Role of thrombopoietin in thrombocytopenic patients with chronic viral hepatitis with and without liver cirrhosis

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

Hyperhomocysteinemia in end stage renal disease: a risk factor for atherosclerotic and/or thromboembolic complications?

To clarify the association of hyperhomocysteinemia with the increased risk of atherosclerotic and thromboembolic vascular complications in patients with end stage renal disease [ESRD] independent of other traditional risk factors, this study was performed. It included 150 patients with established ESRD scheduled on chronic ambulatory peritoneal dialysis [CAPD] or regular hemodialysis using high-flux membrane. All patients were supplemented with multivitamins including B12, B6 and folic acid. These patients were divided into two groups: Group A included 26 patients with clinically documented peripheral vascular events [ten with deep venous thrombosis and 16 with peripheral arterial disease] and group B included 124 patients without any clinically or laboratory documented vascular disease. In addition, 30 apparently healthy individuals were included as a control group. Total fasting plasma homocysteine as well as other risk factors were determined including hypertension, obesity, smoking, diabetes mellitus, hyperuricemia, dyslipidemia, prolonged recumbency and recent operations or trauma. Biochemical analyses were done including blood glucose levels [fasting and 2-hour postprandial], lipid profile [total cholesterol, triglycerides, HDL, LDL], serum uric acid, BUN and creatinine. Hematological analyses were also done including complete blood count, prothrombin time and concentration, aPTT, protein C, protein S, antithrombin III as well as fibrinogen. Imaging was also performed in the form of duplex ultrasound for peripheral arterial and/or venous systems and/or angiography in the selected cases. It was concluded that hyperhomocysteinemia is frequently seen in ESRD patients and it represents an independent risk factor for the atherosclerotic and thrombotic vascular disorders which occur frequently in these patients. It is higher in hemodialysis patients than in those on chronic ambulatory peritoneal dialysis [CAPD]

Anticardiolipin antibodies in chronic hepatitis C virus infection: is there an aetiopathogenetic link to antiphospholipid syndrome?

Chronic hepatitis c virus [HCV] has always been linked to extrahepatic autoimmune phenomena and found to be associated with various diseases known as extrahepatic manifestations of HCV. In addition, a variety of autoantibodies are detected in HCV patients. Recently HCV has been implicated as a cause of antiphospholipid syndrome [APS] which is usually defined by the association of clinical manifestations that comprise venous and/or arterial thrombosis, recurrent fetal losses, and thrombocytopenia, along with the presence of anticardiolipin [ACL] antibodies and/or lupus anticoagulant. Anticardiolipin antibodies can be induced by various infections diseases, however, they are not associated with thrombotic events as in the case of autoimmune diseases in which they are b2-glycoprotein I dependent and produce thrombotic events. To clarify whether an aetiopathogenesis exists between HCV and APS and meanwhile to study the prevalence, nature, and clinical significant of ACL auto antibodies in serum samples of HCV patients, the present study included one hundred and thirty subjects divided into three groups: a included 50 patients with chronic HCV infection, group b included 30 patients with APS [15 patients with primary and 15 with secondary type], and group c included 50 apparently normal age and sex-matched subjects taken as a control group. Clinical events as well as proper history of APS manifestations were recorded. The prevalence of ACL antibodies was detected by Elisa as well as its IgG and IgM isotypes, its B2-glycoprotein dependence was also evaluated. The present of cryoglobulins and other autontibodies as lupus anticoagulant [LA] and antinuclear antibodies [ANA] were determined as well, using indirect immunofkuorescence. HcVRNA and its viraemia titre were determined by RT-PCR and its quantitative testing. Our data showed that the prevalence of ACL antibodies in chronic HCV patients was found to be 42% which proved to be more than that in the normal controls [0%] but, its presence had no clinical significance. Our study clarified also that there is no significant association between a ACL antibodies and the presence of other auto antibodies or cryoglobulins in those patients. Furthermore, all HCV patients with positive ACL antibodies in our study were B-2 glycoprotein I independent. We concluded that the presence of ACL antibodies in chronic HCV patients seem to be an epiphenomenon and their presence has neither a clinical nor a laboratory significance in this category of patients. Thus, testing for HCV infection in APS patients or follow-up for the possibility of APS development in HCV patients might not be recommended. Thus, our study failed to implicate HCV as an aetiopathogeinc factor for APS