Effects of Lusutrombopag on Post-invasive Procedural Bleeding in Thrombocytopenic Patients with Chronic Liver Disease

Abstract

Introduction Thrombocytopenia can increase the bleeding risk in patients with chronic liver disease (CLD) undergoing invasive procedures. Prophylactic platelet transfusion (PT) is often performed to increase platelet counts in patients with CLD undergoing invasive procedures to prevent bleeding. Lusutrombopag, a small-molecule thrombopoietin receptor agonist, is expected to be an alternative therapy to prophylactic PT. This study aimed to compare the effects between lusutrombopag and PT. Methods Data were obtained from a Japanese administrative database (April 2008–May 2019). Patients aged ≥ 18 years who underwent planned invasive procedures after the first CLD diagnosis and were observed for ≥ 30 days prior to invasive procedures were considered eligible. Patients who underwent planned invasive procedures with lusutrombopag prescription at 5–30 days before the procedure were categorized as the lusutrombopag group, whereas those who received PT at 1 day before and/or on the same day as the procedure, without lusutrombopag prescription, were classified as the PT group. Outcomes, including bleeding frequency during hospitalization and average medical costs (costs for prophylactic treatment and total costs between the day of the invasive procedure and 30 days after the invasive procedure), were compared between the groups after matching. Results Among 738,878 patients with CLD, 379 cases for each group were identified after matching. The incidence of bleeding events was lower in the lusutrombopag group than in the PT group (3.7% vs. 8.2%, p < 0.001). Average medical costs were lower in the lusutrombopag group than in the PT group ($6667 as of August 2021 vs. $7170, p = 0.011). Conclusion Lusutrombopag is suggested to be effective as a prophylactic treatment for bleeding prevention in patients with CLD undergoing planned invasive procedures. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01965-7.

Thrombocytopenia in chronic liver disease: Physiopathology and new therapeutic strategies before invasive procedures

“…In addition, the efficacy and safety of the drug have been confirmed in a retrospective Japanese study based on hospital administrative databases. Here the incidence of bleeding events was lower in the lusutrombopag group than in the platelet transfusion group (3.7% vs 8.2%, P < 0.001), with a consequently lower average medical cost[ 85 ]. Finally, real-world data for adverse events (spontaneously reported by healthcare professionals and consumers in a database including about 4000 patients exposed to lusutrombopag from December 2015 to April 2018) confirm the efficacy and the safety of the drug (93% of patients did not require pre-procedural platelet transfusion; 1.2% of serious adverse events, with 0.4% cases of portal vein thrombosis)[ 86 ].…”

Safety and effectiveness of lusutrombopag in patients who have chronic liver disease with thrombocytopenia and undergoing invasive procedures: Real‐world post‐marketing surveillance in Japan

“…The proportion of patients who reported bleeding events was 2.23% (23/1033 patients), and lower than those of two previous studies: (1) a secondary analysis of lusutrombopag studies (phase 2b, L‐PLUS 1, and L‐PLUS 2) reporting a bleeding‐related AEs rate of 11.9% in patients receiving placebo with platelet transfusion and 6.5% in patients receiving lusutrombopag without platelet transfusion 21 ; and (2) a database study in Japan reporting bleeding events in 8.2% of the platelet transfusion group and 3.7% of the lusutrombopag treatment group 22 . These results suggested that lusutrombopag is an effective prophylactic treatment to prevent bleeding in CLD patients undergoing planned invasive procedures.…”

Tips for Preparing and Practicing Thermal Ablation Therapy of Hepatocellular Carcinoma

“…Although hemorrhagic complications are rare with percutaneous ablation therapy, thrombocytopenia or platelet dysfunction in patients with chronic liver disease may increase the risk of post-operative bleeding following invasive procedures [28], and platelet transfusions may be advised in clinical practice for platelet counts <50,000/µL. Additionally, lusutrombopag, an orally active, small-molecule thrombopoietin receptor agonist that induces the production of endogenous platelets, may be used as prophylaxis to reduce the risk of bleeding [29,30]. However, the use of platelet transfusions to prevent post-operative bleeding is controversial because it has not yet been established whether prophylactic platelet transfusion is superior to no prophylaxis, if the platelet count threshold is appropriate as a guide to initiate the transfusion of prophylactic platelets, and what dose of platelets is needed to prevent post-operative bleeding [31,32].…”