Hyperviscosity Syndrome in Cryoglobulinemia: Clinical Aspects and Therapeutic Considerations

ABSTRACT

The term cryoglobulinemia refers to the presence in the serum of proteins that precipitate at temperatures below 37°C and redissolve on rewarming. The cryoglobulins can be divided into three categories: monoclonal, mixed, and polyclonal. Hyperviscosity syndrome is much more common in monoclonal than in mixed or polyclonal cryoglobulinemia. The clinical manifestations of cryoglobulinemia depend on the underlying disease and may involve various organs or systems. Mixed cryoglobulinemia (MC) is dominated by a vasculitic process, and the clinical manifestations can range from mild to life threatening in their severity. Another common feature of this disorder is the presence of a benign smoldering lymphoproliferative process that can evolve (in a limited number of cases) into non-Hodgkin's lymphoma. The elective treatment for hyperviscosity syndrome, whether associated with monoclonal, mixed, or polyclonal cryoglobulinemia, is plasma exchange. In monoclonal cryoglobulinemia, this procedure seems to act by removing large amounts of abnormal proteins, but its mechanism in MC is far from clear. Here it is possible that qualitative and quantitative variations in the circulating cryoglobulins, as well as hemodynamic changes, are at play. This article will focus on the hyperviscosity syndrome in cryoglobulinemia, beginning with a discussion of its clinical features and then examining the role of hemorheological parameters in the condition.

KEYWORDS

Cryoglobulinemia - monoclonal - mixed - hyperviscosity syndrome - management - plasma exchange - hemorheology

REFERENCES

• 1 Brouet J C, Clauvel J P, Danon F, Klein M, Seligman M. Biologic report and clinical significance of cryoglobulins. A report of 86 cases.  Am J Med . 1974;  57 775-788
• 2 Della Rossa A, Ferri C, Bombardieri S. From essential mixed cryoglobulinemia to virus induced autoimmnunity: ten years of research in mixed cryoglobulinemia. In: Shoenfeld Y, ed. The Decade of Autoimmunity Amsterdam: Elsevier Sciences 1999: 235-243
• 3 Winfield J B. Cryoglobulinemia.  Hum Pathol . 1983;  14 350-354
• 4 Buxbaun J. Hyperviscosity syndrome in dysproteinemias.  Am J Med Sci . 1972;  264 123-126
• 5 Siami G A, Siami F. Plasmapheresis and paraproteinemia: cryoprotein-induced diseases, monoclonal gammopathy, Waldenström's macroglobulinemia, hyperviscosity syndrome, multiple myeloma, light chain disease, and amyloidosis.  Ther Apher . 1999;  3 8-19
• 6 Gorevich P D, Kassab H J, Levo Y. et al . Mixed cryoglobulinemia: clinical aspects and long term follow up of 40 patients.  Am J Med . 1980;  69 287-308
• 7 Ferri C, La Civita L, Longombardo G, Zignego A L, Pasero G. Mixed cryoglobulinemia: a cross road between autoimmune and lymphoproliferative disorders.  Lupus . 1998;  7 275-279
• 8 Ferri C, Mannini L, Bartoli V. Blood viscosity and filtration abnormalities in MC patients.  Clin Exp Rheumatol . 1990;  8 271-281
• 9 Carter P W, Cohen H J, Crawford J. Hyperviscosity syndrome in association with kappa light myeloma.  Am J Med . 1989;  86 591
• 10 Kosmo M A, Gale R P. Plasma cell leukemia with IgA paraproteinemia and hyperviscosity.  Am J Hematol . 1988;  28 113-115
• 11 Avnstorp C, Nielsen H, Drachman O, Hippe E. Plasmapheresis in hyperviscosity synmdrome.  Acta Med Scand . 1985;  217 133-137
• 12 Jasin H E, LoSpalluto J, Ziff M. Rheumatoid hyperviscosity syndrome.  Am J Med . 1970;  49 484-493
• 13 Abruzzo J L, Heimer R, Giuliano V, Martinez J. The hyperviscosity syndrome, polysynovitis, polymyositis and unusual 13s serum IgG component.  Am J Med . 1970;  49 258-264
• 14 Meltzer M, Franklin E C, Elias K, McCluskey R T, Cooper N. Cryoglobulinemia. A clinical and laboratory study. Cryoglobulins with rheumatoid factor activity.  Am J Med . 1966;  40 837-856
• 15 Stone M G. Studies on monoclonal antibodies. I. The specificity and binding properties of a Waldenström macroglobulinemia with anti Ig-G activity.  J Lab Clin Med . 1973;  81 393-409
• 16 Galli M, Monti G, Invernizzi F. et al . Hepatitis B virus-related markers in secondary and essential mixed cryoglobulinemias: a multicentre study of 596 cases.  Ann Ital Med Int . 1992;  7 209-214
• 17 Ferri C, Greco F, Longombardo G. et al . Antibodies to hepatitis C virus in patients with mixed cryoglobulinemia.  Arthritis Rheum . 1991;  34 1606-1610
• 18 Ferri C, Greco F, Longombardo G. et al . Association between hepatitis C virus and mixed cryoglobulinemia.  Clin Exp Rheumatol . 1991;  9 621-624
• 19 Agnello V, Chung R T, Kaplan L M. A role for hepatitis C virus infection in type II cryoglobulinemia.  N Engl J Med . 1992;  327 1490-1495
• 20 Tavoni A, Mosca M, Ferri C. et al . Guidelines for the management of essential mixed cryoglobulinemia.  Clin Exp Rheumatol . 1995;  13 (suppl 13) S191-S195
• 21 Lunel F, Cacoub P. Treatment of autoimmune and extrahepatic manifestations of HCV infection.  Ann Med Interne (Paris) . 2000;  151 58-64
• 22 Beck J R, Quinn B M, Meier F A, Rawnsley H M. Hyperviscosity syndrome in paraproteinemia. Managed by plasma exchange, monitored by serum tests.  Transfusion . 1982;  22 51-53
• 23 Bombardieri S, Ferri C, Migliorini P. et al . Immune complex behaviour during prolonged plasma exchange in essential mixed cryoglobulinemia and lupus erythematosus.  Int J Artif Organs . 1984;  8 7-10
• 24 Bombardieri S, Caponi L, Pilo A. et al . Changes in the putative antigen/antibody ratio of circulating immune complexes in mixed cryoglobulinemia and systemic lupus erythematosus following selective removal of macromolecules.  Int J Artif Organs . 1989;  12 (suppl 4) 87-91