Thrombopoietin in acute liver failure

Abstract

Thrombopoietin (TPO) is the primary regulator of platelet production. TPO is produced in the liver and levels are low in patients with cirrhosis. Because thrombocytopenia is common in patients with acute liver failure (ALF), we measured TPO concentrations (normal TPO range, 31 to 136 pg/mL) in 51 patients with ALF to determine if low levels were associated with thrombocytopenia. TPO levels from hospital day 2 were elevated in 43% of patients, normal in 47%, and decreased in 10% of patients. Levels were higher in acetaminopheninduced than in non-acetaminophen-induced ALF, 160 (12 to 549) pg/mL versus 73 (18 to 563) pg/mL, respectively, P ‫؍‬ .031. TPO levels did not correlate with platelet count and were not related with survival or infection. We analyzed daily TPO levels for the first week of hospitalization in 12 patients with acetaminophen-induced ALF and observed a gradual increase from a median admission level of 50 (5 to 339) pg/mL to a median peak level of 406 (125 to 1,081) pg/mL occurring on day 5 (3 to 6). Platelets were reduced in 11 of the 12 patients with a nadir platelet count of 52 (19 to 156) ؋ 10 9 cells/L occurring on day 5.5 (1 to 6). The peak TPO level did not correlate with the nadir platelet count (P ‫؍‬ .43). In conclusion, the normal inverse relationship between platelet count and TPO levels was not observed in ALF. Despite severe hepatic dysfunction, serum TPO levels were initially normal and increased during hospitalization in acetaminophen-induced ALF, but did not prevent the development of thrombocytopenia. (HEPATOLOGY 2003;37:558-561.)

Intratracheal instillation of cerium oxide nanoparticles induces hepatic toxicity in male Sprague-Dawley rats

“…Elevation in these serum biomarkers is thought to be highly correlated with acute hepatic injury. 22,32 Taken together, these data suggest that ceria deposition may be associated with liver damage. Given our findings that CeO 2 nanoparticle instillation, at least at the levels used in the current study, does not induce appreciable damage to the heart, kidney, or spleen.…”

Thrombocytopenia Is Associated With Multi-organ System Failure in Patients With Acute Liver Failure

“…Serum concentrations of thrombopoietin, a liver-derived hormone, do not correlate with the degree of thrombocytopenia and have been shown to be normal or increased in patients with ALF 14 , suggesting the presence of other mechanisms. In patients with ALF, we have recently shown that the plasma concentrations of pro-thrombotic microparticles, the majority of which were platelet-derived, increased in proportion to the severity of the SIRS 15 .…”

Synergism Between Hepatocellular Injury and Shunting in Portosystemic Encephalopathy (PSE): Case Report of Acute Brittle TIPS-Induced PSE

“…Several studies have shown that both in animal models [30] and in humans with cirrhosis [31][32][33], thrombocytopenia is due to a combination of splenic sequestration of platelets and reduced thrombopoietin production, a primary regulator of platelet production. However, the only study that has evaluated thrombopoietin production in acute liver failure evaluated patients with acetaminophen-induced acute liver failure and could not correlate thrombocytopenia with thrombopoietin levels [34].…”