Is inadequate thrombopoietin production a major cause of thrombocytopenia in cirrhosis of the liver?

BACKGROUND/AIMS: Thrombocytopenia secondary to cirrhosis of the liver and portal hypertension is a well-known complication of advanced stage liver disease, but theories about the underlying pathogenetic mechanisms, mostly centering on splenic sequestration and destruction of platelets, have failed to solve the problem so far.

METHODS

Peripheral platelet count and thrombopoietin levels in human plasma were measured in 28 patients with cirrhosis of the liver. Seven of those patients underwent orthotopic liver transplantation and five patients portal decompression by transjugular intrahepatic portosystemic shunt. Thrombopoietin plasma levels were followed for 14 days after the interventions.

RESULTS

No measurable thrombopoietin was detectable in the plasma of 28 thrombocytopenic patients with cirrhosis of the liver, in contrast to thrombocytopenic patients without liver disease. Seven of these patients with cirrhosis underwent orthotopic liver transplantation, resulting in a rise of thrombopoietin levels within 2 days after transplantation. The rise in platelet number followed with a mean lag of 6 days, and shortly thereafter, thrombopoietin levels returned to levels below the limit of detection. Five patients with thrombocytopenia, who underwent only decompression of portal hypertension, showed no rise in either thrombopoietin levels or platelet count.

CONCLUSIONS

Thrombocytopenia associated with liver disease may at least in part be attributable to inadequate thrombopoietin production in the failing liver.