M. J. George1, K. R. Aroom1, M. A. Skibber1, T. Sharma1, C. S. Cox1, C. E. Wade1, B. S. Gill1 1University Of Texas Health Science Center At Houston,Center For Translational Injury Research,Houston, TEXAS, USA
Introduction: Aggregation is the initial phase of platelet activation while contraction is the terminal phase. Both aggregation and contraction are key determinants of clot formation and stability. Optical aggregometry measures platelet aggregation and detects anti-platelet drugs like Aspirin. There is no current Food and Drug Administration (FDA) approved device that measures platelet contraction. We hypothesize that a platelet contraction device can detect the presence of Aspirin. We studied platelet contraction using a novel device employing gain and loss of function experiments. We targeted the TXA2 platelet activation pathway by measuring changes in platelet contraction and aggregation due to inhibition with aspirin or stimulation with arachidonic acid.
Methods: Venous blood samples were taken from consenting healthy adult volunteers before and 120 minutes after oral ingestion of 325 mg non-enteric coated aspirin (ASA) tablets. Platelet contraction was measured in the novel device using fresh native blood (NB) within 5 minutes of collection. Platelet contraction assays were measured in duplicate, with and without stimulation by arachidonic acid (AA). Metrics reflecting platelet contraction include contraction start time (CST) and maximum contraction force (MCF). Platelet aggregation was measured in an optical aggregometer using citrated platelet rich plasma within 20 minutes of collection. Optical aggregometry assays were measured in triplicate and stimulated by AA. Metrics reflecting platelet aggregation include lag time (LT) and max amplitude (MA). ANOVA with repeated measures and Bonferroni post-hoc analysis measured differences among the four treatment groups. Linear regression analysis compared platelet contraction and platelet aggregation among single subjects.
Results: Eight adult subjects were enrolled. MCF or CST was not significantly different when comparing pre and post ASA assays without AA. However with AA added, MCF was significantly higher in pre ASA assays compared to post ASA assays (4082±353 uN vs 3325±741 uN) and CST was significantly lower in pre ASA assays compared to post ASA assays (913±26 seconds vs 1389±266 seconds)(Figure 1, ** denotes p < 0.005, * denotes p < 0.05). Among single subjects prior to ASA administration, platelet contraction CST and platelet aggregation LT correlated with R2 = 0.857; platelet contraction MCF and platelet aggregation MA correlated with R2 = 0.864.
Conclusion: Platelet contraction demonstrates utility as a potential measure of platelet function when detecting effects of anti-platelet drugs like aspirin. The novel platelet contraction device correlates with optical aggregometry.
