Platelet Count Influences Thrombopoietin Metabolism


The biology of thrombopoietin metabolism in advanced liver disease may be influenced by platelet count and degree of liver failure.

The biology of thrombopoietin metabolism in advanced liver disease may be influenced by platelet count and degree of liver failure, according to the results of a new study presented at the 2018 American Association for the Study of Liver Diseases (AASLD) Liver Meeting, November 9-13, 2018, in San Francisco, California.

Thrombocytopenia, otherwise known as low platelet count, is common in patients with chronic liver disease. Thrombopoietin is a cytokine that works to regulate platelet production; however, because of the destructive nature of chronic liver disease on many liver functions, levels of thrombopoietin may be low in patients with the disease. Likewise, the activity of the cytokine may be decreased.

There is not much known about the relationship between thrombopoietin levels and thrombocytopenia severity and the cause of chronic liver disease, as well as hepatic decompensation. As such, a team of investigators led by Stephen Caldwell, MD, professor of medicine, University of Virginia School of Medicine, Charlottesville, Virginia, analyzed baseline thrombopoietin levels in participants enrolled in the ADAPT-1 and ADAPT-2 trials, which were 2 randomized, double-blind placebo-controlled phase 3 trials of 435 adult patients with chronic liver disease and Baseline platelet counts <50x109/L, who were scheduled to undergo a procedure that would require platelet transfusion. They were given a thrombopoietin-receptor agonist avatrombopag or placebo. Based on positive results of the trial, avatrombopag (Doptelet, Dova Pharmaceuticals) was approved in May 2018 to treat thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a medical or dental procedure.

Patients included in the studies were further divided into 2 cohorts for the new analysis, based on their baseline platelet counts. COHORT-1 included patients with low baseline platelet counts (<40x109/L [n = 251 patients]). COHORT-2 included patients with higher baseline platelet counts (40 to <50x109/L [n = 184 patients]). The investigators recorded thrombopoietin levels prior to treatment and characterized them for each cohort based on the following: hepatocellular carcinoma (HCC) status, model for end-stage liver disease (MELD), Child-Turcotte-Pugh (CTP), and liver disease etiology (alcoholic, chronic viral hepatitis, nonalcoholic steatohepatitis), according to the study abstract. Baseline thrombopoietin levels were found to be 126.9 ng/L for COHORT-1 and 116.0 ng/L for COHORT-2.

Patients in COHORT-1 with worsening MELD scores and worsening CTP class were found to have lower levels of thrombopoietin. Conversely, in COHORT-2, those patients with MELD or CTP did not have an observable trend in thrombopoietin levels. Presence of HCC had no impact on thrombopoietin levels in either cohort. No consistent trend was noted in thrombopoietin levels for various liver disease etiologies; however, slight differences were observed.

Based on these results, the authors “hypothesize that [the biology of thrombopoietin metabolism] involves changes in feedback regulation of thrombopoietin levels in addition to impaired hepatic synthesis,” according to the study abstract. In patients with low platelet counts, levels of thrombopoietin are dependent on the capacity of liver synthesis.

The abstract, “Characterization of Baseline Thrombopoietin Levels in Patients with Chronic Liver Disease: Results from 2 Pooled Clinical Studies in Patients with Thrombocytopenia and Liver Disease,” was presented at AASLD.

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