Ginsburg and colleagues [1] are to be commended on their long-term study showing the enhanced risk posed by anticardiolipin antibodies for deep venous thrombosis and pulmonary embolism in healthy adult men. Although their mechanism of action is unknown, the anticardiolipin antibodies lead to a hypercoagulable state not only in systemic lupus erythematosus but also in the absence of disease.

The investigators found that low-dose aspirin was not protective and that thrombosis recurred despite therapeutic anticoagulation. A recent study [2] evaluating thrombosis in patients with antiphospholipid antibodies found that recurrence rates during "no treatment"; aspirin; and low-, intermediate-, and high-intensity warfarin therapy (international normalized ratios [INRs] < 1.9; 2.0 to 2.9; and > 3.0, respectively) were 0.19, 0.32, 0.57, 0.07 (P = 0.12), and 0.00 (P < 0.001) per patient-year, respectively. Although this study found no benefit with aspirin, it did find significant to complete protection when intermediate- to high-intensity warfarin was used as a prophylactic agent [2]. When a decision to treat is made (for example, when high-titer anticardiolipin antibodies are associated with episodes of thrombosis), an INR of 3.0 should be set and reduced if a bleeding risk is perceived. Indefinite anticoagulation may prove useful in reliable patients with recurrent thrombotic episodes.

Another issue of interest is the apparent absence of thrombotic risk in patients who develop anticardiolipin antibodies in the presence of the human immunodeficiency virus (HIV) [3], other infectious processes [4], or chlorpromazine therapy [5]. This suggests that these antibodies are heterogeneous in structure or function, or both, and that different antibodies recognize and react with distinct epitopes, depending on the structural array of phospholipids. Further analysis of anticardiolipin antibodies may provide clues both to the pathogenesis of the coagulation abnormalities and to better mechanisms of prevention.