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Prevalence of antithrombin deficiency in the healthy population
R C Tait1, I D Walker, D J Perry
1Department of Haematology, Royal Infirmary, Glasgow.
Insights
Congenital antithrombin (AT) deficiency is more common than previously thought, found in 1 in 600 blood donors. Most cases are asymptomatic Type II AT deficiency, with low thrombotic risk.
Area of Science:
- Genetics and Molecular Biology
- Hematology
- Thrombosis and Hemostasis
Background:
- Antithrombin (AT) deficiency is a genetic condition associated with an increased risk of venous thromboembolism.
- Previous estimates of AT deficiency prevalence are based on limited data, potentially underestimating its occurrence in the general population.
Purpose of the Study:
- To determine the prevalence of congenital antithrombin deficiency in a large cohort of blood donors.
- To characterize the phenotypes and genetic mutations associated with different types of AT deficiency.
- To assess the thrombotic risk associated with identified AT deficiency variants.
Main Methods:
- Screening of 9669 blood donors for congenital AT deficiency.
- Family studies to investigate symptomatic phenotypes.
- AT gene analysis to identify specific mutations in deficient individuals.
Main Results:
- Identified 16 cases of congenital AT deficiency, a prevalence of approximately 1 in 600 individuals.
- Two cases of Type I AT deficiency (0.21 per 1000) exhibited symptomatic phenotypes in their families.
- Fourteen cases of Type II AT deficiency (1.45 per 1000) were identified, with various mutations; most did not confer high thrombotic risk.
Conclusions:
- Congenital antithrombin deficiency, particularly asymptomatic Type II variants, is more prevalent than previously recognized.
- The identified Type II AT deficiency variants appear to have a low thrombotic risk, challenging existing assumptions.
- Findings may necessitate re-evaluation of management strategies for asymptomatic AT-deficient individuals identified through screening.
Abstract:
In a cohort of 9669 blood donors we have identified 16 cases of congenital AT deficiency (1 in 600) by way of family studies and AT gene analysis. Two donors had type I AT deficiency (prevalence 0.21 per 1000; 95% CI = 0.03/1000 to 0.75/1000), their families displaying a symptomatic phenotype. 14 donors had a type II deficiency (prevalence 1.45 per 1000; 95% CI = 0.79/1000 to 2.43/1000): one recurring and three unique mutations. None of these type II deficiencies appeared to confer a high thrombotic risk despite many of the affected individuals having experienced potentially prothrombotic challenges. The high frequency of these relatively asymptomatic variants may reflect a selection bias in the study population. However, their existence should not only add to our understanding of structure-function relationships of AT but may also influence our management of asymptomatic deficient individuals identified in epidemiological or presurgical screening programmes.