In a trial involving patients with cirrhosis and thrombocytopenia, treatment with eltrombopag before invasive procedures reduced the need for platelet transfusions. More thrombotic events of the portal venous system were observed with eltrombopag than with placebo.
Thrombocytopenia is frequently observed in patients with chronic liver disease, with studies suggesting that it occurs in up to 76% of patients with cirrhosis. The degree of thrombocytopenia is proportional to the severity of the liver disease, and a high degree of thrombocytopenia is an indicator of advanced disease.
- What are the limitations of platelet transfusions in patients with severe liver disease?
Platelet transfusions are commonly used to reduce the risk of bleeding during a procedure, but their short duration of efficacy and the risk of transfusion reactions limit their use. Furthermore, the development of antiplatelet antibodies (alloimmunization) can cause refractory thrombocytopenia in up to half of patients who receive multiple transfusions.
- What is the mechanism of action of eltrombopag?
Eltrombopag is an oral thrombopoietin-receptor agonist approved for use in patients with chronic immune thrombocytopenia
Morning Report Questions
Q: What were the results of this study, which looked at eltrombopag versus placebo in patients with chronic liver disease and thrombocytopenia?
A: Treatment with eltrombopag at a dose of 75 mg once daily for 14 days reduced the need for platelet transfusions in patients with chronic liver disease and thrombocytopenia who were undergoing elective invasive procedures. Platelet counts were increased during treatment with eltrombopag and for up to 2 weeks after treatment. The key secondary end point of noninferiority with regard to the rate of bleeding episodes (with a noninferiority margin of 10 percentage points) was met (23% in the placebo group and 17% in the eltrombopag group; absolute difference, -6 percentage points; 95% CI, -15 to 3).
Q: How did serious adverse events differ in the two study groups?
A: An increased risk of portal-vein thrombosis was observed among patients receiving eltrombopag. Thrombotic events occurred in 6 patients (7 events) in the eltrombopag group and 2 patients (3 events) in the placebo group (odds ratio with eltrombopag, 3.04; 95% CI, 0.62 to 14.82). With the exception of thrombotic events, rates of serious adverse events were similar in the study groups. Nine of the 10 events involved the portal venous system, including all the events in patients who received eltrombopag; these patients presented with symptomatic portal-vein or splanchnic-vein thromboses. Of the 6 patients in the eltrombopag group who had a portal-vein thrombosis, 5 had the event when the platelet count was higher than 200,000 per cubic millimeter.