Cirrhotic thrombocytopenia is a multifactorial condition: evidence of reduced platelet production and incresed platelet destruction

Background: Thrombocytopenia is a common manifestation of liver cirrhosis (LC), but the underlying mechanism is not fully understood. The purpose of our work was to evaluate the platelet kinetics in LC of different etiology by examining platelet production and destruction. Patients: 91 consecutive LC patients (36 HCV, 49 alcoholics, 15 HBV) were enrolled in the study. As controls, 25 cases with idiopathic thrombocytopenic purpura (ITP), 10 with aplastic anemia (AA), and 40 healthy blood donors were studied. Methods: Plasma thrombopoietin (TPO) was measured by ELISA. Absolute reticulated platelet (RP) count was determined by Thiazole Orange method. Plasma glycocalicin (GC) was measured by monoclonal antibodies. Platelet associated and serum circulating antiplatelet antibodies were detected by flow cytometry. The B-cell monoclonality in the PBMC were performed by isotype-specific immunoglobulin fingerprinting. Results: The serum TPO was significantly (p<0.0005) lower in the patients with LC (29.9 ± 18.1 pg/ml) than in normals (82.3 ± 47.6 pg/ml). The GC index was 1.96 ± 1.40 in HCV+ LC (p<0.0005 vs. normals 0.9 ± 0.2), 1.79 ± 1.51 in alcoholic LC (p<0.006) and 1.71 ± 1.69 in HBV + LC (p<0.006). In the patients affected by ITP, the GC index was 12.9 ± 4.4 (p<0.000002). The absolute levels of RP were 4.233 ± 2.367 109/L in alcoholic LC (p<0.0000000012 vs normals) 4.996 ± 3.143 x 109/L in HBV+ LC (p<0.006) and 6.629 ± 7.409 x 109/L in HCV+LC (p<0.005). The prevalence of platelet-associated and circulating anti-platelet antibodies was higher in HCV+ LC than in healthy subjects (p<0.0064), than in alcoholic LC (p<0.018) and than in HBV+ LC (p<0.0001). The B-cell monoclonality was found in 8 (27%) of the HCV-positive patients, whereas no monoclonality was found in HBV (p<0.004) or alcoholic patients (p<0.003). Conclusions: Patients with LC present a decreased plasma TPO, an accelerated platelet turnover and a low platelet production. These findings indicate that cirrhotic thrombocytopenia is a multifactorial condition, involving both increased platelet clearance and impaired thrombopoiesis. The HCV-LC is characterized by an increased prevalence of autoimmune phenomena, including anti-platelet antibodies and, as consequence, a platelet turnover more accelerated than in HBV or alcoholic LC.