REPLY
Risk Factors for Thromboembolism
Francesco Rodeghiero, MD, and
Alberto Tosetto, MD
16 November 1999 | Volume 131 Issue 10 | Pages 790-791
IN RESPONSE:
We thank Dr. Williams for his comment on our test for resistance to activated protein C. As he correctly points out, we measured resistance as originally described by Dahlback in 1993 (1). In fact, our investigation began just a few months before the factor V Leiden mutation was described, and we elected not to change our methods during the study. Dilution of plasma samples with factor V-deficient plasma is an efficient way to identify carriers of the factor V Leiden mutation (2), and many laboratories use this "improved" method to avoid the molecular test. Our findings clearly indicate that resistance to activated protein C is not equivalent to the factor V Leiden mutation. Rather, when the original method is used, a substantial fraction (up to 12%) of the population has a phenotype similar to that of factor V Leiden mutation carriers and has a similarly higher risk for thrombosis. Thus, laboratories relying on the modified activated protein C resistance test (or on molecular diagnosis) could miss some useful information.
Dr. Jay states that our results should have also been adjusted for smoking status. Definite evidence that smoking is an independent risk factor for venous thromboembolism is still lacking. Furthermore, in a previous paper we reported that smokers had a slightly higher response to activated protein C than nonsmokers (3). Assuming that smoking is a risk factor for venous thromboembolism, its effect should result in an underestimation of risk in our cohort. Thus, although we appreciate Dr. Jay's comments, we do not believe that our study results are affected by not controlling for smoking.
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Author and Article Information
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S. Bortolo Hospital; 36100 Vicenza, Italy (Rodeghiero)
S. Bortolo Hospital; 36100 Vicenza, Italy (Tosetto)
1. Dahlback B, Carlsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C Proc Natl Acad Sci U S A. 1993;90:1004-8.[Abstract/Free Full Text]
2. Tosetto A, Rodeghiero F. Diagnosis of APC resistance in patients on oral anticoagulant therapy Thromb Haemost. 1995;73:732-3.[Medline]
3. Tosetto A, Missiaglia E, Gatto E, Rodeghiero F. The Vita Project: phenotypic resistance to activated protein C and FV Leiden mutation in the general population Thromb Haemost. 1997;78:859-63.[Medline]
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