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Shock (Augusta, Ga.) Feb 2007Elevated thrombin-antithrombin complex (TAT) or decreased serum albumin levels suggest heightened vascular permeability in disseminated intravascular coagulation (DIC).... (Clinical Trial)
Clinical Trial Comparative Study
Elevated thrombin-antithrombin complex (TAT) or decreased serum albumin levels suggest heightened vascular permeability in disseminated intravascular coagulation (DIC). In such a situation, plasma antithrombin III (AT-III) may decrease because of the leakage. We thus examined whether AT-III activity before and after administration of an AT-III agent changed depending on plasma TAT and/or serum albumin levels in 20 consecutive patients with DIC. We also analyzed the pharmacokinetics for AT-III using a two-compartment model. Serum albumin levels before AT-III administration correlated with preadministered and postadministered AT-III activity, but TAT levels did not. Regardless of TAT levels, AT-III trough activity on the third day increased significantly. In patients with albumin levels of 2.5 g/dL or less, AT-III trough levels on the third day were significantly lower than those with higher levels of albumin. The half-life of the distribution phase for AT-III agent in the patients was shortened to less than one third the value reported in congenital AT-III deficiency, suggesting increased vascular permeability in the acute state patients here. The distribution volume of the agent increased remarkably compared with the previous control. We report here for the first time that in critical patients with DIC, plasma AT-III levels before and after AT-III administration could be predicted by preadministered serum albumin levels, but not by TAT. These findings could be explained by the pharmacokinetic profile, increased vascular permeability and distribution volume, observed in critical patients.
Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Antithrombin III; Capillary Permeability; Critical Illness; Disseminated Intravascular Coagulation; Female; Humans; Male; Peptide Hydrolases; Serum Albumin
PubMed: 17224787
DOI: 10.1097/01.shk.0000239762.90335.68 -
Orvosi Hetilap Apr 1982
Topics: Antithrombin III; Humans; Immunoelectrophoresis
PubMed: 7078951
DOI: No ID Found -
Thrombosis Research Jul 1983A hereditary abnormal antithrombin III (AT-III) 'Antithrombin III Toyama' was purified from the plasma of a patient with recurrent thrombophlebitis by a procedure...
A hereditary abnormal antithrombin III (AT-III) 'Antithrombin III Toyama' was purified from the plasma of a patient with recurrent thrombophlebitis by a procedure involving barium chloride and ammonium sulfate fractionations, affinity chromatography on anti-AT-III-Sepharose gel, and DEAE-Sephadex chromatography. Purified abnormal AT-III was shown to be the same as normal one in the molecular size, having the same molecular weight, amino-terminal sequence and carboxy-terminal amino acid. Abnormal AT-III gave the same UV spectrum as normal AT-III and both proteins were immunologically identical. Abnormal AT-III, however, showed the different electrophoretic mobility on agarose gel electrophoresis and immunoelectrophoresis. Abnormal AT-III was more electronegative than normal one, before and after a neuraminidase digestion of both proteins. These results suggest that in antithrombin III Toyama an amino acid residue at the heparin-binding site has been replaced by less basic or more acidic one which has no ability to interact with heparin, resulting in a loss of heparin cofactor activity of this protein.
Topics: Adult; Amino Acid Sequence; Antithrombin III; Chromatography, Affinity; Chromatography, Ion Exchange; Electrophoresis, Agar Gel; Electrophoresis, Polyacrylamide Gel; Female; Genetic Variation; Humans; Immunoelectrophoresis; Molecular Weight; Recurrence; Thrombophlebitis
PubMed: 6636046
DOI: 10.1016/0049-3848(83)90334-1 -
American Journal of Hematology Aug 1983Antithrombin III (AT III) was isolated by two procedures using polyethylene glycol-400 (PEG) precipitation as the first stage. The PEG supernatant (PEG-sup) was applied...
Antithrombin III (AT III) was isolated by two procedures using polyethylene glycol-400 (PEG) precipitation as the first stage. The PEG supernatant (PEG-sup) was applied to a heparin-affinity chromatographic system and AT III-heparin cofactor (AT III-HCF) was isolated. The PEG precipitate (PEG-ppt) was separated by a Sephacryl S-200 column. Fractions were collected and those demonstrating maximum AT III antigen and progressive thrombin inhibition were pooled and reapplied to the washed Sephacryl S-200 column. Fractions were again collected and assayed via specific antisera for AT III, alpha 1-antitrypsin (alpha 1 AG), alpha 2-macroglobulin (alpha 2 M), and alpha 1-acid glycoprotein (alpha 1 AT). AT III antigen (AT III AGN) and progressive function were confined primarily to one peak containing virtually no alpha 2 M, a low level of alpha 1 AT, and moderate quantities of alpha 1 AG. The PEG-sup, PEG-ppt, AT III-HCF, and the fraction obtained after two passes across Sephacryl S-200 (S#2) were similar in that they showed reactivity with specific AT III antisera and demonstrated heparin cofactor activity. They differed, however, in that the PEG-sup and AT III-HCF demonstrated considerably reduced progressive antithrombin function assessed over 30 min. This function was present in the PEG-ppt and S#2 fractions and this progressive activity was potentiated by EDTA. AT III two-dimensional immunoelectrophoresis (2-DIE) in the presence of heparin of both the Sephacryl and heparin-affinity purified components were very different, with the Sephacryl-purified AT III AGN showing both a fast peak and a very prominent slow-moving hump. The AT III heparin affinity fraction showed primarily a fast component. Dilution of the S#2 and PEG-ppt fractions resulted in considerable loss of the progressive activity and also the slow-moving component on 2-DIE. On the basis of these observations, it is postulated that AT III purified by PEG precipitation is in an aggregated form and that aggregate formation and dissolution is associated with AT III progressive activity.
Topics: Antithrombin III; Edetic Acid; Heparin; Humans; Sepharose; Thrombin
PubMed: 6410910
DOI: 10.1002/ajh.2830150104 -
Folia Haematologica (Leipzig, Germany :... 1982Laser nephelometry was used to characterize an abnormal antithrombin III (AT III Padua) in comparison with normal antithrombin. Heparinized (0.2 IU/ml) or... (Comparative Study)
Comparative Study
Laser nephelometry was used to characterize an abnormal antithrombin III (AT III Padua) in comparison with normal antithrombin. Heparinized (0.2 IU/ml) or non-heparinized AT III Padua plasma reacts with Laser nephelometry antithrombin III antiserum in a different way compared with pooled normal plasma. There is in fact a slower antigen-antibody reaction during the first 40-45 min both in AT III Padua heparinized and non-heparinized plasmas, compared with pooled normal plasma; then the kinetics overlap. On the contrary the concentrations of antithrombin III Padua in percent correlate well with those obtained by Mancini's and Laurell's methods. These data indicate that Laser nephelometry is suitable for AT III antigen determinations and may also supply useful information for the characterization of abnormal clotting factors.
Topics: Antithrombin III; Humans; Lasers; Nephelometry and Turbidimetry
PubMed: 6187642
DOI: No ID Found -
European Journal of Clinical... Apr 2000Patients with diffuse peritonitis show an overall mortality of about 20%, probably caused by the breakdown of local defence mechanisms combined with a systemic outspread... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
Patients with diffuse peritonitis show an overall mortality of about 20%, probably caused by the breakdown of local defence mechanisms combined with a systemic outspread of bacteria and toxins, which often results in sepsis syndrome.
DESIGN
In a prospective, randomized, controlled study 50 patients with diffuse secondary peritonitis were included. Patients in the therapy group were treated with an adjuvant medication consisting of a continuous intravenous infusion of antithrombin III and two intraperitoneal instillations of fresh frozen human donor serum. The aim of the study was the reduction of mortality and incidence of multiple organ failure.
RESULTS
Mean antithrombin III plasma levels in the therapy group were raised above 140% for 4 days and were significantly higher than in the control group. With the intraperitoneal application of fresh frozen serum and antithrombin III opsonic capacity as well as thrombin, inhibitory activity in the exudate could be significantly elevated over 2 days. The 90-day-mortality rate was 6/26 (23%) in the control group and 6/24 (25%) in the therapy group. Although no improvement of mortality was achieved, a slight but not significant reduction of the severity of the multiple organ failure was seen.
CONCLUSIONS
The chosen therapeutic approach was feasible and showed no side-effects. Yet, neither mortality nor multiple organ failure were significantly improved by the applied short-term adjuvant therapy. Thus, for future trials in severely-ill patients a longer treatment period and/or combinations of antithrombin III with other anti-inflammatory agents should be considered.
Topics: APACHE; Adult; Antithrombin III; Blood Component Transfusion; Critical Care; Female; Humans; Infusions, Intravenous; Male; Peritonitis; Prospective Studies
PubMed: 10759886
DOI: 10.1046/j.1365-2362.2000.00630.x -
Blood Reviews Jun 1996Antithrombin is the major proteinase inhibitor of thrombin and other blood coagulation proteinases. Antithrombin has two functional domains, a heparin binding site and a... (Review)
Review
Antithrombin is the major proteinase inhibitor of thrombin and other blood coagulation proteinases. Antithrombin has two functional domains, a heparin binding site and a reactive centre (that complexes and inactivates the proteinase). Its deficiency results in an increased risk of venous thromboembolism. Appreciable progress has been made in recent years in understanding the structure and function of this protein, the genetic cause of inherited deficiency and its clinical consequence. The structure of antithrombin is now considered in terms of the models derived from X-ray crystallography, which have provided explanations for the function of its heparin interaction site and of its reactive loop. The structural organization of the antithrombin gene has been defined and numerous mutations have been identified that are responsible for antithrombin deficiency: these may reduce the level of the protein (Type I deficiency), alter the function of the protein (Type II deficiency, altering heparin binding or reactive sites), or even have multiple or 'pleiotropic effects' (Type II deficiency, altering both functional domains and the level of protein).
Topics: Antithrombin III; Antithrombin III Deficiency; Crystallography, X-Ray; Humans; Mutation; Polymorphism, Genetic
PubMed: 8813337
DOI: 10.1016/s0268-960x(96)90034-x -
Thrombosis Research May 1983We have previously demonstrated by immunoperoxydase the presence of immunoreactive antithrombin III (AT III) in rat hepatocytes. We now present direct evidence that rat...
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.
Topics: Animals; Antithrombin III; Cells, Cultured; Liver; Male; Methionine; Protein Biosynthesis; Rats; Rats, Inbred Strains
PubMed: 6612676
DOI: 10.1016/0049-3848(83)90228-1 -
Thrombosis Research Nov 1993A case of primary hepatocellular carcinoma with an abnormal increase in the antigenic quantity and activity of Antithrombin III (AT-III) is reported. The patient was a...
A case of primary hepatocellular carcinoma with an abnormal increase in the antigenic quantity and activity of Antithrombin III (AT-III) is reported. The patient was a 53-year-old man. The liver was palpated for a five fingerbreadths, but no jaundice or ascites was noted. Computed tomogram (CT) revealed the presence of many nodules of various sizes in the right hepatic lobe. Both viral markers of HBV and HCV were negative. For tumor markers, PIVKA-II was high (27.7 AU/ml) but AFP was normal. Among coagulation and fibrinolytic factors, the activity and antigenic levels of AT-III were abnormally high (290% and 81.6 mg/dl). An US guided needle biopsy of the tumor revealed hepatocellular carcinoma, Edmondson I. The cellularity was high and the tumor cells were small, well differentiated. The tumor cells were positively stained in immunohistochemical staining using the anti-AT-III antibody. It was believed that AT-III produced by the tumor cells was responsible for this exaggerated level.
Topics: Antigens, Neoplasm; Antithrombin III; Biomarkers, Tumor; Carcinoma, Hepatocellular; Humans; Immunoenzyme Techniques; Liver Neoplasms; Male; Middle Aged
PubMed: 8303658
DOI: 10.1016/0049-3848(93)90186-r -
Journal of Clinical Oncology : Official... May 2009
Topics: Antithrombin III; Blood-Brain Barrier; Brain Neoplasms; Humans; Lymphoma
PubMed: 19332721
DOI: 10.1200/JCO.2008.19.8598