PubMed Health⌕ Search

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 1,243 records · Page 69Linked to original sources
PubMed1992

The effect of ticlopidine on canine platelets, fibrinogen, and antithrombin III activity.

The effect of ticlopidine on platelet function, platelet number, mean platelet volume, antithrombin III activity, and fibrinogen was evaluated in 10 laboratory beagles. Ticlopidine (62 mg/kg) significantly inhibited ADP- and collagen-induced platelet aggregation within 2 days of the beginning of oral administration. Collagen-induced platelet 14C-serotonin release was not inhibited by day 9 of medication but was inhibited by day 20 in two of three beagles given medication for 32 days. Significant increases in mean platelet number were observed on days 2 and 5. The trend toward increased platelet number continued until day 16, at which time platelet number began to decrease toward baseline in three of three dogs treated for 32 days. Mean platelet volume (MPV) was significantly decreased compared to baseline on days 5 and 9. In three dogs treated for 32 days, the lowest MPV was observed on day 9 in two dogs and on day 12 in one dog. Significant changes were not observed in antithrombin III activity or fibrinogen with ticlopidine treatment.

Adenosine Diphosphate↗
PubMed1977

Quenching of tryptophan fluorescence in human antithrombin III by iodide ion.

Iodide is an efficient quencher of antithrombin III intrinsic tryptophan fluorescence. The quenching pattern indicates that about 60% of the tryptophyl fluorescence originates from exposed residues in the multitryptophan-containing protein. In denaturing media all of the tryptophyls are solvent-exposed. The binding of heparin to antithrombin III influences the number of solvent-exposed tryptophan residues. By studying the dependence of the quenching on pH, information regarding the presence of charged residues adjacent to tryptophyls was obtained.

Antithrombins↗
PubMed2006

Antithrombin reduces pulmonary hypertension during reperfusion after cardiopulmonary bypass in a pig.

BACKGROUND: Antithrombin (AT) may alleviate many cardiopulmonary bypass (CPB) and ischemia-reperfusion (I/R)-related adverse effects. Using a porcine model of clinical cardiac surgery on CPB, we tested the effects of supplementary AT on myocardial and lung I/R injury. METHODS: Twenty pigs undergoing 60-min aortic clamping and 75-min normothermic perfusion were randomized in a blinded setting to receive an intravenous (i.v.) bolus of AT (250 IU/kg) (AT group, n = 10) or placebo (n = 10) 15 min before aortic declamping. An additional group of five animals received 500 IU/kg AT in an open-label setting (AT+). Thrombin-antithrombin complexes (TAT), activated clotting times (ACT), AT and myeloperoxidase (MPO) activities, troponin T, and several hemodynamic parameters were measured before CPB and after weaning from CPB up to 120 min after aortic declamping. After 120 min of reperfusion, myocardial and lung biopsies were taken for histological examination. RESULTS: AT effectively inhibited coagulation as assessed by ACT. In the AT and AT+ groups only, cardiac output (CO) and stroke volume (SV) showed a trend of post-ischemic recovery during the first 15 min after CPB. AT-attenuated reperfusion induced an increase in pulmonary arterial diastolic pressure (PAPD) but did not have significant effects on systemic or pulmonary vascular resistance. The effects of AT on SV, CO, and PAPD were fortified in the AT+ group. AT did not show effects on inflammatory changes in either myocardial or pulmonary tissue specimens. AT did not reduce post-ischemic troponin T release. CONCLUSION: Supplementary AT, in doses with significant anticoagulant effect, did not alleviate myocardial I/R injury in terms of histological inflammatory changes or post-ischemic troponin T release. Instead, however, AT-attenuated reperfusion induced an increase in pulmonary pressure after CPB. Mechanisms and clinical implications of these effects remain to be explored.

Animals↗
PubMed1985

Interaction of human alpha-thrombin and gamma-thrombin with antithrombin III, protein C and thrombomodulin.

Conversion of human alpha-thrombin to gamma-thrombin by limited proteolysis resulted in a decrease in the inactivation rate of the enzyme by antithrombin III. The second-order rate constants were similar but significantly different: 11 +/- 1.7 X 10(3) and 7 +/- 0.5 X 10(3) M-1 s-1 for alpha- and gamma-thrombin respectively. This difference is probably related to a slight change in reactivity of the catalytic site, rather than to a structural alteration of the recognition site for antithrombin III. The rate of protein C activation, measured in the absence of thrombomodulin, was greatly reduced by conversion of alpha-thrombin to gamma-thrombin. In addition, gamma-thrombin failed to displace alpha-thrombin from its complex with thrombomodulin, as demonstrated by measuring either the rate of protein C activation by thrombin-thrombomodulin, or the fibrinogen clotting activity of thrombin-thrombomodulin, in the presence of competing diisopropylphospho-thrombin. It is concluded that the recognition sites involved in protein-C-thrombin and thrombomodulin-thrombin interactions are both dramatically affected by the loss of peptide material occurring during the conversion of alpha-thrombin to gamma-thrombin and/or by the resulting conformational changes.

Animals↗
PubMed1988

Interaction of heparin and antithrombin III. The role of O-sulfate groups.

A synthetic pentasaccharide corresponding to the sequence involved in heparin for binding and activation of antithrombin III contains eight sulfate groups. The role of some of them in the interaction with the protein has been demonstrated through the study of fragments obtained from heparin. An approach based on the total chemical synthesis of heparin fragments allows us to provide new information on the O-sulfate groups borne by the iduronic acid and the glucosamine units that constitute the reducing-end disaccharide of the above pentasaccharide sequence. Although not strictly necessary for a weak interaction to take place, these two sulfates co-operate to express maximal activity. This suggests that they belong to a secondary sub-region of interaction with antithrombin III, the primary one being accounted for by other critical parts of the structure and particularly the trisaccharide sequence placed at the non-reducing end of the pentasaccharide.

Antithrombin III↗
PubMed1991

Characterization of the cellular binding domain and the effects of monoclonal antibodies and thrombin inhibitors on the binding and internalization of the antithrombin-III--thrombin complex by cultured cells.

Antithrombin III (AT) binds to cultured cells mainly as a complex with thrombin or other serine proteases rather than in its free form. This implies that, upon complex formation, a new determinant appears on the AT molecule which is recognized by the cells. Fragmentation of AT by cyanogen bromide exposes this determinant and an 8-kDa fragment is recognized by cultured cells. The binding of this fragment to cultured cells is inhibited by antithrombin-III-thrombin (AT-T) complex, but not by free AT. The putative cellular binding domain of AT-T is located over amino acid residues 253-314 of AT, in the large loop close to the carboxy-terminus of the molecule. The cell-associated AT-T is internalized and degraded, forming the thrombin-modified AT (ATM). This process is inhibited by lysosomal degradation inhibitors, such as chloroquine or benzamidine. Thus, the appearance of ATM in cells is not a result of its binding to the cell surface, but probably a result of lysosomal degradation of cell-associated AT-T. Another degradation product, with a molecular mass of 43 kDa, appears in cells along with the appearance of ATM. Hirudin, a specific inhibitor of thrombin, inhibits the cellular internalization of AT-T complexes, indicating a possible role for thrombin activity in the internalization process of complexes. Monoclonal antibodies (mAb) against AT, whose epitopes on the AT molecule have been located, affect the binding of AT-T to cultured cells. Two mAb, A10 whose epitope is found outside of the cellular binding site, and B108 whose epitope may overlap this sequence, totally inhibit the binding of the complex to cells. Inhibition of binding results either from steric hindrance or induced changes in the binding site.

Animals↗
PubMed1988

Genetic studies of low abundance human plasma proteins. VIII. Inherited structural variation in antithrombin III.

Genetically determined structural polymorphism of antithrombin III has been observed using ultra narrow pH polyacrylamide isoelectric focusing gels, followed by immunoblotting. The products of three alleles at the antithrombin III structural locus have been detected in normal U.S. white and black blood donors. The frequencies of the three alleles, AT III* 1, AT III* 2 and AT III* 3, respectively, are: 0.878, 0.103, 0.019 in whites and 0.916, 0.068, 0.016 in blacks. Family data from a large number of families establish an autosomal codominant pattern of inheritance of the three alleles.

Alleles↗
PubMed1990

Thrombin-antithrombin III complex levels in normal pregnancy with hypertensive disorders and after delivery.

The plasma concentration of the thrombin-antithrombin III-complex (TAT) was investigated during uncomplicated pregnancy in 15 women in the first, 22 in the second and 46 in the third trimester, and in 19 women with hypertensive disorders between 25 and 40 weeks gestation. Eight women at term after a normal pregnancy were studied before the onset of labour and within 60 min and 24 h after delivery. A comparison group of 16 healthy, non-pregnant women was investigated. The mean TAT concentration in normal pregnancies increased significantly in the second and third trimester compared with values in the first trimester and in non-pregnant women. In the group with hypertensive disorders during pregnancy TAT levels were significantly higher than in uncomplicated pregnancies. Within 60 min after delivery a distinct increase of TAT concentrations occurred compared to levels before the onset of labour but the levels had returned to normal by 24 h after delivery. Our findings suggest that an activation of the coagulation system occurs in normal pregnancy. A further activation takes place immediately after delivery. The significantly increased TAT levels in pregnancies with hypertensive disorders suggest a state of chronic disseminated intravascular coagulation leading to an enhanced consumption of and a decreased plasma concentration of antithrombin III.

Adult↗
PubMed2004

Role of the gamma-carboxyglutamic acid domain of activated factor X in the presence of calcium during inhibition by antithrombin-heparin.

BACKGROUND: Factor (F)Xa has 11 gamma-carboxylated glutamic acid (Gla) residues that are involved in calcium-dependent membrane binding. The serpin antithrombin (AT) is an important physiological regulator of FXa activity in an inhibition reaction that is enhanced by heparin. Recently, Rezaie showed that calcium further enhanced the heparin-catalyzed AT inhibition of FXa by promoting 'ternary complex' formation, and these results showed a role for the gamma-carboxyl-glutamate (Gla)-domain of FXa. OBJECTIVES: In this study, we used recombinant FXa mutants to assess the role of individual Gla residues in augmenting or antagonizing the AT-heparin inhibition reaction in the presence of calcium. RESULTS AND CONCLUSIONS: In the absence of heparin, AT inhibition of plasma and the recombinant FXas were essentially equivalent. Similar to plasma-derived FXa, calcium increased about 3-fold the inhibition rate of wild-type recombinant FXa by AT-heparin over that in the presence of EDTA. Interestingly, three different effects were found with the recombinant FXa Gla-mutants for AT-heparin inhibition: (i) Gla-->Asp 14 and 29 were enhanced without calcium; (ii) Gla-->Asp 16 and 26 were not enhanced by calcium; and (iii) Gla-->Asp 19 was essentially the same as wild-type recombinant FXa. These results support a theory that mutating individual Gla residues in FXa alters the calcium-induced conformational changes in the Gla region and affects the antithrombin-heparin inhibition reaction.

1-Carboxyglutamic Acid↗
PubMed2006

Anticoagulant and anti-inflammatory effects after peritoneal lavage with antithrombin in experimental polymicrobial peritonitis.

BACKGROUND: In sepsis, coagulation inhibition using high-dose systemic antithrombin (AT) tends to improve survival. However, systemic AT use is complicated by increased risk of bleeding (odds ratio 1,7) and clinically important survival increase is seen only in the non-heparinized subgroup. Local (intra-abdominal) inhibition of coagulation with AT may be more effective. OBJECTIVES: To investigate effects of intra-abdominal high-dose recombinant human AT (rhAT) lavage on coagulation and inflammation in experimental polymicrobial sepsis. METHODS: Murine cecal ligation and puncture model was used with peritoneal lavage after 24 h, containing rhAT (3 IU mL-1) or saline. Clotting time, thrombin-antithrombin complexes (TAT), D-dimers, tissue-type plasminogen activator and plasminogen activator inhibitor-1 assessed coagulation and fibrinolysis responses. Inflammation was assessed by keratinocyte-derived chemokine (KC), interleukin-1beta (IL-1beta), IL-6, tumor necrosis factor-alpha (TNF-alpha), leukocyte count, myeloperoxidase and bacterial load. RESULTS: rhAT lavage prolonged abdominal clotting times and reduced D-dimers and TAT levels, indicating inhibited abdominal coagulation. Pulmonary clotting time and D-dimers decreased towards normal by rhAT lavage. Abdominal fibrinolysis was reduced after rhAT lavage, as were abdominal IL-1beta, KC, leukocytes and bacterial load. Pulmonary TNF-alpha, KC, myeloperoxidase and histopathological injury were decreased. Survival improved from 62% (saline lavage) to 83% (rhAT lavage, P<0.05). CONCLUSIONS: High-dose rhAT lavage inhibited coagulation activation, and reduced inflammatory responses in both abdominal and pulmonary compartments, ultimately improving survival.

Animals↗
PubMed1998

Antithrombin, protein C and protein S levels in 127 consecutive young adults with ischemic stroke.

OBJECTIVES: The aim of our study was to evaluate the prevalence of antithrombin, protein C and protein S deficiencies in consecutive ischemic stroke patients under 45. MATERIAL AND METHODS: We studied 127 consecutive patients with a mean age of 34.4 years admitted for an ischemic stroke, over a 2-year period, after exclusion of those with arterial dissection. Antithrombin, protein C and protein S levels were measured in all patients at the acute stage of the ischemic stroke and measurements were repeated in case of abnormality. RESULTS: We found abnormal levels in 9 patients. Seven had an acquired cause of deficiency (pregnancy, oestrogen, acute inflammation). Two had no obvious acquired cause of deficiency but further controls were normal. CONCLUSIONS: Hereditary deficiencies of coagulation inhibitors are rare in ischemic stroke patients under 45 and their systematic detection seems to be of poor interest.

Adolescent↗
PubMed1989

The disturbance of hemostasis in septic shock: role of neutrophil elastase and thrombin, effects of antithrombin III and plasma substitution.

In 42 patients with septic shock, 29 of whom underwent substitution with antithrombin III concentrate and fresh frozen plasma for coagulation disorders, the proteinase-inhibitor complexes thrombin-antithrombin III and neutrophil elastase-alpha 1 proteinase inhibitor, were elevated on admission. On admission, the elastase complex was significantly higher in the patients receiving substitution (p = 0.0039), but at the endpoint it was higher in the non-survivors (p = 0.0040). The elastase decrease was confined to the substitution group with the thrombin complex decreasing in both groups. Initially the thrombin complex correlated with prothrombin times and factor XIII, while the elastase complex correlated with creatinine, thrombocyte count and prothrombin times in the late stages. Hemostatic disturbance, thrombin generation and neutrophil elastase release were favorably influenced by substitution. Furthermore, in this uncontrolled pilot study, the survival rate was higher in the treated (16 of 29) than in the untreated (1 of 13) patients, although the treated patients initially had pronounced hemostatic disturbances.

Adolescent↗
PubMed1993

Overtight nappy precipitating thrombosis in antithrombin III deficiency.

An antithrombin III deficient infant presented with iliac vein thrombosis, apparently precipitated by an overtight nappy. Venous thrombosis is unusual, both in normal and in antithrombin III deficient children, but children with venous thrombosis should have their natural anticoagulants assayed and obvious risk factors avoided.

Antithrombin III Deficiency↗
PubMed1988

Intravascular coagulation in acute liver failure in rats and its treatment with antithrombin III.

Liver damage was induced in rats by injection of dimethylnitrosamine (DMN) or carbon tetrachloride (CCl4). Fibrin clots were observed in the hepatic sinusoids at 12 hours and soluble fibrin monomer complexes were markedly detected at 24 hours only in the rats given DMN. When antithrombin III concentrate was infused at 12 hours there was a dose dependent improvement of the values of serum total bilirubin, SGPT, prothrombin time, peripheral platelet count, and plasma fibrinogen and coagulation factor VIIIC and of the histological degree of liver injury at 24 hours in the DMN group. The CCl4-group showed no such improvement. Intravascular coagulation may complicate the course of certain types of acute liver injury and contribute to its aggravation in rats. Under such circumstances, treatment with antithrombin III concentrate would be beneficial.

Animals↗
PubMed1983

Preoperative antithrombin III activities and lipoprotein concentrations as predictors of venous thrombosis in patients with fracture of neck of femur.

The presence or absence of venous thrombosis was determined by the technique of autologous 111indium-labelled platelets in 64 patients following reduction and fixation of fractures of the neck of femur. Venous thrombosis was found in 41 (64%) of these patients. Compared to the thrombosis-negative group, the thrombosis-positive group had a significantly lower mean serum antithrombin, and higher mean antithrombin consumption during clotting in the immediate preoperative period. No significant differences were seen between the two groups in plasma ATIII activities, fibrinogen, alpha-2-macroglobulin, serum lipoproteins or age. Significant correlations were seen between ATIII activities and lipoprotein fractions; these are discussed.

Adult↗
PubMed1987

Mesenteric venous thrombosis and antithrombin III deficiency.

Of the 123 patients with acute mesenteric infarction treated over the past 12 years, 16 (13%) had mesenteric venous thrombosis. Eight of the patients with mesenteric venous thrombosis survived the initial episode; two have since died. The remaining six patients were studied for evidence of haemostatic deficiencies or abnormalities. Antithrombin III deficiency, which is known to be associated with recurrent venous thrombosis, was found in three patients. It is recommended that all patients with mesenteric venous thrombosis should be screened for antithrombin III deficiency as treatment with coumarin anticoagulants may be indicated, providing effective prophylaxis against further thrombotic episodes.

Adult↗