Do platelet counts increase in multiple myeloma or monoclonal gammopathy of undetermined significance?

Platelet Counts in Multiple Myeloma and MGUS

Platelet counts typically do NOT increase in multiple myeloma or MGUS; instead, these conditions are characterized by platelet hyperactivation and prothrombotic states without elevated platelet numbers, and anemia is the more common hematologic finding.

Hematologic Profile

Anemia, Not Thrombocytosis

• Anemia is the characteristic hematologic abnormality in multiple myeloma, with patients demonstrating significantly lower hemoglobin levels compared to MGUS patients or healthy controls 1
• The diagnostic criteria for MGUS specifically require absence of anemia (along with hypercalcemia, renal insufficiency, and bone lesions), indicating that cytopenias including low platelets are more concerning than elevated counts 2
• Initial workup should include complete blood count to identify cytopenias, not thrombocytosis 3, 4

Platelet Function, Not Quantity

Hyperactivation Without Increased Numbers

• 74% of MGUS patients and 38% of multiple myeloma patients demonstrate platelet hyperactivation as measured by elevated CD63, annexin V, and PAC-1 antibody binding, but this reflects functional changes rather than increased platelet counts 5
• Platelet hyperactivation is accompanied by marker-specific hyporesponsiveness to agonist stimulation, with reduced P-selectin response to ADP in MGUS patients 5
• Platelet-associated immunoglobulins are elevated in a subset of patients, contributing to altered platelet function 5

Prothrombotic State

Thrombotic Risk Mechanisms

• Alterations in the bone marrow microenvironment result in increased risk of venous and arterial thrombosis in both MGUS and multiple myeloma, driven by hypercoagulability rather than elevated platelet counts 2
• Both MGUS and MM patients demonstrate elevated thrombin generation and procoagulant phospholipid activity compared to controls 6
• Multiple myeloma patients show increased microvesicle-associated tissue factor activity and elevated cell-free DNA (surrogate for neutrophil extracellular traps), contributing to hypercoagulability 6

Coagulation Profile Differences

• Patients with myeloma have significantly elevated D-dimer levels and factor VIII levels compared to normal controls, indicating a prothrombotic state 1
• MGUS patients have a distinct intermediate coagulation profile between myeloma and normal controls, with elevated D-dimers but less pronounced factor VIII elevation 1
• Peak thrombin and velocity index are significantly higher in both MM and MGUS patients compared to healthy controls 7

Clinical Implications

Monitoring Considerations

• Complete blood count should focus on identifying cytopenias (particularly anemia) rather than thrombocytosis as a marker of disease progression 3, 4
• The presence of cytopenias warrants more aggressive evaluation including bone marrow biopsy 4
• Thrombotic risk assessment should focus on coagulation markers and clinical thrombotic events rather than platelet counts 8

Common Pitfall

• Do not expect elevated platelet counts as a feature of MGUS or multiple myeloma; the thrombotic risk comes from qualitative platelet dysfunction and hypercoagulability, not quantitative increases 5, 6
• Overlooking the prothrombotic state despite normal or low platelet counts can lead to inadequate thromboprophylaxis, especially during immunomodulatory therapy 8, 7