Sickle Cell Carriers Research Articles

A qualitative study to explore how professionals in the United Kingdom make decisions to test children for a sickle cell carrier status

European guidelines recommend that, unless there are clear benefits of autosomal recessive carrier testing in childhood, it should be deferred to protect children's autonomous decision making. Although it is believed that children receive testing in the United Kingdom, it is unclear how or why professionals make decisions to provide tests. Semi-structured interviews were conducted with 25 professionals in the United Kingdom who advise about, and undertake, childhood sickle cell trait testing. Data were analysed using thematic analysis. Few professionals were aware of, or used, guidelines to inform testing decisions and instead, considered the reproductive and clinical relevance of testing, and autonomous rights of parents. Many professionals believed testing was important and readily offered it to parents. Professionals who discouraged testing were met with parental resistance and often provided testing when conflict was difficult to manage. Children were rarely considered to be capable of making decisions and few were engaged in discussions. When consulted, older children demonstrated interest, but younger children usually declined testing. Wide variation in testing advice emerged because of opposing beliefs about children's best interests and potential benefits or harms of testing. An explanation of how children's best interests should be determined in light of conflicting evidence regarding the psychosocial and clinical implications of carrier status is needed. Improved awareness of guidelines might encourage professionals to support the role of children in testing decisions. Strategies are also required to help professionals determine children's cognitive capacity and to protect children's future autonomy during discussions with persistent parents.

Actor network theory, agency and racism: The case of sickle cell trait and US athletics

Actor Network Theory (ANT) has invigorated recent social theory. In assessing the agency of things ANT offers a fresh perspective on materiality and on the role of the non-human (animate and inanimate), and has challenged the central place of sociology in social research. One increasingly influential concept associated with ANT is that of ‘assemblage’. The article takes a contemporary concern – the sudden death of student athletes later found to be genetic carriers of sickle cell – and uses this to assess the concept. Although ANT, and the notion of assemblage, offer interesting avenues for research, the difficulty in sustaining a plausible notion of durable, structured social interests carries political consequences.

Parents' responses to receiving sickle cell or cystic fibrosis carrier results for their child following newborn screening.

Universal newborn screening for sickle cell disorders and cystic fibrosis aims to enable the early identification and treatment of affected babies. Screening can also identify infants who are healthy carriers, with carrier results being the commonest outcome for parents and professionals to discuss in practice. However it is unclear what the effect will be on parents on being informed of their baby's carrier result. Semi-structured face-to-face interviews were conducted with a purposeful sample of 67 family members (49 mothers, 16 fathers, 2 grandparents) of 51 infants identified by universal newborn screening as carriers of cystic fibrosis (n=27) and sickle cell (n=24), across all health regions in England. Data were analysed by thematic analysis with subsequent respondent validation. Untoward anxiety or distress among parents appeared influenced by how results were conveyed, rather than the carrier result per se. Parents who had more prior awareness of carrier status or the possibility of a carrier result assimilated the information more readily. Being left in an information vacuum while awaiting results, or before seeing a professional, led some parents to fear that their child had a serious health condition. Parental distress and anxiety appeared mostly transient, subsiding with understanding of carrier status and communication with a professional. Parents regarded carrier results as valuable information and sought to share this with their families and to inform their children in the future. However parents needed greater support after communication of results in considering and accessing cascade testing, and negotiating further communication within their families.

Newborn Blood Spot Screening for Sickle Cell Disease by Using Tandem Mass Spectrometry: Implementation of a Protocol to Identify Only the Disease States of Sickle Cell Disease

The currently recommended technologies of HPLC and isoelectric focusing for newborn blood spot screening for sickle cell disease (SCD) identify both the disease and carrier states, resulting in large numbers of infants being followed up unnecessarily. Analysis of blood spot tryptic peptides performed by using tandem mass spectrometry (MS/MS) is an alternative technology to detect hemoglobin (Hb) variant disorders. We analyzed 2154 residual newborn blood spots and 675 newborn blood spots from infants with Hb variants by using MS/MS after trypsin digestion. Screening cutoffs were developed by using the ratio between the variant peptide-to-wild-type peptide abundance for HbS, C, D(Punjab), O(Arab), Lepore, and E peptides. A postanalytical data analysis protocol was developed using these cutoffs to detect only the disease states of SCD and not to identify carrier states. A parallel study of 13 249 newborn blood spots from a high-prevalence SCD area were analyzed by both MS/MS and HPLC. Screening cutoffs developed distinguished the infants with the disease states of SCD, infants who were carriers of SCD, and infants with normal Hb. In the parallel study no false-negative results were identified, and all clinically relevant cases were correctly identified using the MS/MS protocol. Unblinding the data revealed a total of 328 carrier infants that were successfully excluded by the protocol. The screening protocol developed correctly identified infants with the disease states of SCD. Furthermore, large numbers of sickle cell carrier infants were successfully not identified, thereby avoiding unnecessary follow-up testing and referral for genetic counseling.

CXC Chemokines CXCL1, CXCL9, CXCL10 and CXCL12 are Variably Expressed in Patients with Sickle Cell Disease and Carriers: Are They Predictive Tools for Disease Complications?

Sickle cell hemoglobinopathies are amongst a group of genetic disorders resulting from a single base-pair DNA mutation at the beta chain of hemoglobin. Chemokines and cytokines play a part in the pathogenesis of inflammatory and infectious diseases. They are also involved in balancing angiogenesis/angiostasis processes to form new vascular networks. We aimed the present study to measure the circulating CXC chemokines CXCL1, CXCL9, CXCL10, and CXCL12 in the plasma of sickle cell patients (SCD). This cross-sectional study was conducted at the Kerman Special Disease Center and Rafsanjan Molecular Medicine Research Center during 2010 to 2011. Peripheral blood specimens were collected from 77 children with SCD and 70 controls. Serum samples were isolated and CXCL1, CXCL9, CXCL10, and CXCL12 were measured using ELISA. The findings of this study demonstrated that serum concentrations of CXCL1 and CXCL12 were elevated in SCD patients when compared with controls. Results also showed that the circulating levels of CXCL9 and CXCL10 were decreased in SCD patients in comparison to control subjects. However, we found increased levels of CXC chemokines in SCD patients suffering from pain crisis but the difference was not significant. According to the results of this study it can probably be concluded that the balance between angiogenesis/angiostasis CXC chemokines is an important predictive factor for initiation of complications in SCD patients. The elevated level of pro-inflammatory CXC chemokines may also be related to inflammatory responses associated with SCD complication.

Proposed low-cost premarital screening program for prevention of sickle cell and thalassemia in Yemen.

In Yemen, the prevalence of sickle cell trait and β-thalassemia trait are high. The aim of this premarital program is to identify sickle cell and thalassemia carrier couples in Yemen before completing marriages proposal, in order to prevent affected birth. This can be achieved by applying a low-cost premarital screening program using simple blood tests compatible with the limited health resources of the country. If microcytosis or positive sickle cell is found in both or one partner has microcytosis and the other has positive sickle cell, so their children at high risk of having sickle cell or/and thalassemia diseases. Carrier couples will be referred to genetic counseling. The outcomes of this preventive program are predicted to decrease the incidence of affected birth and reduce the health burden of these disorders. The success of this program also requires governmental, educational and religious supports.

After the Introduction into the National Newborn Screening Program: Who Is Receiving Genetic Counseling for Hemoglobinopathies in The Netherlands?

Objective: Universal newborn screening for hemoglobinopathies started in The Netherlands in 2007. Herewith severe conditions, such as sickle cell disease, β-thalassemia major and hemoglobin H disease are putatively identified. Additionally, at least 1,800 carriers of hemoglobin variants associated with severe conditions in homozygote or compound heterozygote forms are identified yearly. Thus far, approximately 60 patients and 800 healthy sickle cell (HbS) carriers are reported each year among 180,000 newborns. Results are sent to the general practitioner with the recommendation to inform and diagnose both parents of the healthy carriers to exclude genetic risk, while patients and their parents are referred directly to a pediatrician. This study was performed to determine how often parents of identified carriers and affected newborns are seen in genetic centers for counseling. Methods: In this retrospective study, we collected anonymized data from 7 of the 8 Dutch clinical genetic centers from January 1, 2007, until December 31, 2010. Results: After an initial general increase in total counseling intakes, a decline was noticed in the third year, while the requests for prenatal diagnoses remained relatively stable. In 2007 and 2013, genetic counselors were asked for self-reported knowledge. They found hemoglobinopathy counseling complex, but by 2013, they indicated they had acquired sufficient knowledge on most hemoglobinopathy aspects. Conclusion: We could not observe a significant increase in genetic counseling for hemoglobinopathy after its introduction into newborn screening. Although 120 HbS carriers and 60 patients are expected to be born from couples at risk annually, only 33 at risk couples out of 540 families of diagnosed newborns received optimal care and information at a genetics center in 4 years.

CONTRIBUTION OF MARITAL DISTANCE TO COMMUNITY INBREEDING, HOMOZYGOSIS, AND REPRODUCTIVE WASTAGE FOR RECESSIVELY INHERITED GENETIC DISORDERS IN MADHYA PRADESH, INDIA

BackgroundRecessively inherited genetic disorders such as sickle cell anemia and β-thalassemia are commonly encountered in heterozygous and homozygous form in India. These hemolytic disorders cause a high degree of reproductive wastage in vulnerable communities. Inbreeding is usually the mating between two related individuals. Homozygosis is antagonistic process of heterosis.PurposeThis study was aimed at finding reproductive outcome in carrier couples of sickle cell anemia, and β-thalassemia in terms of reproductive wastage in relation to varied marital distance between partners in Madhya Pradesh.MethodsA total of 107 carrier couples, 35 and 72, respectively of β-thalassemia major and sickle cell anemia with confirmed affected offspring after taking detailed reproductive history were studied following the standard methodology in a tertiary hospital in Central India during March 2010 to February 2013.ResultsA majority of sickle cell and β-thalassemia carrier couples, 77.8% and 65.7%, respectively, had married within physical distance of radius less than 50 kms. away from their native places. It was found that as the marital distance between two carrier partners of above disorders decreases, the number of abortions, still-births, neonatal mortality, infant mortality, and mortality under 10 years age increases, and vice versa, implicating inbreeding and homozygosis. The overall reproductive wastage of 28.2% and 18.6% was recorded in carrier couples of sickle cell disease and β-thalassemia, respectively. This combined reproductive wastage is negatively correlated (r= −0.74; p<0.001) to physical marital distance between the life partners.ConclusionsRelative small population size clubbed with small marital distance leads to inbreeding resulting in homozygosity which increases chances of affected offspring by recessive or deleterious traits and contributes to decreased fitness of a couple or population in Central India.

Consulting communities on feedback of genetic findings in international health research: sharing sickle cell disease and carrier information in coastal Kenya.

BackgroundInternational health research in malaria-endemic settings may include screening for sickle cell disease, given the relationship between this important genetic condition and resistance to malaria, generating questions about whether and how findings should be disclosed. The literature on disclosing genetic findings in the context of research highlights the role of community consultation in understanding and balancing ethically important issues from participants’ perspectives, including social forms of benefit and harm, and the influence of access to care. To inform research practice locally, and contribute to policy more widely, this study aimed to explore the views of local residents in Kilifi County in coastal Kenya on how researchers should manage study-generated information on sickle cell disease and carrier status.MethodsBetween June 2010 and July 2011, we consulted 62 purposively selected Kilifi residents on how researchers should manage study-generated sickle cell disease findings. Methods drew on a series of deliberative informed small group discussions. Data were analysed thematically, using charts, to describe participants’ perceptions of the importance of disclosing findings, including reasoning, difference and underlying values. Themes were derived from the underlying research questions and from issues emerging from discussions. Data interpretation drew on relevant areas of social science and bioethics literature.ResultsPerceived health and social benefits generated strong support for disclosing findings on sickle cell disease, but the balance of social benefits and harms was less clear for sickle cell trait. Many forms of health and social benefits and harms of information-sharing were identified, with important underlying values related to family interests and the importance of openness. The influence of micro and macro level contextual features and prioritization of values led to marked diversity of opinion.ConclusionsThe approach demonstrates a high ethical importance in many malaria endemic low-to-middle income country settings of disclosing sickle cell disease findings generated during research, alongside provision of effective care and locally-informed counselling. Since these services are central to the benefits of disclosure, health researchers whose studies include screening for sickle cell disease should actively promote the development of health policy and services for this condition in situations of unmet need, including through the prior development of collaborative partnerships with government health managers and providers. Community consultation can importantly enrich ethical debate on research practice where in-depth exploration of informed views and the potential for difference are taken into account.

Linguistic markers of emotion in mothers of sickle cell carrier infants: What are they and what do they mean?

ObjectiveThe objectives were to examine emotion-related language in mothers’ narratives about newborn screening, and test the correlations between language and self-reported emotion and behavior. MethodsTranscripts of interviews with mothers of infant sickle cell carriers were analyzed with word count software for the prevalence of emotion-related words in narratives about newborn screening. Word counts were compared to population norms for spoken language using one-sample t-tests. Anxiety-related words were correlated with self-reported anxiety and avoidance of genetic testing. Results187 transcripts were analyzed, in which there was a higher percentage of anxiety words (m=.38%) than population norms (m=.18%), t(186)=10.59, p<.001, CI=.16–.23. Anxiety-related word use was positively correlated with self-reported previous anxiety, rs(185)=.24, p=.001. Self-reported previous anxiety, but not word use, was correlated with mothers’ avoidance of undergoing genetic testing themselves rs(152)=.25, p=.002. ConclusionMothers of sickle cell carrier infants reported anxiety upon learning their child's condition. Anxiety-related words in maternal narratives were correlated with their reports of past, but not present, emotions. Practice implicationsResearchers and clinicians should use caution in assuming that word choices reflect state emotions. Self-report methods may be preferable for predicting behavioral outcomes.

Population and Public Health Implications of Child Health and Reproductive Outcomes Among Carrier Couples of Sickle Cell Disorders in Madhya Pradesh, Central India

Sickle cell disease is a major genetic and public health challenge in India. Adequate studies on clinico-hematological aspects of disorders are available, however there are few studies on the public health and reproductive outcomes among sickle cell carrier couples. A total of 383 couples including their offspring with at least one case of sickle cell disorder referred to a testing center from a tertiary hospital from March 2010 to February 2013 were consecutively studied as matched case controls. Out of 383 couples, 200 were found normal and 183 had different sickle cell disorders. Carrier couples of sickle cell disease had significantly higher fertility (mean number of conceptions, i.e. 3.153 versus 1.480) and higher below 10 year mortality (11% versus 2.7%) and lower surviving offspring (877.4 versus 970.6) than of controls. Neonatal and infant mortality was doubled (34.3 versus 14.7) and three-fold higher (44.1 versus 14.7), respectively in carriers of disease per 1000 live-births compared to controls. Couples of AS/SS genotype showed high neonatal, infant, below 10 year mortality (214.3 each) and low surviving offspring (785.7 per 1000 live-births). Sickle cell carrier couples are increasing in both trait and disease offspring (surviving: 56.7% against 43.3% normals). This increased production of carrier and disease offspring leads to increased morbidity, neonatal/infant and childhood mortality, and adversely affects the survival fitness.

Arterial Stiffness and Pulse Wave Reflection in Young Adult Heterozygous Sickle Cell Carriers

Objective: Pulse wave velocity (PWV) and aortic augmentation index (AI) are indicators of arterial stiffness. Pulse wave reflection and arterial stiffness are related to cardiovascular events and sickle cell disease. However, the effect of these parameters on the heterozygous sickle cell trait (HbAS) is unknown. The aim of this study is to evaluate the arterial stiffness and wave reflection in young adult heterozygous sickle cell carriers.Materials and Methods: We enrolled 40 volunteers (20 HbAS cases, 20 hemoglobin AA [HbAA] cases) aged between 18 and 40 years. AI and PWV values were measured by arteriography.Results: Aortic blood pressure, aortic AI, and brachial AI values were significantly higher in HbAS cases compared to the control group (HbAA) (p=0.033, 0.011, and 0.011, respectively). A statistically significant positive correlation was found between aortic pulse wave velocity and mean arterial pressure, age, aortic AI, brachial AI, weight, and low-density lipoprotein levels (p=0.000, 0.017, 0.000, 0.000, 0.034, and 0.05, respectively) in the whole study population. Aortic AI and age were also significantly correlated (p=0.026). In addition, a positive correlation between aortic PWV and systolic blood pressure and a positive correlation between aortic AI and mean arterial pressure (p=0.027 and 0.009, respectively) were found in HbAS individuals. Our study reveals that mean arterial pressure and heart rate are independent determinants for the aortic AI. Mean arterial pressure and age are independent determinants for aortic PWV. Conclusion: Arterial stiffness measurement is an easy, cheap, and reliable method in the early diagnosis of cardiovascular disease in heterozygous sickle cell carriers. These results may depend on the amount of hemoglobin S in red blood cells. Further studies are required to investigate the blood pressure changes and its effects on arterial stiffness in order to explain the vascular aging mechanism in the HbAS trait population. Conflict of interest:None declared.

Use of social support during communication about sickle cell carrier status

ObjectiveTo examine the use of social support behaviors by primary care providers during delivery of positive newborn screening results for Sickle Cell Anemia carrier status. MethodsTranscripts from 125 primary care providers who conveyed Sickle Cell Anemia carrier status to standardized parents were content analyzed using categories derived from Cutrona and Suhr's social support taxonomy. Frequencies and cross-tabulation matrices were calculated to study providers’ social support utilization. ResultsResults showed most primary care providers (80%) incorporate social support behaviors into delivery of Sickle Cell Anemia carrier results and most frequently employed social network (61.6%) and informational support (38.4%) behaviors. Providers used tangible aid (8%), esteem (1.6%), and emotional support (9.6%) behaviors less frequently. ConclusionCutrona and Suhr's taxonomy may be a useful tool for assessing supportive communication during the delivery of Sickle Cell Anemia carrier status and could be incorporated into population scale assessments of communication quality assurance. Practice implicationsPrimary care providers may need training in how to adapt supportive behaviors to parents’ needs during communication of Sickle Cell Anemia carrier status. They also may benefit from specific training about how to use esteem and emotional support.

Communicating With Parents About Newborn Screening

Communicating With Parents About Newborn Screening

A Policy Impact Analysis of the Mandatory NCAA Sickle Cell Trait Screening Program

To estimate the impact of the mandatory National Collegiate Athletic Association (NCAA) sickle cell trait (SCT) screening policy on the identification of sickle cell carriers and prevention of sudden death. We used NCAA reports, population-based SCT prevalence estimates, and published risks for exercise-related sudden death attributable to SCT. We estimated the number of sickle cell carriers identified and the number of potentially preventable sudden deaths with mandatory SCT screening of NCAA Division I athletes. We calculated the number of student-athletes with SCT using a conditional probability based upon SCT prevalence data and self-identified race/ethnicity status. We estimated sudden deaths over 10years based on published attributable risk of exercise-related sudden death due to SCT. We estimate that over 2,000 NCAA Division I student-athletes with SCT will be identified under this screening policy and that, without intervention, about seven NCAA Division I student-athletes would die suddenly as a complication of SCT over a 10-year period. Universal sickle cell screening of NCAA Division I student-athletes will identify a substantial number of sickle cell carriers. A successful intervention could prevent about seven deaths over a decade.

Newborn screening for sickle cell disease: whose reproductive benefit?

Newborn screening for sickle cell disease: whose reproductive benefit?

Lessons from Sickle Cell Disease in the Treatment and Control of Malaria

Persons with sickle cell disease and carriers of the trait are protected against malaria. A study of mice infected with a plasmodium species similar to Plasmodium falciparum provides insight into how the severity of infection in humans may be modulated.

Hb A2′ (Hb B2) in the Omani Population and Diagnostic Significance

Hb A2′ [δ16(A13)Gly→Arg], also called Hb B2, is a δ-globin chain variant that has been identified in several populations of African origin or ancestry and is easily identifiable in alkaline acetate cellulose electrophoresis as doubling of the Hb A2 band. However, in high performance liquid chromatography (HPLC), commonly employed nowadays, it elutes in the S window. Over a period of 2 years at the Sultan Qaboos University Hospital, Muscat, Oman, we identified 25 Omanis with this variant. The quantity of Hb A2 ranged from 0.9 to 1.8% in heterozygotes and was undetectable in the single homozygous case. As both α- and β-thalassemia (α- and β-thal) as well as Hb S [β6(A3)Glu→Val] are common in the Omani population, it is important to be aware of the presence of Hb A2′ in this population to avoid misinterpretation of the HPLC data in terms of underdiagnosis of β-thal carriers and overestimation of α-thal based on Hb A2 levels in sickle cell carriers. The haplotype associated with Hb A2′ in Oman is identical to that described in African populations, suggesting a common origin for this mutation and its introduction into Oman by gene flow.

Hypocholesterolemia is associated negatively with hemolysate lipid peroxidation in sickle cell anemia patients

The oxidative stress levels in plasma and hemolysate and cholesterol levels in plasma of sickle cell anemia patients, carriers and controls were evaluated. A total of 40 cases-17 patients, 13 carriers and 10 controls-were involved in the study. Plasma and hemolysate malondialdehyde (MDA) were detected via thiobarbituric acid reaction with a fluorimetric detector by high-performance liquid chromatography system. Plasma cholesterol was determined by enzymatic colorimetric method. Mean MDA levels of SCA patients were higher than those of the carriers' and healthy children's both in plasma and in hemolysate (P<0.005). The mean plasma and hemolysate MDA levels were 25.3±1.6nmol/l and 86.7±19.3nmol/l in patients, 19.1±0.8nmol/l and 54.1±10.8nmol/l in carriers and 19.6±0.8nmol/l and 56.8±9.3nmol/l in healthy children. Mean plasma total cholesterol levels were 92.1±19.1mg/dl in patients, 116.2±23.3mg/dl in carriers and 126.6±16.4mg/dl in controls (P<0.005). There was a significant negative correlation of -0.520 between hemolysate MDA and plasma cholesterol levels in patients (P<0.05). The degree of correlation increased up to -0.782 (P=0.008) in the patients with HbSS phenotype. This negative correlation between MDA and cholesterol may imply a potential association between oxidative stress and hypocholesterolemia in sickle cell anemia.

Screening Student Athletes for Sickle Cell Trait — A Social and Clinical Experiment

On April 13, 2010, the legislative council for Division I of the National Collegiate Athletic Association (NCAA) approved mandatory testing for sickle cell carrier status (sickle cell trait) for all student athletes participating in Division I sports. Students are to begin being tested for the first season during which they are eligible to compete, and the new rule takes effect this academic year (2010–2011).1 NCAA data for the 2008–2009 academic year suggest that the requirement will ultimately affect more than 166,900 student athletes. The NCAA program is the most extensive and high-profile sickle cell screening program instituted in the past . . .