Mechanism of thrombocytopenia in chronic hepatitis C as evaluated by the immature platelet fraction

Introduction: Thrombocytopenia occurs frequently in chronic hepatitis C. The mechanism of this association was investigated utilizing the immature platelet fraction (IPF%) as an index of platelet production together with assay of thrombopoietin (TPO). Methods: In a cross-sectional study, 47 patients with chronic hepatitis C were studied, 29 with thrombocytopenia and 18 without thrombocytopenia (six patients in each group were on interferon therapy). Results: IPF% was elevated in the thrombocytopenic compared with the nonthrombocytopenic group (9.0 +/- 4.8%vs. 4.7 +/- 2.4%, P < 0.001), and an increase in IPF% was significantly associated with thrombocytopenia on multivariable analysis (P < 0.05). Splenomegaly was more common in thrombocytopenic than in nonthrombocytopenic subjects (66%vs. 6%, P < 0.001), and on multivariable analysis, splenomegaly was the factor associated with the highest relative risk of thrombocytopenia (RR = 1.9, P < 0.05). IPF% values were elevated in a similar proportion of thrombocytopenic patients with and without splenomegaly (58% and 60%, respectively). There was no difference in TPO levels between thrombocytopenic and nonthrombocytopenic patients, and TPO levels were not related to the risk of thrombocytopenia on multivariable analysis. Significantly more thrombocytopenic than nonthrombocytopenic subjects had abnormal liver function tests, cirrhosis, and portal hypertension, and a decrease in serum albumin was significantly associated with thrombocytopenia (P < 0.005) on multivariable analysis. Conclusions: Factors associated with liver disease in general are associated with thrombocytopenia in chronic hepatitis C. Peripheral platelet destruction or sequestration is the major mechanism for thrombocytopenia, with hypersplenism being an important cause. Low TPO levels were not related to the occurrence of thrombocytopenia in this study.