Relationship of thromboxane generation to the aggregation of platelets from humans: Effects of eicosapentaenoic acid

Abstract

A non-linear relationship between the percent aggregation of human platelets and the amount of TXB2 generated requires investigators to use caution when using the data to assess antiplatelet regimens. The relationship approximates a hyperbola with a roughly linear relationship from 0 to 70% aggregation and 0 to 50 ng TXB2 per ml of platelet-rich plasma. Above these values, the amount of TXB2 produced may increase up to 500 ng per ml of platelet-rich plasma with no clear relationship to the observed platelet function of aggregation. Also, appreciable inhibition of TXB2 formation can occur at high TXB2 levels with no detectable decrease in aggregation. Thus, assessment of antiplatelet regimens using TXB2 formation alone are unlikely to be interpretable without reference to this non-linear property of platelet function. We applied this concept when evaluating a study of forty subjects with dietary supplements of 1.8 g or 2.7 g of ethyl eicosapentaenoate (20:5n-3) for four weeks. There was a moderate,but statistically significant decrease in average values for the percent aggregation (60+/-15 to 45+/-30) and thromboxane production (51+/-30 to 33+/-31 ng/ml) the differences in mean values were slight relative to the overall standard deviations, reductions of platelet function were clearly evident in 31 of 40 subjects when paired results were examined relative to the recognized hyperbolic relationship.