6-ketoprostaglandin-f1-alpha and Purpura--Thrombocytopenic

The production of thromboxane A2 (TxA2) and prostacyclin (PGI2) was studied in patients with chronic idiopathic thrombocytopenic purpura (10 patients) compared to central thrombocytopenia (five patients) and healthy subjects (10 subjects). This production was monitored by the assay of urinary 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha as respective breakdown products of TxA2 and PGI2 by stable isotope dilution assays employing negative ion-chemical gas-chromatography-mass-spectrometry. Evidence is presented for the existence of an enhanced PGI2 and TxA2 urinary excretion in the group of idiopathic thrombocytopenic purpura (ITP) patients. Moreover, production of serum TxB2 per platelet was decreased in ITP group. These results provide arguments for an in vivo platelet cyclooxygenase hyperactivity during chronic ITP.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Epoprostenol; Female; Humans; Male; Middle Aged; Platelet Count; Prospective Studies; Purpura, Thrombocytopenic; Thrombocytopenia; Thromboxane A2; Thromboxane B2

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 F1 alpha (6KPGF1 alpha) content in the gel filtrates representing the binding peak was proportionally lower in a TTP serum than normal serum. Although normal and TTP sera bound [14C]arachidonate with similar activity, and neither bound [3H]6KPGF1 alpha, there was a difference in prostaglandin E1 (PGE1) binding. Binding of [3H]PGE1 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 W.J. and H.S., there existed a striking difference in the nature of their response. These observations indicate that there is at least two types of PGI2 binding defects in TTP. 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.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Binding Sites; Biological Availability; Chromatography, Gel; Dose-Response Relationship, Drug; Epoprostenol; Female; Half-Life; Humans; Male; Protein Binding; Purpura, Thrombocytopenic; Serum Albumin