A Thrombelastograph whole blood assay for clinical monitoring of NSAID-insensitive transcellular platelet activation by arachidonic acid

Roger C. Carroll, Robert Craft, Jack Chavez, Carolyn C. Snider, Stuart Bresee, Eli Cohen

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Optical platelet aggregation (OPA) with platelet-rich plasma (PRP) was compared with a Thrombelastograph (TEG) whole blood assay for monitoring arachidonic acid (AA)-induced platelet activation. Assays were performed on 47 interventional cardiology and 24 general surgery patients receiving aspirin therapy for cardiovascular disease, as well as 48 volunteers asked to take nonsteroidal anti-inflammatory drugs (NSAIDs) or 12 volunteers on chronic NSAID therapy unrelated to diagnosed cardiovascular disease. Whole blood TEG monitoring of NSAID inhibition detected NSAID-insensitive AA activation of platelets in a significantly higher number of cardiology (23%) and surgery (25%) patients and normal volunteers on chronic NSAID (25%) therapy relative to normal subjects not on chronic NSAID therapy (0%). Whole blood NSAID insensitivity was observed with cyclooxygenase-I inhibitors, such as aspirin and ibuprofen; was not affected by Celebrex, a cyclooxygenase-II inhibitor; but was completely inhibited by thromboxane-receptor antagonists. This was not due to platelet NSAID insensitivity, because complete inhibition of AA-activation responses in PRP was observed with either TEG or OPA assays. We confirmed that thromboxane B2 formation in PRP from NSAID-insensitive subjects was completely inhibited by NSAIDs. However, significant amounts were formed in whole blood from NSAID-insensitive subjects, but not in whole blood from NSAID-sensitive subjects. Thromboxane formation after AA addition was not found in washed blood cells with 90% reduced platelet counts or in leukocyte-rich buffy coat fractions, but could be restored by addition of PRP. NSAID-insensitive activation was inhibited by nordihydroguaiaretic acid, with an IC50 of 30 μmol, implicating 12- and/or 15-lipoxygenases in this transcellular pathway.

Original languageEnglish (US)
Pages (from-to)30-35
Number of pages6
JournalJournal of Laboratory and Clinical Medicine
Volume146
Issue number1
DOIs
StatePublished - Jul 1 2005

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Platelet Activation
Platelets
Arachidonic Acid
Assays
Blood
Anti-Inflammatory Agents
Chemical activation
Monitoring
Pharmaceutical Preparations
Platelet-Rich Plasma
Drug therapy
Cardiology
Plasmas
Cyclooxygenase Inhibitors
Celecoxib
Prostaglandin-Endoperoxide Synthases
Platelet Aggregation
Drug Therapy
Surgery
Aspirin

All Science Journal Classification (ASJC) codes

  • Medicine(all)
  • Pathology and Forensic Medicine

Cite this

A Thrombelastograph whole blood assay for clinical monitoring of NSAID-insensitive transcellular platelet activation by arachidonic acid. / Carroll, Roger C.; Craft, Robert; Chavez, Jack; Snider, Carolyn C.; Bresee, Stuart; Cohen, Eli.

In: Journal of Laboratory and Clinical Medicine, Vol. 146, No. 1, 01.07.2005, p. 30-35.

Research output: Contribution to journalArticle

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