Evidence for episodic platelet activation in acute ischemic stroke.
OBJECTIVE
Enhanced thromboxane biosynthesis has previously been reported in patients with acute ischemic stroke. In this study we examined the time course of thromboxane biosynthesis after the onset of symptoms in 13 patients with acute cerebral infarction.


METHODS
We obtained five to eight consecutive 6-hour urine samples from each of these 13 patients within the first 48 hours after onset of symptoms to study the dynamics of platelet activation in this setting. The urinary excretion of the major enzymatic metabolite of thromboxane B2, 11-dehydro-thromboxane B2, was measured by a previously validated radioimmunoassay. The excretion rate was compared with that of 20 control patients with nonvascular neurological diseases.


RESULTS
Eleven patients (85%) had at least one value exceeding 2 SD of the control mean (251 pmol/mmol creatinine). The proportion of samples with an elevated 11-dehydro-thromboxane B2 level was markedly similar in each of the eight 6-hour collection periods (mean, 52 +/- 8%; range, 40% to 67%). In 4 patients (31%) the excretion rate was elevated in all measurements obtained. In the 11 patients with enhanced thromboxane biosynthesis, no uniform pattern of changes over time in metabolite excretion emerged, with 3 patients having peak values at 0 to 12 hours, 3 at 12 to 24 hours, 3 at 24 to 36 hours, and 2 at 36 to 48 hours. The level and dynamics of 11-dehydro-thromboxane B2 excretion were related neither to the neurological symptoms nor to the type or site of the cerebral ischemia.


CONCLUSIONS
We conclude that episodes of platelet activation occur repeatedly during the first 48 hours after the onset of symptoms of an acute ischemic stroke. Given its apparent dynamic nature, this ongoing process may be amenable to pharmacologic modulation.
van Kooten
F
F
Department of Neurology, University Hospital Rotterdam, The Netherlands.
Ciabattoni
G
G
Patrono
C
C
Schmitz
P I
PI
van Gijn
J
J
Koudstaal
P J
PJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000652:urine; D002545:Brain Ischemia / Q000097:blood* / Q000652:urine; D003404:Creatinine / Q000652:urine; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation; D012307:Risk Factors; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine
D015415:Biomarkers; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D003404:Creatinine