What causes aggregations of erythrocytes (red blood cells) in a blood smear in a patient with multiple myeloma?

Aggregations of Erythrocytes in Blood Smear in Multiple Myeloma

Erythrocyte aggregation (rouleaux formation) in multiple myeloma blood smears is primarily caused by elevated serum proteins, particularly paraproteins, which reduce the normal repulsive forces between red blood cells and promote their stacking like coins. 1

Mechanism of Rouleaux Formation in Multiple Myeloma

Primary Causes:

• Paraprotein Effect: The monoclonal immunoglobulins produced by malignant plasma cells act as surface-active molecules that adsorb onto red blood cell membranes 2
• Reduced Zeta Potential: Paraproteins neutralize the negative surface charge of erythrocytes, decreasing the electrostatic repulsion between cells
• Bridging Phenomenon: Large immunoglobulin molecules can physically bridge adjacent red blood cells, promoting aggregation

Contributing Factors:

• Hyperviscosity: Increased serum viscosity due to high paraprotein levels facilitates red cell aggregation
• Altered Plasma Composition: Changes in plasma protein composition affect the suspension stability of erythrocytes 2
• Membrane Alterations: Surface properties of red blood cells may be modified in multiple myeloma 2

Clinical Significance of Rouleaux Formation

Diagnostic Value:

• Rouleaux formation is observed in approximately 73% of multiple myeloma patients at diagnosis 3
• It serves as an important peripheral blood finding that should prompt further investigation for plasma cell disorders
• The degree of rouleaux formation often correlates with the concentration of paraproteins

Hematologic Implications:

• Contributes to the normochromic, normocytic anemia commonly seen in multiple myeloma 1
• May affect blood flow in the microcirculation, contributing to impaired tissue perfusion
• Can interfere with accurate erythrocyte sedimentation rate (ESR) measurements, causing markedly elevated results

Laboratory Correlation

Relationship with Paraprotein Types:

• More pronounced in IgG and IgA myeloma compared to light chain-only disease 4
• The degree of aggregation doesn't always correlate directly with immunoglobulin levels 2
• May be influenced by specific physicochemical properties of the monoclonal protein rather than just concentration

Hemorheological Effects:

• Contributes to abnormal blood flow characteristics in multiple myeloma patients
• Can be quantified using specialized hemorheological measurements 2
• The aggregation index is significantly lower in multiple myeloma blood compared to healthy controls, indicating higher aggregability 2

Clinical Implications

Impact on Blood Testing:

• May cause falsely elevated ESR values
• Can interfere with automated complete blood count analysis
• May complicate interpretation of peripheral blood smear morphology

Relationship to Symptoms:

• Contributes to hyperviscosity syndrome in cases with very high paraprotein levels
• May exacerbate anemia by affecting red cell deformability and survival
• Can contribute to microcirculatory disturbances and tissue hypoxia

Management Considerations

Monitoring:

• Peripheral blood smear examination should be part of routine follow-up in multiple myeloma 1
• The degree of rouleaux formation may decrease with effective anti-myeloma therapy
• Persistent or worsening rouleaux formation may suggest disease progression

Treatment Impact:

• Effective myeloma treatment reduces paraprotein levels and consequently decreases rouleaux formation
• In severe hyperviscosity cases, plasmapheresis can rapidly reduce paraprotein levels and improve blood rheology
• Monitoring rouleaux formation can provide a simple visual indicator of treatment response

Rare Complications

In extremely rare cases, malignant plasma cells may directly interact with erythrocytes through phagocytosis, as documented in case reports 5, but this is an exceptional finding rather than the typical mechanism of erythrocyte aggregation in multiple myeloma.