Mechanism
Cryoglobulins
Cryoglobulins consists of one or more of the following components: monoclonal or polyclonal IgM, IgG, IgA antibodies, monoclonal  κ, or λ free light chain portions of these antibodies, and proteins of the blood complement system, particularly complement component 4 (C4). The particular components involved are a reflection of the disorders which are associated with, and considered to be the cause of, the cryoglobulinemic disease. The cryoglobulin compositions and disorder associations in cryoglobulinemic disease are as follows:

Monoclonal IgM-based cryoglobulin occurs in cases of Waldenströms macroglobulinemia and the pre-malignant precursors to this cancer, IgM monoclonal gammopathy of undetermined significance and smoldering Waldenstroms macroglobulinemia. Monoclonal IgG or, rarely, IgA, κ light chain, or λ light chain cryoglobulins occur in cases of multiple myeloma and the pre-malignant precursors to this cancer, non-IgM monoclonal gammopathy of undetermined significance and non-IgM smoldering multiple myeloma. Non-IgM monoclonal immunoglobulin-based cases of cryoglobulinemic disease are less commonly associated with other B-cell lymphocytic diseases viz., Non-Hodgkin lymphoma, Hodgkin lymphoma, B-cell chronic lymphocytic leukemia, and Castleman disease; they occur rarely in non-B cell hematological disorders such as myelodysplastic syndromes and chronic myelogenous leukemia. Among these purely monoclonal immunoglobulin causes of cryoglobulinemic disease, Waldenström macroglobulinemia and multiple myeloma together account for ≈40% of cases; their pre-malignant precursors account for ≈44% of cases; and the other cited hematological diseases account for ≈16% of cases.
Complications commonly requiring this intervention include: hyperviscosity disease with severe symptoms of neurological (e.g., stroke, mental impairment, and myelitis) and/or cardiovascular (e.g., congestive heart failure, myocardial infarction) disturbances; vasculitis-driven intestinal ischemia, intestinal perforation, cholecystitis, or pancreatitis, causing acute abdominal pain, general malaise, fever, and/or bloody bowel movements; vasculitis-driven pulmonary disturbances (e.g., coughing up blood, acute respiratory failure, X-ray evidence of diffuse pulmonary infiltrates caused by diffuse alveolar hemorrhage); and severe kidney dysfunction due to intravascular deposition of immunoglobulins or vasculitis. Along with this urgent treatment, severely symptomatic patients are commonly started on therapy to treat any underlying disease; this treatment is often supplemented with anti-inflammatory drugs such as corticosteroids (e.g., dexamethasone) and/or immunosuppressive drugs. Cases where no underlying disease is known are also often treated with the latter corticosteroid and immunosuppressive medications. Type I cryoglobulinemic disease
Treatment of Type I disease is generally directed towards treating the underlying pre-malignant or malignant disorder (see plasma cell dyscrasia, Waldenströms macroglobulinemia, and chronic lymphocytic leukemia). This involves appropriate chemotherapy regimens which may include bortezomib (promotes cell death by apoptosis in cells accumulating immunoglobulins) in patients with monoclonal immunoglobulin-induced kidney failure and rituximab (antibody directed against CD20 surface antigen-bearing lymphocytes) in patients with Waldenstroms macroglobulonemia). Type II and III cryoglobulinemic disease
Treatment of mixed cryoglobulinemic disease is, similar to type I disease, directed toward treating any underlying disorder. This includes malignant (particularly Waldenströms macroglobulinemia in type II disease), infectious, or autoimmune diseases in type II and III disease.