bims-sicedi Biomed News
on Sickle cell disease
Issue of 2024–09–29
nine papers selected by
João Conrado Khouri dos Santos, Universidade de São Paulo
  1. Establishing the Approach to the Diagnosis of Hemolytic Anemia in the Genetic Era: A Case Series.
  2. Position statement on the management of pregnancy in sickle cell disease.
  3. Black Americans with sickle cell disease (SCD) demonstrate accelerated epigenetic pace of aging compared to Black Americans without SCD.
  4. Adherence to Hydroxyurea Therapy and its Relationship to Clinical Outcomes Among Adults Living With Sickle Cell Disease.
  5. Effects of GBT1118, a voxelotor analog, on bone disease in sickle cell disease mice.
  6. Impact of scheduled partial exchange transfusions on outcomes in pregnant patients with severe sickle cell disease: a retrospective study.
  7. The Aplastic Crisis in HbSS: Observations from the Jamaican Birth Cohort.
  8. Impaired microvascular function in patients with sickle cell anemia and leg ulcers improved with healing.
  9. Novel Single-cell Measurements Suggest Irreversibly Sickled Cells Are Neither Dense Nor Dehydrated.
  1. Cureus. 2024 Aug;16(8): e67952
    Establishing the Approach to the Diagnosis of Hemolytic Anemia in the Genetic Era: A Case Series.
    Aayushi Guru, Pratibha Meena, G K Sawke, Sakshi Tripathi.
       BACKGROUND: Hemolytic anemia is characterized by the premature destruction of red blood cells, a condition that ranges from chronic to life-threatening. Hereditary hemolytic anemias (HHAs) encompass a broad spectrum of disorders including hemoglobinopathies, enzymopathies, and membrane disorders. In India, hemoglobinopathies, notably thalassemia and sickle cell disease, are significant health concerns contributing to high morbidity and mortality rates. Despite many cases being clinically insignificant, these disorders exert a considerable public health burden due to their prevalence. Techniques like next-generation sequencing (NGS) and high-performance liquid chromatography (HPLC) have emerged as powerful tools for identifying and diagnosing HHAs. NGS enables comprehensive genetic analysis, pinpointing mutations associated with hemoglobinopathies and other forms of hereditary anemia. HPLC allows precise quantification and characterization of hemoglobin variants, which is crucial for diagnosing hemoglobinopathies.
    AIMS AND OBJECTIVES: This study aimed to establish a refined approach for diagnosing hemolytic anemias and categorize different types of hemolytic anemia using state-of-the-art technologies for early and precise treatment interventions.
    MATERIALS AND METHODS: This retrospective study was conducted in the Hematology Section of the Department of Pathology at Atal Bihari Vajpayee Government Medical College, Vidisha, Madhya Pradesh. The study included six patients diagnosed with hemolytic anemia based on comprehensive hematological, biochemical, and molecular evaluations.  Results: The retrospective analysis of six cases of hemolytic anemia highlighted the diagnostic approach utilized. Clinical presentations, physical examinations, routine hematological investigations, advanced diagnostic modalities, and hemoglobin electrophoresis were instrumental in identifying specific types of hemolytic anemias.
    CONCLUSION: Despite the availability of advanced diagnostic techniques, basic hematological investigations remain the cornerstone in the initial evaluation of HHAs. Hemoglobin electrophoresis plays a pivotal role in confirming diagnoses. In some cases, subtle hematological findings necessitate thorough evaluation, including familial studies, to guide appropriate management strategies.
    Keywords:  anemia; approach; blood; diagnosis; hemolytic
    DOI:  https://doi.org/10.7759/cureus.67952
  2. Aust N Z J Obstet Gynaecol. 2024 Sep 27.
    Position statement on the management of pregnancy in sickle cell disease.
    Mimi Yue, Kylie Mason, Shelley Rowlands, Zane Kaplan, Debra Kennedy, Giselle Kidson-Gerber.
      Sickle cell disease (SCD) is a hereditary haemoglobinopathy which causes multi-organ dysfunction. Pregnancies in SCD are high risk with significant maternal and fetal morbidity and mortality, including vaso-occlusive crises, thrombosis, anaemia, placental insufficiency, fetal growth restriction, preterm birth and medication effects. High level evidence on this topic is lacking. The Australian Sickle Cell Disease Working Group has reviewed international guidelines on this topic and provide an up-to-date and structured approach to the pre-conception, antenatal, birth and post-partum management of these women. Early and comprehensive multidisciplinary care involving experienced clinicians is recommended.
    Keywords:  anaemia; pregnancy; pregnancy complications; prenatal care; sickle cell
    DOI:  https://doi.org/10.1111/ajo.13888
  3. J Gerontol A Biol Sci Med Sci. 2024 Sep 19. pii: glae230. [Epub ahead of print]
    Black Americans with sickle cell disease (SCD) demonstrate accelerated epigenetic pace of aging compared to Black Americans without SCD.
    VA Mid-Atlantic MIRECC Workgroup
       BACKGROUND: Sickle cell disease (SCD) is a chronic medical condition characterized by red blood cell sickling, vaso-occlusion, hemolytic anemia, and subsequently, end-organ damage and reduced survival. Because of this significant pathophysiology and early mortality, we hypothesized that patients with SCD are experiencing accelerated biological aging compared to individuals without SCD.
    METHODS: We utilized the DunedinPACE measure to compare the epigenetic pace of aging in 131 Black Americans with SCD to 1391 Black American veterans without SCD.
    RESULTS: SCD patients displayed a significantly accelerated pace of aging (DunedinPACE mean difference of 0.057 points) compared to the veterans without SCD, whereby SCD patients were aging approximately 0.7 months more per year than those without SCD (p=4.49x10-8). This was true, even though the SCD patients were significantly younger according to chronological age than the individuals without SCD, making the epigenetic aging discrepancy even more apparent. This association became stronger when we removed individuals with PTSD from the non-SCD group (p=2.18x10-9), and stronger still when we restricted the SCD patients to those with hemoglobin SS and Sβ0 thalassemia genotypes (p=1.61x10-10).
    CONCLUSIONS: These data support our hypothesis that individuals with SCD experience accelerated biological aging as measured by global epigenetic variation. The assessment of epigenetic measures of biological aging may prove useful to identify which SCD patients would most benefit from clinical interventions to reduce mortality.
    Keywords:  DNA methylation; chronic disease pathology; hemoglobinopathy
    DOI:  https://doi.org/10.1093/gerona/glae230
  4. Hosp Pharm. 2024 Oct;59(5): 507-508
    Adherence to Hydroxyurea Therapy and its Relationship to Clinical Outcomes Among Adults Living With Sickle Cell Disease.
    Justin Arnall, Rachel Crawford, Katherine Rector, Margaret Taylor.
      
    DOI:  https://doi.org/10.1177/00185787241238305
  5. Sci Rep. 2024 Sep 27. 14(1): 22330
    Effects of GBT1118, a voxelotor analog, on bone disease in sickle cell disease mice.
    Liping Xiao, Wei He, Marja M Hurley.
      We assessed the effect of GBT1118, a sickle hemoglobin polymerization inhibitor on bone loss in humanized sickle cell disease (SCD) mice. Healthy control (Ctrl) 4-months-old female and male mice were fed Vehicle-chow for 2-months, while SCD mice were fed Vehicle-chow or GBT1118-chow. By micro-CT, GBT1118 significantly increased femur metaphyseal trabecular thickness (Tb.Th) and tissue mineral density (TMD), and significantly decreased trabecular spacing in female SCD mice. In SCD male mice, there was significant reduction in epiphyseal trabecular bone volume fraction (BV/TV), Tb.Th and TMD and GBT1118 significantly increased BV/TV and TMD but not Tb.Th. A significant decrease in cortical area fraction in SCD female mice was rescued by GBT1118 but not SCD males. Markedly decreased mineralized femur trabeculae in SCD females and males was partially rescued by GBT1118. Bone histomorphometry of femurs demonstrated significantly decreased bone formation parameters and increased bone resorption parameters in SCD mice of both sex that were rescued by GBT1118. Significant alteration in bone and hypoxia related genes of SCD mice of both sexes were differentially modulated by GBT1118. We conclude that "a sickle hemoglobin polymerization inhibitor" might be efficacious in improving some parameters of SCD bone loss.
    Keywords:  Bone disease; Hemoglobin allosteric modifier; Sickle cell disease; Voxelotor analog GBT118
    DOI:  https://doi.org/10.1038/s41598-024-69589-9
  6. Hematol Transfus Cell Ther. 2024 Sep 07. pii: S2531-1379(24)00304-3. [Epub ahead of print]
    Impact of scheduled partial exchange transfusions on outcomes in pregnant patients with severe sickle cell disease: a retrospective study.
    Anil Ananthaneni, Sarah Jones, Mohamed Ghoweba, Vishwa Grant, Kenna Leethy, Taras Benzar, Samip Master, Richard Mansour, Poornima Ramadas.
       INTRODUCTION: The incidence of feto-maternal complications is high in women with sickle cell disease. The paucity of high-quality evidence has led to conditional recommendations for transfusional support in pregnant patients. This study aimed to assess if scheduled partial red cell exchanges impact pregnancy outcomes in sickle cell disease patients.
    METHODS: Forty-seven pregnancies were divided into two groups based on whether patients received scheduled partial red cell exchanges. Collected data included demographics, laboratory values, number of hospital visits, and prenatal/perinatal/postnatal outcomes. Data were analyzed using descriptive statistics, t-test, Chi-square and Fisher's exact tests, and binary regression.
    RESULTS: The mean age was 25.09 ± 4.39 years. Of 47 patients, 14 (29.8%) received scheduled red cell exchanges with 78.6% compliance with no evidence of alloimmunization. This procedure during pregnancy was associated with fewer admissions for pain crises (p=0.032), higher gestational age at delivery (p=0.007), and a lower incidence of neonatal intensive care admissions (p=0.011; odds ratio: 0.071; 95% confidence interval: 0.008-0.632). Logistic regression did not show any significant associations.
    CONCLUSIONS: Sickle cell disease patients with complications in previous pregnancies, including high hospitalization/admission rates and preterm deliveries, could benefit from scheduled partial red cell exchanges or simple transfusions. Further research is needed to guide clinical practice pertaining to transfusional support in pregnant patients with sickle cell disease.
    Keywords:  Outcome; Pregnancy; Red cell exchange; SCD; Sickle cell disease; Transfusion
    DOI:  https://doi.org/10.1016/j.htct.2024.07.001
  7. Hemoglobin. 2024 Sep 23. 1-6
    The Aplastic Crisis in HbSS: Observations from the Jamaican Birth Cohort.
    Beryl Elizabeth Serjeant, Karlene Mason, Marvin Reid, Ian Hambleton, Graham Roger Serjeant.
      In order to document the prevalence, clinical features, hematology and outcome of the aplastic crisis in homozygous sickle cell disease (HbSS), a cohort study has been conducted from birth. Newborn screening of 100 000 deliveries at the main government maternity hospital, Kingston, Jamaica between 1973 and 1981 detected 311 cases of HbSS who have been followed at the Medical Research Council Laboratories at the University of the West Indies, Kingston, Jamaica. Clinically defined aplastic crises occurred in 118 (38%) patients at a median age of 7.5 years (range 0.5-23.0 years). All but one event seroconverted to parvovirus B19, the exception being a 9.3 year male with classic aplasia but subsequent IgG did not exceed 3 IU. Defined by zero reticulocyte counts, 94 patients presented with a median hemoglobin of 3.7 g/dL (range 18-87 g/L) representing a median fall from steady state levels of 3.8 g/dL. Clear epidemic peaks occurred at 1979-1980, 1984-1986, and 1990-1993 and the admission rate and use of blood cultures fell with each epidemic, reflecting increased familiarity with the complication. Symptoms were usually nonspecific and all but 7 were transfused. No patient had a recurrence and two died from aplasia (one with remote rural residence and the other following an incorrect diagnosis). Of those seroconverting to parvovirus B19, 68% manifested aplasia and 24% had no hematologic change. Correctly diagnosed and managed, the aplastic crisis is essentially benign. (230 words).
    Keywords:  Birth cohort; Jamaica; aplastic crisis; sickle cell disease
    DOI:  https://doi.org/10.1080/03630269.2024.2407633
  8. Br J Haematol. 2024 Sep 24.
    Impaired microvascular function in patients with sickle cell anemia and leg ulcers improved with healing.
    Judith Catella, Etienne Turpin, Philippe Connes, Elie Nader, Romain Carin, Marie Martin, Hamdi Rezigue, Christophe Nougier, Yesim Dargaud, Audrey Josset-Lamaugarny, Justine Dugrain, Muriel Marano, Alexandre Leuci, Camille Boisson, Celine Renoux, Philippe Joly, Solène Poutrel, Arnaud Hot, Nicolas Guillot, Berengère Fromy.
      Leg Ulcer (LU) pathophysiology is still not well understood in sickle cell anaemia (SCA). We hypothesised that SCA patients with LU would be characterised by lower microvascular reactivity. The aim of the present study was to compare the microcirculatory function (transcutaneous oxygen pressure (TcPO2) on the foot and laser Doppler flowmetry on the arm) and several blood biological parameters between nine SCA patients with active LU (LU+) and 56 SCA patients with no positive history of LU (LU-). We also tested the effects of plasma from LU+ and LU- patients on endothelial cell activation. We observed a reduction of the TcPO2 in LU+ compared to LU- patients. In addition, LU+ patients exhibited lower cutaneous microvascular vasodilatory capacity in response to acetylcholine, current and local heating compared to LU- patients. Inflammation and endothelial cell activation in response to plasma did not differ between the two groups. Among the nine patients from the LU+ group, eight were followed and six achieved healing in 4.4 ± 2.5 months. Among thus achieving healing, microvascular vasodilatory capacity in response to acetylcholine, current and local heating and TcPO2 improved after healing. In conclusion, microcirculatory function is impaired in patients with LU, and improves with healing.
    Keywords:  endothelial cell; leg ulcers; microcirculation; sickle cell disease; transcutaneous oxygen pressure
    DOI:  https://doi.org/10.1111/bjh.19785
  9. Biophys J. 2024 Sep 25. pii: S0006-3495(24)00650-7. [Epub ahead of print]
    Novel Single-cell Measurements Suggest Irreversibly Sickled Cells Are Neither Dense Nor Dehydrated.
    Thomas J Reese, Eli H Worth, Mark K Fugate, M T Levitt, Frank A Ferrone.
      In sickle cell anemia, deoxygenation causes erythrocytes to distort, while reoxgenation permits them to recover a normal biconcave disk shape. Irreversibly sickled cells (ISCs) cells remain distorted when reoxygenated and have been thought to have among the highest intracellular hemoglobin concentration of the sickle red cell population and therefore the greatest vulnerability to vaso-occlusion. Using a new optical method, which we describe, we have made precise measurements of the intracellular hemoglobin concentration, and intracellular O2 saturation, of ISCs, as well as oxygenated sickle cells with a normal biconcave disc shape, and cells with shapes distorted by the sickle fibers they contain. This method also provides good estimates of cell volumes, and hemoglobin per red cell. The concentration distribution of the ISCs is found to be similar to normal, discoid cells. Average ISC volumes exceed their discoid counterparts, with a much broader distribution, arguing against dehydration as their origin. The concentration distribution of the polymer-laden sickled cells is significantly higher in mean value, and their volume distributions indicate some dehydration. Previous assumptions about ISCs may have thus been colored by the presence of sickle cells that did contain polymer, and that true ISC's may be much more benign than once thought, which underscores the importance of accurate measurement on individual cells. This method could be used to follow changes in individual cell properties under various specific perturbations, and where characterization by flow cytometry is infeasible.
    Keywords:  Irreversibly sickled cells; concentration distribution; dehydration; single cell measurement
    DOI:  https://doi.org/10.1016/j.bpj.2024.09.024
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