The Role of Thrombopoietin in the Thrombocytopenia of Patients with Liver Cirrhosis

OBJECTIVES: Thrombocytopenia is a common disorder among cirrhotics that has been traditionally explained by splenic platelet pooling and destruction. Thrombopoietin (TPO), the main stimuli for thrombopoiesis is produced primarily in the liver and degraded by circulating platelets, but its role in the thrombocytopenia of liver cirrhosis is not well understood. The main goal of this study is to clarify the role of TPO in the pathogenesis of thrombocytopenia in cirrhosis. METHODS: The relation among TPO, platelet count, spleen size, portal hypertension, and liver function was studied in 33 cirrhotic patients before and after either partial splenic embolization or liver transplantation. RESULTS: Cirrhotics with thrombocytopenia had lower serum TPO levels than healthy controls (median values (interquartile range: ICR) were 120.7 (42.0-191.6) vs 756.4 (527.0-965.1) pg/mL, respectively; p<0.001). Among cirrhotics with thrombocytopenia, serum TPO was related to spleen size (rho=-0.387, p=0.046), but not to platelet count as occurs physiologically. After partial splenic embolization, TPO and platelet count increased significantly and the physiological relation between TPO and platelet count was restored (rho=-0.665, p=0.026). Similar results were observed after liver transplantation. CONCLUSIONS: Our results suggest that besides impaired production in the failing liver, an increased TPO degradation by platelets sequestered in the congested spleen may contribute to thrombocytopenia in cirrhotic patients.