What are the causes of leukopenia in patients with cirrhosis and splenomegaly (enlargement of the spleen)?

From the Guidelines

Leukopenia in patients with cirrhosis and splenomegaly is primarily caused by hypersplenism, where the enlarged spleen sequesters and destroys white blood cells, as a result of portal hypertension leading to splenomegaly and subsequent hypersplenism 1.

Causes of Leukopenia

The causes of leukopenia in these patients can be multifactorial, including:

• Hypersplenism, which is common in patients with advanced cirrhosis, affecting all hematological cell lines, but thrombocytopenia is the most common feature 1
• Bone marrow suppression from various factors such as alcohol toxicity, myeloid toxicity, and viral infections like hepatitis C 1
• Nutritional deficiencies, particularly folate and vitamin B12, which can contribute to leukopenia 1
• Medication side effects, such as interferon therapy, antibiotics, or certain diuretics, which can suppress bone marrow function 1
• Bacterial infections, which are common in cirrhotic patients and can cause transient leukopenia through increased consumption of white blood cells 1

Management of Leukopenia

Management of leukopenia in patients with cirrhosis and splenomegaly typically focuses on treating the underlying liver disease and portal hypertension, while monitoring for infections that may be masked by the inability to mount a normal leukocyte response 1.

• In severe cases with recurrent infections, growth factors like granulocyte colony-stimulating factor may be considered, though addressing the primary liver disease remains the cornerstone of treatment 1
• The use of viscoelastic tests of coagulation, such as rotational thromboelastometry, may be beneficial in predicting the risk of bleeding during high-risk procedures, including liver transplantation 1
• The correction of a low platelet count is not recommended before low-risk procedures, and blood products should be used sparingly to avoid side effects, including fluid overload 1

From the Research

Causes of Leukopenia in Patients with Cirrhosis and Splenomegaly

• Leukopenia, or a low white blood cell count, is a common complication in patients with cirrhosis and splenomegaly, often due to hypersplenism 2, 3, 4.
• Hypersplenism is defined as the association of anemia, leukopenia, or thrombocytopenia with bone marrow hyperplasia and splenomegaly, and is common in liver cirrhosis and frequent in patients with portal hypertension 2.
• The spleen is a major component of the mononuclear phagocyte system, and splenectomy or partial splenic embolization can reduce antibody synthesis and increase the number of circulating blood cells, including white blood cells 2, 3.
• However, splenectomy may lead to sepsis, and partial splenic embolization may have variable effects on white blood cell counts over time 2, 4.
• Other treatments for hypersplenism, such as portosystemic shunts, pharmacological agents, and radiofrequency ablation, may also be effective in increasing white blood cell counts, but their effects may be temporary or have significant risks 4, 5.

Mechanisms of Leukopenia in Cirrhosis and Splenomegaly

• The exact mechanisms of leukopenia in cirrhosis and splenomegaly are not fully understood, but may involve the sequestration of white blood cells in the spleen, as well as the effects of portal hypertension and liver disease on the bone marrow and immune system 5.
• Splenomegaly and hypersplenism may also contribute to the progression of liver fibrosis to cirrhosis, although the precise mechanisms remain poorly understood 5.
• The diagnosis and management of splenomegaly involve treating the underlying disease process, and may include splenectomies, spleen reduction therapies, and increased vaccination and prophylactic antibiotics for procedures involving the respiratory tract 6.