Abstract
Dear Sir Evers et al. (1) have provided evidence for a distinctive pro-aggregatory effect of ergotamine on platelets, using reasonably standard techniques. The finding was validated internally because the response to acetylsalicylic acid (ASA) was in the opposite direction. The finding was also shown to be specific because the effect did not extend to red cell aggregation, nor was it shared with the specific 5HT1B/1D agonists (‘triptans’) that were tested.
The study used a randomized-order, five-treatment, five-period cross-over design that was controlled for diurnal variability. ‘Wash-out’ periods of at least 2 days elapsed between treatments. One question is whether the wash-out periods after ASA treatment were long enough. The effect of a single dose of ASA can persist for 4–7 days and is dependent upon platelet regeneration (2). Thus, pro-aggregatory effects of treatments following the ASA dose could have been masked if administered after only 2 days. Perhaps the database could be checked to confirm the absence of this confounder, or if it is suspected in some of the subjects, then these could be analysed and compared separately.