ABSTRACT
Thrombocytopenia is a common hematological defect among patients with chronic liver diseases. Thrombocytopenia secondary to liver cirrhosis and portal hypertension is a well known complication of advanced stage liver disease, but theories about the underlying pathogenetic mechanisms, mostly concentrating on splenic sequestration i.e. hypersplenism and destruction of platelets, have failed to solve the problem so far. Thrombopoietin [TPO] was recently cloned and identified as the primary cytokine involved in the megakaryocyte maturation and formation of platelets. The predominant site of TPO-production is the liver, where parenchymal cells are the TPO-producing cells. Therefore, thrombocytopenia in chronic liver disease may be related to deficient production of thrombopoietin. Thus, altered TPO production in patients with chronic liver disease may in part explain the thrombocytopenia found in these patients. To evaluate the relationship between serum TPO concentrations, circulating platelet count, and the state of liver pathology in patients with chronic viral hepatitis with and without liver cirrhosis, this study included ninety subjects divided into two main groups. Group A included sixty chronic hepatitis patients and group B included thirty apparently normal age- and sex-matched subjects taken as a control group. Etiology of the chronic hepatitis patients was either HBV or HCV. Group A was further subdivided into subgroup AI including thirty chronic hepatitis patients with liver fibrosis, while subgroup AII included thirty chronic hepatitis patients with liver cirrhosis, who were all of Child A group according to Child score. Ultrasonography as well as liver biopsy were used to differentiate the two subgroups. Thorough history taking, full physical examination, as well as biochemical blood tests in the form of serum albumin and total bilirubin were done. Prothrombin time, platelet counts, as well as serum TPO concentrations were all determined in addition to abdominal ultrasonography to evaluate the splenic size. Our data showed that serum albumin level was decreased and serum bilirubin level was increased in both subgroups AI fibrosis and AII cirrhosis compared to group B controls. Prothrombin time was prolonged in subgroup AII cirrhosis patients compared to both subgroup Al fibrosis and to group B controls. Splenic size was highly significantly increased in subgroup AII cirrhosis patients compared to subgroup AI fibrosis patients who showed larger spleen compared to group B controls as well. Serum TPO levels were significantly increased in subgroup Al fibrosis patients and significantly decreased in subgroup All cirrhosis patients compared to group B controls, moreover, TPO levels were highly significantly decreased in subgroup All patients compared to subgroup Al patients. Thus, our study clarified that decreased serum TPO levels parallel the increased serum biliruhin levels, the deterioration of the protein producing liver ability, as well as the prolonged prothrombin time. Thus, TPO concentrations decreased with the progression of liver disease and the reduction in the functional hepatic mass indicating that thrombocytopenia in chronic liver disease might highly be correlated with the hepatocellular damage. Our study also detected a negative correlation between the spleen size and the platelet counts, meanwhile we also demonstrated that the spleen size does not correlate with the TPO levels. In addition we demonstrated a significant positive correlation between TPO concentrations and platelet counts and a negative correlation between TPO concentrations and prothrombin time. Thus, we denoted that TPO concentration is an independent factor affecting positively the platelet counts in chronic viral hepatitis patients regardless of the splenic size, which is also partially implicated, also it is negatively related to the prothrombin time, which is an indicator of the functioning liver mass. This study concluded that serum TPO concentrations are increased above control levels in chronic viral hepatitis patients with liver fibrosis, but as the condition progresses to cirrhosis, the functioning liver mass decreases and so the TPO concentrations fall. Thus, the impaired TPO synthesis by the diseased liver may contribute to the development of thrombocytopenia in liver cirrhosis. Therefore, TPO deficiency due to reduced production, seems to be a major factor for thrombocytopenia in chronic liver disease although increased splenic sequestration of platelets in the enlarged spleen may also have an additional role. Our findings may suggest that recombinant TPO could possibly be an effective drug to treat patients with liver cirrhosis and severe thrombocytopenia during bleeding episodes or when undergoing surgical procedures. Moreover, it may decrease the incidence of splenectomy, with all its intraand postoperative hazards, done in such conditions