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Commentary

Department of Laboratory Medicine, Children’s Hospital Boston, Boston, MA.

Address correspondence to the author at: Department of Laboratory Medicine, Children’s Hospital Boston, 300 Longwood Ave. 760, Boston, MA 02115. Fax 617-730-0383; e-mail Carlo.Brugnara{at}childrens.harvard.edu.

Much progress remains to be made in our understanding of the factors underlying the clinical manifestations of sickle cell disease. The severity of the disease has long been known to be highly variable, with some patients experiencing extremely severe disease and major organ-specific complications early in their lifetimes, and other patients with clinically silent disease who receive their diagnoses much later in life and have an almost normal life expectancy.

Epidemiologic and clinical data have suggested that increased concentrations of hemoglobin F (Hb F) are associated with a decreased severity of the disease. White blood cell counts are also an important predictor of mortality and morbidity—both in sickle cell disease and in the general population—with a shortened life expectancy being associated with higher counts.

The case presented in this issue of Clinical Chemistry demonstrates the remarkable effect of double heterozygosity for Hb S and Hb O_Arab on the clinical severity of the disease, compared with the more frequently observed Hb S/C double heterozygote. The worse effect of Hb O_Arab has been attributed to enhanced polymerization of Hb S and to the accompanying dehydration of erythrocytes imposed by the presence of the positively charged Hb O_Arab variant. This case also highlights the important role that the laboratory plays in the diagnosis and treatment of this disease. It is only thanks to the astute clinical and laboratory insights of the team taking care of this patient that the initial diagnosis of Hb S/C disease was questioned and the appropriate studies were conducted to reach the final, proper diagnosis. Although substantial progress has recently been made in modeling the risk for stroke (1) or death(2) in individual patients with sickle cell disease, this case highlights the crucial role of clinical reasoning and proper laboratory investigation when dealing with unexpected complications in particular patients.

Acknowledgments

Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.

Authors’ Disclosures of Potential Conflicts of Interest: No authors declared any potential conflicts of interest.

Role of Sponsor: The funding organizations played no role in the design of study, choice of enrolled patients, review and interpretation of data, or preparation or approval of manuscript.

References

1. Sebastiani P, Ramoni MF, Nolan V, Baldwin CT, Steinberg MH. Genetic dissection and prognostic modeling of overt stroke in sickle cell anemia. Nat Genet 2005;37:435-440.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
2. Sebastiani P, Nolan VG, Baldwin CT, Abad-Grau MM, Wang L, Adewoye AH, et al. A network model to predict the risk of death in sickle cell disease. Blood 2007;110:2727-2735.[Abstract/Free Full Text]

This Article Extract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Brugnara, C. Search for Related Content PubMed Articles by Brugnara, C.