Diagnostic Workup for Rouleaux Formation on Blood Smear
When rouleaux formation is identified on a peripheral blood smear, a focused workup for plasma cell disorders should be initiated, as multiple myeloma is the most clinically significant cause requiring prompt intervention. 1
Initial Laboratory Evaluation
- Complete blood count with differential and peripheral blood smear examination to assess for additional findings such as circulating plasma cells, which may accompany rouleaux formation 2, 1
- Comprehensive biochemistry panel including liver function tests, renal function tests, electrolytes, calcium, and albumin 2, 1
Specific Testing for Plasma Cell Disorders
- Serum protein electrophoresis (SPEP) to detect and quantify monoclonal proteins 2, 1
- Urine protein electrophoresis (UPEP) using a 24-hour urine collection (not random samples) 2, 1
- Immunofixation electrophoresis of both serum and urine to confirm the presence and type of monoclonal protein, even if electrophoresis shows no measurable protein 2, 1
- Serum free light chain assay to detect excess kappa or lambda light chains 1
- Quantitative immunoglobulins by nephelometry, which complements electrophoresis and is particularly useful for measuring low levels of uninvolved immunoglobulins 2, 1
Further Evaluation if Monoclonal Protein is Detected
- Bone marrow aspiration and biopsy to assess for clonal plasma cells 2, 1
- Skeletal imaging (skeletal survey, low-dose whole-body CT, MRI, or PET-CT) to evaluate for bone lesions 1
Clinical Pearls and Pitfalls
- Rouleaux formation appears microscopically as red blood cells lined up against each other, resembling "stacked coins" 3
- Saline replacement can help distinguish true agglutination from rouleaux formation - true agglutination will remain when plasma is replaced with saline, while rouleaux will disappear when plasma proteins are removed 3
- Nephelometric quantitation may overestimate monoclonal protein concentration when values are high, so both densitometer tracing and nephelometric quantitation are recommended 2
- Never delay appropriate workup when rouleaux is identified, as it may be the first indication of a plasma cell dyscrasia requiring urgent intervention 1
- While rouleaux can be caused by increased plasma proteins from conditions other than plasma cell disorders (such as inflammatory states), the diagnostic approach should prioritize ruling out multiple myeloma due to its significant morbidity and mortality implications 1