ABSTRACT
Background: thrombopoietin [TPO] is an important regulator of megakaryocyte maturation and platelet production. The role of TPO [which is mainly produced by the liver] in thrombocytopenic cirrhotic patients is still under investigation. The aim of this study was to measure the serum TPO levels in cirrhotic patients and examine its relationship with circulating platelet count, splenic size and clinical stage of liver cirrhosis
Study design and methods: this study was conducted on 88 subjects, divided into 2 groups, group I [patient group] included 72 patients with liver cirhosis [diagnosed by combination of clinical, laboratory, ultrasound and histopathological data], they were further divided into 2 subgroups, group IA: included cirrhotic patients with thrombocytopenia [36 patients, 28 males and 8 females with age 50.3:8.5 years], and group IB: included cirrhotic patients with normal platelet count [36 patients, 26 males and 10 females, with age 50.64+/-6.8 years]. Group ll comprised 16 healthy persons with matched age and sex, used as a control group. All included persons were subjected to: thorough history taking, full clinical examination, beside the following investigations: complete blood picture, kidney and liver function tests, Hepatitis B and C markers, serum TPO level [by sensitive sandwich ELISA] and abdominal Doppler ultrasound. The following invasive investigations were done for group I [patients] only: bone marrow aspiration, upper gastrointestinal endoscopy, sigmoidoscopy and liver biopsy [the latter was done for 21 patients only]. Patients with pure schistosomal fibrosis were excluded from the study. Patients were classified according to the Child-Pugh score into 3 classes of clinical severity A, B and C
Results: cirrhotic patients were thrombocytopenic in comparison to control [P<0.0001]. Serum TPO levels were lower in cirrhotic patients [130.6-79 Pg/mi] than control group [225.5-36 pg/m] [P<0.0001] and also in patients with thrombocytopenia [101-77.5 pg/m] than in patients with normal platelet count [160.2-70.3 pg/m] [P<0.001]. TPO had a significant positive correlation with platelet count [P-0.0001 for sub-group IA and P=0.04 for subgroup 1B]. However serum TPO did not correlate with spleen size. Splenic size had a significant negative correlation with platelet count in cirrhotic patients [P-0.03 for subgroup IA and P=0.004 for subgroup 1B]. In cirrhotic patients, serum TPO levels were found to be decreased as the disease progressed in subgroup IA, 188.25+73.05 pg/ml in patients of Child-Pugh class A, 63.8:23.28 pg/ml in class B and 51:26 pg/ml in class C, while in group 1B, 247.3:40.49 pg/ml in class A 121.3+/-29.6 pg/ml in class B and 112+/-27 pg/ml in class C]. Child-Pugh score has a significant negative correlation with TPO level in both sub-groups IA and 1B [P=0.0001] and with platelet count [P=0.0001 for subgroup IA and 0.01 for subgroup IB], but no significant correlation with spleen size. In comparing class A, B and C in both subgroups [IA and IB], spleen size was significantly larger in Child class A of subgroup IA when compared to same class of subgroup 1B [P-0.0001] with slight significant decrease in TPO in class A of subgroup I than class A of subgroup B [p-0.02]
Conclusion: we concluded that low TPO production may play a role, along with hypersplenism, in the development of thrombocytopenia in patients with liver cirrhosis. In early stage of cirrhosis [Child-Pugh class A], splenomegaly and hypersplenism may be the main path mechanism of thrombocytopenia. While advanced liver cirrhosis [Child-Pugh class B and C], causing more reduction in TPO production, plays a central role in the pathogenesis of thrombocytopenia