What bloodwork is needed to check for anemia caused by myeloma or other Bone Marrow (BM) processes?

Diagnostic Workup for Anemia Caused by Multiple Myeloma or Other Bone Marrow Processes

For anemia suspected to be caused by multiple myeloma or other bone marrow processes, a comprehensive laboratory workup should include complete blood count with differential, serum protein electrophoresis with immunofixation, serum free light chain assay, and bone marrow examination. 1

Initial Laboratory Testing

• Complete blood count (CBC) with differential and peripheral blood smear evaluation to assess for anemia characteristics, rouleaux formation, and circulating plasma cells 1
• Comprehensive chemistry panel including:
  • Renal function tests (BUN, creatinine) 1
  • Serum calcium 1
  • Serum albumin 1
  • Lactate dehydrogenase (LDH) 1
  • β2-microglobulin 1

Protein Studies

• Serum protein electrophoresis (SPEP) and serum immunofixation electrophoresis (SIFE) to detect and characterize monoclonal proteins 1
• Quantitative immunoglobulin levels (IgG, IgA, and IgM) by nephelometry 1
• Serum free light chain (FLC) assay with kappa/lambda ratio - crucial for detecting light chain myeloma 2, 3
• 24-hour urine collection for:
  • Total protein quantification 1
  • Urine protein electrophoresis (UPEP) 1
  • Urine immunofixation electrophoresis (UIFE) 1

Bone Marrow Evaluation

• Bone marrow aspiration and biopsy to:
  • Quantify plasma cell infiltration (≥10% clonal plasma cells required for myeloma diagnosis) 1, 3
  • Assess erythroid precursors and erythropoiesis 4
  • Evaluate for other bone marrow disorders 3
• CD138 staining to accurately determine plasma cell percentage 2, 3
• Cytogenetic analysis and fluorescent in situ hybridization (FISH) to detect chromosomal abnormalities 1

Additional Testing

• Skeletal survey (X-rays) including spine, pelvis, skull, humeri, and femurs to detect lytic bone lesions 1, 3
• Consider MRI of spine and pelvis if conventional imaging is negative but bone disease is suspected 2, 3
• Iron studies (serum iron, ferritin, transferrin) to rule out concurrent iron deficiency 5, 6
• Vitamin B12 and folate levels if macrocytic anemia is present 6

Interpretation of Results

• Anemia in multiple myeloma is typically normochromic, normocytic with hemoglobin value of ≥2 g/dL below the lower limit of normal, or a hemoglobin value <10 g/dL 1
• Anemia positively correlates with myeloma cell infiltration in the bone marrow and is associated with worse clinical outcomes 4
• Mechanisms of anemia in myeloma include:
  • Direct bone marrow infiltration by plasma cells 4
  • Suppression of erythropoiesis via elevated CCL3 levels 4
  • Relative erythropoietin deficiency (often due to renal impairment) 7
  • Anemia of chronic disease 7

Clinical Pitfalls and Considerations

• A random urine sample is insufficient; always collect a 24-hour urine specimen for proper evaluation 1
• Serum protein electrophoresis alone may miss light chain myeloma; always include serum free light chain assay 2, 3
• Bone marrow examination is essential even if monoclonal protein is detected in serum or urine, as it confirms the diagnosis and rules out other bone marrow disorders 1, 3
• Multiple myeloma can coexist with other causes of anemia (iron deficiency, vitamin deficiencies), so a complete anemia workup may still be necessary 7, 6
• The master regulators of erythropoiesis (GATA1 and KLF1) are often downregulated in myeloma, contributing to anemia 4