Comorbidities in aging patients with sickle cell disease

Abstract

Sickle cell disease (SCD) in general and sickle cell anemia in particular is a highly complex disorder both at the molecular and clinical levels. Although the molecular lesion is a single-point mutation, the sickle gene is pleiotropic in nature causing multiple phenotypic expressions that constitute the various complications of the disease. Moreover, despite the fact that SCD is a chronic malady, its manifestations are both acute and chronic. The former include, among other things, the recurrent vaso-occlusive crises (its hallmark) and acute chest syndrome. The chronic complications include most commonly avascular necrosis and leg ulcers. Currently, survival of patients with SCD has improved dramatically thanks to newborn screening, antibiotic prophylaxis, better vaccine, safer blood transfusion and the use of hydroxyurea. It is the advent of these therapies that improved the survival. This improvement, however, introduced a third dimension of the disease: comorbidities that occur in aging people in the general population. There is concern that the gain in survival may be offset by the comorbidities. Thus it is the purpose of this review to identify the comorbidities in the elderly with SCD and differentiate them from the basis disease to implement proper therapies so that better survival could be maintained.

Prevalência da doença falciforme em adultos com diagnóstico tardio

“…(21) The advent of neonatal screening, antibiotic prophylaxis, better vaccines, safer blood transfusion, iron chelation, and hydroxyurea therapy have improved the survival of patients with SCD. (17,(23)(24)(25)(26)(27) The life expectancy of children has increased, and SCD changed from a childhood disease to become a chronic disease. (14,16,24,26) However, for adult patients, mortality remains high.…”

Sickle cell disease as an accelerated aging syndrome

“…Aging-related bone loss and osteoporosis often leading to fracture or arthritis. 40 Kidney changes in elderly include glomerulosclerosis and tubulofibrosis. Glomerular filtration rate declines steadily from 40 years in normal individuals.…”

Type 2 diabetes in adults with sickle cell disease: can we dive deeper?

“…SCD is characterized by elevated rates of haemolysis, which causes increased protein turnover, resulting in hypermetabolism (Badaloo et al , ). For this reason, individuals with SCD were historically considered to be at low risk of developing type 2 diabetes (T2D) (Ballas, ). However, the intriguing findings of Zhou et al () revealed that the prevalence of T2D in SCD patients in the US is now comparable to the prevalence of T2D among the general African‐American population.…”

“…For example, the most severe forms of SCD are SCA and HbSβ 0 ‐thalassaemia, as these genotypes have the highest concentrations of intracellular HbS, resulting in increased haemoglobin polymerization and erythrocyte sickling, the primary pathological mechanisms of SCD (Chang et al , ). These two genotypes are characterized by more frequent vaso‐occlusive crises (VOC), severe anaemia and acute chest syndrome (ACS) (Ballas, ). On the other hand, HbSC is commonly considered to be a milder form of SCD, due to lower levels of intracellular HbS.…”

“…Notably, SCA subjects had higher triglyceride levels, which were associated with ACS, while non‐high density lipoprotein‐cholesterol levels were associated with osteonecrosis in HbSC subjects (Lalanne‐Mistrih et al , ). Furthermore, obesity has been shown to be on the rise in people with SCD, particularly in those with HbSC (Ballas, ). Interestingly, the results of Lalanne‐Mistrih et al () revealed that mean body mass index (BMI) was significantly lower in the SCA compared to the HbSC subjects.…”