SEARCH · PubMed Health

Results for “ANTITHROMBIN”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 829 records · Page 46Linked to original sources

PubMed1988

Thrombophilia in blood-donation for plasma- and cytapheresis caused by antithrombin III depletion.

Induced by the case of a blood-donor with more than 100 donations-mostly apheresis-who suffered acute thromboembolism caused by antithrombin III depletion, nearly 60 apheresis-donors were examined before, during and after aphereses, as well manual fourfold as computerized (CS-3000 TRAVENOL) cytaphereses with special methods of coagulation, mainly antithrombin III levels and fibrin-monomeres. The findings were described and compared, multifold in manual techniques happened breaks caused by occluded tubules were accompanied with decrease of antithrombin III and positive FM-tests. It was discussed, if apheresis-techniques for themselves (extracorporal multifold manipulation in manual techniques and contact with artificial surfaces in both kinds of techniques) can be the reason for a hypercoagulation. It seems to be important, how is the situation of apheresis-donor before starting, therefore we give the recommendation, to pay more attention in examination this kind of donors, additional with testing antithrombin III levels and tests for fibrin-monomers.

Adult↗

PubMed1988

Mechanisms of the development of acquired antithrombin III deficiency in the experimental nephrotic syndromes.

In the experiments on white rats was studied the role of excessive thrombinogenesis in the development of acquired antithrombin III deficiency in the experimental nephrotic syndrome. It was determined that excess thrombin generation induced the marked acceleration of 125I-antithrombin III clearance from blood stream in consequence formation of thrombin antithrombin III complexes with the following limited proteolysis of the inhibitor by enzyme. These results give evidence that apart from proteinuria the excess thrombin generation accompanied by nephrotic syndrome play a part in the development of acquired deficiency of antithrombin III in this experimental pathology.

Animals↗

PubMed1988

Serum antithrombin III and alpha-2-antiplasmin concentration in patients with lung carcinoma.

Serum antithrombin III and alpha-2-plasmin inhibitor concentrations has been evaluated in 26 patients with lung carcinoma. We observed a twofold decrease in antithrombin III level and no differences between test and control groups in alpha-2-plasmin inhibitor concentrations. Evidently, the decreased antithrombin III level may reflect its consumption because of enhanced plasma thrombin activity, whereas normal alpha-2-plasmin inhibitor may result in no induction of secondary fibrinolysis followed by the stimulation of the coagulation system or no conditions for primary increased fibrinolysis. It seems possible, that the antithrombin III level in the serum may at least partly reflect the tendency for hypercoagulability and spreading of cancer.

Adenocarcinoma↗

PubMed1989

Characterization of antithrombins produced by active site mutagenesis of human alpha 1-antitrypsin expressed in yeast.

Both congenital and acquired antithrombin-III (AT-III) deficiencies are amenable to replacement therapy. We describe two antithrombins produced by recombinant DNA techniques from human alpha 1-antitrypsin (alpha 1AT) cDNA in yeast. Alteration of the alpha 1AT active site, replacing methionine 358 with arginine, results in a thrombin inhibition rate similar to that of heparin-activated AT-III. Alteration of two further residues, to give a five-residue sequence identical to AT-III, does not increase this rate further. Neither antithrombin is activated by heparin; both are unglycosylated and have shorter in vivo half-lives (t1/2) than human alpha 1AT. These antithrombins should be suitable for therapeutic replacement of AT-III in cases of congenital deficiency and in conditions associated with acquired AT-III deficiency, such as disseminated intravascular coagulation.

Amino Acid Sequence↗

PubMed1977

[Electrophoretic mobility of antithrombin III in an agarose gel with heparin. (author's transl)].

The electrophoretic mobility of several forms of antithrombin III in an agarose gel has been compared with the mobility in a gel containing heparin. When a serum was studied, three different compounds were observed. The inactige antithrombin III with higher molecular size, separated by gel filtration, was found to be homogenous even if there was heparin in the gel. A purified antithrombin III, prepared by affinity chromatography, contained an immunoreactive material of higher molecular size which has no activity and a higher mobility in agarose gel. When heparin is incorporated in the agarose plate, the electrophoretic mobility of this polymerized antithrombin III is not modified.

Antithrombins↗

PubMedDate not supplied

[Familial deficiency of antithrombin III].

The systematic search for a deficiency in antithrombin III must be considered in case of: venous thrombosis in a young patient, recurrent venous thrombosis especially if these occurred under Heparin, venous mesenteric infarction since this type of thrombosis is rare and seems relatively frequent in case of congenital deficiency in antithrombin III, familial past history of venous thrombosis in a woman desiring to undergo estrogen-progesterone therapy. The most often used techniques are: study of antithrombin III activity by amidolytic method and titration by immunodiffusion. Anti-vitamin K treatment is the only effective therapy proposed to patients suffering from a hereditary deficiency in antithrombin III.

Anticoagulants↗

PubMed1987

Antithrombin-III Denver, a reactive site variant.

Antithrombin-III Denver is a mutant protein which differs from the normal in being defective in serine protease binding (Sambrano, J. E., Jacobson, L. J., Reeve, E. B., Manco-Johnson, M. J., and Hathaway, W. E. (1986) J. Clin. Invest. 77, 887-893). It was isolated from the blood of an individual heterozygous for the abnormal gene by: affinity separation on heparin-Sepharose to obtain an antithrombin fraction, and gel filtration of the species present following complexing of the antithrombin fraction with a small excess of thrombin. The reduced, S-carboxymethylated protein formed a mixture of soluble tryptic peptides which was fractionated on Vydac C18. A single, unique peptide not present in a parallel experiment with normal antithrombin-III was isolated. This peptide was identified by sequence analysis and synthesis to correspond to residues 394-399 in the known sequence of the inhibitor, with leucine replacing reactive site P'1 residue Ser394. Although chromatograms of the tryptic peptides from the normal and mutant proteins were otherwise indistinguishable, the existence of additional residue replacements is not excluded. Measurements of the rate of thrombin binding by the mutant protein with p-aminobenzamidine as a fluorescent indicator showed that the second-order rate constant is reduced drastically. Meaningful measurements with the mutant protein could only be made in the presence of heparin and revealed a reduction of about 4000-fold in the rate constant.

Amino Acid Sequence↗

PubMed1985

The kinetics of inhibition of thrombin by antithrombin in the presence of components of the hemostatic system.

The inhibition of human thrombin by antithrombin has been measured in pure systems in the presence of other components of the hemostatic system that might affect the kinetics of the reaction. These included fibrinogen, calcium ions, phospholipid, prothrombin, platelets (both adenosine diphosphate [ADP]-stimulated and -unstimulated), and platelet extracts. Inhibition rates were measured in each case by a discontinuous amidolytic assay over a range of antithrombin concentrations, from 0 to 4.5 mumol/L. Under all conditions, rates of inhibition were proportional to antithrombin concentration. Calcium ions at 5 mmol/L caused a small (20%) reduction in rate, but phospholipid and prothrombin had no additional effect. In contrast, both fibrinogen and platelets significantly changed the rate of inhibition. In the presence of calcium, fibrinogen at concentrations from 0 to 12 mumol/L reduced the rate of inhibition in a competitive manner, giving an apparent Kd for fibrinogen of 6.0 mumol/L. As the plasma fibrinogen level is about 8 mumol/L, one may therefore predict that variations in fibrinogen level will have a significant effect on the rate of thrombin inhibition in plasma. More unexpected was the observation that platelets increase the rate of inhibition: unstimulated platelets increased the rate constant by 40%, and ADP-stimulated platelets increased it by 55%. However, this acceleratory effect could not be mimicked with either a KCI extract or a Triton extract of platelets, and its cause remains unknown. In sum, it has been shown that the rate of inhibition of thrombin can be modulated in at least three ways-antithrombin concentration, fibrinogen concentration, and platelets; each of which can vary independently in vivo. It is well known that defects of the first lead to an increased risk of thrombosis, and it is proposed that this may be substantially caused by changes in the kinetics of inhibition such as those described. Additionally, it is suggested that changes in inhibition rate caused by other components may also be significant, for the same reason, in modulating the clotting system in vivo.

Antithrombins↗

PubMed1977

Effect of collagen on thrombin inactivation by antithrombin-III and heparin.

Thrombin inactivation by antithrombin-III and heparin has been found to decrease in the presence of collagen, whereas thrombin activity and the rate of thrombin inactivation by antithrombin-III alone are not affected. Albumin, at the same concentration as collagen, does not influence either thrombin activity or thrombin inactivation by antithrombin-III or by antithrombin-III plus heparin.

Animals↗

PubMed1982

[Preparation and characterization of an antithrombin III concentrate].

Tri-calciumphosphate was found to have not only a known adsorption capacity for factors of the prothrombin complex, but also for antithrombin III. Depending on the inserted blood stabilizer the human plasma fractions Cohn I, PPSB and antithrombin III may be isolated from the same initial material in the area of the transfusion service. Enriching antithrombin III is achieved by a three-stage procedure under aseptic conditions in a closed system. Liberating antithrombin III from calciumphosphate is made with care without using any concentrated salt solutions.

Adsorption↗

PubMed1976

Inhibition of activated factor XII by antithrombin-heparin cofactor.

The activation of Factor XII occurs via fragmentation of this zymogen into a diverse spectrum of enzymatically potent molecular species. To study the interaction of antithrombin-heparin cofactor and heparin with activated Factor XII, we have employed two forms of this enzyme with widely differing physical characteristics and biologic potencies. Antithrombin-heparin cofactor was found to be a progressive, time-dependent inhibitor of both forms. The addition of heparin dramatically accelerated the rates of these interactions. Furthermore, sodium dodecyl sulfate gel electrophoresis of reduced proteins has indicated that antithrombin-heparin cofactor functions by forming an undissociable complex with either species of the enzyme. This complex represents a 1:1 stoichiometric combination of activated Factor XII and inhibitor. In the presence of heparin, both species undergo virtually instantaneous complex formation with antithrombin-heparin cofactor without exhibiting alterations in dissociability or stoichiometry.

Alpha-Globulins↗

PubMed1976

Inactivation of alpha- and beta- thrombin by antithrombin-III and heparin.

Inactivation of alpha- and beta-thrombin by antithrombin-III and heparin was studied, since it had been suggested that two forms of thrombin exist with respect to heparin sensitivity (Machovich 1975b). It was found that the inactivation rates of alpha- and beta-thrombin by antithrombin were different, namely alpha-thrombin was more sensitive to antithrombin than beta-thrombin. Heparin facilitated the complex formation between alpha-thrombin and antithrombin-III, whereas beta-thrombin inactivation was only slightly affected. Furthermore, heparin protected alpha-thrombin against the inactivating effect of heat, while beta-thrombin lost its activity during the heat treatment. These findings suggest that the formation of beta-thrombin in blood circulation may have an important role in thrombosis predisposition.

Alpha-Globulins↗

PubMed1983

[Antithrombin III and fibrinogen after surgical interventions on the abdomen and heart].

We have explored the changes of plasma concentrations of antithrombin III and fibrinogen in patients recovering from major abdominal and cardiac surgery. In one group of patients subjected to major abdominal surgery we detected a statistically significant reduction of antithrombin III in the second and third postoperative day, followed by return to normal values in the fourth or fifth day. Fibrinogen, instead, increased to as much as 180% of the preoperative value in the first four postoperative days and reverted slowly to preoperative values between the fourth and the eighth day. In another group of patients subjected to cardiac surgery procedures utilizing the heart-lung machine, however, we found no significant reductions of antithrombin III in the early postoperative period. These results suggest the possible influence of local tissue factors affecting the plasma levels of antithrombin III differently in the two types of surgery under discussion. The patients subjected to extracorporeal circulation, on the other hand, showed a depletion of plasma fibrinogen down to less than 30 or 40% of preoperative values. This may reflect activation of coagulation processes and the considerable sequestration of fibrin at some interfaces of the heart-lung machine.

Abdomen↗

PubMedDate not supplied

Antithrombin III deficiency in a Romanian family. Pathogenic role of concomitantly increased plasma level of clotting factors VII and X.

Antithrombin III deficiency in a Romanian family is presented. The propositus, a 27 year-old man, had a history of recurrent venous thrombosis and was found to present a plasma antithrombin III level of only 50% of the normal values. His mother and two of his five children had low antithrombin III levels but no episodes of venous thrombosis. In opposition to his family members, the propositus presented overweight, slight hypertriglyceridemia and displayed a high level of clotting factors VII and X. The findings suggest that development of thromboembolic disease in a subject with familial antithrombin III deficiency is enhanced by additional factors, for example by an increased plasma level of vitamin K-dependent clotting factors.

Adult↗

PubMed1982

Lipoprotein fractions and antithrombin III consumption during clotting.

Plasma and serum antithrombin levels were measured in functional (initial rate measurement) and immunological assays together with serum lipid levels in normal subjects and patients with coronary artery disease. Specific antithrombin activity in plasma showed a negative correlation with triglyceride levels. The consumption of antithrombin activity during blood clotting was negatively correlated with both serum total triglyceride and heparin precipitable lipoprotein and positively correlated with serum high density lipoprotein cholesterol. Different blood lipoprotein fractions may influence the activity of the antithrombin III molecule.

Adult↗

PubMed1980

The heparin binding site of antithrombin III. Evidence for a critical tryptophan residue.

Chemical modification of antithrombin III, the major plasma protease inhibitor, with the tryptophan reagent dimethy(2-hydroxy-5-nitrobenzyl) sulfonium bromide, results in the incorporation of one hydroxynitrobenzyl moiety per molecule of antithrombin III. The derivatized inhibitor does not exhibit the heparin-promoted enhancement in rate of thrombin inactivation which is characteristic of the native molecule. However, the rates of thrombin inactivation in the absence of heparin are identical with native and derivatized inhibitors, indicating that the site of protease . inhibitor complex formation is not altered. Unlike native antithrombin III, the modified inhibitor does not bind to a heparin-agarose affinity column. When the modification reaction was performed with added heparin, the extent of modification was decreased and the heparin-promoted enhancement of thrombin inactivation was preserved. These results indicate that the integrity of a specific tryptophan residue is critical to the binding of heparin to antithrombin III.

Animals↗

PubMed1995

Inhibition of prothrombinase by antithrombin-heparin at a macroscopic surface.

The antithrombin-dependent inhibition of prothrombinase, assembled at a macroscopic surface, was studied under flow conditions utilizing a tubular flow reactor that consists of a phospholipid-coated glass capillary. Prothrombinase activity was determined from steady-state rates of thrombin production upon perfusion with prothrombin and from factor Va-associated factor Xa activity present in the flow reactor. The prothrombinase density was maintained at a low level (0.03 fmol/cm2) to assure that the rate of thrombin production reflected the amount of prothrombinase present in the capillary. Perfusion of the flow reactor with antithrombin resulted in an exponential decrease of prothrombinase activity in time. The second order rate constant (8.5 x 10(4) M-1min-1) is comparable with the rate of inactivation of free factor Xa. Inhibition was much faster when antithrombin was complexed with heparin. The second order rate constants of inhibition decreased with decreasing heparin chain length: 9.6 x 10(7), 4.5 x 10(7) and 0.39 x 10(7) M-1min-1 for unfractionated heparin, low molecular weight heparin and synthetic pentasaccharide heparin, respectively. In the presence of prothrombin (0.2 microM), however, the heparin-dependent rate of inhibition of prothrombinase was about 50-fold lower. The heparin-independent inhibition of prothrombinase by antithrombin (4 microM) in the presence of prothrombin (0.2 microM) was virtually negligible. At a 70-fold higher surface density of prothrombinase (2 fmol/cm2) prothrombinase activity was much faster inactivated. The rate of thrombin production, however, was not affected. In conclusion, at low prothrombinase densities, prothrombin efficiently protects prothrombinase from inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Antithrombin III↗

PubMed1979

Dissociation of complexes and their derivatives formed during inhibition of bovine thrombin and activated factor X by antithrombin III.

The complexes formed by antithrombin III with activated bovine Factor X and thrombin have been studied by gel electrophoresis in dodecyl sulfate. When subjected to electrophoresis at pH 7, the complexes remain intact, whereas electrophoresis at pH 9 in the presence of Tris results in their dissociation. Dissociation of both the Factor Xa-antithrombin III complex and the thrombin-antithrombin III complex in dodecyl sulfate produces a modified form of antithrombin III which, unlike the native inhibitor, apparently consists of two chains. Gel electrophoresis of the dissociated complexes has also been used to study the sites where the complexes are cleaved by the respective enzymes. The cleavage of the Factor Xa-inhibitor complex by Factor Xa apparently results from hydrolysis of a single bond in the enzyme part of the complex and releases a 15,000-dalton NH2-terminal fragment of the heavy chain, with the light chain attached. Cleavage of the thrombin-inhibitor complex by thrombin involves several cleavages of the heavy (B) chain of the thrombin part of that complex. Neither enzyme-inhibitor complex is subject to cleavage by free enzyme in the inhibitor part of the complex under the conditions used.

Animals↗