What are the criteria for hyperviscosity syndrome in multiple myeloma?

From the Guidelines

Hyperviscosity syndrome in multiple myeloma is diagnosed when patients have both clinical symptoms and elevated serum viscosity, typically greater than 4.0 centipoise (normal is 1.4-1.8 cp), and is more commonly associated with IgM levels above 3 g/dL, as seen in Waldenström’s macroglobulinemia 1. The clinical manifestations of hyperviscosity syndrome include the classic triad of mucosal bleeding, visual disturbances, and neurological symptoms. Specific neurological symptoms include headache, dizziness, vertigo, nystagmus, hearing loss, ataxia, paresthesias, and altered mental status. Ocular findings may include retinal hemorrhages, exudates, and dilated retinal veins on fundoscopic examination. Patients may also experience epistaxis, gingival bleeding, or gastrointestinal bleeding.

Key Diagnostic Criteria

• Clinical symptoms such as headaches, blurry vision, or confusion
• Elevated serum viscosity, typically greater than 4.0 centipoise
• IgM level above 3 g/dL, as seen in Waldenström’s macroglobulinemia
• Fundoscopic examination showing venous engorgement (sausaging) of the retinal veins

Treatment Approach

• Urgent treatment with plasmapheresis is indicated for symptomatic patients
• Antimyeloma therapy to reduce the underlying paraprotein production
• Consideration of cold agglutinins or cryocrit in patients with suggestive symptoms 1 The pathophysiology involves increased blood viscosity from high concentrations of paraproteins, leading to impaired microcirculation, tissue hypoxia, and the clinical manifestations.

Important Considerations

• Hyperviscosity occurs in approximately 5-10% of multiple myeloma cases, more commonly in IgA myeloma due to the polymeric nature of IgA molecules
• The correlation between protein levels and viscosity is imperfect
• Other conditions such as hepatitis C serology and liver function tests should be considered in the diagnostic workup 1

From the Research

Hyperviscosity Syndrome Criteria in Multiple Myeloma

• Hyperviscosity syndrome (HVS) is a rare but life-threatening complication of multiple myeloma (MM) 2, 3, 4.
• HVS classically presents with the triad of mucosal bleed, neurological, and visual disturbances 2.
• The syndrome is typically associated with immunoglobulin M (IgM) MM and very rarely may complicate immunoglobulin G (IgG) MM 2.
• Even suspicion of HVS necessitates therapy based on clinical severity rather than the calculated degree of viscosity 2.
• Plasmapheresis promptly decreases serum viscosity by 30% to 50% and is effective in treating HVS 2, 3.

Diagnosis and Treatment

• Fundoscopy can lead to diagnosis of HVS, and it is advisable in all patients with MM to perform plasmapheresis as soon as possible if necessary 3.
• Therapeutic plasma exchanges are used in most patients with HVS and are effective and well tolerated 4.
• Early initiation of anti-myeloma therapy is crucial to prevent rebound phenomena 2.
• The treatment of multiple myeloma typically involves a combination of an injectable proteasome inhibitor, an oral immunomodulatory agent, and dexamethasone, followed by autologous hematopoietic stem cell transplantation and maintenance therapy with lenalidomide 5.

Prognosis

• HVS in newly diagnosed multiple myeloma patients is associated with high lethality in older patients and may be a potential dismal prognosis factor in the modern treatment era 4.
• The overall survival of patients with HVS is lower compared to those without HVS, with a median overall survival of 3.6 years versus 7.7 years 4.