Can thrombocytopenia be improved in patients with cirrhosis (liver cirrhosis)?

From the Guidelines

Thrombopoietin receptor agonists, such as avatrombopag or lusutrombopag, are the most effective treatment options for improving platelet count in patients with cirrhosis, particularly those undergoing invasive procedures. These medications have been shown to increase platelet counts and reduce the need for platelet transfusions, without increasing the risk of thrombosis 1. The use of avatrombopag or lusutrombopag requires a 5- to 7-day treatment course prior to the procedure, and has been approved in the US and Europe for use in thrombocytopenic patients with liver disease undergoing an invasive procedure.

Some key benefits of using thrombopoietin receptor agonists include:

• Improvement of patient clinical management, avoiding the risk of cancellation of procedures due to a platelet count that is perceived as too low by the proceduralist
• Avoidance of prophylactic use of platelet transfusions, which can be of unpredictable efficacy and may lead to adverse events such as refractoriness to further platelet transfusions
• Increased availability of platelets for other clinical purposes

A recent meta-analysis showed that thrombopoietin receptor agonists were significantly more likely to result in a preoperative platelet count >50 × 10^9/L, and reduced the incidence of platelet transfusions, without increasing the risk of thrombosis 1. While platelet transfusions can provide temporary improvement in platelet counts, they are not a reliable long-term solution and may be associated with adverse events.

Treating the underlying liver disease is also crucial in managing thrombocytopenia in patients with cirrhosis. This may involve abstaining from alcohol, managing viral hepatitis with appropriate antivirals, or controlling autoimmune hepatitis with immunosuppressants. Regular monitoring of platelet counts and liver function is essential during any treatment approach.

In terms of specific treatment regimens, avatrombopag or lusutrombopag can be used at a dose of 20-60mg daily, with treatment typically starting 5-7 days prior to the invasive procedure. The use of these medications should be individualized based on the patient's specific needs and medical history, and should be guided by the most recent and highest quality evidence available 1.

From the FDA Drug Label

In two controlled clinical trials in patients with chronic hepatitis C and thrombocytopenia, 3% (31/955) treated with eltrombopag experienced a thrombotic event compared with 1% (5/484) on placebo. The majority of events were of the portal venous system (1% in patients treated with eltrombopag versus less than 1% for placebo) In a controlled trial in patients with chronic liver disease and thrombocytopenia not related to ITP undergoing elective invasive procedures (N = 292), the risk of thrombotic events was increased in patients treated with 75 mg of eltrombopag once daily Seven thrombotic complications (six patients) were reported in the group that received eltrombopag and three thrombotic complications were reported in the placebo group (two patients). All of the thrombotic complications reported in the group that received eltrombopag were portal vein thrombosis (PVT).

Eltrombopag may improve platelet count in patients with cirrhosis, but it increases the risk of thrombotic events, particularly portal vein thrombosis.

• The use of eltrombopag in patients with cirrhosis should be approached with caution.
• Patients with cirrhosis should be closely monitored for signs and symptoms of thrombotic events.
• The potential benefits of eltrombopag in improving platelet count should be weighed against the increased risk of thrombotic events 2.

From the Research

Treatment Options for Thrombocytopenia in Cirrhosis

• Several treatment options are available for severe thrombocytopenia in cirrhotic patients, including platelet transfusion, interventional partial splenic embolization, and surgical splenectomy 3.
• Thrombopoietin agonists and targeted agents are alternative tools for noninvasively treating thrombocytopenia due to liver cirrhosis, and their ability to improve thrombocytopenia in cirrhotic patients is under investigation in clinical trials 3.
• Two newly licensed oral thrombopoietin mimetics/receptor agonists, avatrombopag and lusutrombopag, are now available for targeted treatment of thrombocytopenia in patients with advanced liver disease, who are undergoing invasive procedures 4.

Pathophysiology of Thrombocytopenia in Liver Disease

• The pathophysiology of thrombocytopenia in liver disease is multifactorial, including splenomegaly and subsequently increased splenic sequestration of circulating platelets, reduced hepatic synthesis of thrombopoietin, and increased platelet destruction or consumption 4.
• The decrease in thrombopoietin synthesis has been identified as a central mechanism in the development of thrombocytopenia in liver disease 4.

Platelet Count and Perioperative Bleeding

• Major perioperative bleeding was not significantly associated with platelet count in patients with cirrhosis undergoing surgical treatment of hepatocellular carcinoma, even when their platelet count was <50 × 10^9/L 5.
• The association between platelet count and major perioperative bleeding remained nonsignificant after adjusting for other factors, such as age, aspartate aminotransferase, and hemoglobin 5.

Platelet Function in Cirrhosis

• Platelets from patients with cirrhosis showed reduction of aggregation and secretion of ATP, and similar results were observed for platelet activation parameters such as P-selectin expression and PAC-1 platelet binding 6.
• Plasma levels of βeta-thromboglobulin and soluble P-selectin were increased in patients with cirrhosis, indicating a state of in-vivo platelet activation 6.

Use of Thrombopoietin Receptor Agonists

• Thrombopoietin receptor agonists, such as avatrombopag and lusutrombopag, have been approved for use in patients with chronic liver disease undergoing invasive procedures, and have been shown to increase platelet counts and reduce the frequency of platelet transfusions 7.
• The use of thrombopoietin receptor agonists has resulted in less requirement for platelet transfusions, and may be an alternative to platelet transfusions in patients with cirrhosis undergoing invasive procedures 7.