Thromb Haemost 1993; 69(03): 231-235
DOI: 10.1055/s-0038-1651586
Original Article
Coagulation
Schattauer GmbH Stuttgart

An Antithrombin III Assay Based on Factor Xa Inhibition Provides a More Reliable Test to Identify Congenital Antithrombin III Deficiency Than an Assay Based on Thrombin Inhibition

Christine Demers
The Departments of Medicine, Pediatrics and Pathology, McMaster University and the Canadian Red Cross Society, Hamilton, Canada
,
Penny Henderson
The Departments of Medicine, Pediatrics and Pathology, McMaster University and the Canadian Red Cross Society, Hamilton, Canada
,
Morris A Blajchman
The Departments of Medicine, Pediatrics and Pathology, McMaster University and the Canadian Red Cross Society, Hamilton, Canada
,
Michael J Wells
The Departments of Medicine, Pediatrics and Pathology, McMaster University and the Canadian Red Cross Society, Hamilton, Canada
,
Lesley Mitchell
The Departments of Medicine, Pediatrics and Pathology, McMaster University and the Canadian Red Cross Society, Hamilton, Canada
,
Marilyn Johnston
The Departments of Medicine, Pediatrics and Pathology, McMaster University and the Canadian Red Cross Society, Hamilton, Canada
,
Fred A Ofosu
The Departments of Medicine, Pediatrics and Pathology, McMaster University and the Canadian Red Cross Society, Hamilton, Canada
,
Franҫoise Fernandez-Rachubinski
The Departments of Medicine, Pediatrics and Pathology, McMaster University and the Canadian Red Cross Society, Hamilton, Canada
,
Maureen Andrew
The Departments of Medicine, Pediatrics and Pathology, McMaster University and the Canadian Red Cross Society, Hamilton, Canada
,
Jack Hirsh
The Departments of Medicine, Pediatrics and Pathology, McMaster University and the Canadian Red Cross Society, Hamilton, Canada
,
Jeffrey S Ginsberg
The Departments of Medicine, Pediatrics and Pathology, McMaster University and the Canadian Red Cross Society, Hamilton, Canada
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 05. Juni 1992

Accepted after revision 26. Oktober 1992

Publikationsdatum:
05. Juli 2018 (online)

Preview

Summary

Objectives: To determine whether functional antithrombin III (AT-III) levels measured by a factor Xa inhibition (AT-III-Xa) assay identifies AT-III deficient individuals more reliably than functional AT-III levels measured by a thrombin inhibition (AT-III-IIa) assay.

Study design: Cross-sectional study.

Patient population: Sixty-seven members of a large family with type 2 AT-III deficiency.

Intervention: DNA analysis was used as the reference diagnostic standard for AT-III status and subjects were classified as AT-III deficient or non deficient according to these results. Functional AT-III levels were measured in all subjects using: 1) a chromogenic substrate for thrombin and added human thrombin (AT-III-IIa), and 2) a chromogenic substrate for factor Xa and added bovine factor Xa (AT-III-Xa). Functional heparin cofactor II (HC-II) levels were measured using a commercially available kit. The proportions of 125I-α-thrombin complexed to AT-III and HC-II were measured by polyacrylamide gel electrophoresis and autoradiography.

Results: Thirty-one (46%) individuals were classified as AT-III deficient and 36 (54%) as AT-III non deficient. AT-III-Xa assay measured a significantly lower mean AT-III value and a narrower range for individuals classified as AT-III deficient than the AT-III-IIa assay. Using the AT-III-IIa assay, six subjects had borderline AT-III levels compared to none with the AT-III-Xa assay. Thrombin inhibition by HC-II likely accounts for the AT-III-IIa assay giving higher values than the AT-III-Xa assay since 1) there was a significant correlation between the difference in AT-III-IIa and AT-III-Xa levels and HC-II levels, 2) the mean level of HC-II was significantly higher for individuals who had a positive difference between AT-III-IIa and AT-III-Xa levels compared to those who had a negative difference and 3) there was a significant correlation between the difference in AT-III-IIa and AT-III-Xa levels and the percentage of 125I-α-thrombin complexed to HC-II.

Conclusion: The AT-III-Xa assay is a better discriminant between AT-III deficient and AT-III non deficient individuals than the AT-III-IIa assay.