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DOI: 10.1055/s-0038-1655987
Mortality and Causes of Death in Inherited Antithrombin Deficiency
Publication History
Received 25 July 1996
Accepted after revision 15 November 1996
Publication Date:
11 July 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/199703/lookinside/thumbnails/10-1055-s-0038-1655987-1.jpg)
Summary
To assess the contribution of inherited antithrombin deficiency to mortality, we investigated the causes of death in 14 families with inherited antithrombin deficiency. Between 1830 and 1994, 86 of 266 family members who had a probability of 0.5 or more for heterozygosity died. The causes of death were obtained for 58 of 66 deaths occurring between 1940 and 1994. Standardized mortality ratios (SMR) were calculated using mortality rates from the general population adjusted for age, sex and calendar period.
The overall SMR was 0.90 from 1830 to 1994 (95% C.1.0.72-1.11). From 1940 until 1994 44 men and 22 women died (SMR = 1.09, 95% C.I. 0.84-1.39; SMR men = 1.20, 95% C.I. 0.87-1.61; SMR women = 0.92,95% C.I. 0.58-1.39). No excess mortality compared to the general population was found for cancer (14 deaths) or circulatory diseases (28 deaths). A slightly increased mortality caused by respiratory diseases (7 deaths, SMR = 1.68,95% C.I. 0.68-3.47) seemed due to pneumonia (4 deaths, SMR = 2.86, 95% C.I. 0.78-7.32). Venous thromboembolic complications were listed once in association with a risk situation, and one other death could be attributed to fatal pulmonary embolism. Cerebral hemorrhages were listed three times. It could not be verified whether these hemorrhages were related to anticoagulant therapy; the frequency was slightly higher than the expected population figure (SMR = 1.49,95% C.I. 0.31-4.36). The mean age of death for all causes was 64 years; the two fatal thromboembolic episodes occurred at age 20 and 30 years.
The data show that antithrombin deficiency is associated with a normal survival and a low risk of fatal thromboembolic events. The use of long-term anticoagulant treatment in asymptomatic individuals should be considered carefully in view of the greater risk of fatal bleeding associated with long-term anticoagulant prophylaxis.
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References
- 1 Hirsh J, Piovella F, Pini M. Congenital antithrombin III deficiency. Incidence and clinical features. Am J Med 1989; 87: 0034S-0038S
- 2 De Stefano V, Leone G. Mortality related to thrombosis in congenital antithrombin III deficiency (letter). Lancet 1991; 337: 0847-0848
- 3 Rosendaal FR, Heijboer H, Brёt E, Büller HR, Brandjes DPM, de Bruin K, Hommes DW, Vandenbroucke JP. Mortality in hereditary antithrombin-III deficiency -1830 to 1989. Lancet 1991; 337: 0260-0262
- 4 Allaart CF, Rosendaal FR, Noteboom WMP, Vandenbroucke JP, Briёt E. Survival in families with hereditary protein C deficiency, 1820 to 1993. BMJ 1995; 311: 0910-0913
- 5 Levine MN, Raskob G, Hirsh J. Hemorrhagic complications of long-term anticoagulant therapy. Chest 1989; 95: 0026S-0036S
- 6 van der Meer FJM, Rosendaal FR, Vandenbroucke JP, Briёt E. Bleeding complications in oral anticoagulant therapy. An analysis of risk factors. Arch Intern Med 1993; 153: 1557-1562
- 7 van Boven HH, Olds RJ, Thein SL, Reitsma PH, Lane DA, Briёt E, Van denbroucke JP, Rosendaal FR. Hereditary antithrombin deficiency:heterogeneity of the molecular basis and mortality in Dutch families. Blood 1994; 84: 4209-4213
- 8 World Health Organization. Manual of the International Statistical Classification of Disease, Injuries, and Causes of Death. Ninth Revision Geneva:World Health Organization, 1977
- 9 Mackenbach JP, Kunst AE, Lautenbach H, Bijlsma F, Oei YB. Competing causes of death:an analysis using multiple-cause-of-death data from the Netherlands. Am J Epidemiol 1995; 141: 0466-0475
- 10 Centraal Bureau voor de Statistiek. Groote internationale lijst van dood- soorzaken 1938. ‘s-Gravenhage:Centraal Bureau voor de Statistiek, 1940
- 11 World Health Organization. Manual of the International Statistical Classification of Disease, Injuries and C of Death. Sixth Revision Geneva:World Health Organization, 1948
- 12 World Health Organization. Manual of the International Statistical Classification of Disease, Injuries and Cause of Death. Seventh Revision Geneva:World Health Organization, 1957
- 13 World Health Organization. Manual of the International Statistical Classification of Disease, Injuries and Cause of Death. Eighth Revision Geneva:World Health Organization, 1968
- 14 Coleman M, Douglas A, Hermon C, Peto J. Cohort study analysis with a FORTRAN computer program. Int J Epidemiol 1986; 15: 0134-0137
- 15 Breslow NE, Day NE. Rates and rate standardization. In: Statistical methods in cancer research Volume II - The design and analysis of cohort studies. International Agency for Research on Cancer (IARC Scientific publications no 82) Lyon: 1987. pp 0069-0072
- 16 De Stefano V, Leone G, Mastrangelo S, Tripodi A, Rodeghiero F, Casta-man G, Barbui T, Finazzi G, Bizzi B, Mannucci PM. Clinical manifestations and management of inherited thrombophilia:retrospective analysis and follow-up after diagnosis of 238 patients with congenital deficiency of antithrombin III protein C protein S. Thromb Haemost 1994; 72: 0352-0358
- 17 Demers C, Ginsberg JS, Hirsh J, Henderson P, Blajchman MA. Thrombosis in antithrombin-III-deficient persons. Report of a large kindred and literature review. Ann Intern Med 1992; 116: 0754-0761
- 18 Chowdhury V, Lane DA, Mille B, Auberger K, Gandenberger-Bachem S, Pabinger I, Olds RJ, Thein SL. Homozygous antithrombin deficiency:report of two new cases (99 Leu to Phe) associated with arterial and venous thrombosis. Thromb Haemost 1994; 72: 0198-0202