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Thrombosis in Antithrombin-III-deficient Persons: Report of a Large Kindred and Literature Review

Christine Demers, MD; Jeffrey S. Ginsberg, MD; Jack Hirsh, MD; Penny Henderson, ART; and Morris A. Blajchman, MD
[+] Article, Author, and Disclosure Information

Grant Support: By a Research and Development grant HAM-04-89 from the Canadian Red Cross Society, Blood Services. Dr. Ginsberg is a recipient of the Rose Levy Rosenstadt Scholar Award from McMaster University.

Requests for Reprints: Jeffrey S. Ginsberg, MD, McMaster University Medical Centre, 1200 Main Street West, HSC 3W15, Hamilton, Ontario L8N 3Z5, Canada.

Current Author Addresses: Dr. Demers: Department D'Hematologie, Hôpital St-Sacrement, 1050 Chemin Ste-Foy, Quebec G1S 4L8, Canada. Drs. Ginsberg and Blajchman and Ms. Henderson: McMaster University Medical Centre, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada.

Dr. Hirsh: Hamilton Civic Hospitals Research Centre, 711 Concession Street, Hamilton, Ontario L8V 1C3, Canada.

© 1992 American College of PhysiciansAmerican College of Physicians

Ann Intern Med. 1992;116(9):754-761. doi:10.7326/0003-4819-116-9-754
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Purpose: To estimate the prevalence of objectively proven thrombotic complications in antithrombin-III-deficient persons.

Study Design: Cross-sectional study and a critical review of the literature.

Data Sources and Extraction: The prevalence of thrombosis in antithrombin III-deficient and -nondeficient family members of a large kindred was estimated by history, review of diagnostic tests, and examination for venous reflux by Doppler ultrasonography, as an indicator of previous venous thrombosis.

A MEDLINE search and literature review of the published English- and French-language literature from 1966 to 1990 that described antithrombin-III-deficient families was done, and the following information was obtained: the prevalence of thrombosis in deficient and nondeficient family members, the presence or absence of risk factors for thrombosis (surgery, pregnancy, the postpartum state, use of oral contraceptives, immobiization, metastatic cancer, major trauma) at the time of the thrombotic event, and age of onset of the first episode of thrombosis. The validity of the studies was assessed according to predetermined criteria.

Results: Sixty-seven research subjects were evaluated. Six of 31 (19.4%) antithrombin-III-deficient subjects compared with none of 36 (0%) nondeficient subjects had had one or more thrombotic events. The initial episode in five of six subjects had occurred in association with risk factors for thrombosis.

The literature search indicated that the pooled prevalence of symptomatic venous thrombosis among the deficient subjects was 51%, but objective testing was done in only 17% of these subjects at the time of presentation.

Conclusion: Based on the data from this antithrombin-III-deficient kindred, lifelong anticoagulant prophylaxis does not appear to be warranted in asymptomatic carriers, and prophylaxis could be limited to periods of high risk for thrombosis.





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