Hypersplenism: Causes, Clinical Features, and Diagnostic Criteria
Definition and Core Characteristics
Hypersplenism is characterized by the triad of splenomegaly, peripheral cytopenias (affecting one or more cell lines), and compensatory bone marrow hyperplasia, with thrombocytopenia being the most common manifestation. 1, 2
The pathophysiology involves multiple mechanisms including sequestration and retention of blood cells in the enlarged spleen, enhanced phagocytosis, and autoimmune-mediated destruction. 2
Classification and Etiologies
Primary Hypersplenism
- Autoimmune cytopenias without underlying systemic disease 3
Secondary Hypersplenism (Most Common)
Portal hypertension from liver cirrhosis represents the most frequent cause, with 78% of patients with clinically significant portal hypertension developing platelet counts below 100,000/mcL. 1, 2
Hematologic disorders include:
- Myeloproliferative neoplasms with splenic infiltration 1
- Sickle cell disease (particularly HbSC genotype, which rarely undergoes auto-splenectomy) 4
- Lymphoproliferative disorders 5
Other causes include:
- Extrahepatic portal vein obstruction (EHPVO) - consider when portal hypertension features exist with minimal liver dysfunction and normal transaminases 6
- Splenic vein thrombosis 6
- Infiltrative diseases and infections 3
Occult Hypersplenism
- Subclinical hypersplenism may persist after liver transplantation in patients with pre-transplant splenomegaly 6, 2
Clinical Manifestations
Symptoms
Most patients are asymptomatic at presentation, with cytopenias discovered incidentally on routine laboratory testing. 2
When symptomatic, patients may experience:
- Post-prandial abdominal pain from splenic distension 2
- Fatigue related to anemia 2
- Weight loss 2
- Increased bleeding risk (though platelet count alone does not predict bleeding in cirrhosis) 1
Physical Examination Findings
- Splenomegaly is the most frequent physical examination finding - palpable spleen or percussion demonstrating splenic enlargement 2
- Note: Splenomegaly is present in less than 3% of patients with immune thrombocytopenic purpura (ITP), so its presence argues strongly against ITP 1
Complications
- Gastrointestinal bleeding (most frequent complication in EHPVO) 6, 2
- Recurrent thrombosis 2
- Portal cholangiopathy from compression of bile ducts by cavernomatous collaterals 6
- Hepatic fibrosis progression to cirrhosis 5
Diagnostic Criteria and Approach
Laboratory Evaluation
Complete blood count demonstrating cytopenias is the key diagnostic tool, with the following patterns: 1
- Thrombocytopenia (most common - platelets <150,000/mcL)
- Anemia
- Leukopenia/neutropenia
- Any combination of the above
A moderate inverse correlation exists between hepatic venous pressure gradient and platelet counts (Spearman r = -0.44), demonstrating that as portal hypertension worsens, platelet counts decline. 1, 2
Imaging Studies
Hepatic ultrasound with Doppler should be performed to: 2
- Confirm splenomegaly (longitudinal length >11 cm suggests portal hypertension) 7
- Assess for cirrhosis
- Evaluate portal vein patency
- Identify portal hypertension
CT scan or MRI can: 1
- Confirm splenomegaly
- Evaluate for underlying causes
- Assess splenic volume (may exceed ten multiples of normal) 5
Consider elastography to distinguish cirrhosis from isolated portal vein thrombosis 6
Liver Function Assessment
- Liver function tests to diagnose suspected cirrhosis 1
- Transaminases (often elevated early in disease course) 5
Bone Marrow Evaluation
- Bone marrow biopsy may show compensatory hyperplasia (normocellular or hypercellular marrow) 3, 6
- Useful to exclude primary bone marrow disorders
Specialized Testing
For suspected portal vein thrombosis, evaluate: 6
- JAK2V617F mutation (helpful in Budd-Chiari syndrome and portal vein thrombosis)
- Prothrombotic disorders (myeloproliferative neoplasms, antiphospholipid syndrome, inherited thrombophilia)
- Local factors (pancreatitis, inflammatory bowel disease)
Epinephrine stimulation test (EST) measures changes in platelets, neutrophil counts, and spleen size following subcutaneous epinephrine injection - positive in 69.8% of patients with enlarged spleens versus 41.3% with normal-sized spleens (low confidence cutoff). 8
Rotational thromboelastometry may be superior to routine coagulation tests for predicting bleeding risk during high-risk procedures. 6
Diagnostic Pitfalls
- Do not rely solely on platelet count to determine bleeding risk - baseline bleeding risk is low and independent of preprocedure prophylaxis in cirrhotic patients 6
- Liver cirrhosis, portal hypertension, and thrombocytopenia can be present even without enlarged spleen, suggesting involvement of other mechanisms beyond splenic sequestration 7
- Thrombocytopenia etiology in cirrhosis is multifactorial: splenic sequestration, myeloid toxicity, anti-platelet antibodies, and low thrombopoietin levels 6
- Decreased platelet count is more common in cirrhosis of alcoholic etiology than other etiologies 7