home   author    contact   web site dedication



Specific guide to this web site for:

 1.  Medical School
      in Statistics

 2.  Medical Students

 3.  Science media writers

 4.  High School & College
     Statistic Teachers


1. Harvard led MI study

2. JACC study 

   (J. of Amer. Coll.

3. NEJM cath study

4. Amer. J. of Cardio.
    review of literature


Oat bran study

Pregnancy & Alcohol

Are Geminis really
9. Columbia 'Miracle' Study  

Additional Topics:


Limitations of Meta-Analyses

Large Randomized Clinical Trials

Tale of Two Large

Advocate meta-analyses

Network meta-analyses





Low-Dose Aspirin  Inhibits Arachidonic Acid-Precipitated Platelet Aggregation, but not Collagen-Precipitated Platelet Aggregation.      
Roehm E.,  Am J Cardio 1995; 76:637-638

The article by Dabaghi et al1documents the effect of varying doses of aspirin on platelet aggregation in response to arachidonic acid. Whether small, single doses of aspirin are effective in adequately inhibiting platelet aggregation is an important clinical consideration. When aspirin is given as a single, acute dose before emergency coronary angioplasty, it is important to give a dose that is adequate to provide the full effect of aspirin inhibition on platelet aggregation. A prior randomized study2 has documented a fourfold reduction in myocardial infarction with high dose aspirin (330 mg administered 3 times daily) in patients undergoing routine percutaneous transluminal coronary angioplasty.

Dabaghi et al1 document that platelet aggregation is fully inhibited by a single dose of aspirin when arachidonic acid is used as the stimulating agent, regardless of whether 81, 162, or 324 mg is given. They also document that low doses of aspirin effectively inhibit thromboxane B2 metabolism. These results are consistent with the results of Kuster and Frolich,3 who found that a 50 mg dose of aspirin entirely blocked arachidonic acid-induced platelet aggregation at 24 hours in 5 of 6 patients, and that increasing doses of aspirin did not result in further inhibition of platelet aggregation with arachidonic acid as the stimulating agent. (Dabaghi et al1 incorrectly quote the Kuster and Frolich study as showing that 2, 3, and 4 days were required to achieve the full antiplatelet effects of aspirin with daily dosages of 100, 50, and 25 mg when arachidonic acid was used as the precipitating agent. In fact, the data that Dabaghi et al1 are referring to concerns adenosine diphosphate induced aggregation.) The Kuster and Frolich3 study agrees with the study of Dabaghi et al1 with regard to arachidonic acid. Similarly, Kuster and Frolich3 also reported inhibition of thromboxane B2 with low levels of aspirin of a similar magnitude as the Dabaghi et al1 study.

However, when viewed in the context of previously published reports, Dabaghi et al1 do not show that an 80 mg dose of aspirin gives the full potential effect of aspirin inhibition on platelet aggregation when other agents are used to induce platelet aggregation. Collagen is a potent stimulus of platelet aggregation. Kuster and Frolich3 showed that 24 hours after the ingestion of 100 mg of aspirin, less than half of aspirin's inhibitory effect on platelet aggregation is achieved when compared with a 500 mg single, acute dose of aspirin.

The only other investigators looking at the acute effects of low-dose aspirin with collagen stimulation were Paccioretti and Block.4 However, this study did not have adequate numbers for any definitive evaluation. The dose of 81 mg was studied in 7 subjects, and 162 mg was studied in 3 subjects when a collagen stimulus was used. Four of the total 10 tests, using either 81 or 162 mg of aspirin, showed no inhibition of platelet aggregation using a collagen stimulus in the study by Paccioretti and Block. This is equal to a total of 4 of 4 tests showing platelet aggregation inhibition when >200 mg of aspirin was given. These meager data are not definitive in any sense. It certainly does not support the contention by Paccioretti and Block that platelet aggregation is inhibited irrespective of the dose with a collagen stimulus.

There is an additional study by Mehta et al5 on the acute effects of a single dose of aspirin, which compares the effect of different doses of aspirin on platelet aggregation; this was incorrectly represented in the study by Dabaghi et al.1    Mehta et al showed that 40 mg of aspirin produced a modest decrease in platelet aggregation with epinephrine stimulation at 1 hour. Mehta et al state that "the magnitude of the inhibition of platelet aggregation by 325 mg and 650 mg doses was similar." However, they did not say that the 40 mg dosage of aspirin had the same effect on platelet aggregation as higher doses of aspirin. Their data suggest a difference in the extent of platelet aggregation with an epinephrine stimulus when a 40 mg dose is compared with either a 325 or 650 mg aspirin dose.

Thus, a review of the study by Dabaghi et al1 and of previous studies gives the following information: Thromboxane metabolism is inhibited by a single, low dose of aspirin. Low dose aspirin in the 80 to 100 mg range gives the full inhibitory effect on platelet aggregation possible when arachidonic acid is used as a platelet aggregation stimulus. Kuster and Frolich,3 in an outstanding study in which the effect of a collagen stimulus on platelet aggregation was evaluated, showed that a greater degree of inhibition of platelet aggregation was achieved with a single 500 mg dose of aspirin compared with a single 100 mg dose of aspirin.

As noted by Dabaghi et al1, the clinical setting provoking interest in the acute effects of a single dose of aspirin results from patients with an acute ischemic syndrome undergoing either acute angioplasty or receiving thrombolytic therapy. Because there is a strong stimulus to thrombosis in these clinical settings, it is important to consider more intense potentiators of platelet aggregation such as collagen and epine­phrine, in addition to the more easily inhibited arachidonic acid precipitated platelet aggregation. A ruptured plaque has the potential for adenosine phosphate, collagen, and epinephrine-induced platelet aggregation. Hence, though aspirin can achieve only partial inhibition of collagen-precipitated platelet aggregation, it is clinically relevant that a single low dose of aspirin achieves less inhibition of platelet aggregation than a higher dose of aspirin. The therapeutic goal of the cardiologist caring for a patient with a disrupted atherosclerotic plaque in the setting of an acute ischemic syndrome, is to achieve the fullest platelet inhibition possible with aspirin (and not to achieve selective inhibition of arachidonic acid induced platelet aggregation).

1. Dabaghi SF, Kamat SG, Payne J, Marks G, Roberts R, Schafer Al, Kleiman NS . Effects of low-dose aspirin on in vitro platelet aggregation in the early minutes after ingestion in normal subjects. Am J Cardiol 1994;74:720-723.
   2. Schwartz L, Bourassa MG, Lesperance J, Aldridge HE, Kazim F, Salvatori VA, Henderson M, Bonan R, David PR. Aspirin and dipyridamole in the prevention of restenosis after percutaneous transluminal coronary angioplasty. N Engl J Med 1988;318:1714-1719. 
   3. Kuster Ll, Frolich JC. Platelet aggregation and thromboxane release induced by arachidonic acid, collagen, ADP, and platelet-activating factor following low dose acetylsalicylic acid in man. Prostaglandins 1986;32:415-423.
   4. Paccioretti MI, Block LH. Effects of aspirin on platelet aggregation as a function of dosage and time. Clin Pharmacol 1980;27:803-809.
   5. Mehta JL, Mehta P, Lopez L, Ostroski N, Aquila E. Platelet function and biosynthesis of prostacyclin and thromboxane A2 in whole blood after aspirin administration in human subjects. J Am Coll Cardiol 1984;4:806-811.