Usefulness of whole blood aggregometry and its comparison with thromboxane generation assay in monitoring acetylsalicylic acid effectiveness--a multiparametric study in rats.
BACKGROUND
There is a need for consensus concerning universal methodological criteria for detection of suboptimal response to acetylsalicylic acid (ASA) therapy. Therefore, animal models to test for ASA effectiveness remain of interest. Our objective was to verify the usefulness of multiparametric whole-blood impedance aggregometry and thromboxane A(2) generation, which are the most popular techniques used for monitoring of ASA treatment effectiveness.


METHODS
Using multiparametric analysis of whole-blood impedance aggregometry, we examined which parameters of platelet aggregation or disaggregation allow for the best discrimination between ASA-treated (4 or 40 mg/kg for 60 days) and non-treated male rats. The effectiveness of ASA-mediated inhibition of platelet cyclooxygenase-1 was verified by determination of plasma thromboxane B(2) and urine 11-dehydro-thromboxane B(2), accepted as reference assays for monitoring of ASA-mediated platelet cyclooxygenase-1 inhibition.


RESULTS
Two of the platelet agonists used, collagen (1 mg/L) and arachidonic acid (0.5 mmol/L), allowed discrimination of control and ASA-treated animals, whereas adenosine diphosphate (5 micromol/L) was not effective. It is noteworthy that only ASA-mediated changes in duration of the rising phase for platelet aggregation and the area under the curve for collagen-induced aggregation allowed significant discrimination between low and high ASA dose and remained correlated with the reference parameter, plasma thromboxane B(2).


CONCLUSIONS
Analysis of aggregation curves, routinely based only on the amplitude and rate of platelet aggregation, may not be enough discriminative to distinguish between varying ASA doses and treatment schedules.
Nocun
Marek
M
Department of Hemostasis and Hemostatic Disorders, Medical University of Lodz, University Hospital No. 2, Lodz, Poland.
Golanski
Jacek
J
Lapshina
Elena
E
Zavodnik
Leu
L
Dobaczewski
Marcin
M
Kazmierczak
Piotr
P
Markuszewski
Leszek
L
Zavodnik
Ilya
I
Watala
Cezary
C
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D015415:Biomarkers; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002449:Cell Aggregation / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology; D008297:Male; D009391:Nephelometry and Turbidimetry; D010974:Platelet Aggregation / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013931:Thromboxanes / Q000096:biosynthesis*; D013997:Time Factors
D015415:Biomarkers; D013931:Thromboxanes; D000244:Adenosine Diphosphate; D003094:Collagen; D001241:Aspirin