Study: Point-of-Care Monitoring for Optimal Anti-Platelet Therapy in Acute Clinical Settings

Kirk E. Guyer1, David G.M. Carville1, Helen Ridgway2, Richard R. Rullman2.
1Department of Chemistry, Indiana University South Bend, South Bend, IN.2 Helena Laboratories, Beaumont, TX.

Introduction:
> Antiplatelet therapy including aspirin (ASA) and clopidogrel is recognized as clinically important in patients at risk of developing thrombotic events
> Recently it has been realized that empiric therapeutic dosing is suboptimal due to inter-patient variability with regard to response, receptor concentration etc.
> Hence there is a clinical need to monitor such therapies on an individual basis
> Traditional platelet tests including light transmission aggregometry (LTA) are inconvenient for acute diagnostic testing.
> Hence, the introduction of "near-patient" test systems
> Here we describe the utility of a point of-care (POC) test platform (PlateletWorks®) for monitoring platelet response to ADP and arachidonic acid (AA) as the agonists

Methods & Procedure:
PlateletWorks (Helena Laboratories, Beaumont, TX) evaluates non-anticoagulated whole blood as the sample medium. It utilizes the principle of differential platelet counting in either the absence or presence of a platelet agonist (ADP, collagen, AA etc.) as a direct indication of platelet function. Results may be expressed as either % aggregation or %inhibition. In human clinical trials subjects (n=205) were evaluated for their response to ADP (20μM) and a second group of subjects (n=40) were evaluated for their response to AA (either 5μM or 1.25mg) on both the Plateletworks and LTA (Chronolog, Haverstown, PA) test platforms.

Results:
The comparative data for each agonist between the two platforms are shown in Figures 1 & 2. The correlation between the two systems for ADP was r=0.91. For AA, as LTA provides a qualitative and Plateletworks a quantitative measure of response data were analyzed using McNemar test of symmetry with a calculated Cohen's kappa value of 61.5%.

Odoo • Image and Text
Odoo • Image and Text

Conclusions:
> This novel POC test for platelet response maybe a suitable peri-procedural screening assay to determine the effective dose of administered pharmaceutical on an individual patient basis
> It may also provide clinical decision as to alternative antiplatelet therapies
> Large scale studies both in vascular disease and other disease processes are ongoing

Agonists: ADP-FDA approved ('91); AA - currently under FDA review


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