Standard clinical practice underestimates the role and significance of erythropoietin deficiency in sickle cell disease

Br J Haematol. 2011 May;153(3):386-92. doi: 10.1111/j.1365-2141.2010.08479.x. Epub 2011 Mar 21.

Abstract

In sickle cell disease (SCD), vigorous reticulocytosis is required to partially compensate for chronic hemolytic anaemia. Consequently, early renal damage, insufficient to cause azotemia but sufficient to cause erythropoietin deficiency and chronic relative reticulocytopenia (chRR), could have severe clinical consequences. chRR was defined as reticulocytes <250×10(9) /l despite haemoglobin <9 g/dl on ≥ two occasions ≥4 weeks apart. The influence of multiple variables including chRR on time from first clinic visit to death was evaluated in 306 SCD patients. In univariate analyses, fetal haemoglobin, indices of renal damage (serum creatinine, proteinuria), chRR and age, were associated with rate of death. In multivariate analysis, only age and chRR (Hazard ratio 3·6, 95% CI 2·049-6·327, P<0·0001) were significant, underlining that chRR could be an early and important clinical consequence of renal damage. Even in chRR patients with normal serum creatinine levels, low haemoglobin and low reticulocyte counts were associated with low erythropoietin levels. In the general population, evaluation of erythropoietin levels is prompted by the combination of anaemia and abnormal serum creatinine. In SCD patients, this standard approach can miss a substantial risk factor for early death. chRR could be a practical and important criterion for diagnosis of erythropoietin deficiency in SCD.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Anemia, Sickle Cell / blood
  • Anemia, Sickle Cell / complications*
  • Chronic Disease
  • Creatinine / blood
  • Epidemiologic Methods
  • Erythropoietin / deficiency*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Proteinuria / complications
  • Reticulocyte Count
  • Young Adult

Substances

  • Erythropoietin
  • Creatinine