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Blood, Vol. 94 No. 11 (December 1), 1999:
pp. 3702-3706
The Incidence of Venous Thromboembolism in Asymptomatic Carriers of a
Deficiency of Antithrombin, Protein C, or Protein S: A Prospective
Cohort Study
Bernd-Jan Sanson,
Paolo Simioni,
Daniela Tormene,
Marco Moia,
Philip W. Friederich,
Menno V. Huisman,
Paolo Prandoni,
Alessandra Bura,
László Rejt ,
Philip Wells,
Pier M. Mannucci,
Antonio Girolami,
Harry R. Büller, and
Martin H. Prins
From the Departments of Vascular Medicine and Clinical Epidemiology
and Biostatistics, Academic Medical Center, University of Amsterdam,
Amsterdam, The Netherlands; the Institute of Medical Semeiotics,
University of Padova, Padova, Italy; the Hemophilia and Thrombosis
Center, IRCCS Maggiore Hospital, Milan, Italy; the Department of
General Internal Medicine, Leiden University Medical Center, Leiden,
The Netherlands; the Institute of Internal and Vascular Medicine,
University of Perugia, Perugia, Italy; the Second Department of
Medicine, University Hospital of Debrecen, Debrecen, Hungary; and the
Division of Hematology, Civic Parkdale Clinic, Ottawa, Ontario, Canada.
Deficiencies of antithrombin, protein C, and protein S are
associated with an increased risk of venous thromboembolism. The objective of this study was to prospectively assess the incidence of
venous thromboembolism in nontreated asymptomatic subjects with such a
deficiency. We conducted a prospective cohort study in asymptomatic
family members of unselected patients who presented with a venous
thromboembolic event and who were found to have a deficiency of
antithrombin, protein C, or protein S. No anticoagulant prophylaxis was
given to the study participants, except during risk periods for venous
thromboembolism. All venous thromboembolic events were diagnosed by
objective diagnostic tests. A total of 208 individuals with a mean age
of 37 years (range, 15 to 79) were included in the study. A total of
611 patient observation years was obtained. Nine venous thromboembolic
events occurred, resulting in an annual incidence of 1.5% (95%
confidence interval [CI], 0.7 to 2.8) for the 3 deficiencies
combined. Five of these events occurred spontaneously, resulting in an
annual incidence of spontaneous venous thromboembolism of 0.8% (95%
CI, 0.3 to 1.9). For antithrombin, protein C, and protein S
deficiencies separately, this figure was 1.6%, 1.0%, and 0.4%,
respectively. Thirty-four subjects experienced a total of 40 risk
periods during which 4 venous thromboembolic events occurred (10% per
risk period). We conclude that the use of continuous anticoagulant
prophylaxis seems not warranted in asymptomatic individuals with a
deficiency of antithrombin, protein C, or protein S. During risk
periods for venous thromboembolism, adequate anticoagulant prophylaxis is necessary.
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