Is a low platelet (thrombocytopenia) count typically related to a bone marrow or liver problem?

From the Guidelines

Thrombocytopenia (low platelet count) is typically related to bone marrow problems rather than liver issues. The bone marrow is the primary site of platelet production, where megakaryocytes develop and release platelets into the bloodstream. When the bone marrow is damaged or dysfunctional due to conditions like leukemia, aplastic anemia, or certain medications, platelet production decreases. Other causes of thrombocytopenia include increased destruction of platelets (as in immune thrombocytopenia or ITP), consumption during clotting disorders, or sequestration in an enlarged spleen. While the liver does play a role in regulating blood clotting by producing clotting factors, it is not directly responsible for platelet production. However, severe liver disease can indirectly affect platelet counts through portal hypertension leading to splenomegaly and platelet sequestration, or through reduced production of thrombopoietin, a hormone that stimulates platelet production.

Some key points to consider:

• The liver's role in thrombocytopenia is often indirect, through portal hypertension and splenomegaly, rather than a direct result of liver dysfunction 1.
• Bone marrow problems are a more common cause of thrombocytopenia, and investigation of bone marrow function is typically the first step in diagnosis 1.
• The use of thrombopoietin receptor agonists, such as avatrombopag and lusutrombopag, may be considered in patients with cirrhosis and thrombocytopenia undergoing procedures, but their use is not without risks and benefits 1.
• The relationship between platelet count and bleeding risk in patients with cirrhosis is complex, and standard coagulation tests may not accurately predict bleeding risk 1.

In terms of management, a low platelet count per se is not suggested to predict the risk of bleeding in patients with cirrhosis, and correction of a low platelet count is not recommended before low-risk procedures 1. However, in patients with severe thrombocytopenia or coagulopathy undergoing high-risk procedures, decisions about prophylactic blood transfusions should include potential benefits and risks, such as transfusion reactions and alloimmunization 1. Ultimately, the management of thrombocytopenia in patients with liver disease requires a nuanced approach, taking into account the underlying cause of the thrombocytopenia, the severity of the liver disease, and the risks and benefits of different management strategies.

From the FDA Drug Label

In the PETIT study (NCT00908037), patients refractory or relapsed to at least one prior ITP therapy with a platelet count less than 30 x 109/L The efficacy and safety of eltrombopag for the treatment of thrombocytopenia in adult patients with chronic hepatitis C were evaluated in two randomized, double-blind, placebo-controlled trials.

A low platelet (thrombocytopenia) count can be related to either a bone marrow or liver problem.

• Bone Marrow Problem: The PETIT study involved patients with immune thrombocytopenia (ITP), which is often related to bone marrow issues.
• Liver Problem: The ENABLE1 and ENABLE2 studies involved patients with chronic hepatitis C, which can cause thrombocytopenia due to liver disease. However, the provided text does not directly answer whether a low platelet count is more commonly associated with bone marrow or liver problems. 2

From the Research

Low Platelet Count: Bone or Liver Problem

• A low platelet count, also known as thrombocytopenia, can be caused by various factors, including bone marrow or liver problems 3, 4.
• Thrombocytopenia is often associated with chronic liver disease, where the liver's reduced production of thrombopoietin leads to decreased platelet production in the bone marrow 4.
• However, studies have shown that the liver may not be the primary dictator of the circulating platelet count, and the bone marrow may play a more significant role 5.
• In patients with chronic liver disease, thrombocytopenia can be caused by a combination of factors, including hypersplenism, bone marrow suppression, and immunological removal of platelets from the circulation 4.
• Treatment options for thrombocytopenia, such as romiplostim, have been shown to be effective in increasing platelet counts in patients with chronic liver disease and thrombocytopenia secondary to HCV infection 3.
• The bone marrow's role in platelet production is supported by studies showing that the platelet count of related donors of hematopoietic stem cells correlates with the platelet count in the recipient after transplantation 5.
• In contrast, the platelet count in living liver donors does not correlate with the platelet count in the recipient after transplantation, suggesting that the liver may not be the primary determinant of the circulating platelet count 5.
• Overall, while both bone marrow and liver problems can contribute to thrombocytopenia, the bone marrow appears to play a more significant role in determining the circulating platelet count 6, 7, 5.