Variable platelet response to aspirin in patients with ischemic stroke.
BACKGROUND
A large number of patients experience ischemic stroke despite treatment with aspirin (acetylsalicylic acid, ASA). It is not clear whether all of these patients with ischemic stroke respond normally to ASA or are hyporesponsive as assessed by inhibition of aggregation and thromboxane (TX) synthesis.


METHODS
We studied the effect of ASA given orally and ASA in vitro on collagen- and arachidonic-acid-induced TX formation and aggregation in platelet-rich plasma of 90 patients with ischemic stroke and 25 healthy control subjects.


RESULTS
Thirty-seven patients were being treated with ASA at the time of stroke. Arachidonic-acid-induced TX formation was not depressed below a predefined threshold of 25 ng/ml in 9 patients. Eight of these however exhibited a normal platelet sensitivity to ASA in vitro, suggesting poor compliance or a pharmacokinetic mechanism of nonresponse. The addition of ASA in vitro did not inhibit arachidonic-acid-induced TX formation below the above threshold in 6 patients (11%) in the group of 53 stroke patients not receiving oral ASA, indicating an impaired response to ASA at the platelet level. Moreover, platelets from stroke patients showed an increased collagen-induced, TX-independent aggregation as compared with those of healthy individuals.


CONCLUSIONS
Different categories of ASA nonresponders can be distinguished in patients with ischemic stroke. These include patients with poor bioavailability or noncompliance, an impaired platelet response to ASA in vitro and an increased, TX-independent hyperreactivity to collagen.
Hohlfeld
Thomas
T
Institut fur Pharmakologie und Klinische Pharmakologie, Heinrich-Heine-Universitat, Dusseldorf, Deutschland. hohlfeld@uni-duesseldorf.de
Weber
Artur-Aron
AA
Junghans
Ulrich
U
Schumacher
Marc
M
Boucher
Marc
M
Schrör
Karsten
K
Siebler
Mario
M
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016718:Arachidonic Acid / Q000378:metabolism; D001241:Aspirin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001682:Biological Availability; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002545:Brain Ischemia / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D003094:Collagen / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D020521:Stroke / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D013929:Thromboxane B2 / Q000096:biosynthesis; D016896:Treatment Outcome
D016861:Cyclooxygenase Inhibitors; D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D013929:Thromboxane B2; D003094:Collagen; D001241:Aspirin