A Role of Autoantibody–Mediated Platelet Destruction in Thrombocytopenia in Patients With Cirrhosis

Abstract

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-GPIIbIIIa 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. (HEPATOLOGY 2003;37:1267-1276

Role of molecular mimicry of hepatitis C virus protein with platelet GPIIIa in hepatitis C–related immunologic thrombocytopenia

“…The incidence of endemic HCV-ITP in 294 chronic patients was 10%, which increased to 32% with advanced liver disease. 15 The frequency of B-cell production of anti-GPIIb-IIIa Ab was 27-fold greater than with control cells in 37 HCV-ITP patients with cirrhosis 17 ; and an inverse correlation was found between platelet count and B-cell anti-GPIIb-IIIa Ab production in 51 patients with liver cirrhosis (73% with hepatitis C). This would suggest some degree of specificity.…”

“…14 Patients with HCV commonly develop immunologic thrombocytopenia (HCV-ITP) that correlates with severity of disease (eg, chronic active hepatitis, cirrhosis). [15][16][17] The incidence of HCV-ITP in a series of 368 HCV Japanese patients with chronic persistent or chronic active hepatitis was 41%. The incidence of endemic HCV-ITP in 294 chronic patients was 10%, which increased to 32% with advanced liver disease.…”

Association of primary biliary cirrhosis with idiopathic thrombocytopenic purpura

“…Another mechanism of thrombocytopenia in liver cirrhosis is anti-platelet autoantibody-mediated platelet destruction. Kajihara et al [10] have revealed a similar profile of the anti-glycoprotein Ⅱb/Ⅲa autoantibody response between patients with liver cirrhosis and those with ITP, and concluded that immune-mediated platelet destruction may contribute, at least in part, to cirrhotic thrombocytopenia. In the present case, an autoimmune response to platelets might have been induced or enhanced by the underlying liver cirrhosis.…”

Hematological spectrum in patients with alcoholic liver cirrhosis: a model of end-stage liver disease score based approach

“…17,18 Liver transplantation is known to resolve thrombocytopenia due to an increase in serum TPO and increased platelet production. 19,20 As splenomegaly is an important feature of portal hypertension, it is not surprising that splenic platelet sequestration is thought to be an important mechanism in the etiology of thrombocytopenia. Kinetic radiolabelled platelet studies do suggest splenic pooling, but they also report shorter platelet survival time, indicative of splenic destruction rather than mere splenic pooling.…”