scholarly journals Pharmacokinetic/Pharmacodynamic Modelling and Simulation of Lusutrombopag, a Novel Thrombopoietin Receptor Agonist, for the Treatment of Thrombocytopenia in Patients with Chronic Liver Disease Undergoing Invasive Procedures

2019 ◽  
Vol 58 (11) ◽  
pp. 1469-1482 ◽  
Author(s):  
Takayuki Katsube ◽  
Ryosuke Shimizu ◽  
Takahiro Fukuhara ◽  
Takeshi Kano ◽  
Toshihiro Wajima
2019 ◽  
Vol 38 (4) ◽  
pp. 329-334 ◽  
Author(s):  
Yuki Tsuji ◽  
Hideto Kawaratani ◽  
Koji Ishida ◽  
Daisuke Kaya ◽  
Takuya Kubo ◽  
...  

Aims: Thrombocytopenia is a common complication among patients with chronic liver disease (CLD). To increase platelet counts, lusutrombopag, a small-molecule, second-generation thrombopoietin receptor agonist, was developed in September 2015. Lusutrombopag is mainly used in patients with platelet counts <50,000/µL. However, its usefulness in patients with platelet counts ≥50,000/µL remains unknown. We studied the effectiveness of lusutrombopag administration in patients with platelet counts of ≥50,000/µL. Methods: We evaluated 36 patients who received lusutrombopag for CLD. Changes in platelet counts were evaluated. A treatment response was defined as an increasing platelet count ≥20,000/µL from baseline after drug administration. The differences related to these changes between platelet counts ≥50,000 and <50,000/µL were evaluated. Results: Of the patients, 25 had platelet counts ≥50,000/µL. The increase in platelet count and the date in which it reached a maximum did not significantly differ between the groups. The effectiveness of lusutrombopag did not significantly differ between the groups. In both groups, no adverse reaction was observed during lusutrombopag administration. Conclusion: In this study, we showed the effectiveness of lusutrombopag, which had no complications. This study is the first to report that the effectiveness of lusutrombopag was the same for patients with platelet counts ≥50,000/µL and <50,000/µL.


2020 ◽  
Vol 13 (2) ◽  
pp. 863-866
Author(s):  
Sabah E. Mohamed ◽  
Mohamed A. Yassin

Off-label drug use refers to drug use beyond the specifications authorized for marketing [J Med Case Rep. 2014 Dec;8(1):303]. Eltrombopag is a thrombopoietin receptor agonist that has been used in treating thrombocytopenia due to chronic liver disease (CLD) as an off-label medication. Treatment of thrombocytopenia in patients with CLD constitute a real dilemma as the options are limited and some of them are invasive. However, thrombopoietin receptor agonist has been increasingly used for this purpose. Here we report a 34-year-old woman who has been diagnosed with CLD due to autoimmune hepatitis 20 years ago. Her condition was complicated with portal vein thrombosis, chronic thrombocytopenia, and variceal hemorrhage, and she has been listed as a candidate for liver transplantation. Given her high risk of bleeding, we started her on low dose of eltrombopag (25 mg daily) in order to maintain a platelet level of ≥50 × 103/µL. However, 1 year after initiation of the therapy, she developed left lower limb deep vein thrombosis.


Author(s):  
Alexandra Ballantine ◽  
Daniel Martin ◽  
Sonali V Thakrar

The coagulopathy of chronic liver disease causes derangement of the results of traditional laboratory tests. As such, there is an expectation that when undergoing invasive procedures patients with cirrhosis are at increased risk of bleeding. Standard practice is to optimise laboratory values with prophylactic transfusions of platelets, plasma and fibrinogen to reduce perceived bleeding risk. There has been a shift in thinking regarding coagulation in patients with chronic liver disease, whereby a rebalancing of haemostasis occurs with reduction in both procoagulants and anticoagulants. Guidelines for the preprocedural management of patients with chronic liver disease are inconsistent and may not account for this new paradigm. The risk of prophylactic transfusion should be measured against the risk of bleeding while considering the rebalancing of haemostasis. Future management may be guided by whole blood viscoelastic tests or use of thrombopoietin receptor agonists to optimise patients in these scenarios.


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