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Serum viscosity units1/8/2024 ![]() ![]() A single plasma exchange reduces viscosity 20–30% ( 22). Some services substitute 25–50% of replacement volume with 0.9% saline ( 21). Typically, 30–40 mL/kg of plasma (1–1.5 plasma volumes) are removed at each procedure and replaced with isotonic 4.5 or 5.0% human albumin solution. Central line placement is used to allow adequate blood flow. TPE is usually carried out using an automated blood cell separator to ensure fluid balance and maintain a normal plasma volume. The remaining blood components are returned to the patient along with a short-acting anticoagulant, such as citrate. This is done by passing venous blood through an extracorporeal blood centrifugal separation device, which allows for shunting of plasma for removal. Therapeutic plasma exchange (TPE) removes large-molecular-weight substances from patient plasma, including paraproteins, with the return of all cellular components to the patient. Despite the lack of randomized trials, this procedure rapidly reverses the clinical symptoms of hyperviscosity. Plasmapheresis has been used effectively for management of HVS associated with WM since the 1950's. Neurologic manifestations can range from relatively mild headache and lightheadedness to seizures and coma ( 4, 9, 15– 20). The most severe ophthalmologic manifestation of HVS is central retinal vein occlusion, which can result in irreversible vision loss and has been reported for patients with IgM and non-IgM paraproteinemias ( 14). Other ophthalmic findings may include flame hemorrhages, papilledema, exudates, and microaneurysms. Characteristic retinal vein dilation with tortuous “sausage link” appearance on retinal veins can be seen. Due to the high prevalence of ophthalmologic manifestations of HVS, a fundoscopic examination should be performed in any patient with suspected HVS or with a serum IgM > 3 g/dL. Ophthalmologic symptoms include blurred or double vision, retinal hemorrhage. Epistaxis is a common presenting symptom, and if present in a patient with a possible paraproteinemia, should prompt additional evaluation for HVS, particularly fundoscopic examination, as evidence of ocular HVS can be present without visual symptoms and is a treatment indication. Hemorrhage typically occurs in small venules associated with increased viscosity in areas with minimal supporting tissue, such as the nose and oral cavity. The predominant symptoms of HVS are mucocutaneous bleeding, ophthalmologic, and neurologic ( Table 1). Symptoms and Management of Hyperviscosity Syndrome It should be noted that, although the likelihood of HVS increases at higher levels of immunoglobulin, there is no discrete cutoff in any circumstance, and HVS should be considered for patients with characteristic symptoms and evidence of a paraprotein-secreting hematologic malignancy. Even in the context of a paraprotein-excreting hematologic malignancy, the risk of HVS is relatively low until the serum viscosity increases above 4 cP ( 9). IgG is relatively small (180 kDA) and can require levels as high as 10 g/dL to produce significant changes in viscosity, except for the IgG3 subtype, which has a tendency to aggregate and can increase viscosity at lower levels, perhaps due to its elongated hinge region and resultant increases in Fc-Fc interaction ( 9, 12, 13). IgA is smaller (320 kDA) than IgM but circulates as a dimer and is associated with increased viscosity at levels of 6 g/dL or greater ( 5, 11). IgM is pentameric and very large in size (970 kDA), and serum viscosity can increase significantly with IgM levels as low as 3 g/dL, and IgM levels of 6 g/dL or higher are associated with rapid development of hyperviscosity, with a median time to symptomatic HVS of 3 months ( 9, 10). Serum viscosity is correlated with immunoglobulin levels for patients both with and without monoclonal gammopathies ( 8), but the concentration of immunoglobulins required to significantly increase viscosity depends on the specific type of paraprotein. In contrast to most serum proteins, which are spherical in shape, immunoglobulins are relatively large but also linear in shape thus, when they travel through the serum, they spin around their longitudinal axis, increasing serum viscous drag, and therefore viscosity. The increased viscosity of serum relative to water relates primarily to its protein content. A typical serum viscosity for a healthy patient is 1.5 cP, or 1.7 relative to water. Viscosity can be measured in absolute terms in centipoise (cP), or in relative terms compared to the viscosity of water (0.894 cP). Paraprotein Levels and Hyperviscosity Syndrome ![]()
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