Aspirin Resistance. Clinical Questions. How do we define aspirin resistance? Is this concept clinically relevant? Why aren’t we testing for it?. Aspirin Basics. Antithrombotic Trialists’ Collaboration
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Wide acceptance that platelet activity plays a major role in atherothrombosis
Adhesion: Platelet membrane receptors bind to endothelium and subendothelium at sites of damage
Activation: Transmembrane signaling increases surface receptors, granule release, and exposure of membrane phospholipid
Aggregation: Procoagulant surface of the membrane serves as basis for coagulation cascade, amplification of platelet response, and production of fibrin.
Aspirin inhibits platelet cyclooxygenase (COX)-1 thereby preventing formation of thromboxane A2 (TxA2), a potent aggregating and vasocontrictor agent.
want to take it.
Should not be used
Red Blood Cells
Light Transmission Aggregometry
Whole Blood Aggegrometry
Reports: closure time (<193s)
No association with vascular events
Must test within 4hrs of blood collection
Dependent on hematocrit and vWF
Anticoagulated blood is aspirated through a capillary and a 150μm aperture coated with collagen and ADP or epinephrine. Measures time needed until blood flow interruption is recorded.
Urinary 11-dehydrothromboxane B2
Turbidometric-based optical system that measures agglutination of fibrinogen-coated beads by platelets stimulated in citrated whole blood.
Reports: Aspirin Reaction Units
Clinical association with vascular events
Major limitation relates to the diagnostic criteria set for definition of aspirin resistance
Compared to optical aggregometry with epinephrine after one 325mg dose of aspirin
Platelet bound P-selectin
Soluble plasma P-selectin
Flow cytometry allows for the evaluation of platelet reactivity and in vivo activation. However, these techniques require sophisticated and expensive instruments.
A comparison of six major platelet function tests to determine the prevalence of aspirin resistance in patients with stable coronary artery disease.
Marie Lordkipanidze, Chantal Pharand, Erick Shampaert, Jacques Turgeon, Donald Palisaitis, and Jean G. Diodati.
European Heart Journal in June 2007
0 - 0.2Slight
0.2 - 0.4Fair
0.4 - 0.6Moderate
0.6 - 0.8Substantial
“We believe the non-standardized use of these assays and the absence of a formal definition explains much of the disparity reported in the literature in regards to the prevalance of aspirin resistance.”
may occupy nearby catalytic site
Block access of aspirin to serine 529
prostaglandin F2-like compounds
Produced from arachidonic acid in a non-COX process
Amplify platelet response
No laboratory testing to monitor for clinical adherence
“Other than in research trials, it is not currently appropriate to test for aspirin ‘resistance’ in patients or change therapy based on these tests.”