We thank Wilson and Gharavi for drawing attention to the problem of hypercoagulability and thrombosis in patients with the antiphospholipid syndrome. Although we agree that the mechanism of action of antiphospholipid antibodies is not fully understood and that prospective clinical trials are needed to establish definitive recommendations for treatment, we know of no evidence suggesting that the measurement of specific endogenous anticoagulant pathways, such as activated protein C or antithrombin III, provides information useful in the diagnosis or management of patients with the antiphospholipid syndrome. We would like, however, to modify our statement in relation to arterial thrombosis and resistance to activated protein C in light of a recent report showing that young women with factor V Leiden mutation have a fourfold increased risk for myocardial infarction [1]. These recent data suggest that factor V Leiden mutation is a risk factor for arterial disease in young women (particularly if they smoke) but not in older men.

Dr. Kahn raises an interesting point about the risk of HRT in women with factor V Leiden mutation. The three recent reports that she cites do indeed suggest that women receiving HRT have an increased risk for venous thromboembolism. As far as we know, however, there are no data on whether this risk is increased even further in patients with factor V Leiden mutation. We can only agree with Dr. Kahn that this area clearly deserves further study. Until data are available, a prudent approach might be to consider alternative methods to HRT for preventing osteoporosis in women with factor V Leiden mutation. On the other hand, one has to balance the possibly enhanced risk for venous thromboembolism in such patients against the evidence that HRT is associated with reduced mortality from multiple causes of death [2]. Furthermore, in women with coronary risk factors, an impressive reduction of mortality associated with HRT (relative risk, 0.51 [95% CI, 0.45 to 0.57]) could well outweigh any increased risk for venous thromboembolism in patients with factor V Leiden mutation [3]. In short, there are no easy answers to Dr. Kahn's question, and physicians must weigh the issues involved for their patients on an individual basis.