Aspirin does not affect the flow cytometric detection of fibrinogen binding to, or release of alpha-granules or lysosomes from, human platelets.
1. Aspirin inhibits the conversion of arachidonic acid to thromboxane A2 which reinforces the effects of weak agonists such as ADP in platelets. 2. In this study the effect of aspirin (300 mg/day) on platelet agonist response was measured by whole blood flow cytometry of unfixed blood samples from normal subjects (n = 10), an assay that investigates aggregation-independent changes in the platelet. 3. Fibrinogen binding to unstimulated platelets or to platelets stimulated with ADP or thrombin was unaffected by aspirin. 4. Under the conditions of this assay, platelets undergo a partial degranulation of alpha-granules and lysosomes (evidenced by expression of P-selectin and CD63, respectively) in response to ADP, and full degranulation in response to thrombin. P-selectin expression was paralleled by release of beta-thromboglobulin. None of these events was affected by aspirin. 5. Thromboxane formation was totally prevented by the aspirin treatment, as shown by Born aggregometry in which the platelet aggregatory response to arachidonic acid was abolished and secondary aggregation by ADP was inhibited. 6. The flow cytometric assay can therefore be used to investigate platelets in patients, regardless of aspirin therapy. 7. These findings suggest that platelet fibrinogen binding and the release of platelet alpha-granule and lysosomal contents, in response to stimulation with physiological agonists, can continue in patients despite aspirin therapy. This may help to explain why aspirin is only partially effective in preventing thrombotic events.
Chronos
N A
NA
Department of Chemical Pathology and Human Metabolism, Royal Free Hospital, London, U.K.
Wilson
D J
DJ
Janes
S L
SL
Hutton
R A
RA
Buller
N P
NP
Goodall
A H
AH
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D015703:Antigens, CD / Q000097:blood / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005340:Fibrinogen / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D019007:P-Selectin; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D060149:Tetraspanin 30; D013917:Thrombin / Q000494:pharmacology
D015703:Antigens, CD; C554586:CD63 protein, human; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30; D000244:Adenosine Diphosphate; D005340:Fibrinogen; D013917:Thrombin; D001241:Aspirin