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Resistance to activated protein C as an additional genetic risk factor in
hereditary deficiency of protein S
B Zoller, A Berntsdotter, P Garcia de Frutos and B Dahlback
Department of Clinical Chemistry, University of Lund, Malmo General
Hospital, Sweden.
Inherited resistance to activated protein C (APC), which is caused by a
single point mutation in the gene for factor V, is a common risk factor for
thrombosis. In this study, the prevalence of APC resistance in 18 unrelated
thrombosis-prone families with inherited protein S deficiency was
investigated to determine its role as additional genetic risk factor for
thrombosis. In addition, a detailed evaluation of the clinical
manifestations in these families was performed. Venous thrombotic events
had occurred in 47% of the protein S-deficient patients (64/136) and in 7%
of relatives without protein S deficiency (14/191). As estimated from
Kaplan-Meier analysis, 50% of protein S- deficient family members and 12%
of those without protein S deficiency had had manifestation of venous
thromboembolism at the age of 45 years. The age at the first thrombotic
event ranged from 10 to 81 years (mean, 32.5 years) and a large
intrafamilial and interfamilial variability in expression of thrombotic
symptoms was seen. The factor V gene mutation related to APC resistance was
present in 6 (38%) of 16 probands available for testing; in total, the
mutation was found in 7 (39%) of the 18 families. In family members with
combined defects, 72% (13/18) had had thrombosis as compared with 19%
(4/21) of those with only protein S deficiency and 19% (4/21) of those with
only the factor V mutation. In conclusion, APC resistance was found to be
highly prevalent in thrombosis-prone families with protein S deficiency and
was an additional genetic risk factor for thrombosis in these families. The
results suggest thrombosis-prone families with protein S deficiency often
to be affected by yet another genetic defect.
Volume 85,
Issue 12,
pp. 3518-3523,
06/15/1995
Copyright © 1995 by The American Society of Hematology
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