Prevalence of activated protein C resistance and analysis of clinical profile in thromboembolic patients. A Belgian prospective study

Hainaut P, Azerad M-A, Lehmann F, Schlit
A-F, Zech F, Heusterspreute M, Philippe M, Col C,
Lavenne E, Moriau M. (Cliniques Universitaires St
Luc, Bruxelles, Belgium). Prevalence of activated
protein C resistance and analysis of clinical pro®le in
thromboembolic patients. A Belgian prospective
study. J Intern Med 1997; 214: 427±33.
Objectives. To assess the prevalence of activated
protein C resistance (APC-R) among healthy subjects
and thromboembolic patients and to determine the
clinical characteristics associated with APC-R.
Design. A prospective study.
Setting. One academic medical centre.
Subjects. 91 health controls and 126 thromboembolic
patients.
Measurements. Patients and control were genotyped
for the factor V Leiden (VaQ506) mutation. The
anticoagulant response of the patient's plasma to
activated protein C was also determined.
Results. The frequency of APC-R was 3±3% among
healthy control subjects and 22% among thrombotic
Introduction
Thromboembolic disease is a major cause of mortality
and morbidity in the Western world [1]. The frequent
®nding of a positive familial history underlies the role
of genetic factors in the genesis of thromboembolism.
Until recently, inherited de®ciency of physiological
inhibitors (antithrombin III, protein C, protein S)
accounted for most cases of hereditary thrombophilia
; however, the combined incidence of these
de®cits accounts for less than 15% of patients
suffering from thromboembolic disease [2]. In 1993,
Dahlba$ck and colleagues described a family with a
patients of whom 18% were heterozygous and 4%
were homozygous. The mean age at the ®rst thrombotic
event and the severity of thrombotic disease
including the proportion of proximal deep vein
thrombosis and the frequency of lung embolism were
identical among APC-R positive and negative
patients. A family history of thromboembolic disease
was elicited more frequently in APC-R positive than
in APC-R negative patients (57% vs. 22%, P!
0±001). The recurrence rate was higher for APCR-R
positive patients (57% vs. 34%, P!0±05). The
percentage of cases with a factor predisposing to
thrombosis was very similar in APC-R positive (57%)
and negative (68%) patients.
Conclusions. A familial history of thromboembolic
disease and recurrences are signi®cantly more frequent
among APC-R positive than APC-R negative
patients.