Thrombopoietin-receptor agonists in perioperative treatment of patients with chronic liver disease

Table 1 Efficacy and safety results from clinical trials studying the effect of perioperative use of thrombopoietin-receptor agonists in patients with thrombocytopenia

Ref.	Dosing	Efficacy results	AEs
Romiplostim
Basu et al[38], 2012	65 patients with CLD and thrombocytopenia randomized 1:1:1 to 500 μg romiplostim: 75 mg eltrombopag: 7 units of platelet transfusion	Improved platelet count > 180 × 109/L in all groups	Nausea, vomiting, dry mouth, headache, insomnia, irritability, local skin rash, shortness of breath, myalgia, arthralgia, erythema
Moussa et al[3], 2013	35 male patients with thrombocytopenia and CLD secondary to hepatitis C infection, dosed 2 μg/kg romiplostim weekly	Improved platelet count ≥ 70 × 109/L	No serious AEs reported
Marshall et al[39], 2015	18 patients with various etiologies of thrombocytopenia, including CLD, undergoing wide range of procedures	Improved platelet counts in all patients; all patients could receive surgery without delay or cancellation	No venous thromboembolic events
Al-Samkari et al[9], 2018	48 patients with various etiologies of thrombocytopenia, including CLD, undergoing 51 procedures, dosed 3 μg/kg romiplostim weekly (range 1-10 μg/kg/wk)	Improved platelet counts achieved in all patients after 1, 2 or 3 doses	Bleeding and thromboembolic events within acceptable limits
Eltrombopag
ELEVATE (Eltrombopag); Afdhal et al[11], 2012	292 patients with CLD administered	Platelet transfusion not required in 72% of patients in the eltrombopag group and 19% of patients in the placebo group	Early study termination due to six portal vein thrombotic events in the eltrombopag group; headache, pyrexia, abdominal pain, diarrhea, nausea, etc.
	75 mg/d or placebo for 14 d
Avatrombopag
ADAPT-1; Terrault et al[14], 2018	231 patients with CLD and thrombocytopenia divided into low (<40 × 109/L) and high (40 to < 50 × 109/L) baseline platelet count cohorts	Platelet transfusion, or rescue procedure for bleeding not required in 65.6% of avatrombopag-treated patients and 22.9% of placebo-treated patients in the low platelet count cohort and 88.1% of avatrombopag-treated patients and 38.2% of placebo-treated patients in the high platelet count cohort	Mild to moderate in severity in all treatment groups; most common TEAEs: abdominal pain, dyspepsia, nausea, pyrexia, dizziness, and headache; no thromboembolic TEAEs
	Both cohorts were randomized 2:1 to receive avatrombopag or placebo; the low baseline cohort was treated with 60 mg and the high baseline cohort was treated with 40 mg avatrombopag, or placebo
ADAPT-2; Terrault et al[14], 2018	204 patients with CLD and thrombocytopenia; same dosing as ADAPT-1	Platelet transfusion, or rescue procedure for bleeding not required in 68.6% of avatrombopag-treated patients and 34.9% of placebo-treated patients in the low platelet count cohort and 87.9% of avatrombopag-treated patients and 33.3% of placebo-treated patients in the high platelet count cohort	Same as ADAPT-1; three thromboembolic TEAEs reported
Lusutrombopag
L-PLUS-1; Hidaka et al[18], 2018	97 patients with thrombocytopenia and CLD randomized to receive 3 mg of lusutrombopag or placebo once daily for up to 7 d	Platelet transfusion, or rescue procedure for bleeding not required in 79.2% of lusutrombopag-treated patients and 12.5% of placebo-treated patients	Most common TEAEs: Nausea, pyrexia, headache, pain, and portal vein thrombosis; most common SAE with lusutrombopag was portal vein thrombosis
L-PLUS-2; Peck-Radosavljevic et al[17], 2019	215 patients; same dosing as L-PLUS-1	Platelet transfusion, or rescue procedure for bleeding not required in 64.8% of lusutrombopag-treated patients and 29% of placebo-treated patients	Most TEAEs were mild or moderate in severity; four asymptomatic thrombotic events, two each in the lusutrombopag and placebo groups, respectively; none attributed to lusutrombopag

AE: Adverse event; CLD: Chronic liver disease; SAE: Serious adverse event; TEAE: Treatment-emergent adverse event.