Does Acetaminophen Interfere with the VerifyNow Asprin Test?

Does Acetaminophen Interfere with the VerifyNow Asprin Test?
Feb 19, 2015 6:07pm

From Thomas Gage, MD, Lahey Medical Center. Greetings, I have a patient with a VerifyNow Aspirin test showing some inhibition. The patient had exposure to clopidogrel and acetaminophen, but not aspirin.  So now I'm trying to figure out if acetaminophen can interfere with this test, and I'm getting conflicting opinions. Because the VerifyNow Aspirin test is measuring the aspirin pathway, it relies on COX-1 function, and therefore it seems logical that acetaminophen (a weak inhibitor of both COX-1 and COX-2 ) could potentially interfere. I asked a rep from VerifyNow about this issue, and they say “Tylenol is not an interfering substance for the ARU assay and will not affect  results.” So they say no , but I've asked for follow up, because I'd like to see some data or experimental evidence to back up that statement.  Also, in the VerifyNow Aspirin test package insert, there is no mention of Tylenol/acetaminophen within the section “Interference Studies.” If you have some experience in resolving this issue, then I would love to get your input.


Hello, Dr. Gage. and thank you for your question. A 2014 report, Martini AK, Rodriguez CM, Cap AP, Martini WZ, Dubick MA. Acetaminophen and meloxicam inhibit platelet aggregation and coagulation in blood samples from humans.Blood Coagul Fibrinolysis. 2014;25:831–7 indicates that in vitro acetaminophen addition suppresses platelet aggregation in response to collagen and arachidonic acid using a Chromo-Log 700 whole blood lumiaggregometer. In contrast, Galliard-Grigioni KS, Reinhart WH A randomized, controlled study on the influence of acetaminophen, diclofenac, or naproxen on aspirin-induced inhibition of platelet aggregation.Eur J Pharmacol. 2009;609:96–9, report that acetaminophen has no effect on aspirin suppression of platelets as measured using a Siemens PFA-100. The second article may be interpreted to imply acetaminophen does not occupy COX-1 or perhaps occupies it only briefly. Thirdly, Trettin A, Böhmer A, Suchy MT, et al. Effects of paracetamol on NOS, COX , and CYP activity and on oxidative stress in healthy male subjects, rat hepatocytes, and recombinant NOS. Oxid Med Cell Longev. 2014:212576 reports that acetaminophen suppresses prostacyclin production but not thromboxane. Prostacyclin arises primarily from endothelial cells and not platelets, leading to the conclusion that acetaminophen is having no effect on platelets. None of these address acetaminophen and the VerifyNow Aspirin test mechanism, but I speculate that, depending on dosage and timing, the drug may have a transient suppressive effect. Thinking broadly, has there ever been a time when it seemed that the clopidogrel could be affecting results using the aspirin cartridge?

I'll draw attention to this post to colleagues with VerifyNow experience, and also to Accumetrics for further discussion.

 

 

 

2 Comments

From Thomas Gage, MD, Lahey Medical Center. Greetings, I have a patient with a VerifyNow Aspirin test showing some inhibition. The patient had exposure to clopidogrel and acetaminophen, but not aspirin.  So now I'm trying to figure out if acetaminophen can interfere with this test, and I'm getting conflicting opinions. Because the VerifyNow Aspirin test is measuring the aspirin pathway, it relies on COX-1 function, and therefore it seems logical that acetaminophen (a weak inhibitor of both COX-1 and COX-2 ) could potentially interfere. I asked a rep from VerifyNow about this issue, and they say “Tylenol is not an interfering substance for the ARU assay and will not affect  results.” So they say no , but I've asked for follow up, because I'd like to see some data or experimental evidence to back up that statement.  Also, in the VerifyNow Aspirin test package insert, there is no mention of Tylenol/acetaminophen within the section “Interference Studies.” If you have some experience in resolving this issue, then I would love to get your input.


Hello, Dr. Gage. and thank you for your question. A 2014 report, Martini AK, Rodriguez CM, Cap AP, Martini WZ, Dubick MA. Acetaminophen and meloxicam inhibit platelet aggregation and coagulation in blood samples from humans.Blood Coagul Fibrinolysis. 2014;25:831–7 indicates that in vitro acetaminophen addition suppresses platelet aggregation in response to collagen and arachidonic acid using a Chromo-Log 700 whole blood lumiaggregometer. In contrast, Galliard-Grigioni KS, Reinhart WH A randomized, controlled study on the influence of acetaminophen, diclofenac, or naproxen on aspirin-induced inhibition of platelet aggregation.Eur J Pharmacol. 2009;609:96–9, report that acetaminophen has no effect on aspirin suppression of platelets as measured using a Siemens PFA-100. The second article may be interpreted to imply acetaminophen does not occupy COX-1 or perhaps occupies it only briefly. Thirdly, Trettin A, Böhmer A, Suchy MT, et al. Effects of paracetamol on NOS, COX , and CYP activity and on oxidative stress in healthy male subjects, rat hepatocytes, and recombinant NOS. Oxid Med Cell Longev. 2014:212576 reports that acetaminophen suppresses prostacyclin production but not thromboxane. Prostacyclin arises primarily from endothelial cells and not platelets, leading to the conclusion that acetaminophen is having no effect on platelets. None of these address acetaminophen and the VerifyNow Aspirin test mechanism, but I speculate that, depending on dosage and timing, the drug may have a transient suppressive effect. Thinking broadly, has there ever been a time when it seemed that the clopidogrel could be affecting results using the aspirin cartridge?

I'll draw attention to this post to colleagues with VerifyNow experience, and also to Accumetrics for further discussion.

 

 

 

By Dr. Ali Sadeghi-khomami
Feb 19, 2015 9:58pm
From Ali Sadeghi-Khomami, PhD, Precision BioLogic Inc. Hi, clopidogrel inhibits platelet activation even if it is caused by arachidonic acid, the platelet activator (agonist) used in VerifyNow Aspirin. The following information is from the VerifyNow aspirin insert: "Intended use: This test is not for use in patients receiving non-aspirin anti-platelet agents." Also, "Test limitations: Patients receiving the following anti-platelet agents may not be tested with the VerifyNow Aspirin Test, based on documented interference testing results: clopidogrel."
By George Fritsma
Feb 23, 2015 4:49pm
From Dave McGlasson via George's email: I wonder if the patient had been taking some kind of supplement in addition to the acetaminophen? I would like to cite an article I was a co-author on concerning the Effects of glucosamine and celadrin on platelet function. We saw that P2Y1 receptors and effects of platelet aggregation were found with ADP, collagen and arachidonic acid respectively in normal subjects. We did not however see significant differences with the Accumetrics assay for P2Y12 in any subjects. We did not test for the ASA cartridge however on the Accumetrics at that time. See Lin PC, Jones SO and McGlasson DL. Effects of glucosamine and celadrin on platelet function. Clin Lab Sci 2010; 23:32–6. The caretakers should look for some other interfering substance I think.

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