Background: The clinical picture in sickle cell disease (SCD) is highly heterogeneous. Knowledge of the determinants of a severe disease course will help us to unravel the pathophysiological mechanisms underlying the disease process and provide novel targets for therapeutic interventions. To generate this knowledge well designed etiological studies are needed, using a valid outcome measure for disease severity.

Objective: The aim of this systematic review is to identify all indices used to discriminate SCD patients by their current disease severity and to evaluate the methodological foundations of the indices and utility for clinical research.

Method: We performed a systematic search in MEDLINE (Pubmed) (1966- February 2006) using the search terms: anaemia, sickle cell/ [MeSH]; health status indicators/ [MeSH]; severity; severe and clinical spectrum. Reference lists of relevant studies and reviews were screened to identify additional articles. Information was extracted in duplicate by two independent reviewers (XT, KF).

Results: The Medline search yielded 1346 abstracts from which we selected 91 articles. Reference tracking resulted in 20 additional articles. After evaluation of the full text of these 111 articles, 28 articles (27 in English) were included in the review. These 28 indices contained 50 different items, including age at diagnosis, symptoms, findings at physical examination, laboratory values, organ damage, treatments and socio-economic consequences. The five most frequently used items were painful vaso-occlusive crises (86% of the indices), central nervous system abnormalities (59%), aseptic/avascular necrosis of the bone (52% of the indices), acute chest syndrome (48% of the indices) and leg ulcers (48% of the indices). Many indices (37%) were calculated by adding up scores on individual items without making a difference in the weight of the constituent items. In indices that did differentiate between items by allocating scores differentially, the rationale for weighing of the items was not explained. There were no scores that clearly distinguished devastating complications from complications that leave no sequelae. Most severity indices (89%) were not validated.

Conclusion: In order to increase our understanding of the pathofysiology of SCD and identify potential targets for new therapeutic interventions, we need to identify the determinants of a severe phenotype. For this purpose, consensus on the concept of severity in SCD and an instrument or index to measure it are necessary. This review reveals that there is no consensus on a definition of SCD severity and an index to measure it. Given the current state, efforts should be made to reach international consensus on a definition of SCD severity and a core set of items to measure this concept should be developed.

Author notes

Disclosure: No relevant conflicts of interest to declare.