Hyperviscosity Syndrome

Pathophysiology

Increased immunoglobulin or blood cell production can lead to increased serum viscosity.  Viscosity refers to the resistance to flow, or stickiness, of fluid.  Serum or plasma viscosity is typically reported relative to the viscosity of water. Normal viscosity is 1.4 to 1.8 units relative to water.  Increased viscosity causes vascular stasis and the resultant hypoperfusion then leads to the clinical symptoms of HVS.  The viscosity threshold at which symptoms appear differs based on each individual patient.

  • Monoclonal immunoglobulin production
    • Usually seen in Waldenström macroglobulinemia (85%)
  • Polyclonal immunoglobulin production
    • Multiple Myeloma, Cryoglobulinemia (HCV), IgM flare following rituximab treatment, RA, Sjogren’s Syndrome, IgG4 Disease, uncontrolled HIV infection with underlying liver disease.
  • Hyperleukocytosis
    • AML, CML, Polycythemia (Polycythemia Vera, Sickle Cell Disease, R-L Shunting Heart disease)

Clinical Presentation

CLINICAL TRIAD: 

  • Mucosal Bleeding
    • Epistaxis, GI Bleed, Retinal Hemorrhage, Gingival Bleed
  • Visual Changes
    • marked retinal venous engorgement resembling hot dogs on a string (i.e. sausaging), hemorrhages, exudates, microaneurysms and papilledema
    • retinal hemorrhage can cause retinal detachment and blindness
  • Neurological Symptoms
    • Seizures, Ataxia, Cerebral Hemorrhage, AMS
      • These symptoms in combination are highly specific for HVS and are indications to start plasma exchange immediately without waiting for testing.

OTHER SYMPTOMS:

  • Respiratory:  Dyspnea, Hypoxemia,
  • Cardiovascular:  Hypotension, Pulmonary Edema
  • Renal:  Ischemic acute tubular necrosis
  • In hyperleukocytosis, symptoms may also include those associated with DIC and tumor lysis syndrome.

Diagnosis

  • Immunoglobulin
    • Serum Viscosity + Clinical Symptoms.  Serum viscosity is usually greater than 4.
  • Polycythemia
    • Cell count + Clinical Symptoms that are not pre-existing or explained by other conditions.

Management

Apheresis requires coordination with Blood Bank and a Hemodialysis Central Venous Catheter

Immunoglobulin-mediated

  • Plasmapheresis- because the symptomatic threshold of plasma viscosity is different for every patient, there is no set recommendation for levels at which to start plasmapheresis.  Plasmapheresis should not be delayed while waiting for plasma viscosity to confirm the diagnosis
  • Chemotherapy – to treat the underlying process to prevent further hyperviscosity

Hyperleukocytosis:

  • Leukapheresis- indicated if there HVS is clinically suspected. Leukopheresis aims to reduce total WBC count while minimizing RBC removal   
    • AML Blast Count usually >100K
    • CML WBC usually >100K
    • CLL Lymphocyte Count usually >400K
    • The tota
  • Chemotherapy- hydroxyurea is usually started before starting an appropriate induction regimen of rapidly-acting chemotherapy for cytoreduction in AML or CML.
    • Avoid transfusion until after WBC is decreased – a single unit of pRBCs may increase viscosity enough to cause worsening symptoms and clinical decompensation. If a transfusion is indicated, administer it by slow infusion.
    • If plasma/cellular pheresis is not readily available and the patient is decompensating, one may try vigorous intravenous hydration coupled with a 2-3 unit phlebotomy in the interim as a temporizing measure.
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