Intravenous immunoglobulin therapy results in post‐infusional hyperproteinemia, increased serum viscosity, and pseudohyponatremia

Abstract

Intravenous immunoglobulin (IVIG) therapy is associated with rare reports of thromboembolic events and severe hyponatremia. We hypothesized that IVIG therapy may result in hyperproteinemia, increased serum viscosity, and pseudohyponatremia. We conducted a prospective observational study to evaluate the incidence of hyperproteinemia occurring after IVIG therapy and its relationship to serum sodium, viscosity, osmolality, and the serum osmolar gap. Eighteen IVIG infusions at a standard dose of 2 g/kg administered over 2-5 days were evaluated. Serum glucose, sodium, protein, viscosity, osmolality, and a calculated osmolar gap were obtained prior to therapy, 6 hr after the initiation of therapy, 24 hr after the conclusion of therapy, and on post-treatment day 10. Paired t-testing revealed a statistically significant increase in serum protein and viscosity and decrease in serum sodium and calculated osmolality 24 hr after the completion of IVIG therapy. The calculated serum osmolar gap increased insignificantly. In multivariate analysis, hyperproteinemia at the 6-hr time point predicted hyponatremia (P < 0.000), and hyperproteinemia at the 24-hr time point predicted both hyponatremia and increased serum viscosity (P = 0.024). These data demonstrate that increased serum viscosity occurs following IVIG therapy due to hyperproteinemia, and the rare hyponatremia reported is a pseudohyponatremia also due to hyperproteinemia. Am. J. Hematol. 73:97-100, 2003.

Spurious Electrolyte Disorders: A Diagnostic Challenge for Clinicians

“…due to paraproteinemia, hypergammaglobulinemia or intravenous immunoglobulin administration) is also associated with spurious hyponatremia [4,5,8,9]. Another cause of pseudohyponatremia associated with hyperproteinemia is the error produced by hyperviscosity when the sample is aspirated and less than the expected volume is obtained.…”

Safety and Adverse Events Profiles of Intravenous Gammaglobulin Products Used for Immunomodulation

“…Furthermore, it seems that viscosity of the diluent may be a factor that increases the risk for thrombosis as Polygam 10% had a much higher osmolality than Carimune 9% or Gamimune-N 10%. Previous reports have shown that IVIg increases blood viscosity (30), and it is possible that it contributes to the thrombogenic nature of sodium-based IVIg formulations. Other possible explanations for the prothrombotic effects of IVIg suggest that there might be an effect on platelet aggregation.…”

Guillain-Barré-Syndrom und Syndrom der inadäquaten Adiuretinsekretion

“…Mögliche Ursachen hierfür sind einerseits eine Pseudohyponatriämie im Rahmen einer IVIG-Therapie [8] und andererseits ein SIADH [7]. Na + wird in der Labordiagnostik ausschließlich in der flüssigen Phase des Plasmas gemessen, jedoch in Bezug zum Gesamtplasmavolumen gesetzt.…”

“…Hyperproteinämie, beispielsweise nach IVIG-Infusion, zu einer Vergrößerung des nicht wässrigen Kompartiments im Plasma, wird eine zu niedrige Konzentration angegeben, was als Pseudohyponatriämie bezeichnet wird. Diese Situation zeichnet sich durch eine normale Serumosmolalität bei vergrößerter osmotischer Lücke aus und hat keine klinische Relevanz [8].…”