Thrombocytopenia is a common manifestation in patients with
liver cirrhosis (LC), but its underlying mechanism remains controversial. This study examined the role of anti-platelet autoimmunity in cirrhotic
thrombocytopenia by determining the
autoantibody response to GPIIb-IIIa, a major platelet surface
autoantigen recognized by anti-platelet
antibodies in patients with
idiopathic thrombocytopenic purpura (
ITP). Circulating B cells producing anti-GPIIb-IIIa
antibodies as well as platelet-associated and plasma anti-GPIIb-IIIa
antibodies were examined in 72 patients with LC, 62 patients with
ITP, and 52 healthy controls. In vitro anti-GPIIb-IIIa antibody production was induced in cultures of peripheral blood mononuclear cells (PBMCs) by stimulation with GPIIb-IIIa. The frequency of anti-GPIIb-IIIa antibody-producing B cells in patients with LC was significantly greater than in healthy controls (10.9 +/- 6.2 vs. 0.4 +/- 0.3/10(5) PBMCs; P <.0001) and was even higher than the frequency in patients with
ITP (8.2 +/- 5.2; P =.007). Anti-GPIIb-IIIa
antibodies in the patients with LC and
ITP were mainly present on the surfaces of circulating platelets rather than in the plasma in an unbound form. Furthermore, PBMCs from patients with LC and
ITP produced anti-GPIIb-IIIa
antibodies on antigenic stimulation with GPIIb-IIIa in vitro, and the specific
antibodies produced had the capacity to bind normal platelet surfaces. In conclusion, the similar profile of the anti-GPIIb-IIIa
autoantibody response in patients with LC and
ITP suggests that
autoantibody-mediated platelet destruction may contribute at least in part to cirrhotic
thrombocytopenia.