Evidence-based focused review of management of hyperviscosity syndrome

Abstract

Case 1. Patient 1 is a 65-year-old plumber who presents with fatigue, headache, blurred vision, and intermittent nosebleeds for the past 3 months. Examination demonstrates mild generalized lymphadenopathy and a palpable spleen tip. The fundi show marked retinal vein engorgement with "sausaging." Laboratory tests disclose mild anemia and a large monoclonal spike on serum protein electrophoresis. How should he be managed?Elevated blood, plasma, or serum viscosity occurs in a number of hematologic disorders. Hyperviscosity syndrome (HVS) is a clinical feature in 10% to 30% of patients with Waldenström macroglobulinemia (WM), sometimes as its presenting manifestation. 1 HVS also accompanies other conditions, such as multiple myeloma, rheumatoid disease, polycythemia, sickle cell disease, leukemia, and spherocytosis. 2 The latter 4 cellular causes of HVS are beyond the scope of this discussion. The purpose of this paper is to discuss the characteristic features of HVS secondary to elevated plasma or serum viscosity and to evaluate evidence supporting various diagnostic and treatment approaches using the Grade system (Table 1). 3,4 In searching the Medline database on hyperviscosity syndrome, 594 references were listed back to 1965. A limited number of older publications were also used. Only English-language articles were considered. Observational studies, systemic reviews, or case studies were included. No randomized trials on management of HVS were identified. Methods to measure viscosityViscosity refers to resistance to flow or stickiness, from the Latin word "viscum alba" for mistletoe. 5,6 (Mistletoe berries were once used to make a viscous glue.) Viscosity is classically measured in one of 2 ways: by determining the rate of fluid flow as a result of applying a predefined force or by measuring the amount of force required to achieve a predefined rate of fluid flow.Although HVS is caused by hyperviscous blood, clinical laboratories generally only measure the serum or plasma component. Serum and plasma display Newtonian properties in that viscosity is independent of pressure drop or velocity gradient. Consequently, the method of measurement will not dramatically affect the test result. By contrast, whole blood viscosity is complex because of the suspension of red cells in plasma, resulting in non-Newtonian behavior. Different methods of measurement can yield various results.In WM, serum or plasma viscosity measurements reflect the amount and properties of the IgM paraprotein. Monoclonal IgMs display a wide range of intrinsic viscosity values (0.106-0.162 dL/ g), each protein having individual properties. 7,8 However, relative viscosity values are highly reproducible for any individual protein.IgM is a star-shaped pentamer with a molecular size of 925 kDa (IgG is 150 kDa and albumin is 65 kDa). Thus, it is not surprising that this giant IgM molecule, which is 80% intravascular, exerts profound effects on blood flow and cells, especially when present in the high concentrations found in WM patients.The methods used fo...

Guideline for the diagnosis, treatment and response criteria for Bing-Neel syndrome

“…Confirmation of HVS with appropriately increased IgM or serum viscosity measurements can aid in differentiating HVS related CNS symptoms from BNS. 7 Sensory symptoms of the legs due to nerve root/cauda equina involvement may be mistaken for neuropathy related to anti-myelin associated glycoprotein (MAG) antibodies produced in WM and IgM related disorders. 8 These patients mostly present with a sensory ataxia with impaired gait and mild to moderate distal muscle weakness which slowly develops over years.…”

Diabetes Insipidus as Presenting Manifestation of Waldenstrom’s Macroglobulinemia

“…Cryoglobulinemia can cause an exaggerated temperature-dependent elevation of serum viscosity, as is the case in this report [5]. However, cryoglobulin complex formation should not readily occur in the medulla of the kidney, which is at core body temperature, and therefore should not impact the ability to concentrate urine.…”

The association of globulin levels with treatment response and survival in multiple myeloma patients

“…[6] Hypergammaglobulinemia augments serum viscosity leading to serious symptoms such as bleeding and ocular, neurological, and cardiovascular manifestations, all requiring urgent intervention with plasmapheresis. [6,7,12] The hyperviscosity develops mostly in the IgA type MM. [12,13] The relatively low number of patients having IgA type M-protein might be the reason for diminished number of patients with hyperviscosity syndrome in our cohort.…”

“…[1,4] However, there is insufficient data on the prognostic value of globulin levels, and the significance of increased globulin levels emerge as suggestive of hyperviscosity, resulting in concerns among clinicians. [6,7] This study aimed to determine the association of globulin levels at diagnosis with the treatment response and OS in patients with MM.…”