Table 3. Waldenström Macroglobulinemia–Related Complications.

Complication	Pathophysiology	Exam findings	Diagnostic findings
Cold agglutin anemia (occurs in 10% of WM patients)	IgM binds to I antigen on surface of red blood cells. This binding results in hemolysis causing anemia.	Raynaud symptoms	Cold agglutinin titer > 1:64 Anemia Elevated LDH Indirect hyperbilirubinemia Positive compliment
Cryoglobulinemia (occurs in 10%–20% of WM patients)	Immunoglobulins precipitate with temperatures less than 37°C forming capillary globs resulting in impaired circulation. Three types: Type 1: monoclonal immunoglobulin to monoclonal immunoglobulin Type 2: polyclonal Ig binds to monoclonal Ig resulting in immune complexes Type 3: polyclonal Ig binds to polyclonal Ig resulting in immune complexes	Palpable purpura Raynaud symptoms Mucosal bleeding	Increased creatinine if developing glomerulonephritis
Hyperviscosity	The IgM immunoglobulin is a large pentameric molecule with half in the intravascular space. At increased levels, the IgM increases the plasma volume.	Fatigue Vision changes Bleeding Headaches Dizziness Strokes Monitor patients carefully during blood transfusion as the volume expansion may result in heart failure.	Retinal vein hemorrhages or engorgement Increase viscosity level (> 4 CP)
Neuropathy (occurs in 30%–50% of patients with a monoclonal IgM and 20% in WM patients)	The monoclonal IgM binds to the MAG on the surface of the myelin sheath.	Numbness, ataxia, painful neuropathy	Elevated anti MAG level > 20000 BTU/mL EMG reveals a demyelinating neuropathy Evaluate for other causes of neuropathy, including VEGF level, MRI spine, and antiganglioside antibodies

Note. LDH = lactate dehydrogenase; MAG = myelin-associated glycoprotein; EMG = electromyography; VEGF = vascular endothelial growth factor. Information from Bloch & Maki (1973); D'Sa et al. (2017); Desbois et al. (2019); Dimoupolis et al. (2000); Gertz (2018, 2019).