No abstract

The prevalence of antithrombin (AT) deficiency in the general population has been variously estimated to be between 0.05 and 5 per 1,000 in the population; 2,491 blood donors were screened in an attempt to clarify this issue using plasma samples taken from the blood donor units. From this initial population, 122 individuals were identified as having plasma AT levels lower than 2 standard deviations below the normal mean. Twenty-two samples had evidence that thrombin had been generated during blood collection and the remaining cohort of 100 blood donors were asked to return but only 59 complied. The data obtained from these 59 were compared with that from 51 age- and sex-matched control blood donors. Both groups of subjects were assessed for previous evidence, or family history, of thrombotic events, as well as exposure to risk factors associated with the development of deep vein thrombosis (DVT). All had venous blood samples taken from which the supernatant plasma was immediately removed and quick frozen for later assaying. Only 6 of the 59 subjects with initial low AT levels had repeat AT-Xa levels below 0.80 units/ml (normal range 0.94 +/- 0.14). Upon repeating the AT-Xa determinations on new samples from these six individuals, only three were found again to be low. One was found to have a type 3 AT deficiency (an Arg47Cys substitution). The other two with a low AT level had mean functional AT-Xa levels of 0.61 and 0.71 units/ml, respectively, with correspondingly low AT:Ag levels consistent with a type 1 AT deficiency. Two of these three subjects has been in high risk situations without evidence of having developed DVT and none had evidence of venous reflux on Doppler venography. In addition, none had personal or family histories of previous thrombotic events. These present data indicate that the prevalence of AT deficiency in our blood donor population is 2 per 1,000 (95% confidence intervals: 0.7-6/1,000).

SummaryObjectives: 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.