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 1,621 records · Page 90Linked to original sources
PubMed1995

Therapeutic effects of antivenom supplemented by antithrombin III in rats experimentally envenomated with Russell's viper (Daboia russelli siamensis) venom.

The effects of equine antivenom and antithrombin III (AT-III) on the coagulopathy induced by Russell's viper venom (RVV, Daboia russelli siamensis) were investigated in the rat. After taking blood samples from the femoral vein for determination of simple blood clotting time and AT-III activity, all anaesthetized rats received an intramuscular injection of venom (2 micrograms/g). Treatment (antivenom or AT-III or both) was given intravenously through another femoral vein 30 min after venom injection. All untreated rats (n = 7) developed AT-III depletion (< 70%) [mean (S.D.)] 70 (36) min, and incoagulable blood 85 (53) min after venom injection. Supplementation with AT-III (either 0.25 U/g or 0.5 U/g) had no effect on the RVV induced coagulopathy (n = 20). Treatment with antivenom alone (10 micrograms/g) reduced the incidence of abnormal clotting significantly (8/15, 53%) (P = 0.03). When antivenom was given in combination with AT-III (0.5 U/g), abnormal clotting was prevented in all but one animal (1/15, 7%) (P = 0.007). AT-III activity declined progressively in all rats which developed non-clotting blood. These results suggest that coagulopathy in Russell's viper envenoming is associated with activation of coagulation and consumption of AT-III. Antivenom can prevent coagulopathy, but its neutralizing activity is augmented significantly by AT-III supplementation.

Animals↗
PubMed1994

Antithrombin III and antivenom reversal of coagulopathy in rats envenomated with Malayan pit viper venom.

The therapeutic effects of antithrombin III (AT-III) and unrefined equine antivenom in the treatment of coagulopathy induced by Malayan pit viper (Calloselasma rhodostoma) venom were assessed in 42 adult Wistar rats. Following intramuscular venom injection (2 micrograms/g body weight), serial blood samples were taken from the femoral vein for measurement of whole blood clotting time and AT-III activity. There was progressive depletion of AT-III and blood ceased to clot a mean (S.E.) of 164 (8.3) min after venom injection. Coagulopathy was reversed by a high dose antivenom (10 micrograms/g) or a lower dose of antivenom (5 micrograms/g) in combination with AT-III (> or = 0.1 U/g; P < 0.01) but not 5 micrograms/g antivenom or AT-III alone. Following successful treatment, the mean plasma AT-III activity remained above 90%. In this animal model, systemic envenomation by the Malayan pit viper causes uncoagulable blood associated with AT-III consumption. The dose of antivenom required to reverse this coagulopathy can be reduced by half by the addition of AT-III sufficient to maintain blood concentrations within the normal range.

Animals↗
PubMed1982

Comparison of the in vivo hemorrhagic and antithrombotic effects of a low antithrombin-III affinity heparin fraction.

Antithrombin III (ATIII) affinity chromatography of commercial grade heparin yields fractions of high and low affinity for ATIII. In vitro, the high affinity fraction accounts for most of the anticoagulant effect while there is evidence that the low affinity material interferes with platelet function. We have studied the relative antithrombotic and hemorrhagic effects of low affinity heparin. The low affinity heparin fraction, specific activity 43 USP units/mg, was compared with standard heparin (150 USP units/mg) in rabbit experimental models. A residual 12.5% by weight of this low affinity heparin showed high affinity for ATIII. Inhibition of thrombosis in a stasis-hypercoagulability model was directly related to the weight (mg) of high affinity material in each of the heparins. In the bleeding model, when similar weights (mg) of high affinity material were infused, significantly more bleeding was demonstrated with the low affinity fraction which contained a 5-fold excess by weight of low affinity material. We have demonstrated that a low affinity heparin depleted of in vitro anticoagulant and in vivo antithrombotic activity significantly contributes to hemorrhage.

Animals↗
PubMed1982

Effect of sulfinpyrazone upon antithrombin III and platelet factor 4 in chronic renal failure.

Despite the suppressive effects of uremia upon platelet function, patients with chronic renal failure are at increased risk for thrombotic diseases. This increased risk is linked to lowered concentrations of antithrombin III (AT III) and increased platelet release in vivo, as indicated by increased plasma concentrations of platelet factor 4 (PF4). Sulfinpyrazone, a drug capable of reducing the frequency of thrombotic events in uremic patients, allows return toward normal of the AT III while reducing to normal the plasma concentration of PF4. Thus, suppression of platelet function by sulfinpyrazone appears to reduce in vivo clotting, and thus reduces consumption of AT III.

Adult↗
PubMed1982

Substitution therapy with an antithrombin III concentrate in shock and DIC.

In 15 patients admitted to the Intensive Care Unit for shock and with signs of DIC, Antithrombin III (AT III) was substituted. Immediately after the first blood sampling, 1,000 units of AT III was given. This was followed by 500 units AT III after 24 h and after 48 h. A continuous dose of heparin of between 250 and 500 I.U./h was simultaneously given. The following results were obtained: The activity of AT III on admission of 63 +/- 19% increased to 83 +/- 17% 30 min after the initial substitution. There was a clear difference between the recovery of the substituted AT III in acute DIC and in patients in a steady state. AT III recovered in circulation was 47 +/- 15% in the former group but 83 +/- 16% in the latter cases. One unit of AT III per kg body weight increased AT III activity in circulation by 1% in acute DIC but by 1.8% in a steady state. The average half life of the substituted AT III was 4.4 +/- 1.6 h in acute DIC and was 20.2 +/- 4.1 h when the patients were in a steady state.

Adult↗
PubMed1982

Enhancement by heparin of thrombin-induced antithrombin III proteolysis: its relation to the molecular weight and anticoagulant activity of heparin.

Previous findings indicated that binding of heparin to antithrombin III (AT III) facilitates thrombin-induced proteolysis of the inhibitor. We now studied this property of heparin in regard to its molecular weight and anticoagulant activity. Commercial heparin was resolved on Sephadex G-200 into six fractions of decreasing molecular weight. From each fraction high affinity (HA) heparin was isolated by chromatography on AT III-Sepharose and examined in reaction of alpha-thrombin with a molar excess of 125I AT III. Proteolysis of the inhibitor was assessed by SDS polyacrylamide gel electrophoresis. In the presence of the HA heparin from 18% to 38% of AT III participating in reaction appeared in the form of inactive 50,000-dalton fragment, as opposed to 7% of AT III fragmented in the absence of heparin. Although the ability to potentiate proteolysis was at its peak in the medium-molecular-size heparin fraction, the amount of degraded inhibitor relative to anticoagulant activity increased with decreasing molecular weight of the polysaccharide. These findings are consistent with the possibility that the ability of bound heparin to facilitate the cleavage of AT III by thrombin is generally less contingent upon secondary characteristics of the polysaccharide than the anticoagulant activity.

Antithrombin III↗
PubMed1982

Isolation and partial characterization of two distinct types of antithrombin III from rabbit.

Heparin-Sepharose chromatography of rabbit plasma or serum yields two fractions of free antithrombin III (AT). The first of these elutes at a lower salt concentration, represents about 90% of the AT in plasma, and has an approximately 2000 dalton higher molecular weight by SDS polyacrylamide electrophoresis. An antibody to the lower affinity species reacts with the second form. The higher affinity AT is not formed from the lower affinity type during blood coagulation as demonstrated by approximately equal levels in plasma and serum, and lack of conversion of 125I-labelled lower affinity AT to the higher affinity form during blood coagulation. Heparin cofactor and progressive AT activities of the two forms are essentially identical when assayed by chromogenic substrates. The forms are separable by crossed immunoelectrophoresis.

Animals↗
PubMed1982

Antithrombin III in normal pregnancy.

Plasma antithrombin III (AT III) was determined in 94 women during and after normal pregnancy employing an automated amidolytic technique. The patients were selected on the following criteria: no toxaemia, spontaneous delivery at term, birth-weight above the 10th percentile and discharged with a healthy baby. AT III levels during pregnancy and early puerperium were not lower than own control values obtained 6-8 weeks after delivery.

Adult↗
PubMed1983

Effect of glycosaminoglycans and antithrombin III on uptake and inhibition of thrombin by the vascular wall.

Thrombin binds to and is inactivated by the endothelium. The inactivation is potentiated by plasma. The present investigation was designed to clarify the role of vessel wall glycosaminoglycans (GAG) and plasma antithrombin III (AT III) in the inactivation and binding of thrombin by endothelium. Thrombin was shown to bind to vascular endothelium and artificial surfaces containing GAG:s. The binding could be inhibited on both types of surfaces by pretreating them with protamine. Thrombin bound to endothelium was rapidly inactivated in the presence of plasma but only slowly if the plasma was replaced by AT III, AT III-depleted plasma or a balanced salt solution. It is concluded that thrombin binds to vessel wall GAG:s and is inactivated by the endothelium. Potentiation of the inhibition of the endothelially bound thrombin by plasma is dependent upon presence of AT III but an additional plasma factor is also required.

Animals↗
PubMed1983

Fluorogenic substrate assay of antithrombin III: a clinical study.

The fluorogenic substrate assay of antithrombin III (AT III) was compared with a thrombin inhibition (two-stage) clotting test and a radial immunodiffusion assay. Normal ranges based on a population of 25 individuals were 88-121% (fluorogenic substrate), 72-111% (clotting) and 22.5-35.3 mg/dl (RID). A clinical comparison of the methods showed a linear relationship between the fluorogenic substrate and immunologic methods (r = 0.69, p less than 0.005), as well as between the fluorogenic substrate and clotting methods (r = 0.75, p less than 0.005). The fluorogenic substrate assay reflected the highest incidence of low AT III levels in all three clinical groups included (36 patients with arteriosclerosis, 18 with fractures and 37 with thrombosis/embolism).

Antithrombin III↗
PubMed1983

Antithrombin III synthesis in rat liver parenchymal cells.

We have previously demonstrated by immunoperoxydase the presence of immunoreactive antithrombin III (AT III) in rat hepatocytes. We now present direct evidence that rat hepatocytes in culture synthesize AT III like immunoreactive material : 35S-methionine was added to the culture medium and incubated with hepatocytes. After incubation, AT III was immunologically characterized in the medium. We found significant amounts of 35S-AT III among the radioactive proteins synthesized and secreted by the cells.

Animals↗
PubMed1983

The effect of variable fat diets and cholesterol-lowering drugs on Antithrombin III levels in hyperlipoproteinemic and normal subjects.

Functional and immunological Antithrombin III (AT III) levels were studied in normal and hyperlipoproteinemic subjects undergoing crossover therapeutic trials of either diets or hypocholesterolemic drugs. The diet trial subjects, 7 hyperlipoproteinemics and 15 normals, were randomly assigned to crossover between a high saturated fat diet (P/S ratio 1:8) and a high polyunsaturated fat diet (P/S ratio 4:1) for periods of 6-8 weeks, preceded by a baseline period on regular American diet (P/S ratio 1:1). For the drug trials, 33 type II A or B hyperlipoproteinemics were treated in random and double-blind fashion with Colestipol (20 gm/day) or both, for periods of 3 months, preceded by a double placebo period. Mean low density lipoprotein cholesterol levels were significantly different (p less than 0.001) between high saturated and high polyunsaturated fat diets (157 +/- 37 mg/dl vs 137 +/- 31 mg/dl respectively, mean +/- S.D.) and between placebo and drug treatment periods (226 +/- 51 mg/dl vs 183 +/- 44 mg/dl respectively, mean + S.D.). There was no difference in basal functional or immunological AT III levels between normal and hyperlipoproteinemics. AT III levels did not correlate significantly with cholesterol or triglyceride levels and remained unchanged despite significant reductions in serum cholesterol related to the diet and drug therapy. There appears to be no significant association between baseline or post treatment serum cholesterol levels and functional or immunological AT III. Thus, changes in AT III are unlikely to play a role in the link between hypercholesterolemia and thrombosis.

Adult↗
PubMed1983

Changes of the levels of antithrombin III in patients with cerebrovascular diseases.

Dynamic fluctuations of biological activities and antigen amounts of antithrombin III (AT-III) in acute cerebrovascular diseases were analyzed and evaluated. (1) AT-III levels assayed by both biological and immunological methods showed a gradual decrease with increasing age, and levels in patients with cerebral thrombosis were lower than those in patients with cerebral hemorrhage. (2) AT-III in cerebral thrombosis decreased slowly after administration of urokinase. After administration of aspirin (acetylsalicylic acid), however, AT-III levels increased presumably due to inhibition of coagulation activities. (3) Both biological activities and antigen amounts of AT-III increased after administration of an AT-III preparation, but the measured value, especially that of biological activity, was dissociated from the expected one, due to changes of the coagulation system after an operation.

Adult↗
PubMed1984

Reactivity of heparin with the human plasma heparin-binding proteins thrombin, antithrombin III, and apolipoproteins E and B-100.

The heparin-binding properties of human plasma apolipoproteins B-100 and E (apoB-100 and E) of low density lipoproteins (LDL), thrombin, and antithrombin-III (AT-III) were investigated. A highly reactive heparin (HRH) to apoB-100 was isolated by chromatography of crude heparin on a column of LDL immobilized to Affi-Gel 10. This HRH showed a high, Ca2+-dependent precipitating activity towards LDL; 1 microgram HRH uronic acid precipitated 50-70 micrograms LDL-protein. HRH was fractionated further by chromatography on a column of AT-III bound to concanavalin A-Sepharose. The unretained fraction of heparin (HRH1) had a low affinity for AT-III. The bound heparin (HRH2) had a high affinity for AT-III and precipitated LDL in the presence of Ca2+. To assess further their heparin-binding properties, the proteins were subjected to gradient-gel electrophoresis under denaturing conditions, transferred to nitrocellulose by electrophoresis, and then assayed for their ability to bind [125I]-labeled HRH2. Autoradiographic analysis showed that thrombin, apolipoproteins E and B-100, and the AT-III . thrombin covalent complex bound HRH2. Denatured AT-III did not bind HRH2, indicating that its heparin recognition site may depend on conformation.

Antithrombin III↗
PubMed1984

Abolition by dextran sulfate of the heparin-accelerated antithrombin III/thrombin reaction.

Dextran sulfate did not inhibit the amidolytic activity of thrombin on Boc-Val-Pro-Arg-4-methylcoumaryl-7-amide, but abolished inhibition of the enzyme with antithrombin III (AT III) in the presence of heparin. Dextran sulfate did not bind to AT III and had less affinity than immobilized heparin for the protein. Dextran sulfate bound strongly to thrombin and had higher affinity than immobilized heparin for the enzyme. These findings indicate that binding of dextran sulfate to a site other than the active site of thrombin to prevent the approach of AT III in the presence of heparin.

Animals↗
PubMed1984

Identification of heparin cofactor II as the principal plasma cofactor for the antithrombin activity of pentosan polysulphate (SP54).

In antithrombin III depleted plasma only a slight reduction was observed in thrombin inhibitory activity due to potentiation by dermatan sulphate or by pentosan polysulphate (SP54). On gel filtration of normal plasma the peak of pentosan polysulphate dependent activity eluted with a higher apparent molecular weight than that observed with low concentrations of heparin. During purification of heparin cofactor II (1) good coincidence was observed between yields of its activity and the pentosan polysulphate dependent inhibitory activity and cochromatography of the two activities was observed also. Maximal second order rate constant of 2.5 X 10(8) M-1 min-1 (with apparent Kd of 1.8 microM) was found for the potentiation of the thrombin/heparin cofactor II interaction by pentosan polysulphate. A polysaccharide of high charge density may therefore potentiate heparin cofactor II activity and this may be of importance in vivo.

Antithrombins↗
PubMed1984

Antithrombin III in patients with acute deep vein thrombosis during heparin treatment (subcutaneous and intravenous) and during and after treatment with oral coumarins.

The antithrombin III (AT-III) concentration was studied in 98 patients with symptomatic acute deep-vein thrombosis. All patients were initially treated with heparin randomly by subcutaneous injections or by continuous infusions. Then the patients were treated with coumarins during one or six months. The AT-III concentration was estimated daily during heparin treatment and repeatedly during the first year. The mean AT-III concentration decreased progressively 25% during 5 days of heparin treatment regardless of whether heparin was given intravenously or subcutaneously. The mean AT-III concentration during coumarin treatment was higher than after coumarin treatment. Eleven patients developed recurrent thromboembolic episodes during the follow-up period. The mean AT-III concentration in these patients was not lower than in the patients without recurrences.

Adult↗
PubMed1985

Inhibition of antithrombin III by lipid peroxides.

A study was made of the inhibition of antithrombin III (At III) activity by lipid peroxides prepared from autoxidation of unsaturated fatty acids. Lipid peroxides markedly reduced the thrombin neutralising activity of plasma and purified At III with or without albumin carrier. Heparin Sepharose chromatography and heparin cofactor assays suggested that the primary target of lipid peroxides on the At III molecule may be the heparin binding site. Results from electrophoretic studies suggested that interaction between lipid peroxides and At III increased the negative charge of the At III molecule; however, no aggregation of the At III molecule was observed. Lipid peroxidation is being increasingly recognised as a factor in the pathogenesis of several disease states, and it is possible that local inhibition of At III by lipid peroxides could contribute towards the development of a thrombotic event.

Antithrombin III↗