found to consist of peptides of Mr = 220,000 and 150,000. Incubation of released platelet factor V with factor Xa or thrombin yielded the same cleavage pattern, in which two peptides of Mr = 105,000 and 74,000 appeared to be electrophoretically indistinguishable from thrombin-activated plasma factor V. Under the conditions of these studies, factor Xa activated platelet-released factor V 50-100 times more effectively than thrombin. This observation may be due in part to the existence of platelet factor V in a partially proteolyzed state, or its association with platelet microparticles following platelet stimulation. These data collectively suggest that platelet-released factor V may be the foremost initiator of prothrombinase complex assembly and function during the early stages of coagulation with additional cofactor activation accomplished by factor Xa.
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PMID:Functional characterization of human platelet-released factor V and its activation by factor Xa and thrombin. 221 16


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