KINETIC STUDIES <i>IN VIVO</i> OF ANTITHROMBIN III*

Reeve, E. B.; Leonard, B. D.; Carlson, Tim

doi:10.1111/j.1749-6632.1981.tb29775.x

Cited by 14 publications

(4 citation statements)

References 24 publications

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“…With 88 ± 24 min the calculated half-life of F1+2 was nearly comparable with our results, but the estimated half-life time of TAT of 9 ± 6 min was substantially shorter than the 44 min (0.7 h) observed in our study [ 43 ]. However, the results obtained with radiolabeled TAT in animal studies (10–55 min) were in line with our findings [ 25 – 27 ]. One might speculate that the presence of high doses of unfractionated heparin in the cardiopulmonary bypass setting may have enhanced the elimination of TAT [ 44 ].…”

Section: Discussionsupporting

confidence: 92%

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Label-Free Kinetic Studies of Hemostasis-Related Biomarkers Including D-Dimer Using Autologous Serum Transfusion

et al. 2015

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The objective of this study was to evaluate the elimination kinetics of hemostasis-related biomarkers including the prothrombin activation fragment F1+2, thrombin-antithrombin complex (TAT), plasmin-α2-antiplasmin complex (PAP), and D-dimer in humans. Autologous serum was used as a biomarker source and infused into 15 healthy volunteers. Serum was prepared from whole blood in the presence of recombinant tissue-type plasminogen activator (final concentration 20 μg/mL) to induce plasmin generation required for PAP and D-dimer formation. Serum transfusions (50 mL/30 min) were well tolerated by all subjects. Endogenous thrombin formation was not induced by serum infusions as measured using a highly sensitive oligonucleotide-based enzyme capture assay. Median peak levels (x-fold increase over baseline) of F1+2, TAT, PAP, and D-dimer of 3.7 nmol/L (28.9), 393 ng/mL (189.6), 3,829 ng/mL (7.0), and 13.4 mg/L (34.2) were achieved at the end of serum infusions. During a 48 h lasting follow-up period all biomarkers showed elimination kinetics of a two-compartment model. Median (interquartile range) terminal half-lives were 1.9 (1.3–3.6) h for F1+2, 0.7 (0.7–2.6) h for TAT, and 10.8 (8.8–11.4) h for PAP. With 15.8 (13.1–23.1) h the D-dimer half-life was about twice as long as previously estimated from radiolabeling studies in animals and small numbers of human subjects. The serum approach presented here allows label-free and simultaneous analysis of the elimination kinetics of various hemostasis-related biomarkers. Based on these data changes in biomarker levels could more precisely used to estimate the activity level of the hemostatic system.

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Section: Discussionsupporting

confidence: 92%

“…However, studies in humans are sparse, and they have been conducted with small numbers of subjects only [ 21 , 23 ]. This also applies to studies on the elimination kinetics of F1+2 [ 24 ], TAT [ 25 – 27 ], and PAP [ 28 ], in which similar radiolabeling techniques were used.…”

Section: Introductionmentioning

confidence: 99%

Label-Free Kinetic Studies of Hemostasis-Related Biomarkers Including D-Dimer Using Autologous Serum Transfusion

et al. 2015

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“…3 could be from any of the compartments. It has been suggested previously that AT breakdown occurs from the extravascular compartment, because a delay in the disappearance of total body radioactivity was observed in the dog and the human (31). We have also observed this in the majority of our studies.…”

Section: Discussionsupporting

confidence: 77%

In vivo behavior of radioiodinated rabbit antithrombin III. Demonstration of a noncirculating vascular compartment.

Carlson¹,

Atencio²,

Simon³

1984

J. Clin. Invest.

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Abstract. Rabbit antithrombin III (AT), purified by heparin-agarose, was labeled with iodine-131 by either the glucose oxidase-lactoperoxidase or iodine monochloride techniques. When intravenously injected, the disappearance of the '3'I-AT from plasma was characterized by rapid initial decreases, and three-exponential equations were required for best fit of the plasma disappearance curves. This rapid '3'I-AT removal was not caused by denaturation, as shown by comparison with results obtained when '3'I-AT was biologically screened (injected into a first rabbit, and then transferred 16 h later in whole plasma to a second for kinetic evaluation) before injection. Thus, the same rapid initial loss ofplasma '3'I-AT was observed with screened preparations, and the plasma fractional catabolic rates of 0.716±0.048 and 0.673±0.051 day-' for unscreened and screened '3'I-AT were not significantly different. These results support the hypothesis that a vascular-endothelial AT compartment is present in rabbit. The fractions of the total-body AT in the plasma, the vascular-endothelial and the extravascular compartments were 0.337±0.031, 0.178+0.056, and 0.485±0.069, respectively.Two three-compartment kinetic models are discussed. The first pictures AT as distributing independently between plasma and two other compartments, and the second sees AT as first passing to the vascular-endothelial compartment, and then directly into the extravascular

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“…of denatured molecules (not detected by the in vitro tests) or of the small proportion of.the label associated to proteins other thanHC II. At its best,tl;le description of the complete metabolism would require a bio'o.$ically screened tracer (18)(19)(20). In healthy humans, only the twoc compartment mamillary model was CJ.pplied to tpe tuqH~ver.…”

Section: Discussionmentioning

confidence: 99%

Turnover Study of Heparin Cofactor II in Healthy Man

et al. 1985

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SummaryHeparin cofactor II (HC II) is a heparin-dependent inhibitor of thrombin, distinct from antithrombin III (AT III). This study was designed to evaluate its metabolism in healthy subjects. Purified HC II was labelled with 125I by the lactoperoxidase-glucose oxidase technique. The biological activity of the HC II was unchanged after labelling as was its migratory pattern by crossed immunoelectrophoresis in the presence of heparin or dermatan sulfate.Three healthy volunteers were injected with 10 uCi and the plasma radioactivity was measured daily. The data were approximated by a sum of two exponential terms and the metabolism of HC II was described by a two compartment mamillary system.The mean values of fractional catabolic rate, intravascular fraction and half-life of the elimination phase were respectively: 0.44 d-1, 0.60 and 2.53 d. These parameters are of the same order of magnitude as those reported in the literature for AT III. The plasma HC II concentration in the 3 subjects ranged from 61 to 82 ug/ml as estimated using our purified preparation. Accordingly, the absolute catabolic rate ranged from 1.17 to 1.36 mg · kg-1 · d-1.

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KINETIC STUDIES IN VIVO OF ANTITHROMBIN III*

Cited by 14 publications

References 24 publications

Label-Free Kinetic Studies of Hemostasis-Related Biomarkers Including D-Dimer Using Autologous Serum Transfusion

Label-Free Kinetic Studies of Hemostasis-Related Biomarkers Including D-Dimer Using Autologous Serum Transfusion

In vivo behavior of radioiodinated rabbit antithrombin III. Demonstration of a noncirculating vascular compartment.

Turnover Study of Heparin Cofactor II in Healthy Man

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