From the Guidelines
Thrombocytopenia in liver cirrhosis occurs through multiple mechanisms, including splenic sequestration, reduced thrombopoietin production, increased destruction, and possible bone marrow suppression, as evidenced by recent studies 1. The primary cause of thrombocytopenia in cirrhosis is portal hypertension, which leads to splenomegaly and subsequent sequestration of platelets in the enlarged spleen 1. This splenic sequestration can trap a significant portion of platelets, reducing circulating platelet counts. Additionally, cirrhosis impars thrombopoietin production, a hormone responsible for stimulating platelet production in the bone marrow, further contributing to low platelet counts 1. Other mechanisms, such as immune-mediated destruction of platelets, bone marrow suppression, and increased platelet consumption due to low-grade disseminated intravascular coagulation, may also play a role in thrombocytopenia in cirrhosis 1. Understanding these mechanisms is crucial for proper management, which may include treating the underlying liver disease, considering thrombopoietin receptor agonists in severe cases, or platelet transfusions before invasive procedures when counts are dangerously low 1. Key factors to consider in the management of thrombocytopenia in cirrhosis include:
- The presence of a low platelet count should be integrated into the broader picture of cirrhosis affecting both homeostasis 1
- A low platelet count per se is not suggested to predict the risk of bleeding in patients with cirrhosis 1
- Rotational thromboelastometry may be superior to routine coagulation laboratory tests in predicting the risk of bleeding during high-risk procedures 1
- Thrombopoietin receptor agonists, such as avatrombopag and lusutrombopag, may be considered as an alternative to platelet transfusion in severe cases 1
From the Research
Mechanism of Thrombocytopenia in Liver Cirrhosis
The mechanism of thrombocytopenia in liver cirrhosis is multifactorial, involving several key factors. These include:
- Splenic sequestration of platelets, which is the major mechanism for thrombocytopenia in liver cirrhosis 2
- Decreased production of thrombopoietin in the liver, a hormone that stimulates platelet production 2, 3, 4
- Bone marrow suppression by chronic hepatitis C virus infection and anti-cancer agents 2
- Antiviral treatment with interferon-based therapy 2
- Increased platelet destruction or consumption 5
Role of Thrombopoietin
Thrombopoietin plays a crucial role in the development of thrombocytopenia in liver cirrhosis. Studies have shown that:
- Cirrhotic patients with thrombocytopenia have lower serum thrombopoietin levels than healthy controls 3, 4
- Thrombopoietin levels are related to spleen size, but not to platelet count in cirrhotic patients with thrombocytopenia 3
- Increased thrombopoietin degradation by platelets sequestered in the congested spleen may contribute to thrombocytopenia in cirrhotic patients 3
- However, one study found that liver cirrhosis does not cause impaired thrombopoietin production, even in the late stage of disease, and that thrombopoietin has no contribution to the occurrence of thrombocytopenia in cirrhosis 6
Pathophysiology
The pathophysiology of thrombocytopenia in liver disease is complex and involves multiple factors, including:
- Splenomegaly and increased splenic sequestration of circulating platelets 5
- Reduced hepatic synthesis of thrombopoietin, resulting in diminished platelet production and release from the bone marrow 5
- Increased platelet destruction or consumption 5
- Bone marrow suppression by chronic hepatitis C virus infection and anti-cancer agents 2
- Antiviral treatment with interferon-based therapy 2