Thrombopoietin receptor agonists and risk of portal vein thrombosis in patients with liver disease and thrombocytopenia: A meta-analysis

Loffredo, Lorenzo

doi:10.1016/j.dld.2018.06.005

Cited by 25 publications

(30 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…There were four thrombotic TEAEs in this study, two in each group; all were asymptomatic and found as per prespecified, protocol‐defined, or routine imaging. These findings are consistent with a recently published meta‐analysis revealing the prevalence of portal vein thrombosis to be 2.8% in patients with liver disease and thrombocytopenia who were undergoing an elective invasive procedure and treated with TPO receptor agonists . The median maximum PC in patients treated with lusutrombopag was 85.0 × 10 9 /L, with only 1 patient in this study reporting a PC ≥ 200 × 10 9 /L.…”

Section: Discussionsupporting

confidence: 92%

Lusutrombopag for the Treatment of Thrombocytopenia in Patients With Chronic Liver Disease Undergoing Invasive Procedures (L‐PLUS 2)

et al. 2019

View full text Add to dashboard Cite

Thrombocytopenia may be associated with increased bleeding risk impacting timing and outcome of invasive procedures in patients with chronic liver disease (CLD). Lusutrombopag, a small‐molecule, thrombopoietin (TPO) receptor agonist, was evaluated as a treatment to raise platelet counts (PCs) in patients with thrombocytopenia and CLD undergoing invasive procedures. L‐PLUS 2 was a global, phase 3, randomized, double‐blind, placebo‐controlled study. Adults with CLD and baseline PCs < 50 × 109/L were randomized to receive once‐daily lusutrombopag 3 mg or placebo ≤ 7 days before an invasive procedure scheduled 2‐7 days after the last dose. The primary endpoint was avoidance of preprocedure platelet transfusion and avoidance of rescue therapy for bleeding. A key secondary endpoint was number of days PCs were ≥ 50 × 109/L throughout the study. Safety analysis was performed on patients who received at least one dose of study drug. This study occurred between June 15, 2015, and April 19, 2017, with a total of 215 randomized patients (lusutrombopag, 108; placebo, 107); 64.8% (70/108) of patients in the lusutrombopag group versus 29.0% (31/107) in the placebo group met the primary endpoint (P < 0.0001; difference of proportion 95% confidence interval [CI], 36.7 [24.9, 48.5]). The median duration of PCs ≥ 50 × 109/L was 19.2 days with lusutrombopag (without platelet transfusion) compared with 0.0 in the placebo group (with platelet transfusion) (P = 0.0001). Most adverse events were mild or moderate in severity, and rates were similar in the lusutrombopag and placebo groups (47.7% and 48.6%, respectively). Conclusion: Lusutrombopag was superior to placebo for reducing the need for platelet transfusions and achieved durable PC response in patients with thrombocytopenia and CLD undergoing invasive procedures, with a safety profile similar to placebo.

show abstract

Section: Discussionsupporting

confidence: 92%

Lusutrombopag for the Treatment of Thrombocytopenia in Patients With Chronic Liver Disease Undergoing Invasive Procedures (L‐PLUS 2)

et al. 2019

View full text Add to dashboard Cite

show abstract

“…However, a recent meta-analysis of TPO agonists showed that the risk of thrombosis is elevated with eltrombopag only and that avatrombopag and lusutrombopag are associated with minimal risk. 18 However, a larger-scale study and postmarketing surveillance are required to better characterize the risk of thrombotic events more definitively. Third, the invasive procedures performed in the present study were of a minimal to moderately invasive nature and resulted in few bleeding-related events; therefore, the decrease in bleeding-related events with lusutrombopag treatment should be assessed in further studies with patients undergoing more invasive procedures.…”

mentioning

confidence: 99%

Lusutrombopag Reduces Need for Platelet Transfusion in Patients With Thrombocytopenia Undergoing Invasive Procedures

Hidaka

Kurosaki

Tanaka

et al. 2019

Clinical Gastroenterology and Hepatology

189

View full text Add to dashboard Cite

“…A recent meta-analysis from Italy analyzed three of the TPO agonists for risk of PVT-lusutrombopag, avatrombopag, and eltrombopag. 51 In four studies which included 1,953 patients, the risk of PVT was 1.6% in those receiving TPO receptor agonists and 0.6% in the placebo group. There was a trend for an enhanced incidence of PVT in patients treated with TPO receptor agonists compared with placebo, but the difference did not reach significance (OR: 2.8; 95% CI: 0.97-8.16; p ¼ 0.055).…”

Section: Risk Of Portal Vein Thrombosismentioning

confidence: 99%

“…Importantly, a significant association between PVT and TPO receptor agonists was observed only in patients treated with eltrombopag (OR: 3.8; 95% CI: 1.14-13.2; p ¼ 0.03). 51 A further analysis was performed in this same study to assess the effect of TPO receptor agonists versus placebo on PVT in patients with liver disease and thrombocytopenia, who were undergoing an elective invasive procedure. Three studies, including 514 patients, were analyzed; the follow-up was 1 month.…”

Section: Risk Of Portal Vein Thrombosismentioning

confidence: 99%

“…No significant difference was found for incidence of PVT in patients treated with TPO receptor agonists compared with placebo (OR: 2.6; 95% CI: 0.6-11.6; p ¼ 0.212). 51 The analysis also assessed the incidence of arterial and venous thromboembolic events in two studies that included a total of 1,727 patients. These patients were randomized to either eltrombopag or placebo.…”

Section: Risk Of Portal Vein Thrombosismentioning

confidence: 99%

See 1 more Smart Citation

Thrombopoietin Receptor Agonists in Patients with Chronic Liver Disease

Khemichian

Terrault

2020

Semin Thromb Hemost

View full text Add to dashboard Cite

Thrombocytopenia 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.

show abstract

Thrombopoietin receptor agonists and risk of portal vein thrombosis in patients with liver disease and thrombocytopenia: A meta-analysis

Cited by 25 publications

References 8 publications

Lusutrombopag for the Treatment of Thrombocytopenia in Patients With Chronic Liver Disease Undergoing Invasive Procedures (L‐PLUS 2)

Lusutrombopag for the Treatment of Thrombocytopenia in Patients With Chronic Liver Disease Undergoing Invasive Procedures (L‐PLUS 2)

Lusutrombopag Reduces Need for Platelet Transfusion in Patients With Thrombocytopenia Undergoing Invasive Procedures

Thrombopoietin Receptor Agonists in Patients with Chronic Liver Disease

Contact Info

Product

Resources

About