Multilineage hemopoietic stem cell defects in Budd Chiari syndrome

Area of Science:

• Hematology
• Stem Cell Biology
• Vascular Diseases

Background:

• Previous studies identified erythropoietin-independent erythroid colony growth in Budd Chiari syndrome.
• Increased megakaryocyte colony growth has also been documented in this disease.
• Defects in granulocyte-macrophage cell lines in Budd Chiari syndrome have not been previously reported.

Purpose of the Study:

• To investigate erythroid and granulocyte-macrophage colony growth in patients with Budd Chiari syndrome.
• To determine if stem cell defects affect multiple hematopoietic cell lines in Budd Chiari syndrome.
• To explore the potential link between stem cell defects and the pro-thrombotic state in Budd Chiari syndrome.

Main Methods:

• In vitro colony cultures of peripheral blood mononuclear cells were performed for erythroid and granulocyte-macrophage lineages.
• Cultures were assessed with and without specific growth factors (erythropoietin, granulocyte-macrophage colony-stimulating factor).
• Study included 32 Budd Chiari syndrome patients, 20 healthy controls, and 10 portal hypertension patient controls.

Main Results:

• No endogenous colony growth was observed in healthy or portal hypertension controls.
• Endogenous erythroid colony growth was observed in 68.8% of Budd Chiari syndrome patients.
• Endogenous granulocyte-macrophage colony growth was observed in 4 patients, a novel finding in Budd Chiari syndrome.

Conclusions:

• Stem cell defects affecting erythroid, megakaryocyte, and granulocyte-macrophage lineages appear to occur in Budd Chiari syndrome.
• These multi-lineage stem cell defects may represent the primary underlying cause of the pro-thrombotic state.
• Findings suggest a potential mechanism for venous thrombosis in Budd Chiari syndrome.