title: Evaluation of platelet function, a method comparison.
abstract: Platelet function can be studied using many different methods why it is of interest to understand how data from different assays relate to each other. In the present study we compare two methods suitable for screening purposes with two established although laborious methods, impedance aggregometry and platelet-rich plasma (PRP) aggregation. The alternative assays tested were: (i) exposure of active alphaIIbbeta3, in diluted whole blood and (ii) whole blood aggregation assessed by residual platelet counting. The fibrinogen receptor activation assay was found to have the lower variability, higher sensitivity to ADP, and higher signal to noise ratio compared with residual platelet counting. The sensitivity and response profile of the fibrinogen receptor activation assay and residual platelet counting were more similar to PRP aggregation than to impedance aggregometry, whereas impedance aggregometry displayed lower sensitivity to ADP. The two alternative assays correlated well with PRP aggregation as well as with each other. The fibrinogen receptor activation assay displayed the highest potency for AR-C69931MX, possibly due to a lower protein content compared with residual platelet counting. The two studied assays compare well with the more established assays, and are thus both good alternatives for platelet function testing and evaluation of new potential platelet antagonists.
authors.affiliation: Department of Molecular Pharmacology, Preclinical R&D, AstraZeneca R&D, Mölndal, Sweden. sven.nylander@astrazeneca.com
authors.forename: S
authors.initials: S
authors.lastname: Nylander
authors.forename: K
authors.initials: K
authors.lastname: Johansson
authors.forename: J J J
authors.initials: JJ
authors.lastname: Van Giezen
authors.forename: T L
authors.initials: TL
authors.lastname: Lindahl
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000249:Adenosine Monophosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D010976:Platelet Count; D010979:Platelet Function Tests / Q000379:methods*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000494:pharmacology; D039341:Receptors, Fibrinogen / Q000187:drug effects / Q000378:metabolism; D012016:Reference Values; D012044:Regression Analysis; D012680:Sensitivity and Specificity; D013997:Time Factors
chemical_list: D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D039341:Receptors, Fibrinogen; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; C117446:cangrelor