Impact of treatment with acetylsalicylic acid on the proaggregatory effects of adrenaline in vitro in patients with stable angina pectoris: influence of the anticoagulant.
1. The impact of oral acetylsalicylic acid treatment on the enhancing effect of adrenaline on platelet aggregation in vitro was investigated in patients with stable angina pectoris. In addition, the influence of different anticoagulants (i.e. hirudin and citrate) on platelet aggregation in vitro was compared. 2. Eighty-four patients with stable angina pectoris were studied. Sixteen patients were on acetylsalicylic acid treatment (150-250 mg daily), whereas 68 patients were free from acetylsalicylic acid. Platelet-rich-plasma was prepared from citrate- or hirudin-anticoagulated blood. The EC50 (i.e. the concentration of agonist required to produce half-maximal aggregation) for the ADP-induced extent of aggregation was determined. Thereafter the enhancing effect of adrenaline (10 and 50 nmol/l) on ADP-induced aggregation (at EC50) was investigated. 3. In the patients with angina, acetylsalicylic acid caused the expected effects on ADP-induced platelet responses. Adrenaline significantly enhanced both the extent of aggregation and the initial rate of aggregation (primary aggregation), irrespective of the anticoagulant used. In acetylsalicylic acid-treated patients (citrated platelet-rich plasma) the extent of aggregation was partly inhibited, but no significant effect on the rate of aggregation could be observed. 4. A comparative substudy of the anticoagulants in healthy subjects (n = 8) showed that both the aggregating effect of ADP per se and the enhancing effect of adrenaline on ADP-induced aggregation (at EC50) were less influenced by acetylsalicylic acid when evaluated in hirudinized platelet-rich plasma (i.e. with physiological levels of extracellular calcium) as compared with citrated platelet-rich plasma.(ABSTRACT TRUNCATED AT 250 WORDS)
Wallén
N H
NH
Department of Clinical Pharmacology, Karolinska Hospital, Stockholm, Sweden.
Held
C
C
Rehnqvist
N
N
Hjemdahl
P
P
D000244:Adenosine Diphosphate / Q000502:physiology; D000787:Angina Pectoris / Q000188:drug therapy* / Q000503:physiopathology; D001241:Aspirin / Q000627:therapeutic use*; D002951:Citrates / Q000627:therapeutic use; D004357:Drug Synergism; D004837:Epinephrine / Q000502:physiology*; D005260:Female; D024764:Hirudin Therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010976:Platelet Count
D002951:Citrates; D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D001241:Aspirin; D004837:Epinephrine