Portal Hypertension: This condition is often due to cirrhosis of the liver and is characterized by increased pressure in the portal vein, leading to splenomegaly (enlarged spleen) and subsequent thrombocytopenia (low platelet count) due to splenic sequestration.

Chronic Lymphocytic Leukemia (CLL): CLL can cause splenomegaly and thrombocytopenia due to bone marrow infiltration and splenic sequestration.
Lymphoma: Both Hodgkin's and non-Hodgkin's lymphoma can involve the spleen, leading to splenomegaly, and may cause thrombocytopenia through various mechanisms including marrow infiltration and immune-mediated platelet destruction.
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.

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 the most common cause, sickle cell disease can lead to splenic sequestration and subsequent thrombocytopenia, especially in younger patients.
Systemic Lupus Erythematosus (SLE): SLE can cause splenomegaly and thrombocytopenia due to immune complex deposition and consumption of platelets.

Gaucher's Disease: A genetic disorder leading to the accumulation of glucocerebroside in cells, causing splenomegaly and thrombocytopenia among other symptoms.
Niemann-Pick Disease: Another genetic disorder that can cause 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.