Paraproteinemias due to excess concentrations of immunoglobulin molecules represent the main disorder of blood that primarily contribute to HVS. Excess concentrations of immunoglobulins are primarily present in the plasma. There are five immunoglobulin classes: IgG, IgA, IgM, IgD, and IgE.

Immunoglobulin M, with which HVS is most commonly observed, is a large molecular compound that is secreted in a pentamer form and weighs approximately one million daltons. IgM may bind water through its carbohydrate component and can also form aggregates. Due to its large size, 70-95% of the IgM produced is found in the intravascular compartment.1314 As a result of its osmotic draw, IgM leads to expanded blood volume, and can surreptitiously lead to a factitious anemia. Paraproteinemias due to smaller sized immunoglobu-lins, such as IgG and IgA, can also cause HVS, but usually at much higher serum levels than IgM due to their capacity to diffuse across blood barriers. Immunoglobulins, which are cationic, can also lower the repulsive forces between normally anionic erythrocytes and further contribute to HVS through rouleaux formation.15

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