AUTHOR AND EDITOR INFORMATION

Section 1 of 8  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

INTRODUCTION

Section 2 of 8  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

Background

Hyperviscosity syndrome (HVS) refers to the clinical sequelae of increased blood viscosity. Increased serum viscosity usually results from increased circulating serum immunoglobulins and can be seen in Waldenström macroglobulinemia and multiple myeloma. It can also result from increased cellular blood components (typically white or red blood cells) in hyperproliferative states such as the leukemias, polycythemia, and the myeloproliferative disorders.

The complications most commonly associated with this syndrome include mucous membrane bleeding, neurologic and pulmonary symptoms, and the associated retinopathy.

Pathophysiology

Viscosity is a property of liquid and is described as the resistance that a liquid exhibits to the flow of one layer over another. As serum proteins or cellular components increase, the blood becomes more viscous, leading to the clinical symptoms of hyperviscosity syndrome secondary to the vascular stasis and resultant hypoperfusion.

The normal relative serum viscosity ranges from 1.4-1.8 units (reported as Centipoises). Symptoms usually are not seen at viscosities of less than 4 units, and the hyperviscosity syndrome typically requires a viscosity greater than 5 units.

Hyperviscosity syndrome is associated most commonly with plasma cell dyscrasias (the paraproteinemias) and is due to the large size of the excess immunoglobulin M (IgM) paraproteins in these disorders. Waldenström macroglobulinemia is the most common cause and accounts for about 85% of cases of HVS. Less frequently, the disease can occur in multiple myeloma (especially with myeloma proteins of the IgA and IgG₃ types) and connective tissue diseases.

Hyperviscosity syndrome can also be caused by the bone marrow hyperproliferative states: the leukemias, polycythemia, essential thrombocytosis, and the myelodysplastic disorders, which also increase serum viscosity.

Confusion and mental status changes result from the increased viscosity of the blood and decreased cerebral blood flow. This sludging leads to segmental dilatation of retinal veins and retinal hemorrhages. Mucosal bleeding may occur from prolonged bleeding time caused by myeloma proteins interfering with platelet function.

Cardiopulmonary symptoms such as shortness of breath, hypoxemia, acute respiratory failure, and hypotension also result from this sludging of blood and decreased microvascular circulation.

Mortality/Morbidity

Mortality is related to the underlying cause of the hyperviscosity syndrome.

Sex

While no information is available regarding the incidence of hyperviscosity syndrome, one study found that 61% of blood dyscrasias occur in males.

Age

Little information is available regarding the age of patients with hyperviscosity syndrome. Most blood dyscrasias are not diagnosed until the seventh decade of life.

CLINICAL

Section 3 of 8  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

History

Clinical symptoms generally are related to the triad of mucosal bleeding, visual changes, and neurologic symptoms. Constitutional symptoms and cardiorespiratory symptoms also contribute to the clinical presentation.

• Tendency to bleed is the most common symptom of hyperviscosity syndrome.
• • Spontaneous gum bleeding
  • Epistaxis
  • Rectal bleeding
  • Menorrhagia
  • Persistent bleeding after minor procedures
• Visual changes range from blurred vision to vision loss.
• Neurologic manifestations are frequent and varied. The neurologic symptoms of hyperviscosity have been referred to as the Bing-Neal syndrome.
• • Vertigo
  • Hearing loss
  • Paresthesias
  • Ataxia
  • Headaches
  • Seizures
  • Somnolence progressing to stupor and coma
• Other manifestations may include heart failure, shortness of breath, hypoxia, fatigue, and anorexia.
• In fact, one should have a high index of suspicion for HVS in patients with unexplained coma/altered mental status or unexplained shortness of breath especially in those with an underlying hematologic disorder.

Physical

Physical findings are related to the major organ systems involved.

• Bruises, epistaxis, or gum bleeding may be noted.
• Ophthalmic examination may reveal decreased visual acuity, dilated retinal veins, "sausage-linked" or "boxcar segmentation" of the retinal veins, or retinal hemorrhages.
• Neurologic examination may reveal various findings, including diminished mental status, confusion, ataxia, or nystagmus.
• Cardiopulmonary examination may reveal signs of congestive heart failure with volume overload (rales, lower extremity edema, elevated JVP, and hypoxia).

Causes

Increased serum viscosity usually results from increased circulating serum immunoglobulins and can be seen in Waldenström macroglobulinemia and multiple myeloma.

Less commonly, the hyperproliferative blood cell disorders such as the leukemias, myeloproliferative diseases, polycythemia, and thrombocytosis may be implicated for the increased viscosity caused by proliferation of their respective cellular components.

DIFFERENTIALS

Section 4 of 8  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

Other Problems to be Considered

Coma
Multiple myeloma
Waldenström macroglobulinemia

Leukostasis (See eMedicine article Oncologic Emergencies, under Hyperleukocytosis.)

Polycythemia
Thrombocytosis

WORKUP

Section 5 of 8  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

Lab Studies

• Determine serum viscosity.
• • Serum viscosity is diagnostic in evaluating hyperviscosity syndrome when the elevated viscosity is concomitant with characteristic symptoms. No exact diagnostic cut-off exists for viscosity as different patients will have symptoms at different values of viscosity.
  • A clue may be that the laboratory may be having difficulty performing chemical tests on the blood due to the serum stasis and increased viscosity, which may clog analyzers.
  • The normal reference range is 1.4-1.8 Centipoises (1.0 being the viscosity of water).
  • Symptoms usually are not seen before the viscosity reaches 4 Centipoises, and hyperviscosity syndrome usually presents with a serum viscosity greater than 5 Centipoises. Typically, the higher the viscosity, the worse are the symptoms.
• Obtain a peripheral blood smear with the CBC. Rouleaux formation is often present with increased serum viscosity.
• WBC count is typically 100,000 or greater in leukostasis causing HVS, but it may be lower in the blast crises of the leukemias.
• Consider adding total protein (TP) and albumin as in the paraproteinemias; a globulin gap (TP – albumin = 4 or greater) may exist.
• Consider adding a metabolic panel and electrolytes as derangements such as hypercalcemia, hyperphosphatemia, and hyperkalemia are common and may require specific treatment. (Be sure not to contribute to pseudohyperkalemia secondary to the increased cellular lysis from poor venipuncture technique; use a larger needle, withdraw slowly and, if in doubt, send for a plasma rather than serum potassium level, which will be more reliable).
• Consider adding serum and urine electrophoresis in new cases without preceding diagnosis for diagnostic purposes.
• Consider coagulopathy workup (eg, blood count, type and screen, prothrombin time, activated partial thromboplastin time, platelet count) if the patient presents with hemorrhage.
• Tailor additional workup (eg, chest radiography, brain CT or MRI) to the patient's presentation.
• Consider panculture and urinalysis.
• • Multiple myeloma is complicated frequently by infections.
  • In nonneutropenic patients, infections are usually secondary to Streptococcus pneumoniae or Haemophilus influenzae.
• Search for other disorders. Hyperviscosity syndrome is the result of another pathologic process (eg, multiple myeloma, Waldenström macroglobulinemia, hyperproliferative blood cell dysplasias).

Imaging Studies

• Head CT scan is indicated if the patient presents with altered level of consciousness, seizures, or focal neurologic deficits.
• Contrast dye is contraindicated in multiple myeloma because of the increased risk of renal failure.
• Chest radiograph may be indicated to rule out infection. It also may reveal congestive heart failure (CHF). High output failure can be caused by hyperviscosity or anemia.

TREATMENT

Section 6 of 8  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

Prehospital Care

Be attentive to the ABCs and symptomatic support.

Emergency Department Care

• Plasmapheresis is the treatment of choice for initial treatment and stabilization of the hyperviscosity syndrome caused by the paraproteinemias (the majority of cases), while leukapheresis, plateletpheresis, and phlebotomy are indicated for leukostasis, and symptomatic thrombocytosis, and polycythemia, respectively.
• • As plasmapheresis removes the circulating paraproteins, the serum viscosity decreases and symptoms improve.
  • In similar fashion leukapheresis, plateletpheresis, and phlebotomy also decrease the serum viscosity by decreasing the existing cellular component in excess.
  • Although symptoms of CHF from hyperviscosity may not respond to standard therapies, and, in fact, can be exacerbated due to the resultant dehydration from diuresis causing increased viscosity; plasmapheresis and/or cellular pheresis reverses these symptoms.
  • While arranging for plasmapheresis, treat hemorrhage, CHF, and metabolic imbalances with standard therapies. Caveat: Use caution with the decision to proceed with packed red blood cell transfusion (pRBCs) for minor bleeding because a single unit of pRBCs may increase the viscosity enough to cause worsening symptoms and clinical decompensation.
  • 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.
  • Upon commencing pheresis (especially leukapheresis) one should prepare for the possibility of tumor lysis syndrome and treat accordingly.

Consultations

A hematologist should be consulted to arrange plasma/cellular pheresis and plan for interval chemotherapy as indicated.

FOLLOW-UP

Section 7 of 8  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

Further Inpatient Care

• Supportive care should be initiated for the complications of hyperviscosity syndrome pending definitive therapy. Care includes support for blood loss, central nervous system disorders, and cardiovascular effects, and metabolic derangements.
• Note that the definitive treatment of hyperviscosity syndrome is treatment of the underlying disorder (eg, chemotherapy).

Transfer

• Consider transfer if hematology/oncology consultation and plasma or cellular pheresis are unavailable at the treating facility.

Complications

• These depend upon the underlying cause of the hyperviscosity.

Prognosis

• Prognosis depends on the severity of the complications associated with hyperviscosity syndrome and the underlying cause of the hyperviscosity syndrome and the response of the appropriate definitive treatment. For example, multiple myeloma continues to have a poor long-term prognosis.

Patient Education

• The diseases leading to hyperviscosity are chronic, and this condition may recur.
• Patients and their families and/or caregivers should be educated about early signs and symptoms (eg, bleeding, visual symptoms, headache, mental status changes, shortness of breath).

REFERENCES

Section 8 of 8

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

• Bloch KJ, Maki DG. Hyperviscosity syndromes associated with immunoglobulin abnormalities. Semin Hematol. Apr 1973;10(2):113-24. [Medline].
• D'Alessio T, Kupas DF. Altered mental status in a 57-year-old woman with multiple myeloma. Top Emerg Med. 1996;18(2):72-8.
• Fahey JL, Barth WF, Solomon A. Serum hyperviscosity syndrome. JAMA. May 10 1965;192:464-7. [Medline].
• Hussein M. Multiple myeloma: an overview of diagnosis and management. Cleve Clin J Med. Jul-Aug 1994;61(4):285-98. [Medline].
• Kwaan HC, Bongu A. The hyperviscosity syndromes. Semin Thromb Hemost. 1999;25(2):199-208. [Medline].
• Kyle RA. Multiple myeloma: review of 869 cases. Mayo Clin Proc. Jan 1975;50(1):29-40. [Medline].
• Mehta J, Singhal S. Hyperviscosity syndrome in plasma cell dyscrasias. Semin Thromb Hemost. Oct 2003;29(5):467-71. [Medline].
• Ovadia S, Lysyy L, Floru S. Emergency plasmapheresis for unstable angina in a patient with hyperviscosity syndrome. Am J Emerg Med. Oct 2005;23(6):811-2. [Medline].
• Rogers R. Emergencies in Hematology and Oncology - Subtle and Atypical presentations, pearls and pitfalls. EMedHome.com [web site].
• Rosen P et al. Marx: Rosen's Emergency Medicine: Concepts and Clinical Practice. 5th ed. Mosby Inc;2002.
• Zarkovic M, Kwaan HC. Correction of hyperviscosity by apheresis. Semin Thromb Hemost. Oct 2003;29(5):535-42. [Medline].

Article Last Updated: Jan 12, 2007