What is the recommended lab workup for pancytopenia?

Comprehensive Laboratory Workup for Pancytopenia

The recommended laboratory workup for pancytopenia should include a systematic approach starting with basic evaluation tests, followed by specialized testing based on clinical suspicion to identify the underlying cause, as pancytopenia significantly impacts morbidity and mortality.

Initial Basic Evaluation (First-line Testing)

• Complete blood count (CBC) with reticulocyte count - Confirms pancytopenia and provides information about bone marrow response
• Peripheral blood film examination - Essential to assess cell morphology and identify abnormalities
• Quantitative immunoglobulin level measurement - Particularly important in persistent cases
• Direct antiglobulin test (Coombs test) - To evaluate for immune-mediated hemolysis
• HIV testing - Recommended regardless of geographic location 1
• Hepatitis C virus (HCV) testing - Recommended regardless of geographic location 1
• Bone marrow examination - Critical in most cases of pancytopenia to determine cellularity and identify underlying pathology 2, 3

Second-line Testing (Based on Clinical Suspicion)

• Glycoprotein-specific antibody testing - For suspected immune thrombocytopenia, using acid citrate dextrose solution-A (ACD-A) as the anticoagulant 1
• Antiphospholipid antibodies (including anticardiolipin and lupus anticoagulant) - For suspected autoimmune conditions
• Antithyroid antibodies and thyroid function tests - To evaluate thyroid disorders
• Pregnancy test - In women of childbearing potential
• Antinuclear antibodies - For suspected systemic lupus erythematosus or other autoimmune disorders
• Viral PCR for parvovirus and CMV - Particularly important in immunocompromised patients 1, 4
• Blood group (Rh) - For potential transfusion requirements
• Helicobacter pylori testing - As it may be associated with immune cytopenias 1

Specialized Testing (For Specific Etiologies)

• Drug-dependent antibody testing - For suspected drug-induced immune thrombocytopenia, particularly with commonly implicated drugs like quinine, vancomycin, sulfamethoxazole/trimethoprim, and piperacillin/tazobactam 1
• Liver function tests - For suspected liver disease or hypersplenism 5
• Renal function tests - For suspected renal impairment contributing to cytopenias 4
• Vitamin B12 and folate levels - For suspected megaloblastic anemia, which is a common cause of pancytopenia 2, 3
• Iron studies - To evaluate iron deficiency or overload
• Flow cytometry - For suspected hematological malignancies
• Cytogenetic studies - For suspected myelodysplastic syndrome or leukemia
• Next-generation sequencing - For suspected inherited bone marrow failure syndromes 6

Important Considerations

• Sample collection for drug-dependent antibody testing should be done during the acute episode of cytopenia or within 3 weeks of the event 1
• Clotted serum samples or citrate samples are acceptable for testing; EDTA should be avoided as it can cause glycoprotein complexes to dissociate 1
• For platelet autoantibody testing, a minimum of 30 mL of blood for adults and 10 mL for children is recommended 1
• Direct tests for platelet autoantibodies have higher sensitivity than indirect tests 1

Common Pitfalls to Avoid

1. Delayed bone marrow examination - This is crucial for diagnosis in most cases of pancytopenia
2. Incomplete medication review - Many drugs can cause pancytopenia, including chemotherapeutics and certain antibiotics
3. Overlooking nutritional causes - Megaloblastic anemia is one of the most common causes of pancytopenia in many regions 2, 3
4. Failure to consider infections - Various infections can cause pancytopenia, including HIV, viral hepatitis, and tuberculosis 5
5. Missing hypersplenism - This is a common cause of pancytopenia that requires specific evaluation 5

By following this systematic approach to laboratory workup for pancytopenia, clinicians can efficiently identify the underlying cause and implement appropriate therapy to improve patient outcomes.