Increased thromboxane formation in patients with antiphospholipid syndrome.
Thirty-one patients with IgG antibodies to cardiolipin (ACLA) were studied to determine their in vivo formation of the platelet aggregating and vasoconstricting substance thromboxane A2 (TxA2) and the platelet inhibiting and vasodilating substance prostacyclin (PGI2). This was done by measurements in urine of their enzymatically formed metabolites 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha, respectively, using gas chromatography-mass spectrometry. It is demonstrated that patients with IgG ACLA have a highly significant increase in the biosynthesis of TxA2 compared with age-matched healthy controls (807 +/- 163 [SEM] vs. 230 +/- 15 pg mg-1 creatinine, P = 0.0000005). A significant increment of the formation of PGI2 was also found (189 +/- 23 (SEM) vs. 125 +/- 11 pg mg-1 creatinine, P = 0.03), although this was much less pronounced than that for TxA2. We conclude that the highly increased formation of TxA2, reflecting platelet activation, in patients with IgG ACLA is of pathophysiologic relevance for their tendency to arterial and venous thrombosis and hence that they should be considered for prophylactic treatment with inhibitors of TxA2 formation, like aspirin.
Arfors
L
L
Department of Rheumatology, Karolinska Hospital, Stockholm, Sweden.
Vesterqvist
O
O
Johnsson
H
H
Gréen
K
K
D000328:Adult; D001327:Autoimmune Diseases / Q000150:complications / Q000276:immunology / Q000378:metabolism*; D002308:Cardiolipins / Q000276:immunology; D011464:Epoprostenol / Q000096:biosynthesis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010743:Phospholipids / Q000276:immunology*; D015539:Platelet Activation; D013577:Syndrome; D013927:Thrombosis / Q000209:etiology; D013928:Thromboxane A2 / Q000096:biosynthesis*
D002308:Cardiolipins; D010743:Phospholipids; D013928:Thromboxane A2; D011464:Epoprostenol