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  • Clinical Research Article
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Red cell abnormalities characterized by ektacytometry in children with cholestasis

Pediatric Research volume 95, pages 1035–1040 (2024)Cite this article

Abstract

Background

Spur-cell anemia sometimes accompanies cholestasis. We postulated that even in the absence of spur-cells, cholestasis might alter red blood cell (RBC) osmotic fragility and deformability. Therefore, we assessed these RBC measures by ektacytometry in pediatric patients.

Methods

We conducted a single center, prospective, cross-sectional investigation of RBC membrane characteristics by ektacytometry in pediatric patients with intra- and extrahepatic cholestasis followed at Cincinnati Children’s Hospital Medical Center. We measured red cell membrane fragility and deformability in 17 patients with cholestasis and 17 age-matched controls without cholestasis.

Results

Patients with cholestasis had decreased RBC osmotic fragility compared to controls, with a significant left shift in Omin, indicating increased RBC surface-to-volume ratio. One showed spur cell morphology. However, the other 16 had no spurring, indicating that ektacytometry is a sensitive method to detect RBC membrane abnormalities. Left shift of Omin positively correlated with serum conjugated bilirubin levels and even more negatively with serum vitamin E concentration.

Conclusions

This study suggests that subclinical red blood cell membrane abnormalities exist in most pediatric patients with cholestasis, increasing risk for hemolysis when subjected to oxidative stress. Hence minimizing pro-oxidants exposure and maximizing antioxidant exposure is advisable for this group.

ClinicalTrials.gov Identifier

NCT05582447 https://clinicaltrials.gov/ct2/show/NCT05582447?cond=Cholestasis&cntry=US&state=US%3AOH&city=Cincinnati&draw=2&rank=2.

Impact

  • Spur cell anemia due to decreased red cell osmotic fragility and decreased deformability has been reported among patients with cholestasis.

  • Ektacytometry is a reliable, reproducible method to measure red cell osmotic fragility and deformability.

  • Few data describe red cell osmotic fragility or deformability in patients with cholestasis who may or may not have spur cell anemia.

  • Ektacytometry shows that red cell osmotic fragility and deformability are decreased in many children with cholestasis even when spur cell anemia has not yet occurred.

  • Factors associated with decreased osmotic fragility include elevated serum bilirubin, elevated serum bile acids, and decreased serum vitamin E.

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Fig. 1: Ektacytometric curves for a control patient and for three patients with abnormal RBC morphology.
Fig. 2: Omin of each cholestatic patient compared with contemporaneously performed Omin of each agematched control.
Fig. 3: Linear Regression Analyses Between Omin and Serum Bilirubin, Serum Bile Acids, or Serum Vitamin E levels.

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Division of Pediatric Gastroenterology, Hepatology, and Nutrition Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH, 45229, USA

    Theodore S. Kocoshis, Alexander G. Miethke, William F. Balistreri, Crystal G. Slaughter, Ruchi Singh, Mary Mullen & Samuel A. Kocoshis

  2. Division of Hematology, Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH, 45229, USA

    Theodosia A. Kalfa & Katie G. Seu

Authors
  1. Theodore S. Kocoshis
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  2. Theodosia A. Kalfa
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  3. Alexander G. Miethke
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  4. William F. Balistreri
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  5. Katie G. Seu
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  6. Crystal G. Slaughter
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  7. Ruchi Singh
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  8. Mary Mullen
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  9. Samuel A. Kocoshis
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Contributions

T.S.K., T.A.K., A.G.M., W.F.B., and S.A.K designed the study. T.S.K., K.S., C.G.S., R.S., and M.M. conducted the research. T.S.K., T.A.K., A.G.M., and S.A.K. analyzed the data. T.S.K., T.A.K., A.G.M., W.F.B., and S.A.K. wrote the manuscript. T.S.K. and S.A.K. have primary responsibility for the final content. All authors read and approved the final manuscript. All subjects with cholestasis and healthy controls were enrolled following informed parental consent and informed assent among subjects and controls aged 12 or older.

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Correspondence to Samuel A. Kocoshis.

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Kocoshis, T.S., Kalfa, T.A., Miethke, A.G. et al. Red cell abnormalities characterized by ektacytometry in children with cholestasis. Pediatr Res 95, 1035–1040 (2024). https://doi.org/10.1038/s41390-023-02899-2

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