High-dose aspirin inhibits shear-induced platelet reaction involving thrombin generation.
BACKGROUND
A unifying concept of explaining all pharmacological actions of aspirin by the irreversible blockage of the enzyme cyclooxygenase and therefore the inhibition of prostaglandin biosynthesis has left many unanswered questions.


RESULTS
Two hundred ninety-four patients taking 75 mg/day aspirin were tested 3 months after coronary artery bypass surgery. Platelet thromboxane formation (whole blood aggregation to arachidonate) was completely prevented in 80% of patients. Compared with matched healthy controls (n = 95), a significant platelet hyperreactivity was observed in patients (p less than 0.0001 versus less than 0.002). Ninety patients were advised to increase their daily dose of aspirin from 75 mg to 300 mg. Platelet reactivity retested 1 month after increasing the dose has significantly decreased (p = 0.0008; less than 0.0001), whereas it remained unchanged in those patients (n = 84) who continued with the same dose regimens. In normal subjects, ingestion of a single 600-mg aspirin significantly inhibited shear-induced platelet reaction.


CONCLUSIONS
It is concluded that aspirin does affect the platelet response to shear forces, but this requires higher dosage (greater than 300 mg/day), suggesting a mechanism probably different from that of interference with thromboxane formation.
Ratnatunga
C P
CP
Department of Cardiothroracic Surgery, St. Bartholomew's Hospital Medical School, London.
Edmondson
S F
SF
Rees
G M
GM
Kovacs
I B
IB
D001241:Aspirin / Q000008:administration & dosage* / Q000627:therapeutic use; D001026:Coronary Artery Bypass; D004305:Dose-Response Relationship, Drug; D005260:Female; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D011183:Postoperative Complications / Q000517:prevention & control*; D013917:Thrombin / Q000096:biosynthesis*; D013927:Thrombosis / Q000517:prevention & control*; D013931:Thromboxanes / Q000096:biosynthesis
D010975:Platelet Aggregation Inhibitors; D013931:Thromboxanes; D013917:Thrombin; D001241:Aspirin