What is hypersplenism?

Hypersplenism: Definition and Clinical Implications

Hypersplenism is defined as the association of splenomegaly with peripheral cytopenias (anemia, leukopenia, or thrombocytopenia) and compensatory bone marrow hyperplasia, resulting from premature destruction of blood cells in an enlarged spleen. 1

Pathophysiology and Mechanisms

• Hypersplenism involves multiple mechanisms including:

  • Sequestration and retention of blood cells in the enlarged spleen 2
  • Enhanced phagocytosis of blood cells by splenic macrophages 1
  • Autoimmune-mediated destruction of blood cells 1
  • Portal hypertension leading to intra-splenic sequestration (in cirrhosis) 3

• Thrombocytopenia is the most common manifestation, though all cell lines can be affected 2, 3

Classification

• Primary hypersplenism: Intrinsic splenic disorders without identifiable cause 1
• Secondary hypersplenism: Results from underlying conditions such as:
  • Portal hypertension due to liver cirrhosis 3
  • Myeloproliferative neoplasms 4
  • Hematologic disorders (sickle cell disease, thalassemia) 4, 5
  • Infections and inflammatory conditions 4
  • Splenic vein thrombosis 4, 2
• Occult hypersplenism: Cytopenias without obvious splenomegaly 1

Clinical Manifestations

• Splenomegaly (may be massive in some cases) 5
• Peripheral cytopenias:
  • Thrombocytopenia (most common) 2, 3
  • Anemia and/or leukopenia 1
• Symptoms related to the underlying cause 4
• Potential complications:
  • Increased bleeding risk (though platelet count alone doesn't predict bleeding in cirrhosis) 2
  • Splenic sequestration crisis (particularly in sickle cell disease) 4, 5
  • Increased susceptibility to infections (with leukopenia) 6

Diagnostic Approach

• Physical examination to detect splenomegaly 1
• Complete blood count showing cytopenias 2
• Bone marrow examination showing hyperplasia (to exclude primary bone marrow disorders) 1
• Imaging studies (ultrasound, CT scan) to confirm splenomegaly and evaluate for underlying causes 2
• Additional tests based on suspected etiology:
  • Liver function tests for suspected cirrhosis 4
  • JAK2V617F mutation testing for suspected myeloproliferative disorders 2
  • Hemoglobin electrophoresis for suspected hemoglobinopathies 4, 5

Management Strategies

• Treatment of underlying cause when possible 1:

  • Antiviral therapy for viral hepatitis-related cirrhosis 3
  • Cytoreductive therapy for myeloproliferative neoplasms 4

• Non-surgical approaches:

  • Thrombopoietin receptor agonists for thrombocytopenia before procedures 2
  • Platelet transfusions for severe thrombocytopenia with bleeding 2, 7

• Interventional procedures:

  • Partial splenic embolization - reduces splenic volume while preserving some immune function 2, 6
  • Transjugular intrahepatic portosystemic shunt (TIPS) - for portal hypertension-related hypersplenism 7

• Surgical options:

  • Splenectomy (open or laparoscopic) - most effective but carries risks of portal vein thrombosis and post-splenectomy sepsis 3, 6
  • Partial splenectomy - preserves some splenic immune function 7

• Liver transplantation - definitive treatment for hypersplenism due to end-stage liver disease 7

Special Considerations

• In sickle cell disease, most homozygous patients undergo auto-splenectomy by age 6, but those with HbSC genotype may develop hypersplenism in adulthood 5
• After liver transplantation, portal pressure decreases rapidly with normalization of platelet counts within 2 weeks in most patients 2
• Treatment should target the underlying cause rather than just addressing the laboratory abnormalities 3

Prognosis

• The prognosis depends primarily on the underlying cause rather than hypersplenism itself 3
• In cirrhosis, hypersplenism indicates more advanced disease and increased risk of complications 3
• Without treatment of the underlying condition, cytopenias typically persist or worsen 1