LabMed

Platelet Function Disorder Produced by Aspirin

At a Glance

Aspirin resistance is defined as residual platelet activity despite aspirin therapy. A patient may have aspirin resistance if he or she develops a stroke or myocardial infarction while on aspirin therapy as a result of a prior episode of unstable angina/acute coronary syndrome or acute myocardial infarction.

Aspirin is rapidly bound to cyclooxygenase. Aspirin permanently and irreversibly acetylates the enzyme Cyclooxygenase-1, which prevents conversion of arachidonic acid to thromboxane A2, resulting in decreased platelet function.

When aspirin is taken orally, it is rapidly absorbed from the stomach and proximal small intestine. The gastric mucosa is permeable to the nonionized form of aspirin, which passes through the stomach by a passive diffusion process. Once absorbed, it is metabolized to acetic acid and salicylate by esterases in tissue and blood. The free salicylate is then excreted unchanged or converted to other water-soluble compounds that are then excreted by the kidney.

The excretion of salicylate occurs with first-order kinetics with a half-life of 2-19 hours, depending on the dose of aspirin administered.

Treatment strategies for patients with aspirin resistance include switching to another drug, increasing aspirin dose, and adding another drug, such as Clopidogrel, that works to inhibit platelets through a different mechanism.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Inhibition of platelet function by aspirin is routinely monitored by platelet function studies. Three modalities are commonly used for laboratory evaluation of platelet inhibition by aspirin:

  • Platelet aggregation studies: Optical platelet aggregation studies are performed with platelet-rich plasma (PRP) prepared from a citrated whole blood sample. An agonist, such as adenosine diphosphate (ADP) or arachidonic acid, is added to the PRP, and the change in optical density is measured as platelet aggregation.

  • Verify Now ASA: Platelet aggregation detection is performed in a whole blood, citrate anti-coagulated specimen. The aspirin-induced inhibition of platelet function is based on the arachidonic acid-initiated agglutination of platelets with fibrinogen-coated beads by an optical turbidimetry method.

  • Platelet function analyzer (PFA-100): This is an analyzer that aspirates a whole blood sample through a capillary tube at high shear, through an aperture in a membrane coated with either collagen-epinephrine or collagen ADP platelet agonists. The time for a platelet plug to occlude the aperture is inversely related to platelet activity.

Although several tests have been used to identify aspirin resistance, there is little consensus regarding which test to use and there is no standardized laboratory definition of aspirin resistance. (Table 1)

Table 1.

Test Results Indicative of the Disorder
Platelet aggregation studies Residual platelet reactivity with arachidonic acid and ADP ADP >70% plus AA > 20%
Verify Now ASA Aspirin response units (ARU) (ARU ) > 550
Platelet function analyzer (PFA-100) Closure Time with Collagen-Epinephrine (COL/EPI) and Collagen-ADP (COL/AD) cartridges Normal closure time with COL/EPI and COL/ADP (laboratory-specific reference ranges)

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications - OTC drugs or Herbals - that might affect the lab results?

Many medications can inhibit platelet function. If the patient is taking another anti-platelet medication, other than aspirin, the inhibition of platelet aggregation observed may not be attributable to aspirin alone. For example, if a patient is also receiving a glycoprotein IIb/IIIa antagonist, such as abciximab or tirofiban, the ADP and arachidonic acid aggregation may be markedly decreased (<10%). Aspirin response cannot be evaluated in this setting.

What Lab Results Are Absolutely Confirmatory?

Due to the varying laboratory definitions of aspirin resistance, there is no one confirmatory test for this disorder.

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