We read with interest the review by Thomas and Roberts [1], which mainly discussed genetic defects in coagulation that cause hypercoagulability and thrombosis. We question the authors' summary statement: "No evidence indicates that the measurement of endogenous anticoagulant pathways has a useful role to play in assessing patients at risk for arterial thrombosis." This generalization is probably relevant to arteriosclerotic thrombosis, but it does not apply to arterial thrombosis in patients suspected of having the antiphospholipid syndrome. As correctly stated by the authors themselves earlier in their review, "... persons with hypercoagulable states include patients with the antiphospholipid syndrome who can develop both arterial and venous thrombosis."

Unexplained elevation of the activated partial thromboplastin time is often the first clue to the presence of the antiphospholipid syndrome in patients with arterial (or venous) thrombosis, but the dilute Russel viper venom time and anticardiolipin antibody measurements are more sensitive tests for this syndrome [2, 3]. The syndrome may be secondary to a connective tissue disease, usually systemic lupus erythematosus, or it may be primary, occurring without other autoimmune diseases. Recognition of the syndrome is particularly important because recent retrospective analyses have suggested that patients who have the condition may require long-term warfarin therapy to maintain the prothrombin time (international normalized ratio) at relatively high levels and thus prevent recurrences of thrombosis [4]. However, as is also true for thromboses caused by genetic deficiencies affecting antithrombin III, protein C, and protein S, prospective clinical trials are needed to establish definitive recommendations for treatment of thromboses in the antiphospholipid syndrome [5]. Although the origin and mechanisms of action of antiphospholipid antibodies are not fully understood, both genetic and environmental factors may be important [5].