INCREASED IN VIVO FORMATION OF THROMBOXANE AND PROSTACYCLIN IN HUMANS AFTER AORTIC REPLACEMENT WITH SYNTHETIC GRAFTS

Abstract

Replacement of arteries with synthetic grafts causes activation of both plasma coagulation and platelets. In order to measure platelet activation the in vivo production of thromboxane A2 (TxA2) and prostacyclin (PGI2) were measured in patients following graft replacement of the abdominal aorta for aneurysmal disease.Specific methods based on gas chromatography-mass spectrometry using tetra-deuterated internal standards/carriers were used to measure the urinary excretion of 2,3-dinor-TxB2 and 2,3-dinor-6-keto PGF1α, the two major urinary metabolites of TxA2 and PGI2. The excretion of the metabolites increased ten-fold and fortyfold respectively on the first postoperative day and remained elevated up till 10 days postoperatively. In patients undergoing cholecystectomy only minor changes of shorter duration were seen. A marked decrease in platelet count occurred concomitanly with the increase in the urinary metabolites. Platelet counts returned to normal or supernormal values after 10 days when the excretion of 2,3-dinor TxB2had returned to normal values.It is concluded that synthetic grafts cause prolonged increase in the in vivo formation of TxA2 and PGI2 concomitantly with a decrease in platelet count. The reason for the increased TxA2 formation may be platelet interaction with the foreign surface but the increase of PGI2 is unexplained. The latter increase could be part of a vascular defense against the induced thrombotic activity.