OBJECTIVE: Sickle cell disease (SCD) is a genetic hematologic disorder with multi-system impacts contributing to long-term end-organ damage. Our objective was to assess the extent to which associations among SCD complications have been quantified in the literature to inform cost-effectiveness modeling for SCD therapies with curative intent.
METHODS: We conducted a structured review of the literature published from 2010 through 2020 by searching MEDLINE, conference abstracts, and Google Scholar for primary, review, and health technology assessment (HTA) publications quantifying the associations among complications in patients with SCD. Landmark studies published before 2010 also were considered. Abstracts were screened against prespecified criteria, and eligible full texts were assessed further for inclusion. Primary research studies were rated subjectively as high, moderate, or low quality, and low-quality studies were excluded from further review. Reviews and HTAs without primary research were included but did not receive quality ratings.
RESULTS: Of 977 abstracts screened, 34 studies were included (31 primary research studies, 1 review, 2 HTAs). Vaso-occlusive crises (VOCs) and acute chest syndrome (ACS) had the greatest number of quantified associations with other complications. Both were linked to avascular necrosis, pulmonary hypertension (PH), and cholelithiasis, and each was linked to multiple other complications separately. PH also was associated with multiple complications, including venous thromboembolism, chronic kidney disease, stroke, and leg ulcers. Comparatively fewer associations were identified for other cardiovascular and neurological complications.
CONCLUSIONS: Although VOCs and ACS are well-known drivers of acute medical care in SCD, associations involving more insidious complications, such as PH, are less recognized contributors to the downstream multi-system impacts of SCD. Our findings build a foundation for quantifying the interconnectedness of SCD complications, including their downstream clinical and societal impacts and the heterogeneity in patients’ complication histories at the time of treatment, in cost-effectiveness models for SCD therapies with curative intent.
