Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.6 (thromboplastin)
 13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To study factor VII (F VII) hyperactivity in chronic dialysis patients, we measured the plasma levels of F VII activity (F VII c) and antigen (F VII Ag), prothrombin activation fragments 1 + 2 (F1 + 2), thrombin-antithrombin III complexes (TAT), and thrombomodulin in 28 patients on hemodialysis. Marked elevation of F VII c was found in long-term dialysis patients (185 +/- 30%). This hyperactivity was accompanied by both elevation of the F VII Ag level (153 +/- 28%) and enhanced activation of F VII zymogen, expressed as the F VII c/F VII Ag ratio (1.23 +/- 0.23), but pseudocholinesterase activity was decreased. The 6 patients with ischemic heart disease had slightly higher F VII c (200 +/- 25%) than those without ischemic heart disease (181 +/- 30%), although the difference was not significant. Increased F VII c was accompanied by factor Xa hyperactivity (a high plasma F1 + 2 level) in the long-term dialysis patients, but there was no significant elevation of plasma TAT levels when compared with controls matched for age, sex, and the presence or absence of diabetes mellitus. Plasma TAT levels were significantly correlated with plasma thrombomodulin levels, suggesting that thrombin generation in blood as a result of hemodialysis could induce systemic endothelial cell injury.
 ...
PMID:Factor VII hyperactivity in chronic dialysis patients. 133 12

We investigated coagulation system activation following estrogen treatment in 29 healthy postmenopausal women. Study participants received conjugated estrogens at 0.625 and 1.25 mg per day, and placebo for 3-month periods in a randomized crossover protocol. Blood samples were obtained on two consecutive days at the end of each treatment period for immunoassays of F1+2 and fibrinopeptide A (FPA), markers of factor Xa action on prothrombin and thrombin action on fibrinogen in vivo, respectively. Treatment with estrogens at a dose of 0.625 or 1.25 mg resulted in significant increases in mean F1+2 levels of 40 and 98%, respectively, and in mean FPA levels of 37 and 71%, respectively. The measurements of F1+2 were significantly higher in women receiving 1.25 mg of estrogen than 0.625 mg. We also observed significant declines in the levels of antithrombin III and total protein S antigen. Immunologic levels of protein C increased modestly at only the 1.25 mg estrogen dose level. These data indicate that low doses of oral estrogens (< or = 1.25 mg per day) frequently increase the amount of thrombin generated in vivo. Our observations may help to explain the increased thrombotic risk that has been observed with higher doses of this medication (> or = 2.5 mg).
 ...
PMID:Coagulation activation following estrogen administration to postmenopausal women. 133 98

The neutralizing effects of protamine sulfate (PS) on anticoagulant activities of low molecular weight heparin (LHG) and conventional sodium heparin (Heparin) were investigated. The in vitro anti-factor Xa and APTT-prolonging activities of Heparin were almost completely neutralized by PS, whereas the activities of LHG remained partially intact in the presence of PS. Crossed immunoelectrophoresis of antithrombin III (AT III) and affinity chromatography of LHG- and Heparin-cellulose showed that AT III was substantially less dissociated from its binding to LHG than to Heparin in the presence of PS. As in vitro, the in vivo anticoagulant activities of Heparin administered i.v. to rabbits were almost completely neutralized by PS, while the anti-factor Xa and APTT-prolonging activities of LHG remained partially intact in the presence of PS. The thrombin time-prolonging activity of LHG, however, was completely inhibited by PS. Since the bleeding effect of Heparin or LHG is considered mainly due to its anti-thrombin activity, PS may be used as an agent to neutralize LHG, as in the case of Heparin, when bleeding happens to occur during LHG treatment.
 ...
PMID:Study on neutralization of low molecular weight heparin (LHG) by protamine sulfate and its neutralization characteristics. 133 15

Seven rabbits experimentally infected with rabbit haemorrhagic disease virus were examined haematologically and histologically. Haematologically, activated partial thromboplastin time and prothrombin time were markedly prolonged in the terminal phase of the disease, just prior to death (all the animals died between 27 and 40 hr after inoculation with rabbit haemorrhagic disease virus). There was an increase in the titre of fibrin degradation products and a decrease in antithrombin III activity during the same interval. Acute necrotic hepatitis and disseminated intravascular coagulation (DIC) in many organs, including the lung, kidney, spleen and heart were the characteristic histopathological changes. Thus, the haematological and histological changes suggested that DIC was induced by rabbit haemorrhagic disease virus infection. Severe liver necrosis was considered to be a factor causing DIC by inducing a hypercoagulable condition in the systemic blood circulation.
 ...
PMID:Disseminated intravascular coagulation (DIC) in rabbit haemorrhagic disease. 133 94

Most of the linkage of atherosclerosis and thrombosis with estrogens is epidemiologic in origin. Although the effects of estrogens on the mechanisms of hemostasis are wide ranging, many are benign; only a few may account for thrombus formation. Platelet function tests have provided extensive but contradictory data, and interpretation is limited because it is uncertain whether a rise in one or more of these parameters is a primary or secondary effect. The most consistent effects of estrogens on coagulation proteins are elevations of fibrinogen; factors II, VII, IX, X, and XII; protein C; and plasminogen. Although these elevations have been attributed to the estrogenic component in oral contraceptives, the progestogen concentration may also influence these increases. Among other coagulation proteins studied, the following are unaffected by oral contraceptive use: factors V, VIII, and XI; prekallikrein; and high-molecular-weight kininogen. In contrast, protein S values are decreased. The plasma concentration of plasmin inhibitor is unchanged, whereas both proteinase inhibitor and macroglobulin are significantly increased by oral contraceptive use. Cl esterase inhibitor is decreased in women taking oral contraceptives and correlates with the increase in Hageman factor. Antithrombin III is one plasma inhibitor for which a decrease in quantity and activity have been associated with a thrombotic tendency in humans. Although data on estrogen-associated changes in the quantity of antithrombin III have been conflicting, the ability of plasma to inhibit factor Xa is significantly reduced in a dose-dependent manner among pre- and postmenopausal estrogen users.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Estrogen-associated thromboembolism. 134 94

Recent epidemiologic studies found that there is a strong association of hemostatic factors with ischemic heart disease. The Atherosclerosis Risk in Communities (ARIC) Intraindividual Variability (IIV) Study was conducted to estimate the various components of variation in hemostasis factors measured in the ARIC Study and to estimate the measures of repeatability of these factors. A total of 39 subjects (16 men, 23 women) were studied. Each had blood collected three times, with a 1- to 2-week interval between each visit. The contributions of between-person variability, within-person (biologic) variability, and processing and assay variability were estimated. Then the reliability coefficient R was estimated as the proportion of total variance accounted for by between-person variance. The reliability coefficient can be interpreted as the correlation between measures made at repeat visits. Among the various analytes, the reliability coefficients were quite high for activated partial thromboplastin time and plasma factor VIII (R = 0.92, 0.86, respectively). Low repeatability was obtained for antithrombin III activity and protein C (R = 0.42, 0.56, respectively). The lack of repeatability for these variables derives mostly from the processing (field center and laboratory) variation. Other analytes--fibrinogen, plasma factor VII, and von Willebrand factor--were intermediate in repeatability. In comparing the analyte-specific high-level to low-level groups, no substantial difference of within-person plus method coefficient of variation between the two groups was found for any analyte except for factor VIII, whereas the corresponding variance components for most analytes were higher for the higher analyte level. Reliability coefficients from this ARIC IIV study are generally higher than those found in other studies, and this is related to the relative variations in populations studied and to the time between measurements.
 ...
PMID:Short-term intraindividual variability in hemostasis factors. The ARIC Study. Atherosclerosis Risk in Communities Intraindividual Variability Study. 134 24

Plasminogen activator inhibitor 1 (PAI-1), a member of the serpin superfamily of proteins, has been demonstrated previously to interact functionally with the glycosaminoglycan heparin (Ehrlich, H.J., Keijer, J., Preissner, K. T., Klein Gebbink, R., and Pannekoek, H. (1991) Biochemistry 30, 1021-1028). Heparin specifically enhances the rate of association between PAI-1 and thrombin about 2 orders of magnitude, whereas no effect is detected with other serine proteases (e.g. factor Xa). For the heparin-dependent serpins antithrombin III and heparin cofactor II, basic amino acid residues in and around the helix D subdomain were proposed to be involved in the binding of glycosaminoglycans. Here we employed site-directed mutagenesis of full-length PAI-1 cDNA to identify the amino acid residues that mediate heparin binding. To that end, 15 single-point mutants of PAI-1, each having individual arginyl, lysyl, or histidyl residues replaced by a neutral (alanyl) residue ("ala-scan"), and one double mutant were constructed, expressed in Escherichia coli, and purified to apparent homogeneity. The purified biologically active proteins were subjected to the following analyses: (i) heparin-dependent inhibition of thrombin; (ii) heparin-dependent formation of sodium dodecyl sulfate-stable complexes with thrombin; and (iii) binding to and elution from heparin-Sepharose. Based on the data presented, we propose that the amino acid residues Lys65, Lys69, Arg76, Lys80, and Lys88 constitute major determinants for heparin binding of PAI-1. These residues are located in and around the helix D domain and are conserved in the other heparin-dependent thrombin inhibitors, antithrombin III and heparin cofactor II.
 ...
PMID:Elucidation of structural requirements on plasminogen activator inhibitor 1 for binding to heparin. 137 44

Orgaran is a mixture of glycosaminoglycans extracted from animal mucosa. It consists of heparan, dermatan and chondroitin sulfate; a small proportion of heparan sulfate (4%) has high affinity for antithrombin III (AT III). Orgaran is devoid of heparin or heparin fragments. Orgaran catalyses the inactivation of factor Xa and thrombin. Compared to heparin and most low-molecular-weight heparins, Orgaran has a much higher anti-Xa/anti-IIa ratio. The inactivation of factor Xa is mediated by AT III and that of thrombin by both AT III and heparin cofactor II. Compared to heparin, which is a strong inhibitor of thrombin generation, Orgaran has only moderate inhibitory effects on thrombin generation. Orgaran shows minimal or no effects on platelet function in vitro or in vivo. It inhibits the formation of various types of thrombi (clot-like and mixed thrombi) with approximately the same potency as heparin. Both the high- and low-affinity fraction for AT III contribute to the antithrombotic activity. In contrast to heparin, Orgaran does not inhibit platelet deposition in experimental mixed thrombi unless very high doses of the heparinoid are used. Orgaran is more efficacious than heparin in preventing the extension of established venous thrombosis. Orgaran promotes less bleeding-enhancing activity than heparin in various experimental models. In addition, compared to heparin, it has only minimal effects on platelet degranulation during hemostatic plug formation.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Orgaran (Org 10172): its pharmacological profile in experimental models. 137 65

Orgaran (Org 10172), which has antithrombotic activity in man with apparently minimal bleeding side effects, is a mixture of low-molecular-weight heparan, dermatan, and chondroitin sulfates. The degrees to which the minimum concentrations of Orgaran, its fraction with high affinity for antithrombin III (Org 10849; AT III) and unfractionated heparin, which double the activated partial thromboplastin time (APTT) of pooled normal plasma, inhibit intrinsic activation of factor IX, factor X, and prothrombin were compared. Specific ELISAs were used to quantify the activation of each clotting factor. Factor IX activation, which began without a lag phase, preceded factor X and prothrombin activation by approximately 15 and approximately 25 s, respectively. When used at these functionally equivalent concentrations, heparin (2 micrograms/ml plasma), Orgaran (50 micrograms/ml plasma), and Org 10849 (20 micrograms/ml) could delay the onset of factor IX activation. Compared to control plasma, however, only Orgaran reduced the initial rate of factor IX activation. Heparin and Orgaran delayed the onset of factor X activation by 20 and 15 s, respectively, while Org 10849 could not delay the onset of factor X activation. In addition, each anticoagulant delayed the onset of prothrombin activation. Thus, at concentrations which double the APTT of normal plasma, the combined actions of heparan and dermatan sulfate present in Orgaran can apparently suppress factor IX activation more effectively than heparin, and delay the onset of factor X activation nearly as effectively as heparin. The coordinated inhibition of factor IX and factor X activation by Orgaran may contribute to its antithrombotic effectiveness.
 ...
PMID:Anticoagulant mechanisms of Orgaran (Org 10172) and its fraction with high affinity to antithrombin III (Org 10849). 137 66

The effect of 5 years' use of Norplant on blood clotting factors was assessed in 97 Singaporean women. The subjects were healthy, non-smoking non-alcohol drinking and non-lactating. Blood was sampled at 6, 12, 18, 24, 36, 48 and 60 months, after an overnight fast, and resting 30 minutes before venipuncture. Hemoglobin and hematocrit increased 10% in the 1st year (p0.001), fell for the next 2 years, reaching pre-insertion levels by 3 years, then increased 10% for the last 2 years. There was a significant shortening of the prothrombin time (PT) throughout the 5 years, and of activated partial thromboplastin time (APTT) for 3 years. Vitamin K-dependent Factors II, V, VII, decreased throughout the 5 years, and fibrinolytic activity decreased at 2 and 4 years of use. Fibrinogen increased at the end of the 1st year only. Platelet numbers rose 25.6% to 43.4%, and platelet aggregation to both ADP and collagen increased throughout the 5 year period. Alpha2-macroglobulin and antithrombin III antigen levels were heightened for 4 years. Most of the observed changes were different from those seen in oral contraceptive users, except for alterations in platelet function. While some of the measured clotting factors were significantly different, none were of any clinical significance, nor were these women in a state of hypercoagulation.
 ...
PMID:Effect of long-term use of Norplant implants on haemostatic function. 138 Sep 4


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>