Sickle Cell Trait

The present study was conducted to review the literature about sickle cell disease. Molecular and patho-physiological features were discussed. Furthermore, we discussed its prevalence, clinical picture, diagnosis, and therapeutic options. We also reviewed connective tissue diseases associated with sickle cell disease. Vascular changes associated with sickle cell disease were also discussed. We also discussed the impact of MTHFR polymorphism on the vascular complications of sickle cell disease.

In the 1980s, a research team led by Parisian scientists identified several unique DNA sequences, or haplotypes, linked to sickle cell anemia in African populations. After casual observations of how patients managed this painful blood disorder, the researchers in question postulated that the Senegalese type was less severe. The Enculturated Gene traces how this genetic discourse has blotted from view the roles that Senegalese patients and doctors have played in making sickle cell "mild" in a social setting where public health priorities and economic austerity programs have forced people to improvise informal strategies of care.

Duana Fullwiley shows how geneticists, who were fixated on population differences, never investigated the various modalities of self-care that people developed in this context of biomedical scarcity, and how local doctors, confronted with dire cuts in Senegal's health sector, wittingly accepted the genetic prognosis of better-than-expected health outcomes. Unlike most genetic determinisms that highlight the absoluteness of disease, DNA haplotypes for sickle cell in Senegal did the opposite. As Fullwiley demonstrates, they allowed the condition to remain officially invisible, never to materialize as a health priority. At the same time, scientists' attribution of a less severe form of Senegalese sickle cell to isolated DNA sequences closed off other explanations of this population's measured biological success.

The Enculturated Gene reveals how the notion of an advantageous form of sickle cell in this part of West Africa has defined--and obscured--the nature of this illness in Senegal today.

We have analysed, at the hematological and molecular level, 51 Hb lepore heterozygotes and three compound heterozygotes for Hb Lepore and HbS (HbLep/HbS) in 26 unselected Portuguese families. The Lepore Boston variant was present in one family, in association with classical haplotype V. All of the other Lepore alleles present haplotype III in association with XmnI (+)5′ of Gγ gene, in tight linkage disequilibrium to the major mutation found in the Portuguese population, the Lepore Baltimore variant ( δ68Leu-β84Thr). The three compound heterozygotes are the first HbLep/HbS individuals reported in the literature, with the Lepore Baltimore mutation linked to haplotype III. In agreement with other studies, these Lepore Baltimore heterozygotes have higher HbF (1.4–14.1% of total hemoglobin) than published cases of Lepore Boston (0.8–5.4%), which is associated with XmnI(–). Among the Lepore Baltimore heterozygotes, the (AT)xTy repeat region at –540 bp of the β globin gene intrans to the Lepore chromosome, can account for much of the variability in HbF level. The allele (AT)7T7 is associated with lower HbF, and (AT)9T5 is associated with higher HbF. As we previously reported for β thalassemic carriers, we observe in Lepore Baltimore carriers an effector<?tklgp> intrans, linked to the (AT)xTy sequence, acting as an HPFH (Hereditary Persistence of Fetal Hemoglobin) determinant. Am. J. Hematol. 69:95–102, 2002. © 2002 Wiley-Liss, Inc.

OBJECTIVE To determine the levels of serum uric acid, urea and creatinine in subjects with sickle cell disease and compare them to those reported in literature. SETTING Department of Paediatrics, College of Medicine, University of Basrah. METHODS Plasma uric acid, urea and creatinine was estimated by Varley&#39;s method, group of 65 sickle cell patients (35 Hb AS, 30 Hb SS) aged between 2-11 years. The results were compared with those obtained in a group of 45 age and sex-matched controls with normal haemoglobin (Hb AA). RESULTS The uric acid level was elevated in sickle cell patients as compared with the normal control group. The 95% confidence intervals for differences in the mean of the two groups: HbAA vs HbAS was 4.22 (0.3), while for HbAA for HbSS was 3.4 (0.06), both being statistically highly significant [p &lt; 0.0001]. Urea and creatinine levels were considerably lower in the sickle cell disease patients. The difference in the patient&#39;s mean for urea compared to the me...

To determine the effect of maternal anaemia on pregnancy outcome and describe its impact on infant haemoglobin level in the first 18 months of life, we conducted a prospective study of 617 pregnant women and their children in Benin. Prevalence of maternal anaemia at delivery was 39.5%, and 61.1% of newborns were anaemic at birth. Maternal anaemia was not associated with low birth weight [OR = 1.2 (0.6-2.2)] or preterm birth [OR = 1.3 (0.7-2.4)], whereas the newborn&#x27;s anaemia was related to maternal anaemia [OR = 1.8 (1.2-2.5)]. There was no association between an infant&#x27;s haemoglobin level until 18 months and maternal anaemia. However, malaria attacks during follow-up, male gender and sickle cell trait were all associated with a lower infant haemoglobin level until 18 months, whereas good infant feeding practices and a polygamous family were positively associated with a higher haemoglobin level during the first 18 months of life.

In this article, I call for enlarging the conceptual terrain for viewing local biological expressions of illness. To date, a specific DNA sequence pattern, called “the Senegalese sickle cell haplotype,” has enjoyed extraordinary purchase on explanations for why Senegalese people may live with a “milder”form of sickle cell anemia when compared with other African populations. I argue, however, that “mild sickle cell” in Senegal emerges as a lived construct through a constitutive bond of biology, economy,and kinship. I show how patients’ enactments of biological difference are situated within larger informal economies and North–South donor priorities for health. In the absence of state funding to address patients’ needs, Senegalese sicklers create networks of care, health, and normalcy by drawing on Wolof idioms of “shared blood” that come to life in ways beyond metaphor. Their biosocial kinships result in therapeutic economies that restructure valuations of sickle cell despite serious medical constraints in this global context.

[biosociality, genetic causation, informal economies, kinship, Senegal, sickle cell, therapeutic economies.]

Transfusion of blood at the limits of approved storage time is associated with lower red blood cell (RBC) post-transfusion recovery and hemolysis, which increases plasma cell-free hemoglobin and iron, proposed to induce endothelial dysfunction and impair host defense. There is noted variability among donors in the intrinsic rate of storage changes and RBC post-transfusion recovery, yet genetic determinants that modulate this process are unclear. We explore RBC storage stability and post-transfusion recovery in murine models of allogeneic and xenogeneic transfusion using blood from humanized transgenic sickle cell hemizygous mice (Hba(tm1Paz)Hbb(tm1Tow)Tg(HBA-HBBs)41Paz/J) and human donors with a common genetic mutation sickle cell trait (HbAS). Human and transgenic HbAS RBCs demonstrate accelerated storage time-dependent hemolysis and reduced post-transfusion recovery in mice. The rapid post-transfusion clearance of stored HbAS RBC is unrelated to macrophage-mediated uptake or intra...

Connecting theoretical discussion with empirical qualitative work, this paper examines how sickle cell became a site of public health intervention in terms of ‘racialised’ risks. Historically, sickle cell became socio-politically allied to ideas of repair, in terms of the state improving the health of a neglected ethnic minority population. Yet, we elucidate how partial improvements in care and education arose alongside preventative public health screening efforts. Using qualitative research based in the United Kingdom, we show how a focus on collective efforts of repair can lie in tension with how services and individuals understand and negotiate antenatal screening. We illustrate how screening for sickle cell calls into question narrative identity, undoing paradigms in which ethnicity, disablement and genetic impairment become framed. Research participants noted that rather than ‘choices’, it is ‘risks’ and their negotiation that are a part of discourses of modernity and the new genetics. Furthermore, while biomedical paradigms are rationally and ethically (de)constructed by participants, this was never fully engaged with by professionals, contributing to overall perception of antenatal screening as disempowering and leading to disengagement.
doi:10.1177/1363459315595850
http://hea.sagepub.com/content/early/2015/07/22/1363459315595850.full.pdf+html

Many physicians in Senegal and France, where most Senegalese sickle cell specialists are partially trained, assume that genetic testing that could imply selective abortion for people with sickle cell would run counter to the religious and cultural ethics of people living in Dakar. Senegalese affected by this genetic disease, however, often cite ‘‘traditional’’ rationales to indicate why such testing, if offered, might appeal to them. The reluctance of medical practitioners to entertain such testing technologies for their patients evinces a protectionist attitude toward care—an attitude that emerges within a context in which family planning and a blind concentration on HIV=AIDS have created a public health system that completely overlooks sickle cell anemia. This discriminate biopower leaves everyday biopolitics largely in the hands of families faced with this disease. It falls to them to pragmatically calculate the value that genetic testing may, or may not, hold for their own lives.

The paper begins with a brief description of sickle cell anaemia and beta-thalassaemia, the main haemoglobin disorders considered here. It then moves to a consideration of the bases of deconstruction as derived from Jacques Derrida, and mediated through the medical sociology of Nicholas Fox. In doing so it raises questions of whether genetic counselling increases or reduces choices, the ideology behind the notion of 'non-directive counselling', and its relationship to the rationing of health services. The paper briefly discusses the implications of moving beyong modernist conceptions of the professions to the potential insights afforded by postmodernism. The contingent, fragmented and sometimes contradictory positions of haemoglobinopathy counsellors are highlighted as possible examples of these insights. Sociological analysis of the professions is itself amenable to deconstruction which suggest that critiques of the professions which only identify the ( very real) repressive tendencies of professional work are in danger of oversimplification and neglect other tendencies within professional roles. The paper concludes that haemoglobinopathy counsellors encompass tendencies which may both increase and decrease choices for clients, and the operational consequences of such professional roles must be sought at the level of local agency as well as historical and material structures.

The aim of the study was to examine the effects of endurance exercise on circulating vascular cell adhesion molecule-1 (sVCAM-1) and intercellular adhesion molecule-1 (sICAM-1) in sickle cell trait (SCT) athletes with or without alpha-thalassemia. Five athletes with SCT, 7 athletes with both SCT and alpha-thalassemia (SCTAT) and 8 control athletes (CONT) performed an incremental test on cycloergometer followed 72 hours later by a 60-min endurance exercise with a workload set at 70% P(peak) (peak power). We assessed levels of sICAM-1, sVCAM-1 and TNF-alpha at rest, immediately after endurance exercise and 1, 2, and 24 hours of recovery. Although, CONT and SCTAT groups exhibited similar basal plasma levels of adhesion molecules and TNF-alpha, SCT group had higher sVCAM-1 basal concentrations. No significant variation in sVCAM-1, sICAM-1 and TNF-alpha was measured following endurance exercise. Consequently, sVCAM-1 remained elevated in the SCT group after exercise and during the recove...

In 2010, the National College Athletic Association began requiring college athletes to undergo a test for sickle cell trait, an inherited condition linked in athletes to a potentially fatal condition. The NCAA now runs one of the largest genetic screening programs in the U.S., but college athletes are often uniformed about what they've been tested for.

To assess the effects of regular physical activity on muscle functional characteristics of carriers of sickle cell trait (SCT), 39 untrained (U) and trained (T) hemoglobin (Hb)AA (CON) and SCT subjects (U-CON, n = 12; U-SCT, n = 8; T-CON, n = 10; and T-SCT, n = 9) performed a graded exercise and a time to exhaustion (T(ex)) test, and were subjected to a muscle biopsy. Maximal power, total work performed during T(ex), citrate synthase and cytochrome c oxidase (COX) activities, respiratory chain complexes I and IV content, and capillary density (CD), diameter (COD), and surface area (CSA) were upregulated by the same proportion in T-CON and T-SCT compared with their untrained counterparts. These proportionally similar differences imply that the observed discrepancies between U-SCT and U-CON remained in the trained subjects. Specifically, both CD and COX remained and tended to remain lower, and both COD and CSA remained and tended to remain higher in T-SCT than in T-CON. Besides, carri...

The high frequencies of both + thalassemia and the sickle cell trait (hemoglobin AS (HbAS)) found in many tropical populations are thought to reflect selection pressure from Plasmodium falciparum malaria. For HbAS, but not for + thalassemia, protection appears to be mediated by the enhanced phagocytic clearance of ring-infected erythrocytes. We have investigated the genotype-specific distributions of peripheral blood leukocyte populations in two groups of children living on the coast of Kenya: a group of healthy P. falciparum parasite-negative children sampled at cross-sectional survey during a period of low malaria transmission, and a group of children attending the hospital with acute malaria. We report distinctive distributions of peripheral blood myeloid dendritic cells and monocytes in children with + thalassemia and HbAS during healthy periods and disease, and suggest ways in which these might relate to the mechanisms of protection afforded by these conditions.

Objective: To evaluate the incidence of variant hemoglobins of newborn samples from the Neonatal Screening Center in the state of Mato Grosso do Sul, Brazil, and to analyze the distribution and spatial autocorrelation of newborns with sickle cell trait. Methods: Samples from 35,858 newborns screened by the Neonatal Screening Center. The samples with inconclusive diagnosis were submitted to electrophoretic, chromatographic, cytological and molecular analyses. The spatial distribution analysis of newborns with sickle cell trait was performed by spatial autocorrelation. Results: A total of 919 newborns showed an abnormal hemoglobin profile; in that, ten genotypes had significant clinical impacts identified. Among the asymptomatic newborns, the sickle cell trait was the most frequent (incidence of 1.885 cases/100 newborns). The highest incidence rates were registered in the municipalities of Terenos, Figueirão, Corguinho and Selvíria. There was positive spatial autocorrelation between the proportion of declared individuals of black race/ color and the incidence of newborns with sickle cell trait. Conclusion: The early diagnosis by neonatal screening and laboratory tests was very important to identify abnormal hemoglobin profiles and guide the spatial autocorrelation analysis of sickle cell trait newborns in Mato Grosso do Sul, serving as a support to anticipate health measures aimed to discuss efficient therapeutic behaviors and effective planning of municipalities with the greatest need for care, monitoring and orientations for affected families.

OBJECTIVE It is predicted that Africa will have the greatest increase in the number of patients with type 2 diabetes mellitus (T2DM) within the next decade. T2DM patients are at risk for cardiovascular disorders. In Sub-Saharan African countries, sickle cell trait (SCT) is frequent. Despite the presence of modest abnormalities in hemorheology and oxidative stress, SCT is generally considered a benign condition. Little is known about vascular function in SCT, although recent studies demonstrated an increased risk of cardiovascular disorders, including venous thromboembolism, stroke, and chronic kidney disease. We hypothesized that SCT could accentuate the vascular dysfunction observed in T2DM. RESEARCH DESIGN AND METHODS The current study, conducted in Senegal, compared vascular function, hemorheological profile, and biomarkers of oxidative stress, inflammation, and nitric oxide metabolism in healthy individuals (CONT), subjects with T2DM or SCT, and patients with both T2DM and SCT (...