Monitoring of aspirin (ASA) pharmacodynamics with the platelet function analyzer PFA-100.
BACKGROUND
Anti-platelet drug therapy is currently performed without monitoring, because the established method of platelet aggregometry is cumbersome. The recently developed platelet function analyzer PFA-100 measures shear stress dependent, collagen epinephrine (CEPI) and collagen adenosine diphosphate (CADP) induced platelet plug formation. As the PFA-100 provides a valuable tool to detect patients with platelet dysfunction more efficiently and cost-effectively than aggregometry, we investigated its potential to monitor the efficacy of aspirin treatment.


METHODS
All healthy volunteers (n = 10) received a fractionated infusion of L-aspirin to establish individual dose-response curves. Further, in a randomized, double-blind, placebo controlled two-way cross over study the same volunteers received either 50 or 100 mg aspirin/day p.o. for a period of 11 days to determine the day-to-day variability CEPI induced closure time (CT) under constant intake of low dose aspirin, and to compare the efficacy of those two doses.


RESULTS
Intra- and intersubject variability of CEPI-CT averaged 9% and 22%, respectively. Seven volunteers exceeded the maximum of CEPI-CT (>300 s) already after infusion of 100 mg L-aspirin. Intake of 100 mg of aspirin elicited a more rapid onset of effect than 50 mg, which was only significant on days 3 and 4 of aspirin intake. The aspirin induced CEPI-CT prolongation correlated positively with basal CEPI-CT values (r = 0.86; p = 0.001) and were strongly dependent on von Willebrand Factor levels (r = -0.9; p = 0.001).


CONCLUSIONS
Thus, the PFA-100 system appears suitable to demonstrate an aspirin-induced platelet effect in a longitudinal study, and may be adequate to monitor a patient's compliance. However, prospective trials have to be conducted to demonstrate whether the EPI-CT achieved under ASA-intake has predictive value for cardiovascular outcome.
Homoncik
M
M
Department of Clinical Pharmacology-TARGET, Vienna University Hospital School of Medicine, Austria.
Jilma
B
B
Hergovich
N
N
Stohlawetz
P
P
Panzer
S
S
Speiser
W
W
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D000941:Antigens / Q000097:blood / Q000187:drug effects; D015703:Antigens, CD / Q000097:blood / Q000235:genetics / Q000494:pharmacology; D001241:Aspirin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001780:Blood Coagulation Tests / Q000295:instrumentation / Q000379:methods* / Q000592:standards; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D003094:Collagen / Q000494:pharmacology; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D005343:Fibrinolytic Agents / Q000493:pharmacokinetics; D005434:Flow Cytometry; D005838:Genotype; D006720:Homozygote; D006801:Humans; D039421:Integrin alpha2; D008137:Longitudinal Studies; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics; D010976:Platelet Count; D017354:Point Mutation; D011446:Prospective Studies; D013929:Thromboxane B2 / Q000097:blood; D013997:Time Factors; D014841:von Willebrand Factor / Q000276:immunology
D000941:Antigens; D015703:Antigens, CD; D005343:Fibrinolytic Agents; D039421:Integrin alpha2; D010975:Platelet Aggregation Inhibitors; D014841:von Willebrand Factor; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; D003094:Collagen; D001241:Aspirin; D004837:Epinephrine