• hemp3quilt posted an update 4 months, 1 week ago

    A clear threshold of platelet counts, below which the bleeding risk clearly increases, cannot be proposed, but the following data provide some insight. http://www.selleckchem.com In patients from the HALT-C trial, 75% of liver biopsy-related haemorrhages occurred in patients with platelet counts below 60,000/μl [5]. In an Italian study, analysing bleeding events after common diagnostic and therapeutic interventions in 125 patients with cirrhosis and thrombocytopenia, bleeding occurred in 32% of those with platelet counts below 75,000/μl, compared to none of those with platelet counts between 75 and 150,000/μl [6]. The platelet count was a better predictor of bleeding than the international normalized ratio (INR). Thrombocytopenia in cirrhosis is of multifactorial origin (Fig. 1), resulting from splenic sequestration of platelets, increased destruction of platelets within the spleen, intrasplenic production of autoantibodies, plasma expansion resulting in haemodilution and decreased activity of thrombopoietin [7]. The liver is an important site of thrombopoietin production. Levels of circulating thrombopoietin, as well as those of messenger RNA in hepatocytes, are decreased in patients with cirrhosis and are restored in the weeks following liver transplantation [8], [9] and [10]. This study by Terrault et al. is important because it is the first published experience of the second-generation thrombopoietin receptor agonist avatrombopag in patients with CLD and paves the way for a larger, phase III trial. Experience from the first-generation thrombopoietin receptor agonists, romiplostim and eltrombopag, in patients with CLD warrants a note of caution. Romiplostim, a parenteral thrombopoietin analogue administered weekly, seemed promising in raising platelet counts before elective minor surgeries (mostly cataract, hernia and fracture fixation) in patients with Child-Pugh C hepatitis C-related cirrhosis and severe thrombocytopenia (<50,000/μl) in a small single-centre, single-arm, open-label Egyptian study [11]. In the ELEVATE trial, 292 patients with thrombocytopenia (<50,000/μl) and CLD were randomized to receive eltrombopag or placebo for 14 days before an invasive procedure, again mostly dental or endoscopic [12]. The drug avoided platelet transfusions in a large number of patients (72% vs. 19%). However, PVT developed in 4% of patients in the eltrombopag group as compared to 1% in the placebo group. This finding led to the early termination of the trial. Eltrombopag has also been tested in patients with hepatitis C-related cirrhosis and thrombocytopenia to increase platelet counts and permit interferon-based therapy.