Serum prostacyclin binding defects in thrombotic thrombocytopenic purpura.

To understand the pathophysiologic significance of abnormal serum prostacyclin (PGI2) binding activities in thrombotic thrombocytopenic purpura (TTP), we evaluated the PGI2 binding characteristics in three chronic TTP sera and 19 normal sera.PGI2 binding by serum was rapid and reversible.The binding activity in TTP sera (22.1±SD, 4.4%) was significantly lower than that of normal sera (42.2±6.2%).Moreover, the antiaggregating activity and 6-keto-prostaglandin Fja(6KPGFi,) con- tent in the gel filtrates representing the binding peak was proportionally lower in a TTP serum than normal serum.Although normal and TTP sera bound ['4Clarachidonate with similar activity, and neither bound 13H16KPGF,,, there was a difference in prostaglandin El (PGE,) binding.Binding of 13HIPGE, was subnormal in two TTP sera (W.J. and T. G.) and normal in the third (H.S.).Normal serum corrected the binding defects of TTP serum.Interestingly, the mixture of two TTP sera (W.J. and H.S.) mutually corrected their PGI2 binding defects.In addition, although in vivo plasma transfusions improved the PGI2 binding activity of WJ. and H.S., there existed a striking difference in the nature of their response.These observations indicate that there are at least two types of PGI2 binding defects in TIP.Our data indicate that TTP is associated with diminished serum binding of PGI2.This defect may reduce the availability of PGI2 to damaged vascular sites and decrease an important modulator of platelet thrombus formation at times of severe vascular insult.in a Packard scintillation spectrometer (Packard Instrument Co., Inc., Downers Grove, IL).As the radioactivity recovered in all the fractions was 99-100% of the radioactivity added, the recovered radioactive counts were used as the basis for determining the percentage ofbinding.The percentage of total radioactivity eluted with the non-included serum proteins (peak I, Fig. 1) gave a measure of PGI2 binding.