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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:1026-1033.)
© 1999 American Heart Association, Inc.

Original Contributions

Risk of Venous Thromboembolism and Clinical Manifestations in Carriers of Antithrombin, Protein C, Protein S Deficiency, or Activated Protein C Resistance

A Multicenter Collaborative Family Study

Paolo Bucciarelli; Frits R. Rosendaal; Armando Tripodi; Pier Mannuccio Mannucci; Valerio De Stefano; Gualtiero Palareti; Guido Finazzi; Francesco Baudo; Roberto Quintavalla; on Behalf of the GIRTE (Italian Research Group on Inherited Thrombophilia)

From the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center (P.B., A.T., P.M.M.), IRCCS Maggiore Hospital and University of Milan, Italy; the Department of Clinical Epidemiology and Hemostasis and Thrombosis Research Center (F.R.R.), Leiden University Medical Center, The Netherlands; the Department of Hematology (V.D.S.), Catholic University of Rome, Italy; the Department of Angiology and Coagulation (G.P.), S Orsola Hospital, Bologna, Italy; the Department of Hematology (G.F.), Riuniti Hospital, Bergamo, Italy; the Hematology Department (F.B.), Niguarda Cà Granda Hospital, Milan, Italy; and the Hemostasis Center (R.Q.), V Medical Department, Regional Hospital, Parma, Italy.

Correspondence to Paolo Bucciarelli Hemophilia and Thrombosis Center, IRCCS Maggiore Hospital, Via Pace 9, 20122 Milano, Italy. E-mail bucciare{at}imiucca.csi.unimi.it

Abstract—Deficiencies of antithrombin (AT), protein C (PC) or protein S (PS), and activated protein C resistance (APCR) are very well-established coagulation defects predisposing to venous thromboembolism (VTE). We performed a retrospective cohort family study to assess the risk for VTE in individuals with AT, PC, or PS deficiency, or APCR. Five hundred thirteen relatives from 9 Italian centers were selected from 233 families in which the proband had had at least 1 episode of VTE. We calculated the incidence of VTE in the whole cohort and in the subgroups after stratification by age, sex, and defect. The overall incidence of VTE (per 100 patient-years) in the group of relatives was 0.52. It was 1.07 for AT, 0.54 for PC, 0.50 for PS, 0.30 for APCR, and 0.67 in the group with a double defect. The incidence was associated with age, but not with sex. The mean age at onset was between 30 and 40 years for all the coagulation defects. Women had the peak of incidence in the age range of 21 to 40 years, earlier than men. The lifetime risk for VTE was 4.4 for AT versus APCR, 2.6 for AT versus PS, 2.2 for AT versus PC, 1.9 for PC versus APCR, and 1.6 for PS versus APCR. AT deficiency seems to have a higher risk for VTE than the other genetic defects. There is a relation between age and occurrence of thrombosis for both men and women. The latter had the peak of incidence earlier than the former.

Key Words: venous thromboembolism • antithrombin • protein C • protein S • activated protein C resistance

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