Framing the research agenda for sickle cell trait: Building on the current understanding of clinical events and their potential implications

Abstract

Sickle Cell Trait (HbAS), the heterozygous state for the sickle hemoglobin beta globin gene is carried by as many as 100 million individuals including up to 25% of the population in some regions of the world (World Health Organization, Provisional agenda item 4.8, EB117/34 (22 December 2005) or World Health Organization, Provisional agenda item 11.4 (24 April 2006)). Persons with HbAS have some resistance to falciparum malaria infection in early childhood (Piel FB, Patil AP, Howes RE, et al., Nat Commun 2010;1104:1–7 and Aidoo M, Terlouw DJ, Kolczak M, et al., Lancet 2002;359:1311–1312) and as a result individuals with HbAS living in malarial endemic regions of Africa have a survival advantage over individuals with HbAA. Reports from the US emphasize possible health risks for individuals with HbAS including increased incidence of renal failure and malignancy, thromboembolic disorders, splenic infarction as a high altitude complication, and exercise-related sudden death. The National Heart, Lung, and Blood Institute, National Institutes of Health convened a workshop in Bethesda, Maryland on June 3–4, 2010, Framing the Research Agenda for Sickle Cell Trait, to review the clinical manifestations of HbAS, discuss the exercise-related sudden death reports in HbAS, and examine the public health, societal, and ethical implications of policies regarding HbAS. The goal of the workshop was to identify potential research questions to address knowledge gaps.

Adverse events in cancer patients with sickle cell trait or disease: case reports

“…With hundreds of millions of SCT carriers worldwide, the possibility of subclinical sickling during systemic cancer treatment warrants future analytic investigations. Given that the majority of SCT carriers are unaware of their genetic status, 3,4 translational implications might include genotyping among patients with newly diagnosed cancer for optimal agent selection, dose adjustment, and differential diagnoses of nonspecific events (e.g., renal decline, joint discomfort). With the current void of high-quality evidence, however, the magnitude and scope of poor outcomes are not known, nor are optimal clinical strategies for cancer patients with SCT or SCD genotypes.…”

“…With an estimated 300 million SCT carriers worldwide, 4 identification of sickling triggers and related complications offers an opportunity to improve quality of care and survival for a vast number of cancer patients.…”

“…For SCT, however, conventional wisdom has held that frank sickling is rare but is known to occur under certain physiological challenges such as extreme hypoxia and other stressors. 4 A recent review, however, reports emerging data about various health complications associated with SCT such as renal deterioration, hematuria, renal medullary carcinoma, and exercise-related sudden death, and calls for a national research agenda to determine triggers of sicklingrelated events in SCT. 4 Although the underlying pathology in the development of these complications in SCT remains virtually unknown, a recent in vitro study by Maciaszek et al 5 of blood cell reactivity in SCT patients observed increased frequency and strength of adhesion events in red blood cells (RBCs) on exposure to epinephrine, a hormone secreted during the sympathetic stress response.…”

Emerging drugs for sickle cell anemia

“…The World Health Organization has estimated that each year 220,000 babies are born with SCD in Africa, and that SCD accounts for up to 16% of deaths of children aged <5 years in some African countries [1,2]. The reported prevalence of the sickle cell trait in African Americans varies from 6.7% to 10.1% and in Africans the range is from 10 to 40% across equatorial Africa and decreases to between 1 and 2% on the North African coast and less than 1% in South Africa [3][4][5]. The prevalence of the sickle cell trait varies widely worldwide and may be as high as 50% in certain regions [5][6][7].…”

“…The reported prevalence of the sickle cell trait in African Americans varies from 6.7% to 10.1% and in Africans the range is from 10 to 40% across equatorial Africa and decreases to between 1 and 2% on the North African coast and less than 1% in South Africa [3][4][5]. The prevalence of the sickle cell trait varies widely worldwide and may be as high as 50% in certain regions [5][6][7]. The prevalence of SCA is approximately 1 in 600 newborn African American infants and 150,000 to 300,000 newborn Africans [8][9][10].…”