Two automated methods for plasma antithrombin III compared, and the clinical significance of the results.

1982 ◽  
Vol 28 (11) ◽  
pp. 2249-2253 ◽  
Author(s):  
W Prellwitz ◽  
K F Schmitt ◽  
M Machner ◽  
C J Schuster ◽  
L Weilemann
Keyword(s):  
Antithrombin Iii ◽  
Heparin Therapy ◽  
Disseminated Intravascular Coagulopathy ◽  
Continuous Therapy ◽  
Men And Women ◽  
Short Intervals ◽  
At Iii ◽  
Intravascular Coagulopathy ◽  
Abdominal Operations ◽  
Automated Methods

Abstract Antithrombin III (AT III) activity was determined with two different new chromogenic substances--Chromozym-TH (Tos-Gly-Arg-p-nitroanilide; Boehringer Mannheim) and alpha-N-carbobenzyl-oxy-L-lysine-thiobenzyl ester (Du Pont)--with both a discrete (aca) and a centrifugal analyzer (COBAS BIO). The correlation between the Chromozym-TH/centrifugal analyzer and Du Pont ester/aca methods was good (r = 0.9890). Precision within and between runs was similar to that for typical enzymic determinations. AT III in plasma of 226 healthy men and women ranged from 76.6 to 141.1% (100% = "normal"). We found no significant differences ascribable to oral contraceptives. AT III activity was decreased in 27% of patients with acute thromboembolic diseases (n = 62), in 48% of patients the first day after abdominal operations without complications (n = 78), and in 100% of patients with reversible or irreversible shock (n = 58). In patients receiving continuous therapy with heparin (1500 USP units/h) we saw no decrease in AT III within 96 h of beginning treatment. Plasma from 14 of 16 patients with disseminated intravascular coagulopathy showed a decrease in AT III of from 17 to 51% of normal before and during heparin therapy. We then treated all 16 patients with AT III concentrate. During such treatment, AT III in plasma must be monitored over short intervals to assure that sufficiently high proportions of AT III (greater than 70% of normal) are reached.

Comparison of Progressive Antithrombin Activity and the Concentration of Three Thrombin Inhibitors in Nephrotic Syndrome

1981 ◽  
Vol 46 (03) ◽  
pp. 623-625 ◽  
Author(s):  
B Boneu ◽  
F Bouissou ◽  
M Abbal ◽  
P Sie ◽  
C Caranobe ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Antithrombin Iii ◽  
Heparin Therapy ◽  
Thrombin Inhibitors ◽  
Compensatory Mechanism ◽  
Dramatic Reduction ◽  
Antithrombin Activity ◽  
Α2 Macroglobulin ◽  
At Iii ◽  
A Prospective Study

SummaryIn order to compare the plasmatic progressive antithrombin activity to the concentration of three thrombin inhibitors, antithrombin III (AT III), α2 macroglobulin (α2, M), α1 anti-trypsin (α1 AT) in nephrotic syndrome, a prospective study was carried out on a group of 28 children affected with the disease. A dramatic reduction of the level of AT III and of α1 AT, two inhibitors of molecular weight close to that of albumin, was observed. The decreased level of AT III was counterbalanced by an increase in α2 M. This phenomenon accounts for the increased progressive antithrombin activity observed in all the affected children. It is suggested that the above compensatory mechanism explains the absence of thrombotic accidents in this series and that the benefit of heparin therapy is doubtful in these conditions.

Biological Activity Of Antithrombin III In Blood Plasma And Edematous Fluids Of Patients With A Nephrotic Syndrome

1981 ◽  
Author(s):  
L V Podorolskaya ◽  
G V Andreenko ◽  
L R Polyantseva
Keyword(s):  
Biological Activity ◽  
Nephrotic Syndrome ◽  
Blood Plasma ◽  
Prognostic Value ◽  
Antithrombin Iii ◽  
Venous Occlusion ◽  
Heparin Therapy ◽  
Renal Lesions ◽  
At Iii ◽  
In Blood Plasma

The biological activity of antithrombin (AT) III was tested by the Abilgaard method in blood plasma of 149 patients with renal lesions of various etiology, of 27 donors and in 17 samples of edematous fluid of patients with nephrotic syndrome (NS). The majority of patients had a decreased AT III content in blood plasma, which was especially well pronounced in NS patients irrespective of etiology. In edematous fluids the level of AT III was 10% of that in the plasma. The functional activity of AT III in the plasma was well-correlated with IIS manifestations, i.e, 24 hr-proteinuria, hypoalbuminemia, hyperchole- sterinemia) and with hemocoagulation and fibrinolysis parei:.eters (SFMC content, plasma tolerancy to heparin, contents of heparin, plasminogen activator and kallikrein and total antitryptic activity). A reactive increase of AT III in NS patients with venous occlusion is of essential prognostic value. Heparin therapy results in an increase of the originally low AT III content and in positive dynamics of NS.

Antithrombin-III Activity and the Efficacy of Heparin in Progressing Ischemic Stroke

1998 ◽  
Vol 4 (2) ◽  
pp. 129-132
Author(s):  
Åsa Rödén-Jüllig ◽  
Mona Britton ◽  
Jan Svensson
Keyword(s):  
Ischemic Stroke ◽  
Antithrombin Iii ◽  
Heparin Therapy ◽  
Substantial Part ◽  
Activity Levels ◽  
Significant Difference ◽  
At Iii ◽  
Patients At Risk ◽  
The Individual ◽  
Antithrombin Iii Activity

Heparin is often used in progressing ischemic stroke. However, a substantial part of the patients continue to progress while on treatment. The purpose of this study was to evaluate if antithrombin (AT) III activity before treatment could predict patients at risk for continued progression or if heparin-induced reduction in AT-III activity during treatment is related to continued progression. The study included 42 acute stroke patients with heaprin treatment for progression of isch emic stroke. The patients were continuously supervised for progression. Intravenous heparin therapy was started as soon as possible after the progression was noticed. Antithrombin-III activity was assessed before initiation of treatment and daily during the treatment period. Nine (21 %) of the 42 patients continued to progress while on treatment. There was no statis tically significant difference in AT III activity before treatment between patients who continued to progress and those where the progression ceased when treatment was initiated. Nor were there any differences in the mean AT III activity levels during treatment for patients with more or less favorable clinical course. The individual changes (Δ AT III) were similar in both patient groups as was the proportion of patients with their low est AT III activity in the thrombogenic range (continued: 22% vs. ceased: 27%). No clinically relevant influence of AT III activity on heparin efficacy in progressing ischemic stroke was found. Key Words: Stroke progression—Heparin treatment— Antithrombin activity.

Therapeutic Implications Of Heparin Metabolism In Newborns

1981 ◽  
Author(s):  
M M McDonald ◽  
W E Hathaway ◽  
E B Reeve
Keyword(s):  
Antithrombin Iii ◽  
Specific Activity ◽  
Heparin Therapy ◽  
Normal Adult ◽  
Clotting Time ◽  
Heparin Infusion ◽  
Therapeutic Implications ◽  
Major Vessel ◽  
At Iii ◽  
Plasma Heparin

While thrombotic complications are relatively frequent in the sick newborn, therapeutic heparinization is often difficult to achieve. The clearance of one bolus dose of heparin has been found to be more rapid in the newborn (T% of 35.5 min. in babies 33-36 weeks gestation vs. 63.3 min. in the normal adult). Decreased levels of antithrombin III (AT-III) in the newborn (20-50% of normal adult) may explain the relatively short T1/2; however, an adult with congenital AT-III deficiency (50% level) was found to have a prolonged plasma heparin T1/2 of 106 min. The function of fetal AT-III was studied by isolating the protein from cord blood of nine term and preterm babies by heparin affinity chromatography. Evaluation by SDS-PAGE, immunoelectrophoresis, heparin cofactor specific activity, progressive neutralization of thrombin and Xa at 37°C, pH related antithrombin kinetics and thrombin neutralization relative to heparin concentration revealed a fetal protein with structure and function indistinguishable from that isolated from normal adults.Clinical use of heparin included the evaluation of the Laidlaw (LL) micro whole blood clotting time. The mean LL time of 79 newborns was 96.2 sec. (SD=23). The LL time was not related to gestational age (24-42 weeks) nor to size (600-3980 g). Nine babies were heparinized for three days to six weeks for major vessel thromboses. Heparin infusion rates were compared with heparin levels achieved, LL clotting time prolongations and AT-III levels. The newborns required heparin infusion rates of 25 to 40 U/kg/hour to achieve plasma heparin levels of 0.3-0.5 U/ml. The prolongation of the LL correlated with the heparin level achieved. In these nine babies, AT-III levels did not decrease during the course of heparin therapy.These studies suggest that the newborn has an increased heparin requirement for anticoagulation not completely explained by a low level of a normal antithrombin III.

scholarly journals Effect of Heparin on Circulating Antithrombin III Level

1977 ◽  
Author(s):  
E. Marciniak ◽  
J. P. Gockerman
Keyword(s):  
Antithrombin Iii ◽  
Binding Capacity ◽  
Factor Xa ◽  
Heparin Therapy ◽  
Heparin Infusion ◽  
Natural Defense ◽  
Average Maximum ◽  
At Iii ◽  
Maximum Decrease ◽  
Inhibitory Potential

Both the natural defense against thrombosis and the anticoagulant effect of heparin rely essentially on the presence of antithrombin III (AT III) in blood. The rationale for heparin therapy is to strengthen the existing inhibitory potential of AT III by increasing the velocity of binding. It has not been established whether there is a modifying effect of heparin on the circulating levels of AT III. Twenty-two patients with documented or suspected thromboembolism, including one with hereditary AT III deficiency, were studied before, during and after continuous intravenous infusion of 750–2000 heparin u/hr. AT III was evaluated in plasma 1) as a total factor Xa binding capacity in a method independent of the velocity of inhibition, 2) by immunodiffusion, 3) by rocket Immunoelectrophoresis.In all patients, regardless of their initial AT III level, there was a marked progressive decrease in AT III during heparin infusion, with an abrupt return to original levels in 2–3 days after cessation of therapy. The average maximum decrease in the 5th-7th day of therapy was of 0.38+0.09 u/ml (normal AT III = 1.0 u/ml) or 11.2 + 2.5 mg/dl and was not affected by concurrent therapy with Coumadin.Heparin given in repeated intravenous bolus injections also gradually lowered the quantity of circulating AT III but no changes were seen after a single intravenous injection in normal volunteers or subjects with congenital AT III deficiency. These results give evidence for a possible mechanism of a paradoxical, thrombosis inducing effect of heparin and indicatethat low AT III levels in heparinized patients should not be mistaken for a cause or result of the underlying thromboembolic episode.

scholarly journals Antithrombin-III as a Diagnostic AID in Disseminated Intravascular Coagulation

1977 ◽  
Author(s):  
R.L. Bick ◽  
M.L. Dukes ◽  
W.L. Wilson ◽  
L.F. Fekete
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Serine Proteases ◽  
Antithrombin Iii ◽  
Degradation Products ◽  
Clinical Manifestations ◽  
Heparin Therapy ◽  
Diagnostic Aid ◽  
Intravascular Coagulation ◽  
At Iii ◽  
Initiation Of Therapy

Antithrombin-III (AT-III )/heparin cofactor is now recognized as a major inhibitor of thrombin and other serine proteases in coagulation. Since the reaction between AT-III and serine proteases is irreversable.AT-III consumption should be expected in pathological intravascular coagulation and attendent generation of thrombin and other serine proteases. Using a new AT-III assay system, unaffected by heparin or fibrino(geno)lytic degradation products, AT-III was monitored in 17 patients with DIC, It was found that early and significant decreases occured in all pts. It was further noted that monitoring of AT-III during therapy for DIC reflected a cessation of AT-III consumption and, thus, appeared to reflect efficacy of therapy in stopping the clotting process. Only 1 of 17 patients failed to show an increase in AT-III with initiation of therapy. In this group of patients, mini-heparin therapy appeared to be as efficacious as large doses of heparin in correcting AT-III consumption and other laboratory abnormalities of acute DIC, and in controlling hemorrhage of acute DIC. Four patients had chronic DIC with malignancy; the use of ASA and dipyridamole corrected AT-III consumption and clinical manifestations in these patients, although the response required more time than with heparin or mini-heparin. These findings suggest that the monitoring of DIC with AT-III levels may be useful in both confirming the diagnosis and, more importantly, in monitoring efficacy of therapy. Significant rises in AT-III were noted in all but 1 patient after initiating therapy, presumably reflecting cessation of consumption. In addition, mini-heparin appeared to be as efficacious as large heparin doses in stopping acute DIC and antiplatelet therapy appeared to stop AT-III consumption and clinical manifestations in patients with chronic DIC associated with malignancy.

Molekularbiologische Grundlagen und Diagnostik der hereditären Defekte von Antithrombin III, Protein C und Protein S

2002 ◽  
Vol 22 (02) ◽  
pp. 57-66
Author(s):  
I. Witt
Keyword(s):  
Protein C ◽  
Antithrombin Iii ◽  
Protein S ◽  
Klinische Relevanz ◽  
At Iii

ZusammenfassungDie enormen Fortschritte in der Molekularbiologie in den letzten Jahren ermöglichten sowohl die Aufklärung der Nukleotidsequenzen der Gene für Antithrombin III (AT III), Protein C (PROC) und Protein S (PROS) als auch die Identifizierung zahlreicher Mutationen bei hereditären Defekten dieser wichtigen Inhibitoren des plasmatischen Gerinnungssystems. Da die Gene für AT III (13,8 kb) und PROC (11,2 kb) nicht groß und relativ leicht zu analysieren sind, gibt es bereits umfangreiche »databases« der Mutationen (50, 73). Für AT III sind 79 und für PROC 160 unterschiedliche Mutationen beschrieben.Sowohl beim AT-III-Mangel als auch beim Protein-C-Mangel hat die Mutationsaufklärung neue Erkenntnisse über die Struktur-Funktions-Beziehung der Proteine gebracht. Beim Protein-C-Mangel steht die klinische Relevanz der DNA-Analyse im Vordergrund, da die Diagnostik des Protein-C-Mangels auf der Proteinebene nicht immer zuverlässig möglich ist.Das Protein-S-Gen ist für die Analytik schwer zugänglich, da es groß ist (80 kb) und außerdem ein Pseudogen existiert. Es sind schon zahlreiche Mutationen bei Patienten mit Protein-S-Mangel identifiziert worden. Eine Database ist bisher nicht publiziert. Die klinische Notwendigkeit zur Mutationsaufklärung besteht ebenso wie beim Protein-C-Mangel. Es ist zu erwarten, dass zukünftig die Identifizierung von Mutationen auch beim Protein-S-Mangel beschleunigt vorangeht.

Increased Heparin Cofactor II Levels in Women Taking Oral Contraceptives

1990 ◽  
Vol 64 (03) ◽  
pp. 365-368 ◽  
Author(s):  
P Toulon ◽  
J M Bardin ◽  
N M Blumenfeld
Keyword(s):  
Oral Contraceptives ◽  
Antithrombin Iii ◽  
Thrombin Inhibitor ◽  
Control Groups ◽  
Normal Range ◽  
Heparin Cofactor Ii ◽  
Men And Women ◽  
Pooled Data ◽  
Contraceptive Pills ◽  
Increased Risk

SummaryHeparin cofactor II (HCII) is a thrombin inhibitor present in human plasma whose activity is enhanced by heparin. HCII exhibits important homologies with antithrombin III, the main heparin-enhanced thrombin inhibitor. Cases of recurrent thromboembolism have been recently reported in patients with HCII deficiency. Since the use of oral contraceptives (OC) is associated with an increased risk of thrombosis, the study of the plasma levels of HCII was undertaken in women taking contraceptive pills. Plasma HCII levels were found significantly higher in 62 women taking low-estrogen content OC (1.20 ± 0.28 U/ml) than in 62 age matched women not taking OC (0.94 ± 0.16 U/ml) or in 62 men (0.96 ± 0.19 U/ml). Significant correlations between HCII and fibrinogen levels were reported in the three groups. From the pooled data of the two control groups (men and women not taking OC), the normal range for plasma HCII levels was defined to be between 0.60 and 1.30 U/ml (mean ± 2 SD). Two cases of low HCII levels (<0.60 U/ml) were found in the control groups, but none in the group of women taking OC. It is concluded that the use of oral contraceptives is associated with a rise in HCII levels and that the screening for HCII deficiency has to be performed at distance of any OC therapy.

Immunologic Studies of Antithrombin III Heparin Cofactor in the Newborn

1978 ◽  
Vol 39 (03) ◽  
pp. 624-630 ◽  
Author(s):  
W E Hathaway ◽  
L L Neumann ◽  
C A Borden ◽  
L J Jacobson
Keyword(s):  
Gestational Age ◽  
Antithrombin Iii ◽  
Newborn Infants ◽  
Term Infant ◽  
Sick Newborn ◽  
At Iii ◽  
Thrombotic Complications ◽  
Low Levels ◽  
Collection Methods ◽  
Made In

SummarySerial quantitative immunoelectrophoretic (IE) measurements of antithrombin III heparin cofactor (AT III) were made in groups of well and sick newborn infants classified by gestational age. Collection methods (venous vs. capillary) did not influence the results; serum IE measurements were comparable to AT III activity by a clotting method. AT III is gestational age-dependent, increasing from 28.7% of normal adult values at 28-32 weeks to 50.9% at 37-40 weeks, and shows a gradual increase to term infant levels (57.4%) by 3-4 weeks of age. Infants with the respiratory distress syndrome (RDS) show lower levels of AT III in the 33-36 week group, 22% vs. 44% and in the 37-40 week group, 33.6% vs. 50.9%, than prematures without RDS. Infants of 28-32 week gestational age had only slight differences, RDS = 24%, non-RDS = 28.7%. The lowest levels of AT III were seen in patients with RDS complicated by disseminated intravascular coagulation and those with necrotizing enterocolitis. Crossed IE on representative infants displayed a consistent pattern which was identical to adult controls except for appropriate decreases in the amplitude of the peaks. The thrombotic complications seen in the sick preterm infant may be related to the low levels of AT III.

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