title: Standard clinical practice underestimates the role and significance of erythropoietin deficiency in sickle cell disease.
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.
authors.affiliation: Department of Medicine, University of Illinois, Chicago Center for Clinical and Translational Research, University of Illinois, Chicago, IL, USA.
authors.forename: Santosh
authors.initials: S
authors.lastname: Saraf
authors.forename: Mohammed
authors.initials: M
authors.lastname: Farooqui
authors.forename: Giovanni
authors.initials: G
authors.lastname: Infusino
authors.forename: Bharvi
authors.initials: B
authors.lastname: Oza
authors.forename: Seema
authors.initials: S
authors.lastname: Sidhwani
authors.forename: Michel
authors.initials: M
authors.lastname: Gowhari
authors.forename: Stephen
authors.initials: S
authors.lastname: Vara
authors.forename: Weihua
authors.initials: W
authors.lastname: Gao
authors.forename: Lani
authors.initials: L
authors.lastname: Krauz
authors.forename: Donald
authors.initials: D
authors.lastname: Lavelle
authors.forename: Joseph
authors.initials: J
authors.lastname: DeSimone
authors.forename: Robert
authors.initials: R
authors.lastname: Molokie
authors.forename: Yogen
authors.initials: Y
authors.lastname: Saunthararajah
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000755:Anemia, Sickle Cell / Q000097:blood / Q000150:complications*; D002908:Chronic Disease; D003404:Creatinine / Q000097:blood; D004812:Epidemiologic Methods; D004921:Erythropoietin / Q000172:deficiency*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000150:complications; D017701:Reticulocyte Count; D055815:Young Adult
chemical_list: D004921:Erythropoietin; D003404:Creatinine