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Answer 3
  1. Urgent initiation of plasmapheresis. Symptomatic hyperviscosity is a medical emergency, and immediate initiation of appropriate therapy is critical. This patient has developed classic symptoms of hyperviscosity syndrome, which can include headache, mental status changes, dizziness, nystagmus, retinal hemorrhages, and, less commonly, congestive heart failure or respiratory compromise. Symptoms frequently develop when serum viscosity is greater than 5 centipoise, as may be observed following an acute increase of an already elevated IgM level. Urgent plasmapheresis is indicated to rapidly lower the IgM level (and thus serum viscosity). If the serum viscosity level is not immediately available, patients with strongly suggestive symptoms should be treated empirically. A relatively small decrease in serum IgM can result in a large change in viscosity and dramatic symptom improvement. An ophthalmologic consultation with retina-directed therapy would not treat the underlying problem. Although patients with WM can develop symptoms due to central nervous system involvement (Bing-Neel syndrome), this is sufficiently rare as to obviate the need for a head CT until the possibility of hyperviscosity has been addressed. This patient most likely developed symptomatic hyperviscosity due to a transient increase in the IgM level following therapy with rituximab. The IgM level may initially increase in approximately 40% of patients with WM treated with rituximab, but some patients will subsequently respond to therapy.4 Therefore, it is too early to conclude that this patient will not respond to rituximab, and therapy should not be changed.

    4.  Treon SP, Branagan AR, Hunter Z, et al. Paradoxical increases in serum IgM and viscosity levels following rituximab in Waldenström’s macroglobulinemia. Ann Oncol 2004;15:1481-3.

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