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

Peck‐Radosavljevic, Markus; Zacherl, Johannes; Meng, Yuesheng; Pidlich, Johann; Lipinski, Emanuel; Längle, F.; Steininger, R.; Mühlbacher, Ferdinand; Gangl, Alfred

doi:10.1016/s0168-8278(97)80291-7

Cited by 159 publications

(131 citation statements)

References 14 publications

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“…Platelet count on day 2 was 139 (31 to 328) ϫ 10 9 cells/L; the nadir platelet count was 80 (16 to 283) ϫ 10 9 cells/L and occurred on median day 3. [1][2][3][4][5][6][7] Platelet counts did not differ significantly between acetaminophen and nonacetaminophen patients.…”

Section: Resultsmentioning

confidence: 99%

Thrombopoietin in acute liver failure

et al. 2003

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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.)

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Section: Resultsmentioning

confidence: 99%

Thrombopoietin in acute liver failure

et al. 2003

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“…8,9,19,20 Furthermore, Ishikawa et al 20 measured in weekly intervals the TPO mRNA/GAPDH mRNA ratios in livers from rats treated with dimethylnitrosamine, which causes cirrhosis. The authors noted a progressive decrease in hepatic TPO mRNA levels for the 4-week observation period, which was related to reduced TPO mRNA expression by parenchymal cells as well as the loss of hepatocytes.…”

Section: Discussionmentioning

confidence: 99%

“…Some investigators have proposed that impaired production of TPO may also play a role. 8,9 Others measured no differences in serum TPO concentrations when the values were compared in normal persons and cirrhotic patients. 10 In a recent editorial in HEPATOLOGY, 11 the need for additional studies on TPO production in cirrhotic patients was indicated.…”

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confidence: 99%

Hepatic thrombopoietin mRNA levels in acute and chronic liver failure of childhood

Wolber¹,

Ganschow

Burdelski

et al. 1999

Hepatology

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The liver is the main production site of the hormone thrombopoietin (TPO), the major regulator of megakaryopoiesis. To investigate the role of an impaired TPO gene expression in the pathogenesis of thrombocytopenia in pediatric patients suffering from liver failure, we measured hepatic TPO mRNA in children with acute or chronic end-stage liver disease undergoing orthotopic liver transplantation. Tissue samples for RNA extraction were obtained from 12 children with compensated cirrhosis (CC), 22 children with decompensated cirrhosis (DC), and 9 children with acute liver failure (ALF). The glycoprotein hormone, thrombopoietin (TPO), is the major regulator of megakaryopoiesis and platelet production. 1,2 Northern blot analyses have demonstrated that TPO mRNA is expressed predominantly in liver, and to a minor degree, in kidney, spleen, and brain. 3,4 A recent report from this laboratory has shown that hepatic TPO mRNA accounts for 94% of the total in the perinatal period. 5 In situ hybridization studies have localized TPO mRNA in parenchymal cells of the human 6 and murine 7 liver. Hepatocytes appear to produce TPO at a constant rate. The plasma concentration of the hormone is regulated by the degree of receptor-mediated binding and degradation of TPO by platelets and, in all likelihood, megakaryocytes.

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“…Although there are some conflicting reports, most studies have shown inappropriately low endogenous TPO levels in cirrhotic patients with thrombocytopenia. [13][14][15] An inverse relationship between TPO levels and platelet counts has not been found in cirrhotic patients with thrombocytopenia. Several studies have also evaluated serial plasma TPO levels in cirrhotic patients undergoing liver transplantation.…”

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confidence: 99%

“…Several studies have also evaluated serial plasma TPO levels in cirrhotic patients undergoing liver transplantation. 13,15 In 16 of 17 patients undergoing liver transplantation at the University of California, San Francisco, the TPO levels, which were low or undetectable before transplantation, became detectable within 3 days post-transplantation. Peak TPO levels occurred by approximately 1 week posttransplantation and all patients had normalization of their platelet counts.…”

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confidence: 99%