Jones and Alving's comments offer us the opportunity to further emphasize the difference between the APC response test and DNA analysis for factor V Leiden mutation. We agree that diagnosis of factor V Leiden mutation by DNA assay is the gold standard and that initial screening for factor V Leiden mutation is best performed by the APC response test with addition of factor V-deficient plasma. We would, however, like to emphasize that factor V Leiden mutation is but one determinant of the response to APC. Ranges of the response to APC are broad, indicating that other factors determine a patient's response to APC. Our findings show differences between men and women and show that age, smoking status, and serum total cholesterol level have an effect in men. Thus, apart from the mutation, response to APC has importance in its own right.

The focus of our study was not to diagnose factor V Leiden mutation but to examine this mutation and, as a separate variable, response to APC in relation to cardiovascular and cerebrovascular disease. To ensure reproducibility of our results and to allow comparison with other studies, we used a commercially available test. The general characteristics of the test can be found elsewhere [1]. The inverse association between response to APC and cerebrovascular disease points to the potential clinical value of the APC response test with respect to risk for cerebrovascular disease and mechanisms that may be involved with this risk.