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.
OBJECTIVE
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.


METHODS
Cross-sectional study.


METHODS
Sixty-seven members of a large family with type 2 AT-III deficiency.


METHODS
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-alpha-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.(ABSTRACT TRUNCATED AT 250 WORDS)
Demers
C
C
Department of Medicine, McMaster University, Hamilton, Canada.
Henderson
P
P
Blajchman
M A
MA
Wells
M J
MJ
Mitchell
L
L
Johnston
M
M
Ofosu
F A
FA
Fernandez-Rachubinski
F
F
Andrew
M
M
Hirsh
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000990:Antithrombin III / Q000032:analysis*; D020152:Antithrombin III Deficiency; D001778:Blood Coagulation Disorders / Q000175:diagnosis* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D005069:Evaluation Studies as Topic; D065427:Factor Xa Inhibitors; D005260:Female; D015844:Heparin Cofactor II / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D011516:Prothrombin / Q000037:antagonists & inhibitors; D012680:Sensitivity and Specificity
D065427:Factor Xa Inhibitors; D015844:Heparin Cofactor II; D000990:Antithrombin III; D011516:Prothrombin; C025337:Factor IIa