Comprehensive Quality Management of Multiple Electrode Platelet Aggregometry.

Abstract 4463

Platelet function analysis provides quantitative results which may reveal platelet disorders, platelet inhibition during anti-platelet therapy or anti-platelet drug resistance. The results may have important consequences on patients therapy. As in all laboratory methods, a comprehensive quality management approach is crucial and increasingly demanded by regulatory authorities.

In platelet function methods quality control is hampered by the fact that platelets are not stable over longer time periods and loose their functional activities after freezing and freeze-drying. Therefore for most platelet function tests no control materials are available. When no biological quality control material is available, it is even more important to install and maintain a quality management approach, which covers as many influence factors and sources of error as possible. Here we present the quality management procedures of Multiple Electrode Aggregometry (MEA) a relative new platelet function test based on the analysis of whole blood (Multiplate analyzer, Dynabyte medical, Munich, Germany).

In the MEA device temperature of the measurement system is controlled by the analyser and can be verified by an external QC kit. The signal reaction of this method is based on the rise of electrical resistance induced by the adhesion and aggregation of activated blood platelets on metal sensor electrodes in a disposable test cell. In order to control possible sensor inconsistencies and improve precision, the test cell incorporates two independent sensor units, each consisting of 2 silver-coated highly conductive wires. The duplicate sensors thus serve as an internal control. During each measurement Pearson's correlation coefficient of single measurements of the curves assessed by the two electrode pairs and the difference of the two AUCs are calculated automatically by the analyzer's software. The result is flagged if the values are outside of the acceptance range (correlation coefficient <0.98, difference to the mean curve >20%). The instrument has an integrated procedure for an electronic control which checks the function of the electronic amplifier in the analyzer. In addition liquid controls are available, based on solutions with different ional strength. Using these solutions the instrument, pipettor and test cells are controlled. Using blood from a healthy individual, users can control qualitatively all aspects of the analysis (instrument, test cells, reagents, pipettor). Abnormal control reagents are available, containing either aspirin, a GpIIbIIIa antagonist or prostaglandin E1, which can produce an abnormal result when added to a normal blood sample before the analysis. The instrument provides an electronic pipettor with interactive software-guided operation procedures, which help standardise the analysis and minimize user-related errors. Using artificial liquid control materials a pilot external QC was performed in 6 individual centers and the results were centrally analyzed. Level I control was determined as 125+-6 aggregation units (AU, mean+-sd), level II control was 64+-5 AU. Coefficients of variation of all determinations were 4.6% and 7.3% respectively.

In conclusion it is shown that while a stable biological control material for platelet function analysis is not available, it is possible to perform quality controls covering many parts of the analytical procedure. Manufacturers and users of platelet function tests should try to implement control procedures that cover as many aspects of the technology they apply as possible to ensure correct performance of the tests over the lifetime of the instrument, test cells and reagents. As long as stable biological quality control materials for platelet function analysis are not available, qualitative biological controls using normal blood or plasma should be combined with artificial control materials or electronic test procedures according to the analytical reaction which is performed. If the biological reaction cannot be quantitatively controlled, then at least the physical process leading to the signal of the respective test procedure should be verified (measurement of pressure, optical density or electrical impedance). Using a step by step approach comprehensive quality management of platelet function analysis is feasible and should be implemented in routine.