Imbalance of thromboxane/prostacyclin biosynthesis in patients with lupus anticoagulant.
The mechanism involved in the association between antiphospholipid antibodies and thrombosis or fetal loss remains unclear. We assessed the biosynthesis of thromboxane A2 and prostacyclin in 31 samples from 25 patients with lupus anticoagulant and in 32 controls. The urinary excretion of the major thromboxane metabolite of platelet origin (11-dehydrothromboxane B2) was very significantly increased (P less than .0003) in the patients. In contrast, the urinary metabolite reflecting the vascular production of prostacyclin (2,3-dinor-6-keto-prostaglandin F1 alpha) was much less increased (P less than .02). We found no correlation between the levels of anticardiolipin antibodies and the urinary excretion of 11-dehydro-thromboxane B2. Six patients with elevated urinary 11-dehydrothromboxane B2 were treated with low-dose aspirin (20 mg/d during 7 days). In these patients, there was a close relationship between the extent of inhibition of the thromboxane urinary metabolite (72%) and serum thromboxane B2 (79%). In contrast, the urinary excretion of 2,3-dinor-6-ketoprostaglandin F1 alpha was nearly unchanged (13% reduction). In addition, the F(ab')2 fragments isolated from six patients presenting increased urinary 11-dehydro-thromboxane B2 enhanced the generation of thromboxane B2 (P = .04) and the release of 14C serotonin (P = .009) by normal washed platelets, as compared with F(ab')2 from controls. In summary, our study shows that in patients with lupus anticoagulant, platelet activation may occur without a compensatory increment in the vascular biosynthesis of prostacyclin. This observation may be crucial to cause or reflect an increased risk for thrombosis. In addition, our results may suggest a rationale for antiplatelet agents for the prophylaxis of thrombosis in many patients with the antiphospholipid syndrome.
Lellouche
F
F
U348 INSERM, Hôpital Lariboisière, Paris, France.
Martinuzzo
M
M
Said
P
P
Maclouf
J
J
Carreras
L O
LO
D001323:Autoantibodies / Q000276:immunology; D002308:Cardiolipins / Q000276:immunology; D011464:Epoprostenol / Q000096:biosynthesis* / Q000378:metabolism; D005260:Female; D006801:Humans; D016682:Lupus Coagulation Inhibitor / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000503:physiopathology*; D008297:Male; D012701:Serotonin / Q000378:metabolism; D013928:Thromboxane A2 / Q000378:metabolism; D013931:Thromboxanes / Q000096:biosynthesis*
D001323:Autoantibodies; D002308:Cardiolipins; D016682:Lupus Coagulation Inhibitor; D013931:Thromboxanes; D012701:Serotonin; D013928:Thromboxane A2; D011464:Epoprostenol