Platelet activation induced by combined effects of anticardiolipin and lupus anticoagulant IgG antibodies in patients with systemic lupus erythematosus - Possible association with thrombotic and thrombocytopenic complications

Antiphospholipid antibodies (aPL) are well known to be associated with arte rial and venous thrombosis. In a series of 180 patients with systemic lupus erythematosus (SLE), the prevalence of arterial thrombosis was obviously h igher in the patients who had both anticardiolipin antibodies (aCL) and lup us anticoagulant (LA) (17/35, 48.6%, p < 0.05) (Table 1) than in the other patients bearing aCL or LA alone or neither of them (2/145, 1.4%). Since a substantial fraction of the former group of patients with arterial thrombos is also had thrombocytopenia (12/17, 70.6%), there was a possibility that a CL and LA might have enhanced platelet activation and aggregation. To test this possibility, we studied the in vitro effects of aCL and LA on the enha ncement of platelet activation by flow cytometric analysis using anti-CD62P and anti-CD41 monoclonal antibodies directed against platelet activation-d ependent granule-external membrane (PADGEM) protein and platelet glycoprote in IIb (GPIIb), respectively. Platelet activation defined by the surface ex pression of CD62P was not induced by aCL(+). LA(+) plasma only, but was sig nificantly augmented by aCL(+).LA(+) plasma in combination with adenosine d iphosphate (ADP) at a low concentration that had only a modest effect on pl atelet activation. In contrast, aCL(+).LA(-), aCL(-).LA(+) and aCL(-).LA(-) plasma samples were incapable of enhancing platelet activation in the pres ence or absence of ADP stimulation. In addition to plasma samples, the puri fied IgG from aCL(+).LA(+) plasma (aCL(+).LA(+)-IgG) also yielded apparent. enhancement of platelet activation induced by ADP. Furthermore, platelet a ctivation was generated by the mixture of aCL(+). LA(-)-IgG and aCL(-).LA()-IgG fractions prepared from individual patients, but not by each fraction alone. These results suggest that aCL and LA may cooperate to promote plat elet activation, and may be involved, at least partially, in the pathogenes is of arterial thrombosis and thrombocytopenia in patients with SLE.