What is the hospital workup for a patient presenting with pancytopenia (low blood cell count)?

Hospital Workup for Pancytopenia

The initial hospital workup for pancytopenia should include a complete blood count with differential, peripheral blood smear examination, reticulocyte count, and bone marrow examination in most cases, along with targeted testing for reversible causes including vitamin B12/folate levels, HIV/HCV screening, and autoimmune markers. 1, 2

Initial Laboratory Evaluation

Essential First-Line Tests

• Complete blood count (CBC) with differential and platelet count to confirm pancytopenia and assess severity of each cell line 3, 1
• Peripheral blood smear examination is critical to exclude pseudothrombocytopenia, identify morphological abnormalities (blasts, schistocytes, hairy cells), and assess for dysplastic changes 3, 1, 2
• Reticulocyte count to differentiate between bone marrow production defects versus peripheral destruction 3, 1

Comprehensive Metabolic and Coagulation Panel

• Blood chemistry profile including liver function tests, renal function, and electrolytes 3
• Lactate dehydrogenase (LDH), uric acid, potassium, phosphate, and calcium to assess for tumor lysis syndrome 3
• Coagulation studies including PT, PTT, fibrinogen, and D-dimer to evaluate for disseminated intravascular coagulation 3

Infectious Disease Screening

All adult patients with pancytopenia should undergo HIV and hepatitis C virus testing regardless of geographic location. 3, 1

Additional infectious workup includes:

• Hepatitis B virus screening 3
• Helicobacter pylori testing in appropriate clinical contexts 3
• Viral PCR for parvovirus and CMV if clinically indicated 3
• Blood cultures if febrile or signs of infection present 3
• Brucellosis testing (bone marrow culture has highest sensitivity) in endemic areas or with compatible exposure history 1
• Ehrlichiosis testing in patients with tick exposure, particularly those with leukopenia and thrombocytopenia 1

Nutritional and Metabolic Assessment

• Vitamin B12 and folate levels as megaloblastic anemia is among the most common and rapidly reversible causes of pancytopenia 1, 2, 4, 5
• Quantitative immunoglobulin levels, particularly in children or those with persistent/chronic pancytopenia 3
• Copper and ceruloplasmin levels in select cases, especially with history of gastrointestinal surgery, B12 deficiency, or vacuolation of myeloid/erythroid precursors 1

Autoimmune Evaluation

When systemic symptoms or clinical features suggest autoimmune disease:

• Antinuclear antibodies (ANA) 3, 1
• Anti-dsDNA antibodies 1
• Antiphospholipid antibodies including anticardiolipin and lupus anticoagulant 3
• Direct antiglobulin test (Coombs) to rule out concurrent Evans syndrome 3
• Antithyroid antibodies and thyroid function tests 3

Bone Marrow Examination

Bone marrow aspiration and biopsy should be performed simultaneously in most cases of pancytopenia, as aspiration alone may be inadequate. 3, 1, 6

Indications for bone marrow examination:

• Patients over 60 years of age 1
• Presence of systemic symptoms or abnormal physical findings (fever, weight loss, lymphadenopathy, hepatosplenomegaly) 1
• Cases where diagnosis remains unclear after initial testing 1
• Suspected hematological malignancy, aplastic anemia, or myelodysplastic syndrome 3, 1, 2
• Patients on immune checkpoint inhibitors to rule out marrow infiltration, secondary MDS, or aplastic anemia 1

Bone marrow studies should include:

• Morphological assessment for cellularity, dysplasia, megaloblastic changes, and infiltrative processes 3, 1
• Immunophenotyping to establish leukemia-associated phenotypes and classify lineage 3
• Cytogenetic analysis essential for diagnosing myelodysplastic syndromes and identifying chromosomal abnormalities that guide prognosis and treatment 1
• Flow cytometry when lymphoproliferative disorder suspected 3
• Special stains including CD20, annexin-1, and BRAFV600E (VE1) for suspected hairy cell leukemia 3

A common pitfall is performing bone marrow aspiration alone without biopsy, which frequently yields inadequate samples in pancytopenic patients. 6

Imaging Studies

• Chest X-ray to rule out pulmonary infections, malignancies, or thymoma 3, 2
• CT chest warranted for all patients with T-cell lineage malignancies 3
• CT or MRI scans if specific organ involvement suspected (hepatosplenomegaly, lymphadenopathy) 2
• Echocardiogram or cardiac scan particularly important before anthracycline-based therapy, in elderly patients, or those with prior cardiac history 3

Additional Specialized Testing

For suspected specific conditions:

• Glycoprotein-specific platelet antibodies if immune thrombocytopenia component suspected 3
• Ferritin, triglycerides, and fibrinogen if hemophagocytic lymphohistiocytosis (HLH) suspected, along with assessment for fever and hepatosplenomegaly 1
• Pregnancy test in women of childbearing potential 3
• Blood group (Rh typing) 3
• HLA typing should be performed at workup except in patients with major contraindications to hematopoietic stem cell transplantation 3

Tests of uncertain benefit (not routinely recommended):

• Thrombopoietin (TPO) levels 3
• Reticulated platelets 3
• Platelet-associated immunoglobulin G (PaIgG) 3
• Platelet survival studies 3
• Bleeding time 3

Clinical Assessment Priorities

History should focus on:

• Medication exposure including chemotherapy, immunosuppressants, methotrexate, tetracyclines, azathioprine, and recent dose changes 1, 7
• Lymphocyte-depleting therapies (fludarabine, ATG, corticosteroids, radiation) 3
• Infection symptoms and exposures including tick bites, travel history, and sick contacts 1
• Autoimmune disease history (personal and family) 3
• Nutritional status and gastrointestinal surgery history 3, 1
• Bleeding symptoms, bruising, and petechiae 3

Physical examination should assess:

• Spleen and liver size (hypersplenism is a leading cause) 3, 4
• Lymphadenopathy 3
• Testicular examination in males, especially with T-cell lineage disease 3
• Signs of bleeding (petechiae, purpura, mucosal bleeding) 3
• Skin changes suggesting autoimmune disease or infiltrative processes 3

Admission Criteria and Monitoring

Patients with newly diagnosed pancytopenia and platelet count <20 × 10⁹/L who are asymptomatic or have minor mucocutaneous bleeding should be considered for hospital admission, particularly with social concerns, diagnostic uncertainty, significant comorbidities, or more significant mucosal bleeding. 3

Immediate management considerations:

• Severe anemia (Hb <7 g/dL) requires blood transfusion 2
• Severe thrombocytopenia (platelets <10,000/μL) may require platelet transfusion if bleeding or high bleeding risk 2
• Severe neutropenia (ANC <500/μL) requires infection prophylaxis and prompt treatment of fever with broad-spectrum antibiotics 2
• Temperature monitoring every 4 hours with immediate workup if fever develops 2
• Strict infection control measures including avoidance of rectal procedures, fresh flowers, and raw fruits/vegetables 7

Patients not admitted should receive education and expedited follow-up with a hematologist within 24-72 hours of diagnosis. 3