Using Platelet Function Testing to Guide Antiplatelet Therapy

Abstract

Clinical Development Phases I‐III Regulatory, Quality, Manufacturing Platelets are subcellular fragments in blood whose activation is central to atherothrombosis and cardiovascular events. Platelet activation is complex, with multiple pathways of initiation and amplification involved. Antiplatelet drugs may target any of these pathways to diminish the propensity of platelets to become activated. The most well‐established antiplatelet drugs, aspirin and thienopyridines, target the thromboxane and adenosine diphosphate auto‐amplification pathways of platelet activation, respectively. These are very effective medicines, but response varies and residual on‐treatment platelet function is associated with poorer clinical outcomes. Alternative antiplatelet therapies are available and more are in development. Therefore, tailoring antiplatelet therapy to on‐treatment platelet activation is an appealing strategy and the subject of investigation. There are many different approaches to measuring platelet activation and response to stimulation with antiplatelet therapy, but there is very little agreement between them regardless of the cutoffs used. Therefore, selection of the appropriate platelet function test is important in assessing on‐treatment platelet activation for guided therapy. Recent research has shown that tailoring antiplatelet therapy can improve these laboratory measures of platelet activation, but clinical studies that assess cardiovascular benefit against potential for increased bleeding are required.

Gemtuzumab Ozogamicin Treatment Results in Decreased Proliferation and Differentiation of Human Megakaryocytes but Does Not Inhibit Mature Platelet Function

“…In addition, regulators requested an evaluation of the effects of GO in patients with severe renal dysfunction as this population frequently exhibits altered hemostasis. [37][38][39] However, performing controlled in vitro investigations on platelet function using samples from specific patient populations was logistically challenging. Light transmittance aggregometry, which is widely used for assessment of platelet function, must be performed on PRP samples prepared immediately after blood sampling, and most standardization documents recommend that that blood samples be exposed to minimal agitation and vibration to minimize artifactual platelet activation and that testing take place within 4 hours.…”

Antiplatelet Therapy Monitoring in Neonates and Children

“…Additionally, studies in adults suggest that on-treatment platelet function reflects pretreatment platelet function and much of the on-drug variability is unrelated to the failure of the drug per se. 22 Therefore, ideally to properly monitor biochemical response to antiplatelet therapy, monitoring would require testing of a pre-drug sample, which is often very challenging.…”

“…Both studies using platelet-derived microparticle monitoring for platelet activation dynamics in Kawasaki's disease illustrated a rebound after discontinuing aspirin, suggesting that timing for aspirin discontinuation should be evaluated individually. 19,22…”

Personalizing Anticoagulant and Antiplatelet Therapeutics: A Timely Task

“…Some of the following manuscripts highlight the need for better personalized treatment for thrombotic disorders along with the emerging new therapeutics. For example, covered topics include the potential use of mRNA and miRNA profiling of blood platelets for guiding antiplatelet drug therapy [Gnatenko, ]; the individualization of antithrombotic treatment with low‐molecular weight heparins, and vitamin K antagonists [Bloemen et al., ]; and measuring ex vivo platelet reactivity for improved treatment personalization [Linden, ]. In recent years, the largest attention for improving the personalized medicine of thrombotic disorders has been focused on studying and implementing the pharmacogenetics of warfarin.…”