Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ANTITHROMBIN”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,297 records · Page 72Linked to original sources
PubMed1999

The procoagulant state of the VX-2 tumor in rabbit lung in vivo--relative accumulation of fibrinogen, prothrombin, plasminogen, antithrombin and heparin cofactor II within the tumor.

During their growth, many malignant solid tumors elicit a hemostatic response in the host. In this report, the fluxes of various rabbit plasma hemostatic proteins into pulmonary VX-2 tumors have been measured in vivo. VX-2 cells were contained within a small rabbit plasma clot which was injected intravenously into rabbits. At 28 d, each rabbit was injected intravenously with two radiolabeled (131I, 125I) proteins selected from fibrinogen, prothrombin, antithrombin-alpha, heparin cofactor II, or plasminogen-I or -II. After allowing the labeled proteins to circulate for 10-200 min, each rabbit was perfused with Krebs-Henseleit solution and the lungs excised. Solid tumors were isolated, weighed and measured for radioactivity content. A mean of 14 tumors/pair of lungs with a mean tumor weight of 0.3 g was obtained. Radioactivity per g of tumor was related to radioactivity/ml of blood at exsanguination for each protein at each time interval. Maximum flux rates were calculated (as pmol/g of tumor/min): Fibrinogen, 65.0; prothrombin, 53.0; antithrombin-alpha, 24.1; HCII, 17.2; plasminogen-II, 5.0; and plasminogen-I, 3.2. Using immunocytochemical staining, fibrin(ogen) was distributed heterogeneously within the VX-2 tumor, appearing largely in the perinodular region and in the necrotic core. From the net fluxes of these proteins, the profile of chronic hemostasis associated with the VX-2 tumor was shown to differ markedly from the hemostatic response that occurs after an acute vascular injury.

Animals↗
PubMed2000

Surface-loop residue Lys316 in blood coagulation Factor IX is a major determinant for Factor X but not antithrombin recognition.

The active site of activated Factor IX (FIXa) and related blood-coagulation enzymes is surrounded by a number of highly variable surface loops, which contribute to the characteristic substrate specificity of each individual enzyme. FIX residue Lys(316) is located in one of these loops and mutation of this residue to Glu is associated with haemophilia B. In the present study we investigated the functional role of Lys(316) in human FIXa by analysing the purified and activated FIX mutants FIXa-K316E and FIXa-K316A. FIXa-K316E was indistinguishable from normal FIXa in binding the competitive active-site inhibitor p-aminobenzamidine. In addition, substitution of Glu for Lys(316) had no significant effect on the reactivity towards various synthetic tripeptide substrates. Inhibition by the macromolecular inhibitor antithrombin was only slightly reduced for both FIXa mutants (less than 2-fold). In contrast, proteolytic activity of FIXa-K316E towards the natural substrate Factor X (FX) was virtually lacking, while the Lys(316) to Ala mutation resulted in a more than 10-fold reduction in FX activation. Thus residue Lys(316) plays a key role in FIXa activity towards FX. The requirement for Lys at position 316 for FX activation was also evident in the presence of the cofactor activated Factor VIII, although to a lesser extent than in its absence. These data demonstrate that Lys(316) specifically determines the reactivity of FIXa towards its natural substrate FX, but not to synthetic peptide substrates or antithrombin.

Antithrombins↗
PubMed2000

Duration of oral anticoagulant treatment in patients with venous thromboembolism and a deficiency of antithrombin, protein C or protein S--a decision analysis.

Patients with a first venous thromboembolic event and a deficiency of the coagulation inhibitors antithrombin, protein C or protein S have an increased risk of recurrent venous thromboembolism compared to patients without such a deficiency. A decision analysis was performed to assess the effect of continuing treatment with vitamin K antagonists on mortality by a reduction in fatal recurrent pulmonary embolism and an induction of fatal haemorrhages associated with their use. The treatment decision involves continuation or discontinuation of vitamin K antagonists in patients with a first spontaneous or secondary venous thromboembolism and an antithrombin, protein C or S deficiency. Although the efficiency of oral anticoagulation is high in all age groups early after the first thromboembolic event, it decreases over time. Our analysis indicates that the optimal treatment duration will vary, depending on the type of the initial event (spontaneous or secondary; deep venous thrombosis or pulmonary embolism), age, and time passed since the initial thromboembolic episode. Moreover, life-long duration of the prophylaxis seems not warranted in all patients.

Administration, Oral↗
PubMedDate not supplied

Children with acute lymphoblastic leukemia: is there any subgroup of children without elevated thrombin generation? A preliminary study utilizing measurements of thrombin-antithrombin III complexes.

UNLABELLED: The mechanisms contributing to thromboembolic complications in children with acute lymphoblastic leukemia (ALL) are complex, but it is believed that two factors are of critical importance, i.e. increased thrombin generation and decreased antithrombotic potential of the blood plasma. We evaluated generation of thrombin in three periods of observation of the children: a) prior to chemotherapy, b) after remission-inducing chemotherapy, and c) after infusion of L-asparaginase in the consolidation phase. The study group consisted of 23 children (x = 6.8 years of age), and a control group of 11 children (x = 7.3 years of age). Thrombin-antithrombin III complex (TAT) was selected as a marker of thrombin generation and it was measured by ELISA method. TAT levels prior to chemotherapy were found to be normal in a small subgroup of children (7/23--ca 30%), i.e. they were within the control range (1.5-4.5 micrograms/l), but all the levels increased following remission-inducing chemotherapy. In contrast, in the major subgroup of children whose TAT levels were elevated at presentation (16/23--ca 70%) no significant changes were observed following chemotherapy. CONCLUSION: There is a subgroup of children with ALL whose thrombin generation is normal as measured by its marker--thrombin-antithrombin III (TAT). Only in those children thrombin generation increases following chemotherapy.

Adolescent↗
PubMed2000

[Thrombin-antithrombin III complexes in plasma and subretinal fluid in patients with perforated retinal detachment].

PURPOSE: To study the thrombin generation in plasma and subretinal fluid (SRF) by evaluation of thrombin-antithrombin III complexes (TAT) and antithrombin III (AT III) activity in patients with rhegmatogenous retinal detachment. MATERIAL AND METHODS: Prospective study of 54 patients subjected to retinal detachment surgery. Patients with vein or arterial disease and with other factors which could change evaluated parameters were excluded. Subretinal fluid samples were obtained at the time of routine drainage during retinal detachment surgery. Venous blood samples were taken from the cubital vein to natrium citrate solution (9:1) immediately after induction of anaesthesia but before surgery. TAT concentration in citrate plasma and in SRF was assessed in 22 patients aged from 15 to 78 years (mean: 49.5 years). AT III activity in blood plasma and SRF was measured in 32 patients aged from 20 to 77 years (mean: 53.8). The correlations between the TAT concentration in SRF were evaluated as well as AT III activity in SRF, and age, sex of patients, the duration and extent of retinal detachment, number of retinal tears and the cryopexy application. RESULTS: The median value of TAT concentration in citrate plasma was 9.08 micrograms/l (interquartile range: 59.3 micrograms/l). In 20 cases out of 22 eyes studied TAT levels were higher than 60 micrograms/l. The mean level of AT III activity in blood plasma was 105% (SD: 24.0%). The median level of AT III activity in 32 samples of SRF was 16.5% (interquartile range: 14.5%). The levels of AT III in SRF were significantly lower than AT III values in blood plasma (p < 0.001). We found no correlation between the levels of AT III activity in plasma and AT III activity in SRF nor between TAT concentration, AT III activity in SRF and sex, age of patients, the degree of myopia, the duration and extent of retinal detachment, nor retinal degenerative changes and cryopexy application. CONCLUSION: Our study revealed high TAT concentration and AT III activity and in all studied samples of SRF disclosing the signs of thrombin generation in SRF.

Adolescent↗
PubMed2002

The role of antithrombin III in critical patients in obstetrics.

A preliminary study was conducted to detect significant differences between the inflammatory cytokines network recorded in mild and severe preeclampsia compared with normal pregnancy. 36 patients were divided in two groups: (NP) normal pregnancy and (SPH) Severe Preeclampsia and HELLP syndrome. Inflammatory cytokines (IL 6, TNF, IL 10), Antithrombin III (AT III), Protein C (PC) and Tissue Factor Pathway Inhibitor (TFPI) plasma level and Organ Disfunction modified Score (ODS) were recorded. Results shows a difference (P<0,05 ) for AT III and other markers levels in the two groups and, inside of the SPH group, between Severe preeclampsia patients and HELLP syndrome patients. A correlation was found between coagulation natural inhibitors, specially antithrombin III, and the clinical scores. Performing a Caesarean section did not change these results. Based on results of the study we have designed a monitoring and a treatment protocol in our obstetric and general ICU. A multicentric study is now ongoing to validate the preliminary data on the substitutive treatment with AT III.

Adolescent↗
PubMed2002

Long-term analytical performance of hemostasis field methods as assessed by evaluation of the results of an external quality assessment program for antithrombin.

BACKGROUND: It is important for a laboratory to know the stability of performance of laboratory tests over time. The aim of this study was to adapt from the field of clinical chemistry a method to assess the long-term analytical performance of hemostasis field methods. METHODS: The linear regression model was used to compare the laboratory results with the consensus mean value of a survey. This model was applied to plasma antithrombin activity using the data for 82 laboratories, collected between 1996 and 1999 in the European Concerted Action on Thrombosis (ECAT) external quality assessment program. The long-term total, random, and systematic error were calculated. The variables introduced to define the long-term performance in this model were the long-term analytical CV (LCV(a)) and the analytical critical difference (ACD), which indicates the minimum difference necessary between two samples measured on a long-term time-scale to consider them statistically significantly different. RESULTS: The systematic error (bias) ranged from 4.5 to 103 units/L. The random error ranged from 24.4 to 242 units/L. For the majority of the laboratories, random error was the main component (>75%) of the total error. The LCV(a), after adjustment for the contribution of the bias, ranged from 2.8% to 48%. The ACD ranged from 78 to 1290 units/L with a median value of 190 units/L. No statistically significant differences were observed for either LCV(a) or ACD between the two different measurement principles for antithrombin activity based on the inhibition of either thrombin or factor Xa. CONCLUSIONS: This linear regression model is useful for assessing the total error, random error, and bias for hemostasis field methods. The LCV(a) and ACD for measurement on a long-term time-scale appear to be useful for assessing the long-term analytical performance.

Antithrombins↗
PubMed2002

Bacteroides fragilis bacteremia associated with portal vein and superior mesentery vein thrombosis secondary to antithrombin III and protein C deficiency: a case report.

Hypercoagulability is one of the causes of portal vein and superior mesentery vein thrombosis. We report a case of Bacteroides fragilis bacteremia associated with portal vein and superior mesentery vein thrombosis secondary to antithrombin III and protein C deficiency. The patient presented with high fever for more than 3 weeks. Abdominal sonography revealed a liver cyst of 1.7 cm in diameter over segment 4 and a renal stone of 0.7 cm in size over the lower portion of the right kidney but no evidence of hydronephrosis. Elevation of liver enzymes was also noted. Intermittent fever was noted despite treatment with ceftriaxone and doxycycline. On Day 15 of hospitalization, blood culture revealed B. fragilis, which prompted further investigation of the source of intraabdominal and pelvic infection. Abdominal computed tomography revealed portal vein and superior mesentery vein thrombosis. Endoscopic studies of the gastrointestinal tract showed no tumor or diverticulum. Study of coagulation factors disclosed deficiency of antithrombin III and protein C. Clinicians should remain aware of the need to promptly search for a portal or mesentery vein thrombosis in cases of Bacteroides bacteremia of unknown origin.

Adult↗
PubMedDate not supplied

[Polymeric systems with antithrombin activity for thermally activated targeting].

Copolymers of N,N-diethylacrylamide and N-acryloylphthalimide with lower critical solution temperature (LCST) were synthesized by radical copolymerization. Polymeric systems with antithrombin activity and LCST were prepared via a reaction of amino groups of hirudin with phthalimide groups of the copolymers. On increasing hirudin content, LCST of the polymeric systems increased. The antithrombin activity of polymeric systems obtained by hirudin immobilization on copolymer carriers was inversely related to the content of the copolymer, amounting to 6% of the activity of native hirudin.

Acrylamides↗
PubMed2002

Hereditary deficiencies of antithrombin III, protein S, and the protein C pathway in Jordanian thrombosis patients.

Hereditary thrombophilia is caused by various inherited disorders. Most lead to a familial tendency to recurrent venous, not arterial, thrombosis, usually at a young age, and with spontaneous onset. Most of the genetic defects known today affect the function of natural anticoagulant pathways, in particular, the protein C system. In this study, 602 (265 female, 337 male) patients with suspected thrombosis, arterial or venous, were referred to King Hussein Medical Center in Amman, Jordan. The prevalence of hereditary deficiencies of antithrombin (AT), protein S (PS), and protein C (PC) were studied over a seven-year period (1993-2000). Activated protein C (APC-R) resistance subjects were studied over four years (1996-2000). The mean age was 30 years in females and 42 years in males. A diagnosis was established in 22.4% (n = 135) of the subjects (20.3% venous, 2.1% arterial). Protein C deficiency was found in 3.8%, protein S deficiency in 2.3% and antithrombin deficiency in 1.4% of our sample group. An APC-R problem was seen in 23.0% (n = 89) of the surveyed population. Out of the APC-R patients, 75.0% had the DNA analysis of a factor V Leiden mutation present. Of the subjects found to have the mutation 87.0% were heterozygous and 13.0% were homozygous. These results confirm that APC-R, as a result of factor V Leiden mutation, is the most prevalent cause of thrombosis, and thrombophilia is related to venous, not arterial, thrombosis.

Adolescent↗
PubMed1992

Antithrombin III (AT3) polymorphism in the marsupial Monodelphis domestica: identification and genetics.

Antithrombin III polymorphism was observed in the gray short-tailed opossum, Monodelphis domestica, by either one-dimensional polyacrylamide gel electrophoresis (PAGE; pH 7.9), two-dimensional PAGE (agarose, pH 5.4; 12% T, pH 7.9), or isoelectric focusing (pH 4.2-4.9) followed by immunoblotting with rabbit antiserum to human antithrombin III. Family studies demonstrated an inheritance of three codominant autosomal alleles, AT3A, AT3B, and AT3C, and a population study revealed frequencies of 0.70, 0.10, and 0.20, respectively.

Alleles↗
PubMed1992

The consumption of antithrombin III during coagulation, its consequences for the calculation of prothrombinase activity and the standardisation of heparin activity.

The decay rate of thrombin in plasma is shown to be linearly proportional to the concentration of antithrombin III (AT III), not only in the absence but also in the presence of heparin. This is a consequence of partitioning of heparin between AT III and other plasma proteins. In previous articles were calculated the prothrombin converting activity assuming a fixed concentration of AT III. Since AT III is consumed during the clotting process, prothrombinase activity is more accurately approximated using an algorithm that counts with the decrease of the AT III concentration. It is shown this leads to higher prothrombinase activities. The (absence of) inhibition of prothrombin conversion by prothrombinase in the presence of heparins found with the previous method is also found using the new algorithm. From the results presented it is evident that characteristic parameters of heparin action have to be normalised to the AT III concentration. On this basis we define a Standard Independent Unit of the antithrombin activity of heparin.

Antithrombin III↗
PubMed1992

Fibrinogen and antithrombin III blood levels fluctuations during isoniazid or isoniazid plus rifampicin administration.

Nineteen randomized patients, treated with isoniazid (INH, CAS 54-85-3) for tuberculosis chemoprophylaxis or isoniazid plus rifampicin (RMP, CAS 13292-46-1) combination for tuberculosis therapy, were studied in order to explore the effects of these drugs on fibrinogen and antithrombin III blood levels. Other hepatic biology indices were also measured (aminotransferases, alkaline phosphatase, prothrombin time etc). The results suggested a relationship between INH or INH + RMP administration and fibrinogen as well as antithrombin III blood levels. The data indicate a protective effect of the RMP synchronous administration (by enzyme induction mechanisms) in the preservation of fibrinogen blood levels.

Adult↗
PubMed1992

Prevention of thrombus growth by antithrombin III-dependent and two direct thrombin inhibitors in rabbits: implications for antithrombotic therapy.

We compared the abilities of heparin and two direct thrombin inhibitors to prevent fibrin accretion onto pre-existing thrombi in rabbits. Inhibition of thrombus growth was measured as the ability of each test compound to inhibit the accretion of 125I-fibrin onto thrombi pre-formed in jugular veins of rabbits. When administered as a continuous infusion, the two direct (i.e. antithrombin III-independent) thrombin inhibitors, r-hirudin and a tripeptide, Ac(D)-Phe-Pro-bor-Arg (P-8714) inhibited fibrin accretion as effectively as heparin, but did so in doses which generated little systemic anticoagulation, as compared to the marked anticoagulation associated with the heparin effect. However, both r-hirudin and P-8714 were more effective when they were administered as a single bolus injection than as a continuous infusion. Under the former conditions, there was only a transient systemic anticoagulant effect. We conclude that direct or antithrombin III-independent thrombin inhibitors are more effective than heparin in preventing thrombus growth. The limited effect of heparin is likely due to fibrin impairing the ability of heparin/antithrombin III to inactivate thrombin.

Amino Acid Sequence↗
PubMed1977

Role of heparin in the interaction of serine proteinases with antithrombin III.

To characterize the mode of action of heparin, the kinetics of inhibition of thrombin, factor Xa, and plasmin by antithrombin III was studied without and in the presence of heparin. Following the concentration dependence of inactivation a linear dependence was found between the apparent first-order inactivation rate constant and the anti-thrombin III concentration. This behaviour is typical of enzyme-activator interaction. Values of kinetic constants of the inactivation reaction could be determined. Thus, heparin acts obviously as an activator of the enzymes and enhances their affinity for antithrombin III.

Antithrombin III↗
PubMed2003

Evaluation of platelet activation, plasma antithrombin III and alpha2-antiplasmin activities in hypertensive patients.

The aim of the study was to evaluate the degree of platelet activation and plasma antithrombin III and alpha2-antiplasmin activities in hypertensive patients. The studied group consisted of 21 patients with hypertension. The control group included 19 healthy volunteers. The values of platelet and plasma coagulation factors were determined using the synthetic chromogenic substrates and the spectrophotometric method. Compared to the healthy individuals, the hypertensive patients show increased platelet activity confirmed by a statistically significant increase in the platelet factor 3 activity, which is likely to intensify the plasma proaggregation and procoagulation activities. In the hypertensive patients, a significant decrease in antithrombin III (the endogenous inhibitor of the coagulation system) concentration is observed. In arterial hypertension, a significant decrease in alpha2-antiplasmin activity is found, which may reflect decreased fibrinolytic activity of plasma in the hypertensive patients.

Adult↗
PubMed1992

Antithrombin-III-Stockholm: a codon 392 (Gly----Asp) mutation with normal heparin binding and impaired serine protease reactivity.

Antithrombin-III-Stockholm is a new structural variant of antithrombin-III (AT-III) with normal heparin affinity but defective serine protease inhibitory activity. The proposita, a white female born in 1966, was diagnosed to have developed a pulmonary embolus while on oral contraceptives at age 19. The proposita, as well as her father, were diagnosed to have a type 2 AT-III deficiency as they had normal levels of immunoreactive AT-III associated with decreased (approximately 60%) functional AT-III when measured with either alpha-thrombin or factor Xa as the substrate, either in the presence or absence of heparin. There was no evidence of abnormal electrophoretic mobility of AT-III from the proposita either in the presence or absence of heparin. Genomic DNA was prepared and all seven AT-III exons were polymerase chain reaction (PCR)-amplified and sequenced in both directions using nested primers. Only exon 7 provided evidence for the presence of a mutation, with the second base of codon 392 having a G----A substitution. Such a mutation would cause the substitution of aspartic acid at the site of the normally appearing glycine in the translated product. Furthermore, this mutation caused the destruction of an Hae III restriction site at this point in the AT-III gene. The absence of this Hae III site was confirmed using restriction fragment length polymorphism analysis of PCR-amplified material from the proposita. Experiments with AT-III from the proposita together with experiments with cell-free translated AT-III-Stockholm provided evidence that the mutant AT-III protein does not efficiently form a stable covalent inhibitory complex with alpha-thrombin, although it exhibits normal heparin affinity. The minimal thrombin-complexing ability of the mutant AT-III protein that was observed was accelerated by heparin, but to subnormal levels.

Adult↗
PubMed1992

Molecular cloning and expression of rabbit antithrombin III.

A cDNA containing the complete open-reading frame encoding rabbit antithrombin III (AT-III) was isolated from a rabbit liver cDNA expression library, using a specific antibody as a probe. Sequence analysis showed 84% identity between the deduced amino acid sequences of the rabbit and human proteins. A previously described cell-free expression system was used to verify the identity of the clone. The full-length cDNA was inserted into an expression vector, and messenger RNA (mRNA) transcripts generated. In vitro translation of these transcripts, in the presence of [35S]methionine, in an mRNA-dependent rabbit reticulocyte lysate system resulted in the synthesis of a 51-Kd polypeptide, as shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). This nonglycosylated protein was capable of forming SDS-stable complexes with human alpha-thrombin. Complex formation was significantly enhanced following the deletion of nucleotides encoding the signal peptide, and the resultant generation of a 47-Kd nonglycosylated mature protein product. When the template DNA giving rise to this product was internally truncated, two rabbit AT-III deletion mutants were generated that lacked the ability to interact with thrombin, but retained the ability to bind heparin. Cell-free expression plasmids encoding the human and rabbit AT-III mature molecules were manipulated to produce two interspecies fusion proteins. For the first, human codons were used to replace rabbit codons from residue 369-433, while in the second human codons replaced rabbit codons from residue 217-433. Both fusion proteins exhibited less efficient thrombin-complexing ability than the original cell-free-derived mature rabbit AT-III. Thus, portions of AT-III molecules from the two species, despite their high degree of homology, are not interchangeable. Knowledge of the structure of rabbit AT-III, combined with the availability of the rabbit cDNA, will permit defined experimentation aimed at understanding antithrombin III structure relative to its function in vivo.

Amino Acid Sequence↗