Sickle cell disease in the older adult

doi:10.1016/j.pathol.2016.10.002

Pathology

Volume 49, Issue 1, January 2017, Pages 1-9

https://doi.org/10.1016/j.pathol.2016.10.002 Get rights and content

Summary

Sickle cell disease (SCD) is an inherited haemoglobin disorder, associated with recurrent painful episodes, ongoing haemolytic anaemia and progressive multi-organ damage. Until the early 1990s, survival beyond the fourth decade for a patient with SCD was considered unusual and prompted case reports. Nowadays, in countries with developed health care systems, more than 90 percent of newborns with SCD survive into adulthood. Nevertheless, their life expectancy is still shortened by more than two decades compared to the general population. With an increasing life expectancy, SCD has now evolved into a debilitating disorder with substantial morbidity resulting from ongoing sickle cell vasculopathy and multi-organ damage. Limited data on health care issues of older adults with SCD poses multiple challenges to patients, their families and health care providers. In this review, we will address and discuss acute and chronic complications of SCD with a special focus on the older adult.

Section snippets

Introduction, background and scope of the problem

With an estimate of 275,000 newborns every year, sickle cell disease (SCD) is considered a public health burden by the World Health Organization (WHO) and United Nations (UN).¹ Two-thirds of newborns with SCD occur in sub-Saharan Africa where malaria is endemic. However, due to population movements, substantial numbers of children are now being born in countries where SCD is previously considered rare (e.g., northern and western Europe).² Although the majority of children in Africa do not reach

Pathophysiology and manifestations of sickle cell disease

Polymerisation of deoxygenated HbS and the formation of irreversibly sickled red blood cells lead to a downstream cascade of vaso-occlusion, release of cytokines and inflammatory factors.³⁴ Subsequent reperfusion of the ischaemic tissue generates free radicals and reactive oxygen species, which scavenge nitric oxide (NO).³⁵ Chronic NO deficiency can lead to platelet activation, increased vascular resistance, and endothelial dysfunction contributing to the development of vasculopathy.36, 37

Complications and management of sickle cell disease in older adults

Providing care for older adults with SCD can be challenging as little data or evidence-based guidelines are available. Recently, National Heart Lung and Blood Institute (NHLBI) published evidence-based guidelines that are based on pragmatic and expert consensus opinions rather than findings from randomised controlled trials.32, 40 A lack of high quality evidence-based recommendations and relative rarity of the disease makes it difficult to identify health care professionals with expertise and

Importance of health maintenance and available treatment options

Health maintenance encompasses early recognition, prevention and treatment of organ damage, and should be an essential part of routine health care in older adults with SCD. Box 1 lists the recommended health maintenance for older adults with SCD.

The two most widely available therapies for patients with SCD are hydroxyurea and blood transfusion.

Emerging therapies

To date, allogeneic HSCT is the only disease-reversing treatment modality for SCD.¹¹³ Although human leukocyte antigen (HLA)-matched related HSCT is widely accepted as a standard of care for children, it is still investigational for older adults. The commonly accepted indications for HSCT in adults include a history of cerebrovascular accident, recurrent vaso-occlusive crisis despite hydroxyurea therapy, osteonecrosis, red cell immunisation and recurrent acute chest syndrome. Experience with

Conclusion

There has been a significant understanding of the pathophysiology and factors contributing to the severity of SCD over the past decade. Yet, many patients still face a lifetime of complications and management remains a challenge. As the life expectancy of patients with SCD has increased compared to their historical peers, there is an urgent need for large-scaled randomised clinical controlled trials for older adults to obtain evidence-based management and effective therapeutic agents.

Conflicts of interest and sources of funding

The authors state that there are no conflicts of interest to disclose.

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Cited by (44)

Consensus of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy (ABHH) and the Brazilian Ministry of Health - General management of blood and blood products on the tests necessary for the release of exceptional medicines for sickle cell disease
2024, Hematology, Transfusion and Cell Therapy
To date, hydroxyurea is the only effective and safe drug that significantly reduces morbidity and mortality of individuals with Sickle cell disease. Twenty years of real-life experience has demonstrated that hydroxyurea reduces pain attacks, vaso-occlusive events, including acute chest syndrome, the number and duration of hospitalizations and the need for transfusion. The therapeutic success of hydroxyurea is directly linked to access to the drug, the dose used and adherence to treatment which, in part, is correlated to the availability of hydroxyurea. This consensus aims to reduce the number of mandatory exams needed to access the drug, prioritizing the requesting physician's report, without affecting patient safety.
Reproductive Health Counseling among Youth with Sickle Cell Disease
2023, Journal of Pediatric and Adolescent Gynecology
Reproductive health counseling is important for youth with sickle cell disease (SCD) given that they experience potential infertility risks from SCD and its treatments and high rates of unplanned pregnancies. Thus, the objective of this study was to describe documented occurrences of reproductive health counseling among youth with SCD and examine differences in counseling by sociodemographic and treatment characteristics.
Data were abstracted from 167 electronic medical records of patients (age = 14-21, 54% female) with SCD (1/01/2015-12/31/19) at 2 sites (Nationwide Children's Hospital and Hassenfeld Children's Hospital at NYU Langone). Descriptive statistics, point-biserial correlations, and χ² tests were used to examine sample characteristics and relationships between sociodemographic factors, clinical characteristics, site, and reproductive health counseling (fertility, contraception, and genetic counseling).
Seven of 167 (4%) youth had documented discussions about the potential impacts of SCD on fertility. Fertility counseling was also low among those who received a bone marrow transplant or hydroxyurea (n = 1/2, 50%; and n = 1/104, 1%, respectively). Only 57% of youth received contraception counseling, and only 55% of sexually active youth used birth control; birth control use was associated with older age (P = .028), severe clinical disease (P = .003), and documentation of contraception counseling (P = .047). Most youth received genetic counseling (80%), although more genetic counseling occurred at Nationwide Children's Hospital (P < .001). There was no association between gender and any type of counseling.
Findings suggest reproductive health counseling gaps in this population, with important implications for future infertility distress and unplanned pregnancies. Future research should examine barriers to counseling, explore fertility impacts of SCD and treatments, and inform evidence-based guidelines for reproductive health care in SCD.
Sickle Cell Trait and Risk for Common Diseases: Evidence from the UK Biobank
2022, American Journal of Medicine
Citation Excerpt :
Sickle cell disease is an autosomal recessive disease caused by the inheritance of 2 pathogenic mutations of the hemoglobin subunit beta gene (HBB; usually Glu6Val, although other pathogenic mutations exist).1 The altered hemoglobin makes red blood cells prone to being crescent shaped, which can cause vasoocclusion and result in numerous serious complications and comorbidities, including vasoocclusive crisis, acute chest syndrome, infections, pulmonary hypertension, stroke, pulmonary embolism, renal failure, retinopathy, splenic sequestration, priapism, cholelithiasis, and osteonecrosis.2-5 Sickle cell disease affects approximately 100,000 Americans and is significantly more prevalent in the Black population, occurring in about 1 of 365 African American births.6
Sickle cell trait is typically considered benign. Although evidence remains inconsistent, recent studies suggest that it is associated with several common diseases. We systematically assessed associations of sickle cell trait with reported diseases in a large population-based cohort.
Study subjects were self-reported Blacks from the UK Biobank (UKB), a United Kingdom population-based cohort of subjects aged 40-69 years at recruitment in the United Kingdom. Sickle cell status was based on the International Classification of Diseases, Tenth Revision (ICD-10) or mutations in the HBB gene. Diagnoses of diseases were obtained from ICD-10 and self-reports. Associations of sickle cell trait and diseases were tested using logistic regression, adjusting for age at recruitment, sex, and genetic background (top 10 principal components).
Among the 8019 Blacks in the UKB, 699 (8.72%) were sickle cell trait carriers; the rate was significantly higher in females (9.74%) than males (7.48%), P = .0005. Sickle cell trait was under-diagnosed; most heterozygous hemoglobin subunit beta (HBB) gene Glu6Val carriers did not have a sickle cell trait ICD-10 record. Compared with non-sickle cell trait, sickle cell trait carriers had significantly increased risk for type 2 diabetes; odds ratio 1.38; 95% confidence interval, 1.12-1.68; P = .002. Sickle cell trait was also significantly associated with increased risk for renal diseases (rhabdomyolysis, end-stage renal disease, chronic kidney disease, renal papillary necrosis) and vascular diseases (hypertension, retinopathy, non-ischemic stroke), P < .05. While most of these diseases are complications/comorbidities of diabetes, their associations with sickle cell trait remained significant after adjusting for diabetes. Association with end-stage renal disease was stronger in subjects without diabetes, odds ratio 6.45; 95% confidence interval, 1.93-19.61; P = .001.
Sickle cell trait is significantly associated with increased risk for diabetes and diabetes-related complications/comorbidities.
The Effect of Progressive Muscle Relaxation Exercises on Pain on Patients with Sickle Cell Disease: Randomized Controlled Study
2021, Pain Management Nursing
The study aimed to evaluate the effect of progressive muscle relaxation exercises on pain in patients with sickle cell disease.
This randomized controlled interventional study was conducted in a hospital in Mersin, Turkey between October 2017 and July 2018. The study sample comprised 58 patients who were aged >18 years, conscious, had sickle cell disease, reported pain, and were treated with non-opioid or weak opioid analgesic based on the physician's recommendation (treatment group = 29, control group = 29). Data were collected by the individual presentation form and visual analog scale. During the study, both groups were treated with analgesics prescribed by the physician for three days. In addition to the analgesics, the treatment group was performed progressive muscle relaxation exercises for 30 minutes whereas the control group was rested. Pain level of both groups was evaluated at three time points every day for three days. In the study, frequency distributions and descriptive statistics were presented for categorical and numerical variables, respectively. Chi-square analysis, independent samples t-test, Mann–Whitney U test, three-way ANOVA, and Sidak test were used to analyze the difference between the variables.
The mean age of the patients was 29.59 ± 6.94 years, and 53.4% of the patients were female and 69% were single. The mean pain score of the treatment group at the third time point on days 1, 2, and 3 was significantly lower than the control group (p < .05). There was no statistically significant difference between the two groups in terms of coping methods for pain, pain location, and complaints accompanying pain (p > .05).
Progressive muscle relaxation exercises were found to be effective in the pain management of patients with sickle cell anemia.
Standard management of sickle cell disease complications
2020, Hematology/ Oncology and Stem Cell Therapy
Sickle cell disease remains a major public health concern in sub-Saharan Africa, Europe, and the United States. The survival rate of children and adolescents has increased immensely in developed countries, whereas the survival rate for adults lagged behind. The increase in the pediatric survival rate is attributable to the institution of hydroxyurea treatment as well as stroke prevention strategies. In this review, we discuss the management of the sickle disease major complications such as pain, stroke, and acute chest syndrome with the most current hydroxyurea use and transfusion therapy.
Endari treatment ameliorates sickle cell-related disruption in intestinal barrier functions and is associated with prolonged survival in sickle cell mice
2024, Hematology (United Kingdom)

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Published by Elsevier B.V. on behalf of Royal College of Pathologists of Australasia.

ReviewSickle cell disease in the older adult

Summary

Section snippets

Introduction, background and scope of the problem

Pathophysiology and manifestations of sickle cell disease

Complications and management of sickle cell disease in older adults

Importance of health maintenance and available treatment options

Emerging therapies

Conclusion

Conflicts of interest and sources of funding

Lancet

Blood

J Biol Chem

Lancet

Blood

Blood

Blood

J Clin Epidemiol

Am J Med

Blood Rev

J Pain Symptom Manage

J Arthroplasty

Blood

Blood

Hematol Oncol Clin North Am

Blood

Blood

Blood

Clin Gastroenterol Hepatol

Blood

Gastroenterology

Clin Gastroenterol Hepatol

Blood

Blood

Blood

A global perspective on sickle cell disease

Pediatr Blood Cancer

Sickle cell disease related mortality in the United States (1999–2009)

Pediatr Blood Cancer

Mortality in sickle cell disease. Life expectancy and risk factors for early death

N Engl J Med

Factors associated with survival in a contemporary adult sickle cell disease cohort

Am J Hematol

Mortality rates and age at death from sickle cell disease: US, 1979–2005

Public Health Rep

Outcome of sickle cell anemia: a 4-decade observational study of 1056 patients

Medicine

Peculiar elongated and sickle-shaped red blood corpuscles in a case of severe anemia

Arch Intern Med

Sickle cell anemia: a molecular disease

Science

Gene mutations in human haemoglobin: the chemical difference between normal and sickle cell haemoglobin

Nature

The inheritance of sickle cell anemia

Science

Genetic factors modifying sickle cell disease severity

The linear effects of alpha-thalassaemia, the UGT1A1 and HMOX1 polymorphisms on cholelithiasis in sickle cell disease

Br J Haematol

Effect of alpha-globin genotype on the pathophysiology of sickle cell disease

Pediatr Pathol Mol Med

Concurrent sickle-cell anemia and alpha-thalassemia: effect on severity of anemia

N Engl J Med

Concurrent sickle cell anemia and alpha-thalassemia. Effect on pathological properties of sickle erythrocytes

J Clin Invest

Association between hemolysis and albuminuria in adults with sickle cell anemia

Haematologica

Haptoglobin, alpha-thalassaemia and glucose-6-phosphate dehydrogenase polymorphisms and risk of abnormal transcranial Doppler among patients with sickle cell anaemia in Tanzania

Br J Haematol

Genetic modifiers of sickle cell disease

Hemoglobin

Evidence for the multicentric origin of the sickle cell hemogloin gene in Africa

Proc Natl Acad Sci USA

Common haplotype dependency of high G gamma-globin gene expression and high Hb F levels in beta-thalassemia and sickle cell anemia patients

Proc Natl Acad Sci USA

Pain in sickle cell disease: rates and risk factors

N Engl J Med

MRI abnormalities of the brain in one-year-old children with sickle cell anemia

Pediatr Blood Cancer

Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members

JAMA

Review
Sickle cell disease in the older adult