Key Takeaways

✅ Most common definition of hypersplenism includes 4 criteria:

• Splenomegaly
• Cytopenia(s)
• Hyperplasia of the respective marrow precursors of the deficient cell type
• Correction of the blood cytopenia(s) by splenectomy

✅ Caveats:

• Most but not all patients with hypersplenism have splenomegaly.⁵⁰
• There is no correlation between spleen size and degree of cytopenias.
• Hyperplasia of the respective marrow precursors may not occur if there is concomitant condition suppressing hematopoietic such as primary bone marrow process or nutritional deficiencies.
• There may be other factors contributing to cytopenias, e.g., reduced thrombopoietin levels in patients with cirrhosis.
• The diagnosis is made before splenectomy, and moreover patients rarely their spleen removed.

✅ Any condition that leads to splenic sequestration +/- destruction of blood cells and secondary cytopenia(s) may cause hypersplenism:

• If there is an inherently defective blood cell (for example in hereditary spherocytosis or thalassemia), or if there are humoral factors affecting blood cells (for example in autoimmune hemolytic anemia of ITP), the removal of that cell type by the spleen and subsequent reduction in their circulating levels does not count as hypersplenism. It is only when the hyperactive (usually enlarged) spleen starts to indiscriminately pool +/- destroy additional blood cell types that hypersplenism emerges.
• Any cause of splenomegaly may in theory lead to hypersplenism by virtue of indiscriminate pooling/destruction of blood cells. It seems likely that those causes leading to work hypertrophy/expansion of the red pulp have a greater likelihood of causing hypersplenism than conditions associated with immune hyperplasia or infiltration since this is the region of the spleen where cells tend to pool.

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