Monitoring of aspirin (ASA) pharmacodynamics with the platelet function analyzer PFA-100

Thromb Haemost. 2000 Feb;83(2):316-21.

Abstract

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).

Conclusion: 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adenosine Diphosphate / pharmacology
  • Adult
  • Antigens / blood
  • Antigens / drug effects
  • Antigens, CD / blood
  • Antigens, CD / genetics
  • Antigens, CD / pharmacology
  • Aspirin / administration & dosage
  • Aspirin / blood
  • Aspirin / pharmacokinetics*
  • Blood Coagulation Tests / instrumentation
  • Blood Coagulation Tests / methods*
  • Blood Coagulation Tests / standards
  • Blood Platelets / drug effects
  • Blood Platelets / physiology*
  • Collagen / pharmacology
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Epinephrine / pharmacology
  • Female
  • Fibrinolytic Agents / pharmacokinetics
  • Flow Cytometry
  • Genotype
  • Homozygote
  • Humans
  • Integrin alpha2
  • Longitudinal Studies
  • Male
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / pharmacokinetics
  • Platelet Count
  • Point Mutation
  • Prospective Studies
  • Thromboxane B2 / blood
  • Time Factors
  • von Willebrand Factor / immunology

Substances

  • Antigens
  • Antigens, CD
  • Fibrinolytic Agents
  • Integrin alpha2
  • Platelet Aggregation Inhibitors
  • von Willebrand Factor
  • Thromboxane B2
  • Adenosine Diphosphate
  • Collagen
  • Aspirin
  • Epinephrine