Thrombocytosis: a paraneoplastic syndrome in patients with hepatocellular carcinoma

Abstract

Aim: Hepatocellular carcinoma (HCC) patients manifest a variety of paraneoplastic syndromes. Thrombocytosis was reported in children with hepatoblastoma. The aims of this study were to evaluate the prevalence and clinical significance of thrombocytosis in HCC patients and its relationships with serum thrombopoietin (TPO).

Methods: We retrospectively reviewed clinical, biochemical and image data of 1,154 HCC patients. In addition, we measured platelet count and serum TPO in HCC patients with and without thrombocytosis, in patients with cirrhosis, chronic hepatitis and healthy subjects in a cross-sectional study.

Results: Thirty-one (2.7%) of 1,154 HCC patients had thrombocytosis (platelet count > or = 400 K/mm3). HCC patients with thrombocytosis were significantly younger, had a higher serum alpha-fetoprotein, higher rate of main portal vein thrombosis, larger tumor volume, shorter survival, and were less likely to receive therapy than HCC patients without thrombocytosis. Multivariate logistic regression analyses showed that tumor volumes > or = 30% and serum alpha-fetoprotein > or = 140,000 ng/mL could significantly predict thrombocytosis. HCC patients with thrombocytosis had a significantly higher mean serum TPO than those without, as well as patients with cirrhosis, chronic hepatitis and healthy subjects. Platelet count and serum TPO dropped significantly after tumor resection in HCC patients with thrombocytosis and re-elevated after tumor recurred. Furthermore, the expression of TPO mRNA was found to be more in tumor tissues than in non-tumor tissues of liver in an HCC patient with thrombocytosis.

Conclusion: Thrombocytosis is a paraneoplastic syndrome of HCC patients due to the overproduction of TPO by HCC. It is frequently associated with a large tumor volume and high serum alpha-fetoprotein.

Figure 1

Distribution of serum thrombopoietin levels in hepatocellular carcinoma (HCC) patients with and without thrombocytosis, patients with cirrhosis, chronic hepatitis and healthy subjects. The mean serum thrombopoietin level in HCC patients with thrombocytosis was significantly higher than in HCC patients without thrombocytosis, patients with cirrhosis, chronic hepatitis and healthy subjects.

Figure 2

Clinical course of a hepatocellular carcinoma patient with thrombocytosis. The serum alfa-fetoprotein (AFP) level was 164000 ng/mL before tumor resection. Hypercholesterolemia (serum cholesterol level: 602 mg/dL) and thrombocytosis (platelet count: 403 K/mm³) were noted before operations. The platelet counts, serum levels of cholesterol and AFP fell significantly after a surgical removal of the tumors. However, all re-elevated when the tumor recurred 18 wk after surgical treatments.

Figure 3

Analyses of thrombopoietin from tumor tissues (T) and non-tumor liver tissues (L) in a hepatocellular carcinoma patient with thrombocytosis using reverse-transcription polymerase chain reaction. β-actin was used as an internal standard (B). N: negative control. Results from an agarose gel electrophoresis showed a more intense density of thrombopoietin band from tumor tissues when compared with non-tumor liver tissues.