What is the relationship between platelets and the liver or gallbladder?

From the Guidelines

Platelets have a complex relationship with the liver, and liver disease can significantly impact platelet production and function, leading to thrombocytopenia and increased risk of bleeding or thrombosis, as noted in the 2022 EASL clinical practice guidelines on prevention and management of bleeding and thrombosis in patients with cirrhosis 1. The liver plays a crucial role in platelet production by synthesizing thrombopoietin, the primary hormone that stimulates platelet formation in bone marrow. When liver function is compromised, as in cirrhosis or other liver diseases, platelet production often decreases, leading to thrombocytopenia (low platelet count) [ 1 ]. Some key points to consider in the relationship between platelets and the liver or gallbladder include:

• Liver disease can cause splenomegaly, where the enlarged spleen sequesters and destroys platelets, further reducing their numbers.
• Liver disease can also affect platelet function, even when counts appear normal.
• For the gallbladder, the relationship is less direct but still significant, with gallbladder disease triggering systemic inflammatory responses that activate platelets.
• In severe cases of cholecystitis or cholangitis, disseminated intravascular coagulation may occur, rapidly consuming platelets.
• Medications used to treat gallbladder disease may also affect platelet function; for example, some antibiotics can reduce platelet aggregation. Monitoring platelet counts and function is essential in patients with either liver or gallbladder disease to prevent bleeding complications or inappropriate clotting, and thrombopoietin agonists like avatrombopag and lusutrombopag can be used to increase platelet count before invasive procedures 1.

From the FDA Drug Label

Thrombotic/thromboembolic complications may result from increases in platelet counts with Nplate use. Portal vein thrombosis has been reported in patients with chronic liver disease receiving Nplate. People with chronic liver disease may be at risk for a type of blood clot in the stomach area (abdomen)

The relationship between platelet and liver or gallbladder is that thrombotic/thromboembolic complications, including portal vein thrombosis, may occur in patients with chronic liver disease who receive romiplostim or eltrombopag, due to increases in platelet counts. Key points include:

• Chronic liver disease increases the risk of thrombotic/thromboembolic complications
• Portal vein thrombosis is a specific type of blood clot that may occur in the stomach area (abdomen)
• Platelet count increases with romiplostim or eltrombopag use may contribute to the risk of thrombotic/thromboembolic complications 2, 3

From the Research

Relationship Between Platelet and Liver or Gallbladder

The relationship between platelet and liver or gallbladder is complex, with several studies indicating a strong correlation between liver disease and thrombocytopenia (low platelet count) 4, 5, 6, 7, 8.

• Thrombocytopenia is a common complication of advanced liver disease or cirrhosis, with an incidence of up to 75% 5.
• The pathophysiology of thrombocytopenia in liver disease is multifactorial, including splenomegaly, reduced hepatic synthesis of thrombopoietin, and increased platelet destruction or consumption 5, 6.
• Thrombopoietin receptor agonists, such as avatrombopag and lusutrombopag, have been approved for use in patients with chronic liver disease undergoing invasive procedures to increase platelet counts and reduce the risk of bleeding 4, 7, 8.
• The use of thrombopoietin receptor agonists has resulted in less requirement for platelet transfusions, which can carry risks such as transfusion-related complications 7, 8.
• A treatment algorithm for patients with chronic liver disease and severe thrombocytopenia undergoing elective medical procedures has been proposed, which includes the use of thrombopoietin receptor agonists as an alternative to platelet transfusion 8.

Management of Thrombocytopenia in Liver Disease

The management of thrombocytopenia in liver disease depends on several factors, including the severity of thrombocytopenia, the type of invasive procedure, and the individual patient's risk factors for bleeding 6, 7, 8.

• For patients with a platelet count higher than or equal to 50,000/µL, platelet-directed therapy is rarely required 6.
• For patients with a platelet count below 50,000/µL who require a high-risk procedure, platelet-directed therapy should be considered, especially if the patient has other risk factors for bleeding 6.
• Thrombopoietin receptor agonists, such as avatrombopag and lusutrombopag, can be used to increase platelet counts and reduce the risk of bleeding in patients with chronic liver disease undergoing invasive procedures 4, 7, 8.