- Definition/Pathophysiology
- Stacking of RBCs on a peripheral blood smear that resembles a “stack of coins”.
- Caused by high levels of circulating plasma proteins (e.g., immunoglobulins, fibrinogen), which are positively charged.
- These proteins coat the negatively charged surface of RBCs, neutralizing the normal repulsive forces (zeta potential) between them and allowing them to aggregate.
- Key Associations (High-Yield)
- Multiple Myeloma (MM): This is the classic and most tested association. It is caused by the excessive production of monoclonal immunoglobulins (paraproteins or M-proteins) by malignant plasma cells.
- Waldenström’s Macroglobulinemia: Characterized by high levels of monoclonal IgM.
- Chronic Inflammatory States: Any condition that increases acute-phase reactants, particularly fibrinogen. This includes infections, malignancies, and connective tissue disorders.
- Pregnancy: A physiologic increase in fibrinogen can lead to mild rouleaux formation.
- Lab Findings
- Markedly elevated Erythrocyte Sedimentation Rate (ESR) is a hallmark finding. The increased protein concentration causes RBCs to aggregate and settle faster.
- The background of the Wright-Giemsa stained smear may appear bluish due to high serum protein levels.
- DDx (on Peripheral Smear)
- RBC Agglutination: This involves irregular, 3-D grape-like clumping of RBCs, not neat stacks.
- Agglutination is typically caused by IgM antibodies cross-linking RBCs, as seen in cold agglutinin disease (e.g., secondary to Mycoplasma pneumoniae or infectious mononucleosis).
- Differentiating Test: Adding a drop of saline to the slide will disperse rouleaux, but true agglutination will persist.
- Clinical Workup
- The presence of rouleaux formation warrants an investigation for an underlying plasma cell disorder or other cause of hyperglobulinemia.
- Initial workup includes:
- Serum Protein Electrophoresis (SPEP) to identify a monoclonal (M-spike) or polyclonal gammopathy.
- Urine Protein Electrophoresis (UPEP) for Bence-Jones proteins.
- Serum free light chain assay.