Su1468 - Superiority of Avatrombopag to Placebo in Increasing Platelet Counts and Reducing Platelet Transfusions in Patients with Chronic Liver Disease-Associated Thrombocytopenia Undergoing Scheduled Procedurespooled Analysis of 2 Randomized Phase 3 Studies

2018 ◽  
Vol 154 (6) ◽  
pp. S-529 ◽  
Author(s):  
Fred Poordad ◽  
Michael Vredenburg ◽  
Lee F. Allen ◽  
Kavita Aggarwal ◽  
Naim Alkhouri
Keyword(s):  
Liver Disease ◽  
Chronic Liver Disease ◽  
Chronic Liver ◽  
Phase 3 ◽  
Platelet Counts ◽  
Platelet Transfusions

Thrombopoietin Receptor Agonists in Patients with Chronic Liver Disease

2020 ◽  
Vol 46 (06) ◽  
pp. 682-692
Author(s):  
Saro Khemichian ◽  
Norah A. Terrault
Keyword(s):  
Liver Disease ◽  
Chronic Liver Disease ◽  
Invasive Procedure ◽  
Bleeding Risk ◽  
Chronic Liver ◽  
Bleeding Complications ◽  
Invasive Procedures ◽  
Platelet Counts ◽  
Receptor Agonists ◽  
Platelet Transfusions

AbstractThrombocytopenia is one of the most common hematologic complications in cirrhosis. Despite limited data linking platelet count and bleeding risk in patients with cirrhosis, the use of platelets transfusions for invasive procedures has been a common practice. Recently, thrombopoietin (TPO) receptor agonists have been approved for use in patients with chronic liver disease (CLD) undergoing invasive procedures. The aim of this study was to review current literature on bleeding risk in patients with cirrhosis and the use of platelet transfusions and TPO receptor agonists in the context of invasive procedures. PubMed search was conducted to find articles relating to cirrhosis, thrombocytopenia, and new novel treatments for this condition. Search terms included CLD, cirrhosis, thrombocytopenia, bleeding, thrombosis, coagulopathy, hemostasis, and TPO receptor agonists. Romiplostim, eltrombopag, avatrombopag, and lusutrombopag are approved TPO receptor agonists, with avatrombopag and lusutrombopag specifically approved for use in patients with CLD undergoing invasive procedures. In patients with platelet counts < 50,000/mm3, avatrombopag and lusutrombopag increased the platelet counts above this threshold in the majority of treated patients and reduced the frequency of platelet transfusions. At the approved doses, incidence of thrombosis was not increased and therapies were well tolerated. Studies were not powered to assess whether risk of bleeding complications was reduced and the fundamental question of whether correction of thrombocytopenia is warranted in patients undergoing invasive procedures remains unanswered. The use of TPO receptor agonists has resulted in less requirement for platelet transfusions. In patients with cirrhosis undergoing invasive procedures for whom platelet transfusion is planned, TPO receptor agonists are an alternative and avoid the risks associated with transfusions. However, there is need for a thoughtful approach to manage bleeding risk in patients with cirrhosis undergoing procedures, with the consideration of a comprehensive hemostatic profile, the severity of portal hypertension, and the complexity of the invasive procedure to guide decisions regarding transfusions or use of TPO receptor agonists.

scholarly journals Avatrombopag, an Alternate Treatment Option to Reduce Platelet Transfusions in Patients with Thrombocytopenia and Chronic Liver Disease-Integrated Analyses of 2 Phase 3 Studies

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Fred Poordad ◽  
Norah A. Terrault ◽  
Naim Alkhouri ◽  
Wei Tian ◽  
Lee F. Allen ◽  
...  
Keyword(s):  
Platelet Count ◽  
Liver Disease ◽  
Chronic Liver Disease ◽  
Treatment Option ◽  
Platelet Transfusion ◽  
Chronic Liver ◽  
Phase 3 ◽  
Baseline Platelet Count ◽  
Link Type ◽  
Platelet Transfusions

Aims. Thrombocytopenia complicates the management of patients with chronic liver disease (CLD) undergoing invasive procedures with a bleeding risk. Until recently, prophylactic platelet transfusion was the only treatment option, but has significant safety and efficacy limitations. Phase 3 data demonstrated the superiority of avatrombopag to placebo in reducing platelet transfusions for bleeding, supporting its recent approval. Methods. Integrated analyses of pooled data (N=435) from two randomized, double-blind, placebo-controlled, phase 3 studies assessed the original efficacy endpoints. Additional analyses included subgroup analyses, alternate Baseline platelet count definitions, and another efficacy endpoint. Results. Avatrombopag was superior to placebo in increasing patients not requiring a platelet transfusion or rescue procedure, those achieving a platelet count ≥50 × 109/L on Procedure Day, and the change in platelet counts from Baseline. The avatrombopag treatment effect was consistently positive across clinically important disease and Baseline clinical characteristic subgroups, and using alternate Baseline platelet count cohort definitions. Similarly, more avatrombopag-treated patients achieved ≥50 × 109/L platelets with an increase of ≥20 × 109/L from Baseline. The incidence and severity of adverse events were similar between avatrombopag and placebo. Further, safety data demonstrated a low risk for thromboembolic events and hepatotoxicity. Conclusion. These integrated analyses confirmed the superiority of avatrombopag to placebo in reducing platelet transfusions or rescue procedures for bleeding in patients with thrombocytopenia and CLD scheduled to undergo an invasive procedure, and its tolerable safety profile. Importantly, these data warrant reconsideration of clinical decision making regarding the need to treat thrombocytopenia in patients with CLD. This trial was registered with NCT01972529 and NCT01976104.

scholarly journals The burden associated with thrombocytopenia and platelet transfusions among patients with chronic liver disease

2019 ◽  
Vol 23 (4) ◽  
pp. 378-385 ◽  
Author(s):  
Mohamed I. Elsaid ◽  
Vinod K. Rustgi ◽  
Nicole Loo ◽  
Kavita Aggarwal ◽  
Josephine Li-McLeod ◽  
...  
Keyword(s):  
Liver Disease ◽  
Chronic Liver Disease ◽  
Chronic Liver ◽  
Platelet Transfusions
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