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Vox Sanguinis 1987The biochemical and biological properties of antithrombin III (AT III) and the clinical consequences of a deficiency of this inhibitor are described. Therapy with... (Review)
Review
The biochemical and biological properties of antithrombin III (AT III) and the clinical consequences of a deficiency of this inhibitor are described. Therapy with concentrates of purified AT III has been carried out for about 10 years and the present experience is reviewed. In a relatively small number of patients with congenital AT III deficiency it is necessary, under certain condition to substitute AT III. A considerably more frequent use of AT III concentrates has been made in acquired AT III deficiency, especially in shock and diffuse intravascular coagulation (DIC). This therapy was shown to be promising since the duration of DIC could be considerably shortened and the frequency of fatal events could be significantly diminished. No undesirable side effects of substitution with virus-sterilized AT III concentrates have been hitherto observed.
Topics: Antithrombin III; Antithrombin III Deficiency; Disseminated Intravascular Coagulation; Humans
PubMed: 3326267
DOI: 10.1111/j.1423-0410.1987.tb05065.x -
The Journal of Thoracic and... Feb 2002The purpose of this report is to describe the clinical use of antithrombin III concentrate in 53 patients who were found, in the operating room before cardiopulmonary...
OBJECTIVE
The purpose of this report is to describe the clinical use of antithrombin III concentrate in 53 patients who were found, in the operating room before cardiopulmonary bypass, to be heparin resistant.
METHOD
Resistance to heparin was determined to be present when greater than 600 U/kg body weight of heparin failed to prolong the kaolin-activated clotting time to more than 600 seconds in 53 aprotinin-treated patients. Blood samples were obtained for subsequent antithrombin III activity determination. Patients were then administered 500 U of antithrombin III concentrate, and the activated clotting time was remeasured. If the activated clotting time remained less than 600 seconds, a second 500-U dose was given.
RESULTS
Of the 53 patients, 45 (85%) had subnormal measured antithrombin III activity, and the mean plasma antithrombin III activity level for the entire group was 67% (normal 80%-120%). Administration of antithrombin III concentrate (500 U in 45 patients and 1000 U in 8 patients) resulted in prolongation of the mean activated clotting time from 492 to 789 seconds without additional heparin. The mean heparin dose response increased from 36.5 to 69.3 s x U(-1) x mL(-1) with antithrombin III treatment. Only one patient did not achieve the target activated clotting time, despite administration of greater than 600 U/kg heparin and 1000 U of antithrombin III concentrate, and was treated with fresh-frozen plasma.
CONCLUSIONS
On the basis of the criterion used in this report, most of the patients defined as being heparin resistant had subnormal plasma antithrombin III activity. Treatment with antithrombin III concentrate resulted in potentiation of the heparin effect to meet predetermined activated clotting time thresholds and allow for cardiopulmonary bypass.
Topics: Aged; Anticoagulants; Antithrombin III; Cardiac Surgical Procedures; Coronary Artery Bypass; Dose-Response Relationship, Drug; Drug Resistance; Female; Heparin; Humans; Male; Whole Blood Coagulation Time
PubMed: 11828278
DOI: 10.1067/mtc.2002.119060 -
Critical Care Medicine Sep 2000To review the preclinical evidence that provides the therapeutic rationale for antithrombin as a novel treatment for human sepsis. (Review)
Review
OBJECTIVE
To review the preclinical evidence that provides the therapeutic rationale for antithrombin as a novel treatment for human sepsis.
DATA SOURCES
A summary of published medical literature from MEDLINE search files and other reviews published about antithrombin use in sepsis.
DATA SUMMARY
Antithrombin has a variety of antiinflammatory properties in addition to its functions as an endogenous anticoagulant that appear to have an important therapeutic role in the prevention of microvascular dysfunction and multiple organ injury in sepsis. Appropriate timing and dosing of antithrombin III is critical to realize its full therapeutic potential as an anti-sepsis therapy.
CONCLUSIONS
Antithrombin is a potent inhibitor of thrombin-mediated vascular injury in the microcirculation in severe sepsis. This endogenous anticoagulant is rapidly depleted in the early phases of sepsis as a result of decreased synthesis, increased destruction, and enhanced clearance by thrombin-antithrombin complex formation. The therapeutic efficacy of antithrombin in experimental sepsis is readily demonstrable in numerous animal systems. Appropriately defined patient populations with early onset severe sepsis and/or septic shock may benefit from antithrombin therapy if it is administered in adequate doses at the optimal time interval.
Topics: Animals; Antithrombin III; Humans; Sepsis
PubMed: 11007195
DOI: 10.1097/00003246-200009001-00008 -
Transfusion Medicine Reviews Jan 1990
Topics: Amino Acid Sequence; Antithrombin III; Base Sequence; Humans; Molecular Sequence Data
PubMed: 2134618
DOI: No ID Found -
Revista Espanola de Anestesiologia Y... 2012
Topics: Academies and Institutes; Antithrombin III; Antithrombin III Deficiency; Cardiac Surgical Procedures; Cooperative Behavior; Extracorporeal Circulation; Gene Expression; Hemorheology; Hospitals, University; Humans; Intraoperative Complications; Multicenter Studies as Topic; Pharmacy Service, Hospital; Postoperative Complications; Thrombosis
PubMed: 22749326
DOI: 10.1016/j.redar.2012.05.026 -
Blood Coagulation & Fibrinolysis : An... Apr 2007In 85 patients undergoing aorto-coronary bypass for atherosclerotic coronary disease, we measured the antithrombin III activity levels and the thrombin-antithrombin III...
In 85 patients undergoing aorto-coronary bypass for atherosclerotic coronary disease, we measured the antithrombin III activity levels and the thrombin-antithrombin III complex concentrations in blood from the pulmonary and the radial arteries, taken before the aorto-coronary bypass procedure, with the aim of investigating the role of the pulmonary endothelium in the metabolism of the inhibitor. Results showed significantly lower mean antithrombin III activity levels, expressed as a percentage of normal plasma, in blood from the radial artery with respect to levels from the pulmonary artery (0.78 +/- 0.12 versus 0.80 +/- 0.12, P<0.0001), while no significant difference was found in thrombin-antithrombin III complex concentrations. The results seem to show that the pulmonary endothelium contributes to the antithrombin III metabolism with a 0.023 breakdown rate, corresponding to about a 0.1 fraction of the reported 0.22-0.25 total body catabolic rate, as well as the pulmonary endothelial surface (50-70 m2) corresponding to about a 0.1 fraction of the peripheral vessels' endothelial surface (500-700 m2). The data support the hypothesis of a main endothelial catabolism of antithrombin III.
Topics: Antithrombin III; Endothelium, Vascular; Humans; Kinetics; Peptide Hydrolases; Pulmonary Artery; Radial Artery
PubMed: 17413759
DOI: 10.1097/MBC.0b013e328040c127 -
Haemostasis 1985Plasma antithrombin III (AT III) and fibrinogen were measured in 25 Saudi children with nephrotic syndrome during both relapse and remission. During relapse the mean AT... (Comparative Study)
Comparative Study
Plasma antithrombin III (AT III) and fibrinogen were measured in 25 Saudi children with nephrotic syndrome during both relapse and remission. During relapse the mean AT III level was 46.6% (range 7-84%) and mean fibrinogen was 992 mg/dl (range 413-1,433), while during remission, AT III levels increased remarkably to a mean value of 120.6% (range 81-160) and plasma fibrinogen dropped to a mean level of 431 mg/dl (range 230-693). In 10 of these patients AT III was measured simultaneously in urine. During relapse urine AT III levels were of the same magnitude as plasma AT III, while during remission no AT III was detected in urine. These findings confirm the hypercoagulable state during the relapse of nephrotic syndrome and the quick recovery during remission. None of our patients showed any clinical evidence of thromboembolism. Loss of AT III in urine during relapse and/or its consumption is the probable cause of low AT III during relapse while excessive production of AT III by liver probably accounts for the high levels in remission.
Topics: Antithrombin III; Child; Child, Preschool; Female; Fibrinogen; Humans; Male; Nephrotic Syndrome; Serum Albumin
PubMed: 4076845
DOI: 10.1159/000215177 -
Journal of Burn Care & Research :... 2009
Review
Topics: Animals; Antithrombin III; Humans; Serine Proteinase Inhibitors; Smoke Inhalation Injury
PubMed: 19060754
DOI: 10.1097/BCR.0b013e3181923f08 -
The Journal of Clinical Investigation Mar 1986A hereditary (three family members) deficiency of antithrombin III (AT-III) in which AT-III antigen (AT-III ag) is normal in spite of low heparin cofactor and...
A hereditary (three family members) deficiency of antithrombin III (AT-III) in which AT-III antigen (AT-III ag) is normal in spite of low heparin cofactor and antithrombin activity is described. Plasma levels were: AT-III ag, 0.92-0.96 U/ml; AT-III heparin cofactor activity, 0.54-0.62 U/ml; progressive antithrombin activity index, 0.13-0.18; anti-Xa activity, 0.50-0.56 U/ml. Plasma crossed immunoelectrophoresis (CIE) patterns performed with and without added heparin were normal, but serum CIE revealed a decreased complex peak. Purification of the patient's plasma AT-III by heparin-sepharose affinity chromatography showed a normal protein recovery and elution profile, but the purified AT-III fraction showed only 50% of the normal progressive thrombin neutralization and anti-Xa activity. When thrombin-antithrombin (TAT) complexes were formed by incubating with excess thrombin, SDS-polyacrylamide gel electrophoresis (PAGE) analysis revealed that half the patient AT-III formed TAT complexes while the remainder migrated as free AT-III. All the control AT-III formed TAT complexes. The patient's nonreacting AT-III (AT-III "Denver"), isolated by affinity chromatography, showed CIE and SDS-PAGE migration patterns characteristic of normal AT-III but failed to bind thrombin or Xa. Calculations from turnover studies in one patient and normal subjects with autologous 131I-AT-III suggested that AT-III "Denver" is removed from the plasma slightly more rapidly than normal. These studies indicate that the patients' variant AT-III molecule was characterized by normal heparin interaction but defective binding and inhibition of thrombin and Xa. These characteristics allow isolation of the nonreactive variant molecule by heparin-sepharose affinity chromatography.
Topics: Antithrombin III; Antithrombin III Deficiency; Endopeptidases; Humans; Immunoelectrophoresis, Two-Dimensional; Mutation; Pedigree; Protein Binding; Serine Endopeptidases
PubMed: 3512602
DOI: 10.1172/JCI112386 -
Pediatric Nephrology (Berlin, Germany) Apr 1989Levels of antithrombin III (AT-III) activity and antigen in plasma and urine in children with renal diseases, and their correlation with the light microscopic findings...
Levels of antithrombin III (AT-III) activity and antigen in plasma and urine in children with renal diseases, and their correlation with the light microscopic findings of kidney tissue and the fluorescence of glomeruli, were investigated. AT-III activity in plasma was reduced slightly during the acute stage of acute glomerulonephritis and moderately in the relapse stage of nephrotic syndrome, whereas a small increase of AT-III antigen level in urine was noted in the acute stage of glomerulonephritis and considerably more was observed during the relapse stage of nephrotic syndrome. During the acute stage of glomerulonephritis or in some primary persistent glomerulonephritis (IgA nephritis, non-IgA nephritis), Henoch-Schönlein purpura nephritis and nephrotic syndrome, localization of small amounts of AT-III was noted on the capillary walls of glomeruli. These findings were in parallel with the proliferative changes of glomeruli. However, the AT-III localization did not change in parallel with the light microscopic findings or degree of the fluorescence of the fibrinogen/fibrin-related antigen. It was thought that the existence of AT-III antigen on the capillary walls of the glomeruli might be associated with the inhibition of excessive fibrin formation by AT-III.
Topics: Acute Disease; Adolescent; Antigens; Antithrombin III; Child; Child, Preschool; Chronic Disease; Female; Humans; Kidney Diseases; Kidney Glomerulus; Male
PubMed: 2642093
DOI: 10.1007/BF00852896