Eltrombopag for Thrombocytopenia in Patients with Cirrhosis Associated with Hepatitis C

McHutchison, John G.; Dusheiko, Geoffrey; Shiffman, Mitchell L.; Rodrı́guez-Torres, Maribel; Sigal, Samuel H.; Bourlière, Marc; Berg, Thomas; Gordon, Stuart C.; Campbell, Fiona; Theodore, Dickens; Blackman, Nicole; Jenkins, Julian; Afdhal, Nezam H.

doi:10.1056/nejmoa073255

Cited by 400 publications

(277 citation statements)

References 17 publications

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“…In addition to splenectomy and partial splenic embolization, administration of thrombopoietin is another method for inducing thrombocytosis. Orally active thrombopoietin receptor agonist increases platelet count in patients with thrombocytopenia due to hepatitis C virusrelated CLD and cirrhosis (McHutchison et al 2007). Thrombocytosis by administering thrombopoietin improves liver regeneration and reduces liver fibrosis in vivo (Murata et al 2007;Murata et al 2008b;Myronovych et al 2008;Watanabe et al 2009).…”

Section: Discussionmentioning

confidence: 99%

Platelet Transfusion Improves Liver Function in Patients with Chronic Liver Disease and Cirrhosis

Maruyama

Murata

Takahashi

et al. 2013

Tohoku J. Exp. Med.

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Section: Discussionmentioning

confidence: 99%

Platelet Transfusion Improves Liver Function in Patients with Chronic Liver Disease and Cirrhosis

Maruyama

Murata

Takahashi

et al. 2013

Tohoku J. Exp. Med.

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“…Eltrombopag is an orally available nonpeptide thrombopoietin (TPO) receptor agonist which interacts with the transmembrane domain of the receptor on bone marrow megakaryocytes and upstream progenitor/ stem cells. It has been studied in patients with chronic idiopathic thrombocytopenic purpura [5] and in patients with thrombocytopenia secondary to hepatitis C infection [6]. Unlike the case with recombinant human TPO, its use has not been associated with anti-platelet antibody production [7].…”

mentioning

confidence: 99%

Use of eltrombopag, a thrombopoietin receptor agonist, in post‐transplantation thrombocytopenia

et al. 2012

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using the STA-Compact instrument (Diagnostica Stago, Parsippany, NJ) was used to quantify anti-Factor Xa (LMWH) activity for enoxaparin. The sensitivity of this assay is 0.2 U/mL and within run imprecision is 5.5 (% CV) at 1 U/mL. The assay is linear between 0.2 and 2.0 U/mL. All anti-Factor Xa levels were analyzed by technicians blinded to the assigned treatment regimen. The target range for peak anti-Factor Xa levels was chosen to be 0.2-0.5 IU/mL [14].Statistical analyses.. The sample size for this pilot study was chosen to provide a cohort large enough to identify differences between groups, based on previous studies [17]. Descriptive statistics were used to calculate summary data. Data are represented as the mean ± SD, unless otherwise indicated. For all analyses, continuous variables were assessed for normality visually and with skewness and kurtosis tests (version 11.0, StataCorp, College Station, TX 77845). Parametric, two-tailed t-tests or ANOVA were used for continuous variables and the chi-square and Fisher's exact test for categorical variables with a predetermined alpha level of P < 0.05. Stepwise, multiple regression analyses were used to identify any pre-specified variables potentially affecting peak anti-Factor Xa levels, including age, actual body weight, BMI, time (enoxaparin dose administration to anti-Factor Xa measurements), gender, or estimated creatinine clearance. AcknowledgmentsAuthors thank all the patients that agreed to participate in this study, Ms. Pam Proctor and Linda Kelly for their research oversight, Dr. Chris Lehman for his assistance with anti-Factor Xa measurements, and Diana Lim for her assistance with illustrations and tables.

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“…Furthermore, eltrombopag has been investigated outside the context of primary chronic ITP in adults, with a report showing that eltrombopag administered to patients with hepatitis C-associated thrombocytopenia with cirrhosis produced a dose-dependent increase in platelet count [60].…”

Section: Chance Of Spontaneous Recoverymentioning

confidence: 99%

Moving towards a new era in the management of chronic immune thrombocytopenia

Wadenvik

Olsson

2010

Ann Hematol

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Immune thrombocytopenia (ITP) is an organspecific autoimmune disease in which a low concentration of plasma thrombopoietin (TPO) contributes to the thrombocytopenia. Functional thrombopoietin deficiency in response to thrombocytopenia is central to the pathophysiology of chronic ITP. Decreased platelet production in ITP patients has been described only in recent years, however. Following the development of TPO-mimetics, it has become clear that the augmentation of thrombopoiesis is a key therapeutic target. TPO mimetics are novel effective treatments providing durable platelet responses in ITP. Two agents have reached clinical practice, the 'peptibody' romiplostim (Nplate®) approved for treatment of thrombocytopenia in patients with chronic ITP in Europe, Canada, Australia and the USA and the non-peptide TPO mimetic, eltrombopag (Promacta®), approved in the USA. This review summarises the background to the development of these agents and presents an update on data from randomised phase III trials and open-label studies. These novel drugs provide a noteworthy treatment option for patients with chronic ITP, in whom thrombocytopenia and bleeding risk have not been controlled by standard treatments. The first candidates for treatment in clinical practice are undoubtedly refractory patients with lack of response to other therapies or at continued risk for bleeding despite treatment. Appropriate inclusion of TPO mimetics into the treatment paradigm will most likely have a positive impact on the long-term outcome of ITP and allow carefully monitored patients to remain well controlled, with good tolerability for prolonged periods.

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Eltrombopag for Thrombocytopenia in Patients with Cirrhosis Associated with Hepatitis C

Abstract: Eltrombopag therapy increases platelet counts in patients with thrombocytopenia due to HCV-related cirrhosis, thereby permitting the initiation of antiviral therapy. (ClinicalTrials.gov number, NCT00110799.)

Cited by 400 publications

References 17 publications

Platelet Transfusion Improves Liver Function in Patients with Chronic Liver Disease and Cirrhosis

Platelet Transfusion Improves Liver Function in Patients with Chronic Liver Disease and Cirrhosis

Use of eltrombopag, a thrombopoietin receptor agonist, in post‐transplantation thrombocytopenia

Moving towards a new era in the management of chronic immune thrombocytopenia

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