Red blood cell rigidification during cyclosporin therapy: a possible early warning signal for adverse reactions

Scand J Clin Lab Invest. 1998 Dec;58(8):617-23. doi: 10.1080/00365519850186049.

Abstract

In a previous retrospective study with kidney-transplant patients, immunosuppressive treatment with Cyclosporin A (CsA) was found to be associated with impaired red blood cell (RBC) deformability. The aim of the present study was to evaluate and substantiate a possible causal relationship between the use of CsA and its effect on RBC deformability in a prospective study on non-transplant patients. Blood samples of 12 patients with psoriasis were taken before and after 2, 4, 8, 12 and 16 weeks of treatment with CsA (3-5 mg/day). Red cell deformability, expressed as Elongation Index (EI), was measured with the Laser-assisted Optical Rotational Cell Analyzer (LORCA), a new ektacytometric instrument. Mean values +/- SD for EI found after 16 weeks of treatment with cyclosporin (0.570 +/- 0.008) were significantly (p < 0.001) lower than the value before treatment (0.589 +/- 0.011). A dose-response relation could not be established within the small range of CsA doses used in this study. Irrespective of the dose, however, a significant correlation (r = -0.55; p = 0.0001) between duration of treatment and decrease in EI was demonstrated. In vitro incubation of blood with cyclosporin was not able to reproduce this effect, suggesting that a direct effect of the drug on RBCs is unlikely. Despite its use in relatively low doses, CsA causes a reduction in RBC deformability, an effect that increases during the course of treatment. It is suggested that this slow, but continuously increasing, RBC rigidification plays a role in the early pathogenesis of the adverse nephrotoxic complications frequently associated with this immunosuppressive regimen.

Publication types

  • Clinical Trial

MeSH terms

  • Cyclosporine / adverse effects*
  • Erythrocyte Aggregation / drug effects
  • Erythrocyte Deformability / drug effects*
  • Hematology / methods
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Kidney Diseases / chemically induced
  • Postoperative Complications / chemically induced
  • Predictive Value of Tests
  • Prospective Studies
  • Psoriasis / drug therapy

Substances

  • Immunosuppressive Agents
  • Cyclosporine