Impedance-Based Whole Blood and Optical-Based Platelet Rich Plasma Aggregation Methods for the Assessment of Celexocib Effects on Platelet Function: A Preliminary Report.

Abstract

Cyclooxygenase-2 (COX-2) is the inducible cyclooxygenase isoform expressed by cells involved in inflammation. Platelets normally lack COX-2; however, the enzyme is expressed in megakaryocytes and newly formed platelets and may play a role in clinical syndromes associated with high platelet turnover (1, 2). Selective COX-2 inhibitors (coxibs), have become the mainstay for treatment of patients with arthritis and also have been widely used in cancer chemoprevention. Coxibs were found to have a safer GI toxicity profile when compared with classic NSAIDS; however, in some patients they may increase the risk of GI bleeding (3). The underlying mechanism has not yet been elucidated. Moreover, the role of coxibs in hemostatic alterations has been a subject of controversy. The aim of the study was to investigate the possible anti-platelet effects of celecoxib (200 mg/d for 7 days) in 7 healthy volunteers (2 females, 5 males; mean age = 35.7 ± 8; mean platelet count = 230 ± 23; mean Ht = 42.3 ± 6). A very sensitive whole blood impedance platelet aggregation assay, previously unused for this purpose, was employed for the assessment of celecoxib influence on platelet function. The test was performed along with a traditional, optical-based platelet rich plasma (PRP) aggregation method. Arachidonic acid (0.5; 0.25 mM), Collagen (2; 1mg/mL) and ADP (20, 10 mM) were used as platelet agonists in both tests.Celexocib did not affect platelet function in neither whole blood nor in PRP. The preliminary results of this study indicate that the increased bleeding tendency in patients treated with celecoxib is probably not related to platelet dysfunction.AssayArachidonic AcidCollagenADP0.5[mM]0.25[mM]2[μg/mL]1[μg/mL]20[μM]10[μ M]WB Impedance17.5±4.720.9±3.825.4±3.925.9±6.114.3±2.614.1±5Aggregation: Pre-drugPost-drug18±421±527.1±4.724±418.7±6.216.3±7PRP Optical118.1±10.3118.1±6.7101.4±13.7110±2.2104±15108±8.9Aggregation: Pre-drugPost-drug119.6±6.7112.9±10.2105.4±11.5110.4±7.5102.1±18.3107.7±9.6