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