ANTIPHOSPHOLIPID ANTIBODIES ENHANCE THROMBIN-INDUCED PLATELET ACTIVATION AND THROMBOXANE FORMATION

In a group of 6 patients with lupus anticoagulant (LA) and antiphospho lipid (aPL) antibodies detected by ELISA overnight urine and blood wer e simultaneously collected. A significantly increased urinary excretio n of the platelet-derived thromboxane (TX) metabolite 11-dehydro-TXB2 was found in this group, as compared to 12 healthy individuals. In con trast, a small but significant reduction of the vascular prostacyclin (PGI2) metabolite 2,3-dinor-6-keto-prostaglandin F1alpha was observed. To further elucidate the effect of these antibodies on platelet activ ation we isolated the F(ab')2 fragments from IgG of the 6 patients and 5 controls, and we evaluated the effect of these fragments on the res ponses of isolated normal platelets to thrombin. Patients' F(ab')2 inc reased platelet aggregation and serotonin release of platelets stimula ted by low dose thrombin (0.01 U/ml). At threshold thrombin concentrat ion (0.05 U/ml) an enhanced TXB2 production was also observed. In summ ary, our results show, in addition to the altered TXA2/PGI2 balance ob served in vivo, a direct stimulatory effect of aPL antibodies on plate let activation in vitro. This effect is related to recognition of phos pholipid epitopes on platelets as shown by its neutralization upon pre incubation with phospholipids. This phenomenon may be relevant for, th e thrombotic tendency of these patients.