What lab work is recommended for an enlarged spleen?

Laboratory Workup for Enlarged Spleen

Obtain a complete blood count with differential, peripheral blood smear review, comprehensive metabolic panel including liver function tests, lactate dehydrogenase (LDH), and abdominal ultrasound as your essential first-line workup for any patient with splenomegaly. 1, 2, 3

Confirm Splenomegaly First

• Abdominal ultrasound is the first-line imaging modality to confirm splenomegaly and assess for focal lesions, hepatomegaly, and lymphadenopathy 1, 3
• Spleen size 11-13 cm represents mild splenomegaly, while >13 cm is clinically significant and warrants aggressive workup 1, 3
• Document exact spleen size below the costal margin with careful percussion and palpation, measuring liver span at the mid-clavicular line 1, 3

Essential Laboratory Panel

Hematologic Assessment

• Complete blood count with differential to identify cytopenias, leukocytosis, lymphocytosis, or abnormal cell populations suggesting hematologic malignancy 1, 2, 3
• Peripheral blood smear review is critical to identify blasts, atypical lymphocytes (>10% suggests infectious mononucleosis despite negative monospot), or other abnormal cells suggestive of leukemia or lymphoma 1, 2
• Flow cytometry of peripheral blood for immunophenotyping should be performed immediately if lymphoproliferative disorder is suspected based on CBC findings 1, 2, 3

Metabolic and Organ Function

• Comprehensive metabolic panel including liver function tests is essential since liver disease is one of the three most common causes of splenomegaly in the United States 1, 2, 3
• Lactate dehydrogenase (LDH) to screen for hemolysis or malignancy 1, 2, 3

Infectious Disease Workup

• Test for EBV, CMV, HIV, and hepatitis viruses as infectious causes are among the top three etiologies in developed countries 1, 3

Advanced Testing Based on Initial Findings

If Myeloproliferative Neoplasm Suspected

• Testing for JAK2, CALR, and MPL mutations if myeloproliferative neoplasm is suspected (particularly with leukocytosis, thrombocytosis, or unexplained splenomegaly) 1, 2, 3
• Serum tryptase and vitamin B12 levels to evaluate for myeloproliferative disorders, particularly in patients with eosinophilia 3

If Acute Presentation or Malignancy Suspected

• Disseminated intravascular coagulation panel including D-dimer, fibrinogen, PT, and PTT in acute presentations, particularly in acute leukemia 1
• Tumor lysis syndrome panel including uric acid, potassium, phosphates, and calcium when malignancy is suspected 1

When to Proceed to Bone Marrow Evaluation

Bone marrow aspiration and biopsy is indicated when:

• Abnormal cells are found in peripheral blood 1, 2, 3
• Unexplained cytopenias are present 1, 2, 3
• Myeloproliferative or lymphoproliferative disorder is suspected 1, 2, 3
• Peripheral smear shows blasts or abnormal lymphocytes beyond typical reactive changes 1, 2

Critical Pitfalls to Avoid

• Do not delay bone marrow evaluation in patients with concerning peripheral blood findings (blasts, significant cytopenias, or abnormal cell populations) 1, 3
• Do not miss lymphoma-associated hemophagocytic lymphohistiocytosis (HLH): approximately 40-70% of adult HLH cases are malignancy-associated, particularly with Hodgkin lymphoma, diffuse large B-cell lymphoma, and T-cell lymphomas 1
• Do not assume alcoholic liver disease in patients with alcohol use; other causes must be excluded through appropriate testing 1
• Consider PET-guided imaging and repetitive tissue sampling if lymphoma is suspected but initial biopsies are negative, as tumor-infiltrating reactive lymphocytes can mask underlying lymphoma 1

Advanced Imaging Considerations

• CT or MRI of the abdomen should be obtained if ultrasound findings are equivocal, lymphadenopathy needs characterization, or focal splenic lesions are present 1, 2, 3
• Imaging should evaluate for hepatomegaly, lymphadenopathy, and focal splenic lesions that may require tissue diagnosis 1

Immediate Hematology Referral Warranted When

• Peripheral smear showing blasts or abnormal lymphocytes beyond typical reactive changes 1, 2
• Presence of cytopenias 1, 2
• Symptomatic splenomegaly without clear etiology after initial workup 1