Resistance to activated protein C in an unselected population of patients with pulmonary embolism

Background Resistance to activated protein C (APC) is the most frequent cause of inherited thrombophilia. This phenomenon has been reported in 10-50% of selected patients with venous thromboembolism, a variation that might result from different degrees of selection in different reports. Methods We measured the APC sensitivity ratio in 494 frozen blood samples from unselected consecutive outpatients suspected of pulmonary embolism and referred over a 30-month period to the emergency ward of the University Hospital of Geneva, the only public primary-tertiary care hospital in the region of Geneva (400 000 inhabitants). Findings Prevalence of resistance to APC was 55% (95% CI 2.4-10.5%) (8/146) in patients with confirmed pulmonary embolism and 4.0% (2.2-6.7%) (14/348) in patients in whom the diagnosis could be ruled out (p=0.66), giving an odds ratio of 1.36 (0.56-3.32). Interpretation The very different risks of venous thromboembolism in the presence of resistance to APC that have been reported in trials published so far are probably due to variable recruitment conditions. The lower prevalence observed in our totally unselected population of patients with pulmonary embolism may be more representative of the real risk with which clinicians will be confronted. Therefore, more data are needed from various populations of patients with venous thromboembolism to help decide which patients will benefit from screening for resistance to APC.