Getting personal with B19 parvovirus.

ticulated platelets in ET draws attention to another major mechanism—namely, COX-1 activity in newly released platelets not inhibited by the once-daily low-dose aspirin. This is because of the relatively short half-life of aspirin in plasma. In states with rapid platelet generation, one daily dose of low-dose aspirin may be insufficient because of the immense capacity of bone marrow to accelerate platelet production (even 10-fold of basal rate). Dragani et al go on to show that addition of aspirin (50 M) in vitro abolishes thromboxane production in patients already receiving aspirin, consistent with an effect on COX-1 not acetylated by the single dose of aspirin administered 24 hours earlier. In a study of 60 healthy subjects, Guthikonda et al showed increased thromboxane production in healthy subjects with higher reticulated platelets, while ex vivo addition of COX-1 or COX-2 inhibitor attenuated the thromboxane production; the effect was greater with a COX-1 inhibitor.4 They also showed decreased inhibitory effects of aspirin and clopidogrel in patients with coronary artery disease with higher numbers of reticulated platelets.3 The findings of Dragani et al raise important issues regarding optimum regimen to suppress thromboxane production. What is clear is that low-dose aspirin administered once daily is inadequate to fully suppress thromboxane production in ET and likely in other disorders with increased platelet production. The addition of a COX-2 inhibitor may not be the answer, because of the persistent thromboxane production following a 7-day dual drug therapy with a COX-2 antagonist and aspirin. The short plasma half-life of aspirin argues against added benefits of higher doses at the same dosing interval. The studies of Dragani et al advance strong support for a dosing interval shorter than the traditional oncedaily aspirin—and this remains to be tested with clinical endpoints of thrombotic events. Conflict-of-interest disclosure: The author declares no competing financial interests. ■