The Use of Thrombopoietin Receptor Agonists for Correction of Thrombocytopenia prior to Elective Procedures in Chronic Liver Diseases: Review of Current Evidence
75 mg/day for 2 weeks versus placebo for 2 weeks prior to procedure
N = 292 subjects with CLD and platelet count of <50,000/L and a planned elective procedure Cirrhosis: 86% (10% Child-Pugh C) Etiology: 80% viral hepatitis
Majority: 59% low bleeding risk procedures (endoscopy, interventions, and paracentesis) Also 15% mild bleeding risk procedures (liver biopsy, laparoscopy, and HCC ablation)
Subjects in whom a platelet transfusion was avoided before, during, and up to 7 days after the elective invasive procedure: 72% (104/145) in the study group compared with 19% (28/147) in the placebo group did not require platelet transfusion ()
Rate of bleeding episodes: nonsignificant for noninferiority (23% in the placebo group and 17% in the study group) Quantity of platelets units transfused: median of 3 units in the study group was lower than 4 units in placebo group Side effects: similar in both groups (headache, pyrexia, and abdominal pain, being most common)
Deaths: 3 in study group (with 1 due to sepsis and possibly related to therapy) versus 2 in placebo group Hepatic decompensation: similar in both groups, most common being hepatic encephalopathy PVT: 9 events identified (7 in study group versus 2 in placebo, OR 3.04)
2 g/kg SC every 1 week for a maximum of 4 weeks or until 2 consecutive platelet counts of >70,000/L were observed prior to procedure
N = 35 subjects with refractory thrombocytopenia and platelet count of <50,000/L and a planned surgical procedure Cirrhosis: 100% (all with Child-Pugh score of 10 and above) Etiology: HCV
Cataract, hernia repair, joint replacement, and fracture fixation
The number of subjects achieving a platelet count >70,000/L and thereby eligible for surgery: 94% achieved this end point and underwent procedure
Platelet response: 33/35 achieved the desired goal in 9–30 days. All subjects showed rapid response and 7/35 showed positive long-term response (a platelet count > 50,000/L at 3-month follow-up) Safety: no serious adverse effects reported
Romiplostim (SC) versus Eltrombopag (oral) versus platelet transfusion Basu et al. [26]
500 mcg SC (as a 1 time dose) given 2 weeks prior to the procedure versus 75 mg/day for 2 weeks till the day of procedure versus 7 units of platelet transfused the night prior to procedure
N = 65 subjects with baseline platelet count of <60,000/L prior to study Cirrhosis: 100% (mean MELD score 20) Etiology: 57% HCV, 15% HBV, and other diseases
Outpatient percutaneous liver biopsy
Platelet response: Romiplostim group had significantly higher prebiopsy and postbiopsy platelet counts as compared to the other groups
Cost effectiveness: Romiplostim single dose is cost-effective approach Adverse effects: injection site erythema (39%) being most common
Death: not available Postbiopsy bleeding: none Hepatic decompensation: not available PVT: not available
Avatrombopag: first-generation and second-generation formulation (oral) Terrault et al. [27]
Cohort A (first-generation Avatrombopag group): 100 mg loading dose followed by 20, 40, or 80 mg/day on days 2–7 in three parallel arms and also Cohort B (second-generation Avatrombopag group): 80 mg loading dose followed by 10 mg/day for days 2–7 or 20 mg/day for days 2–4 in two parallel arms versus placebo with each study cohort
N = 130 subjects with CLD and thrombocytopenia (baseline platelet count of <50,000/L) who were scheduled to undergo elective procedure Cirrhosis: 100% (13% Child-Pugh class C) Etiology: 80% viral hepatitis
Majority had endoscopic procedures Also dental procedure, liver biopsy, and paracentesis
An increase in platelet count >20,000/L above baseline and at least one platelet count >50,000/L within days 4–8 was achieved by 49% of treated subjects in Cohort A and 47.6% in Cohort B compared to 6.3% and 9.5% in placebo The proportion of subjects achieving a platelet count >75,000/L or >100,000/L at least once within days 4–8: each Avatrombopag regimen had a higher proportion of responders compared with their respective cohort placebo arms ()
Platelets response: the maximum median platelet count increase from baseline in all study subjects occurred within 10–13 days. A platelet count >100,000/L prior to procedure occurred in 17.6% in subjects with Avatrombopag and none in placebo group Safety: overall similar rate of adverse events in combined study (29%) and combined placebo group (29.7%)
Death: 1 in study (80/10 mg) arm possibly related to study drug Hepatic decompensation: constituted mainly serious adverse effects and were similar in combined study (17.9%) and placebo (10.8%) groups () Bleeding episodes: only 4 subjects had gastrointestinal bleeding episodes PVT: 1 in 100/80 mg arm
