Dose-andtime-dependent antiplateleteffects of aspirin Platelets andBlood Cells

Abstract

Summary Aspirin is widely used,but dosagesindifferentclinical situations and the possible importance of "aspirin resistance" aredebated. We performeda no penc ross-over study comparing no treatment (baseline)with three aspirindosage regimens -37.5 mg/ dayfor 10 days, 320mg/dayfor 7days, and, finally, asingle 640 mg dose (cumulativedose 960mg) -in15healthymale volunteers. Platelet aggregability was assessedinwholeblood(WB)and plateletrich plasma (PRP).The urinaryexcretions of stable thromboxane (TxM)and prostacyclin (PGI-M)metabolites, and bleeding timewerealsomeasured.Platelet COXinhibitionwas nearly complete already at 37.5 mg aspirin daily, as evidencedby>98 % suppression of serumthromboxane B 2 and almost abolishedarachidonicacid (AA) induced aggregation in PRP2-6 hafter dosing. Bleeding timew as similarlyp rolonged by all dosageso fa s- Keywords Platelet function, thromboxane,prostacyclin,acetylsalicylicacid, dosage pirin. Once daily dosing wasa ssociated with considerabler ecovery of AA inducedplateletaggregation inWB after 24 hours, even after 960 mg aspirin.Collageninduced aggregation in WB with normal extracellular calciumlevels(hirudin anticoagulated) wasi nhibited <40%a ta ll dosages. TxMe xcretion was incompletely suppressed, andi ncreased< 24 hoursa fter the cumulative960 mg dose.Aspirin treatment reducedPGI-M already at thelowestdosage (by ≈ 25%), but PGI-M excretion and platelet aggregability were not correlated. Antiplateleteffects of aspirin arelimited in WB with normalcalcium levels.Since recovery of COX-dependent plateletaggregation occurred within 24 hours, oncedailydosing of aspirinmight be insufficientinpatientswith increasedplateletturnover