A comparison of the effects of aspirin on bleeding time measured using the Simplate method and closure time measured using the PFA-100, in healthy volunteers.
OBJECTIVE
The aim of this study was to compare the effects of aspirin on platelet function as measured by the 'classical' template bleeding time with a new ex vivo method measuring closure times using the PFA-100 machine. Platelet aggregation in response to arachidonic acid was also measured ex vivo.


METHODS
The trial was a randomized, double-blind, placebo-controlled crossover design, with each volunteer taking 750 mg aspirin (BP) or placebo, three times a day for 5 days, with an 18 day wash-out period between treatments. Bleeding times and closure times were measured before the first dose on the first day and 0.5 h after the last dose on the fifth day of each treatment period. They were also measured 2 weeks after the last day of the trial.


RESULTS
Baseline bleeding times (pre-placebo) were 415 s using the Simplate, whilst baseline closure times were 115 s using the PFA-100. Aspirin treatment caused an increase of both the template bleeding time (61%) and the closure time of the PFA-100 (79%) when compared with the effects of placebo. The platelet aggregatory response to arachidonic acid was completely inhibited following aspirin treatment and was unaffected following placebo. Two weeks after the end of the trial, all values had returned to pre-treatment levels. The template bleeding time was unaltered in 1 of the 12 volunteers during aspirin treatment and was significantly prolonged in 3 of the 12 volunteers during placebo treatment. The PFA-100 closure time was unaltered in 1 of the 12 volunteers during aspirin treatment and was prolonged in 1 subject during placebo treatment.


CONCLUSIONS
The change in closure time using the PFA-100 is as sensitive and reproducible to the effects of aspirin on platelet function as is the template bleeding time test. However, the PFA-100 produced less variable effects with fewer false positive results.
Marshall
P W
PW
Clinical Pharmacology Unit, Zeneca Pharmaceuticals, Alderley Park, Macclesfield, UK.
Williams
A J
AJ
Dixon
R M
RM
Growcott
J W
JW
Warburton
S
S
Armstrong
J
J
Moores
J
J
D000328:Adult; D000368:Aged; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors; D001241:Aspirin / Q000494:pharmacology*; D001760:Bleeding Time; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D012016:Reference Values
D010919:Placebos; D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D001241:Aspirin