Programme Hospitalier Recherche Clinique, Institut Pasteur, Inserm, French Public Health Agency.

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.

Increased frequency of thromboembolic events has been recently observed in patients with beta-thalassemia major (TM). Platelet function anomalies including impaired aggregation, increased circulating aggregates, and our finding of shortened platelet survival indicate that platelets may be involved in the hypercoagulability in thalassemia. Consequently, we used a technique based on thin layer chromatography purification and enzyme immunoassay to measure urinary metabolites of thromboxane A2 (TXA2) and prostacyclin (PGI2) in nine splenectomized patients with beta-TM regularly transfused, five non- splenectomized patients with beta-thalassemia intermedia (TI), and 20 healthy individuals. A significant 4- to 10-fold increase was observed in the urinary excretion of 2,3-dinor-TXB2, 11-dehydro-TXB2 and 2,3- dinor-6-keto-PGF1 alpha in patients with TM and TI as compared with healthy controls. No significant differences were found in the concentrations of these metabolites between TM and TI patients. Six TM patients received a very low dose of aspirin (20 mg/day) for 7 days. A significant decrease was observed in the urinary concentrations of 2,3- dinor-TXB2 and 11-dehydro-TXB2 derived from platelets. However, the levels of urinary 2,3-dinor-6-keto-PGF1 alpha reflecting vascular production and TXB2 and 6-keto-PGF1 alpha originating from the kidney were not significantly changed. These results are consistent with those of increased in vivo production of TXA2 because of endogenous platelet activation.

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