Differential Diagnosis for Splenomegaly with Thrombocytopenia

Single Most Likely Diagnosis

• Portal Hypertension: This condition is often due to cirrhosis and leads to splenomegaly and thrombocytopenia (hypersplenism) due to increased pressure in the portal vein, causing the spleen to enlarge and sequester platelets.

Other Likely Diagnoses

• Chronic Lymphocytic Leukemia (CLL): CLL can cause splenomegaly and thrombocytopenia due to bone marrow infiltration and hypersplenism.
• Lymphoma: Both Hodgkin's and non-Hodgkin's lymphoma can involve the spleen, leading to splenomegaly, and may cause thrombocytopenia through marrow involvement or hypersplenism.
• Myeloproliferative Neoplasms (MPN): Conditions like essential thrombocythemia, polycythemia vera, and primary myelofibrosis can cause splenomegaly and, paradoxically, thrombocytopenia in some cases due to hypersplenism or bone marrow fibrosis.

Do Not Miss Diagnoses

• Sepsis: Although not a primary hematologic condition, sepsis can cause splenomegaly and thrombocytopenia due to disseminated intravascular coagulation (DIC) and should be considered in acutely ill patients.
• HIV Infection: HIV can cause splenomegaly and thrombocytopenia due to immune system dysregulation and should be considered, especially in high-risk populations.
• Tuberculosis: TB can involve the spleen, leading to splenomegaly, and may cause thrombocytopenia through mechanisms like hypersplenism or bone marrow involvement.

Rare Diagnoses

• Gaucher's Disease: A lysosomal storage disorder that can cause splenomegaly and thrombocytopenia due to the accumulation of glucocerebroside in the spleen and bone marrow.
• Sarcoidosis: Although more commonly associated with lung and lymph node involvement, sarcoidosis can rarely cause splenomegaly and thrombocytopenia.
• Histiocytosis: Rare conditions like Langerhans cell histiocytosis can involve the spleen, leading to splenomegaly and potentially thrombocytopenia through marrow involvement or hypersplenism.