Differential Diagnosis of Splenomegaly with Thrombocytopenia

Single Most Likely Diagnosis

• Portal Hypertension: This is often the most common cause of splenomegaly with thrombocytopenia, typically due to cirrhosis. The increased pressure in the portal vein leads to splenic congestion and enlargement, and the spleen's increased sequestration of platelets results in thrombocytopenia.

Other Likely Diagnoses

• Chronic Lymphocytic Leukemia (CLL): CLL can cause splenomegaly due to infiltration of the spleen by malignant cells, and thrombocytopenia can occur due to bone marrow failure or splenic sequestration.
• Lymphoma: Similar to CLL, lymphoma can infiltrate the spleen, causing enlargement, and lead to thrombocytopenia through various mechanisms including marrow infiltration and splenic sequestration.
• Myeloproliferative Neoplasms (MPN): Conditions like essential thrombocythemia, polycythemia vera, and primary myelofibrosis can cause splenomegaly and, paradoxically, thrombocytopenia in some cases, especially in the later stages or due to splenic sequestration.

Do Not Miss Diagnoses

• Splenomegaly due to Infection (e.g., Endemic Diseases like Malaria, Kala-Azar): Certain infections can cause significant splenomegaly and thrombocytopenia. Missing these diagnoses can be fatal if not treated promptly.
• Hypersplenism due to Sickle Cell Disease: While not as common, sickle cell disease can lead to splenic enlargement and thrombocytopenia, especially in early stages before autosplenectomy occurs.
• Systemic Lupus Erythematosus (SLE): SLE can cause splenomegaly and thrombocytopenia due to autoimmune mechanisms, including antibody-mediated platelet destruction.

Rare Diagnoses

• Gaucher's Disease: A rare genetic disorder that can cause splenomegaly due to the accumulation of glucocerebroside in the spleen, leading to thrombocytopenia.
• Niemann-Pick Disease: Another rare genetic disorder that can result in splenomegaly and thrombocytopenia due to the accumulation of sphingomyelin in cells.
• Primary Splenic Lymphoma: A rare condition where lymphoma originates in the spleen, potentially causing splenomegaly and thrombocytopenia.

Each of these diagnoses has a distinct pathophysiology leading to splenomegaly and thrombocytopenia, emphasizing the importance of a thorough diagnostic workup to determine the underlying cause.