Semin Thromb Hemost 2003; 29(5): 467-472
DOI: 10.1055/s-2003-44554
Copyright © 2003 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Hyperviscosity Syndrome in Plasma Cell Dyscrasias

Jayesh Mehta1,2 , Seema Singhal2
  • 1Professor of Medicine, The Feinberg School of Medicine, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University , Chicago, Illinois
  • 2Multiple Myeloma Program, Division of Hematology/Oncology, The Feinberg School of Medicine, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois
Further Information

Publication History

Publication Date:
21 November 2003 (online)

ABSTRACT

Hypergammaglobulinemia increases serum viscosity and is the most common cause of hyperviscosity syndrome. Monoclonal hypergammaglobulinemia resulting in hyperviscosity syndrome is seen in multiple myeloma and Waldenström's macroglobulinemia. The reasons for elevated viscosity are increased protein content and large molecular size, abnormal polymerization, and abnormal shape of immunoglobulin molecules. Other hematologic and metabolic abnormalities seen in patients with plasma cell dyscrasias also contribute to hyperviscosity. Symptomatic hyperviscosity is much more common in Waldenström's macroglobulinemia (10 to 30%) than it is in myeloma (2 to 6%). Symptoms of hyperviscosity usually appear when the normal serum viscosity of 1.4 to 1.8 cp reaches 4 to 5 cp, corresponding to a serum immunoglobulin M (IgM) level of at least 3 g/dL, an IgG level of 4 g/dL, and an IgA level of 6 g/dL. Symptoms of hyperviscosity include constitutional symptoms; bleeding; and ocular, neurological, and cardiovascular manifestations. Immediate therapy of symptomatic hyperviscosity is directed at reduction of blood viscosity by plasmapheresis to control symptoms. Long-term management is directed at control of the underlying disease to prevent production of the monoclonal protein. There may be a small proportion of individuals, usually old or with severely compromised performance status, who undergo plasma exchange as the sole symptomatic therapy of hyperviscosity secondary to plasma cell dyscrasia.

REFERENCES

  • 1 Kwaan H C, Bongu A. The hyperviscosity syndromes.  Semin Thromb Hemost . 1999;  25 199-208
  • 2 Rosenson R S, McCormick A, Uretz E F. Distribution of blood viscosity values and biochemical correlates in healthy adults.  Clin Chem . 1996;  42 1189-1195
  • 3 Somer T. Rheology of paraproteinaemias and the plasma hyperviscosity syndrome.  Baillieres Clin Haematol . 1987;  1 695-723
  • 4 McGrath M A, Penny R. Paraproteinemia: blood hyperviscosity and clinical manifestations.  J Clin Invest . 1976;  58 1155-1162
  • 5 Crawford J, Cox E B, Cohen H J. Evaluation of hyperviscosity in monoclonal gammopathies.  Am J Med . 1985;  79 13-22
  • 6 Rajkumar S V, Greipp P R. Plasma cells and immunoglobulins. In: Mehta J, Singhal S, eds. Myeloma London: Martin Dunitz 2002: 3-23
  • 7 Roberts-Thomson P J, Mason D Y, MacLennan I C. Relationship between paraprotein polymerization and clinical features in IgA myeloma.  Br J Haematol . 1976;  33 117-130
  • 8 Mestecky J, Hammack W J, Kulhavy R, Wright G P, Tomana M. Properties of IgA myeloma proteins isolated from sera of patients with the hyperviscosity syndrome.  J Lab Clin Med . 1977;  89 919-927
  • 9 Preston F E, Cooke K B, Foster M E, Winfield D A, Lee D. Myelomatosis and the hyperviscosity syndrome.  Br J Haematol . 1978;  38 517-530
  • 10 Chandy K G, Stockley R A, Leonard R C. et al . Relationship between serum viscosity and intravascular IgA polymer concentration in IgA myeloma.  Clin Exp Immunol . 1981;  46 653-661
  • 11 MacKenzie M R, Babcock J. Studies of the hyperviscosity syndrome. II. Macroglobulinemia.  J Lab Clin Med . 1975;  85 227-234
  • 12 Hall C G, Abraham G N. Size, shape, and hydration of a self-associating human IgG myeloma protein: axial asymmetry as a contributing factor in serum hyperviscosity.  Arch Biochem Biophys . 1984;  233 330-337
  • 13 Joles J A, Willekes-Koolschijn N, Koomans H A. Hypoalbuminemia causes high blood viscosity by increasing red cell lysophosphatidylcholine.  Kidney Int . 1997;  52 761-770
  • 14 Lane D W, L'Anson S. Viscosimetric effect of fibrinogen.  J Clin Pathol . 1994;  47 1004-1005
  • 15 Shaver-Lewis M J, Shah S V. The kidney in plasma cell disorders. In: Mehta J, Singhal S, eds. Myeloma London: Martin Dunitz 2002: 203-221
  • 16 Reinhart W H, Gaudenz R, Walter R. Acidosis induced by lactate, pyruvate, or HCl increases blood viscosity.  J Crit Care . 2002;  17 68-73
  • 17 Alkner U, Hansson U B, Lindstrom F D. Factors affecting IgA related hyperviscosity.  Clin Exp Immunol . 1983;  51 617-623
  • 18 Lokhorst H. Clinical features and diagnostic criteria. In: Mehta J, Singhal S, eds. Myeloma London: Martin Dunitz 2002: 151-168
  • 19 Singh A, Eckardt K U, Zimmermann A. et al . Increased plasma viscosity as a reason for inappropriate erythropoietin formation.  J Clin Invest . 1993;  91 251-256
  • 20 Russell J A, Powles R L. The relationship between serum viscosity, hypervolaemia and clinical manifestations associated with circulating paraprotein.  Br J Haematol . 1978;  39 163-175
  • 21 Dalakas M C. High-dose intravenous immunoglobulin and serum viscosity: risk of precipitating thromboembolic events.  Neurology . 1994;  44 223-226
  • 22 Kelleher P, Chapel H. Infections: principles of prevention and therapy. In: Mehta J, Singhal S, eds. Myeloma London: Martin Dunitz 2002: 223-239
  • 23 Bloch K J, Maki D G. Hyperviscosity syndromes associated with immunoglobulin abnormalities.  Semin Hematol . 1973;  10 113-124
  • 24 Tichy M. Viscosity of paraproteinemic sera.  Acta Medica . 1996;  39 41-43
  • 25 Reinhart W H, Lutolf O, Nydegger U R, Mahler F, Straub P W. Plasmapheresis for hyperviscosity syndrome in macroglobulinemia Waldenström and multiple myeloma: influence on blood rheology and the microcirculation.  J Lab Clin Med . 1992;  119 69-76
  • 26 Riccardi A, Gobbi P G, Ucci G. et al . Changing clinical presentation of multiple myeloma.  Eur J Cancer . 1991;  27 1401-1405
  • 27 Preston F E, Cooke K B, Foster M E, Winfield D A, Lee D. Myelomatosis and the hyperviscosity syndrome.  Br J Haematol . 1978;  38 517-530
  • 28 Dimopoulos M A. Waldenström's macroglobulinaemia. In: Mehta J, Singhal S, eds. Myeloma London: Martin Dunitz 2002: 465-480
  • 29 Garcia-Sanz R, Montoto S, Torrequebrada A. et al . Waldenström macroglobulinaemia: presenting features and outcome in a series with 217 cases.  Br J Haematol . 2001;  115 575-582
  • 30 Kyrtsonis M C, Vassilakopoulos T P, Angelopoulou M K. et al . Waldenström's macroglobulinemia: clinical course and prognostic factors in 60 patients. Experience from a single hematology unit (Erratum: Ann Hematol 2002;81:124).  Ann Hematol . 2001;  80 722-727
  • 31 Rosenbaum E H, Thompson H E, Glassberg A B. Priapism and multiple myeloma. Successful treatment with plasmapheresis.  Urology . 1978;  12 201-202
  • 32 Facon T, Brouillard M, Duhamel A. et al . Prognostic factors in Waldenström's macroglobulinemia: a report of 167 cases.  J Clin Oncol . 1993;  11 1553-1558
  • 33 Ludwig H, Fritz E. Supportive therapy. In: Mehta J, Singhal S, eds. Myeloma London: Martin Dunitz 2002: 397-412
  • 34 Singhal S, Mehta J. Thalidomide in cancer.  Biomed Pharmacother . 2002;  56 4-12
  • 35 Hoffkes H G, Heemann U W, Teschendorf C, Uppenkamp M, Philipp T. Hyperviscosity syndrome: efficacy and comparison of plasma exchange by plasma separation and cascade filtration in patients with immunocytoma of Waldenström's type.  Clin Nephrol . 1995;  43 335-338
  • 36 Zucchelli P, Pasquali S, Cagnoli L, Ferrari G. Controlled plasma exchange trial in acute renal failure due to multiple myeloma.  Kidney Int . 1988;  33 1175-1180
    >