scholarly journals Compound heterozygous sickle cell disease and β0-thalassaemia: An interesting case

2013 ◽  
Vol 7 (2) ◽  
pp. 70
Author(s):  
Rose Von Fintel ◽  
R Schwyzer ◽  
J Poole ◽  
N A Alli
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Interesting Case ◽  
Compound Heterozygous ◽  
Cell Disease

scholarly journals Compound Heterozygous Sickle and Thalassemia Trait: A Case Report

2011 ◽  
Vol 31 (2) ◽  
pp. 130-133
Author(s):  
Bikash Shrestha ◽  
Kavita Karmacharya ◽  
Jasjit Singh ◽  
Jyoti Kotwal ◽  
Amit Devgan
Keyword(s):  
Case Report ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Interesting Case ◽  
Compound Heterozygous ◽  
Cell Disease ◽  
The World ◽  
Thalassemia Trait

Sickle cell disease is a type of hemoglobinopathy, which is fairly common in certain parts of the world. We would like to report an interesting case of a child who was labeled as sickle cell anemia but subsequently turned out to be a case of compound heterozygous sickle cell and thalassemia trait. Keywords: Sickle cell disease; haemoglobinopathy; thalassemia; hydroxyurea; globin; electrophoresis; HPLC DOI: 10.3126/jnps.v31i2.4414 J Nep Paedtr Soc 2010;31(2):130-133

scholarly journals Sickle Cell Anemia Presenting with Vaso-Occlusive Pain: Should We Screen for COVID-19?

2021 ◽  
pp. 1-4
Author(s):  
Mohammad Ali ◽  
Lina Okar ◽  
Nabil E. Omar ◽  
Jabeed Parengal ◽  
Ashraf Soliman ◽  
...  
Keyword(s):  
High Risk ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Signs And Symptoms ◽  
Risk Groups ◽  
Position Statement ◽  
Interesting Case ◽  
International Federation ◽  
Cell Disease ◽  
The World

Despite the widespread of coronavirus disease-19 (CO­VID-19) infection around the world, there are very scarce reported literature about the care of patients with a known diagnosis of hemoglobin disorders such as sickle cell disease (SCD) or thalassemia and confirmed COVID-19 infection. Thalassemia International Federation issued a position statement to include patients with thalassemia and SCD among the high-risk groups of patients. Here, we present an interesting case of a 42-year-old patient know to have SCD presenting with Vaso-occlusive (VOC) pain episode in the absence of COVID-19 signs and symptoms, who tested positive for COVID-19 infection and had a smooth recovery. This case highlights the importance of screening SCD patients presenting with VOC-related events even in the absence of COVID-19 signs and symptoms.

scholarly journals Genome editing using CRISPR-Cas9 to create the HPFH genotype in HSPCs: An approach for treating sickle cell disease and β-thalassemia

2016 ◽  
Vol 113 (38) ◽  
pp. 10661-10665 ◽  
Author(s):  
Lin Ye ◽  
Jiaming Wang ◽  
Yuting Tan ◽  
Ashley I. Beyer ◽  
Fei Xie ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Genome Editing ◽  
Sickle Cell ◽  
Globin Gene ◽  
Autologous Transplantation ◽  
Clinical Manifestations ◽  
Fetal Hemoglobin ◽  
Compound Heterozygous ◽  
Cell Disease ◽  
Hematopoietic Stem

Hereditary persistence of fetal hemoglobin (HPFH) is a condition in some individuals who have a high level of fetal hemoglobin throughout life. Individuals with compound heterozygous β-thalassemia or sickle cell disease (SCD) and HPFH have milder clinical manifestations. Using RNA-guided clustered regularly interspaced short palindromic repeats-associated Cas9 (CRISPR-Cas9) genome-editing technology, we deleted, in normal hematopoietic stem and progenitor cells (HSPCs), 13 kb of the β-globin locus to mimic the naturally occurring Sicilian HPFH mutation. The efficiency of targeting deletion reached 31% in cells with the delivery of both upstream and downstream breakpoint guide RNA (gRNA)-guided Staphylococcus aureus Cas9 nuclease (SaCas9). The erythroid colonies differentiated from HSPCs with HPFH deletion showed significantly higher γ-globin gene expression compared with the colonies without deletion. By T7 endonuclease 1 assay, we did not detect any off-target effects in the colonies with deletion. We propose that this strategy of using nonhomologous end joining (NHEJ) to modify the genome may provide an efficient approach toward the development of a safe autologous transplantation for patients with homozygous β-thalassemia and SCD.

scholarly journals Successful Outcome of Chronic Intrahepatic Cholestasis in an Adult Patient with Sickle Cell/β+Thalassemia

2014 ◽  
Vol 2014 ◽  
pp. 1-3 ◽  
Author(s):  
Efthymia Vlachaki ◽  
Panagiotis Andreadis ◽  
Nikolaos Neokleous ◽  
Aleka Agapidou ◽  
Evaggelia Vetsiou ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Adult Patient ◽  
Sickle Cell ◽  
Intrahepatic Cholestasis ◽  
Interesting Case ◽  
Successful Outcome ◽  
Variant Form ◽  
Cell Disease ◽  
Hb S ◽  
Chronic Intrahepatic Cholestasis

Sickle cell/β+thalassemia (Hb S/β+thal) is considered as a variant form of sickle cell disease. Acute episodes of vasoocclusive pain crisis are characteristic for sickle cell disorders and may be complicated by an acute or chronic life-threatening organ dysfunction. Chronic intrahepatic cholestasis is a rare and severe complication in sickle cell disease, characterized by marked hyperbilirubinemia and acute hepatic failure with an often fatal course. Despite the fact that patients with Hb S/β+thal usually have a mild type of disease, herein we describe an interesting case of chronic intrahepatic cholestasis with successful outcome in an adult patient with Hb S/β+thal.

Sickle Cell Trait: A Benign State?

2016 ◽  
Vol 136 (3) ◽  
pp. 147-151 ◽  
Author(s):  
Taiwo R. Kotila
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Dna Analysis ◽  
Sickle Cell Trait ◽  
Beta Thalassemia ◽  
Compound Heterozygous ◽  
Cell Disease ◽  
Benign Condition ◽  
Red Cell Indices ◽  
Heterozygous Form

Background: Sickle cell trait (SCT) is the heterozygous form of sickle cell disease and expectedly should be a benign state with no complications ascribed to it. There are numerous reports challenging its being a benign condition, though this is controversial. Methods and Results: A review of the results of the accompanying investigations done on some of the patients show that beta thalassemia may be responsible for many of the ascribed symptoms and complications. These patients may therefore have sickle cell beta thalassemia, a compound heterozygous form of sickle cell disease. Conclusion: It is important to screen for beta thalassemia using red cell indices and quantitation of the different hemoglobin fractions before attributing any symptoms to SCT. DNA analysis, though useful in ascertaining the presence of the sickle cell gene, is not sufficient. There is the need to exclude the presence of mutations for beta thalassemia, which often is geographical region-specific.

Severe Sickle Cell Disease Is Characterized by Low ADAMTS13/VWF: Ag Ratio

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3235-3235
Author(s):  
Despoina Adamidou ◽  
Erasmia Rouka ◽  
Despoina Kyriakou ◽  
Stamatia Theodoridou ◽  
E Vetsiou ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Normal Values ◽  
Clinical Phenotype ◽  
Severe Disease ◽  
Control Group ◽  
Compound Heterozygous ◽  
Cell Disease ◽  
Significant Difference ◽  
Lower Ratio

Abstract Abstract 3235 Endothelial damage is one of the major mechanisms causing most of the manifestations in sickle cell disease (SCD). We hypothesized that a possible defect in the cleavage of large vWF multimers through the protease ADAMTS13 could add further to the well established chronic activation of the endothelium and consequently to the severity of the disease. For this purpose we measured the activity of the enzyme and looked for any correlations with regard to the clinical phenotype of patients with SCD. We studied 22 steady state patients (9 men/13 women) with a median age of 35(22–74) years. Of them, 3 were in homozygous state(HbSS) and 19 were compound heterozygous for thalassamia β(HbS/β+, HbS/β0). The clinical phenotype was mild in 12 patients, moderate in 3 and 7 were suffering from severe symptoms (history of frequent vaso-occlusive and acute chest crises and need for regular exchange transfusion). We applied FRET (fluorescence resonance energy transfer) technique to measure ADAMTS13 activity (normal values>65%). Factor VIII and vWF: Ag was measured using 1-stage clotting assay and immunoassay respectively (normal values 50–150%). We considered all relevant clinical parameters (spleen size, transfusion frequency, comorbidities, and medications with special regard to iron chelation, hydroxyurea and antiplatelet agents) together with laboratory readings (markers of haemolysis, proportion of haemoglobin fractions using high-performance liquid chromatography HPLC).We used as control group 22 healthy volunteers blood donors with their written consent matched for age, sex, body mass index and ABO blood group. All samples were taken at least 30 days post last transfusion. We found higher levels of both vWF: Ag [189(33–345)] and ADAMTS13 [164(75–310)] in the patients compared to the control group [87(44–152) και 126(55–171) (p<0.001/p<0.025)] respectively. When we analyzed the ratio ADAMTS13/vWF: Ag we found significant difference between the two groups: 1,041(0.3–4.6) vs 1.56(0.5–2.6) (p<0.020). Furthermore, patients with severe disease experienced significantly lower ratio ADAMTS/vWF 0.7(0.5–1.2) compared to both control group (p<0.001) as well as patients with milder clinical phenotype [1.30(0.3–4.6)].Of note, in patients with severe SCD despite the fact that vWF: Ag levels were found considerably higher and in significant difference with the control group [196(130–345) vs 87(44–152)p<0.001], we could not find the same pattern for ADAMTS13 [140(75–210) vs 126(55–171)].The lower ratio found in patients with SCD and in particular in those with severe disease might indicate the need for higher protease levels in comparison to healthy controls. It looks like in this group of patients ADAMTS13, although normal, is not sufficient enough to manage the reasonably high vWF levels that characterize the chronic endothelial activation. This relevant deficiency of the metaloprotease might be caused by either biggest consumption due to large and constant release of its substrate-vWF or by an acquired inhibition of its action as the free intravascular hemoglobin might exhibit an antagonistic role for the binding site of vWF. In conclusion, the low ADAMTS13/vWF: Ag ratio seems to detect patients with severe SCD and would be of interest to prospectively investigate its role both as a prognostic tool as well as a potential therapeutic target. Disclosures: No relevant conflicts of interest to declare.

Methodological aspects of oxygen gradient ektacytometry in sickle cell disease: Effects of sample storage on outcome parameters in distinct patient subgroups

2020 ◽  
pp. 1-4
Author(s):  
Camille Boisson ◽  
Minke A.E. Rab ◽  
Elie Nader ◽  
Céline Renoux ◽  
Brigitte A. van Oirschot ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Genetic Disorder ◽  
Compound Heterozygous ◽  
Cell Disease ◽  
Oxygen Gradient ◽  
Abnormal Hemoglobin ◽  
Methodological Aspects ◽  
Patient Subgroups ◽  
Rbc Deformability

Sickle cell disease (SCD) is a genetic disorder characterized by the production of an abnormal hemoglobin (Hb), which, under deoxygenation, may polymerize and cause a mechanical distortion of red blood cell (RBC) into a crescent-like shape. Recently a method, using ektacytometry principle, has been developed to assess RBC deformability as a function of oxygen tension (pO2) and is called oxygen gradient ektacytometry (oxygenscan). However, standardization of this test is needed to properly assess the tendency of sickling of RBCs under deoxygenation and to allow comparisons between different laboratories. The study compared the oxygenscan responses during blood storage between distinct populations of SCD patients. Blood from 40 non-transfused homozygous SCD patients (HbSS), 16 chronically transfused HbSS patients, and 14 individuals with compound heterozygous hemoglobin SC disease (HbSC)at steady-state was collected in EDTA tubes. Measurements were performed within 4 hours after collection and after 24 hours of storage at 4°C. We showed that storage affected the minimum RBC deformability reached during deoxygenation (EImin) in both non-transfused HbSS and HbSC patients and the maximum RBC deformability (EImax) measured before deoxygenation (i.e., in normoxia) in the three groups. In contrast, the tendency of RBCs to sickle under deoxygenation (i.e., the point of sickling; PoS) remained rather stable between the two time of measurements. Collectively, since the time between blood sampling and analysis affects some key oxygen gradient ektacytometry-derived parameters we recommend that each laboratory performs oxygenscan measurements at a standardized time point.

Genomic variants in members of the Krüppel-like factor gene family are associated with disease severity and hydroxyurea treatment efficacy in β-hemoglobinopathies patients

2019 ◽  
Vol 20 (11) ◽  
pp. 791-801
Author(s):  
Apostolos Stratopoulos ◽  
Alexandra Kolliopoulou ◽  
Kariofyllis Karamperis ◽  
Anne John ◽  
Kyriaki Kydonopoulou ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Gene Family ◽  
Disease Severity ◽  
Sickle Cell ◽  
Treatment Efficacy ◽  
Clinical Severity ◽  
Compound Heterozygous ◽  
Cell Disease ◽  
Genomic Variants ◽  
Hydroxyurea Treatment

Aim: β-Type hemoglobinopathies are characterized by vast phenotypic diversity as far as disease severity is concerned, while differences have also been observed in hydroxyurea (HU) treatment efficacy. These differences are partly attributed to the residual expression of fetal hemoglobin (HbF) in adulthood. The Krüppel-like family of transcription factors (KLFs) are a set of zinc finger DNA-binding proteins which play a major role in HbF regulation. Here, we explored the possible association of variants in KLF gene family members with response to HU treatment efficacy and disease severity in β-hemoglobinopathies patients. Materials & methods: Six tag single nucleotide polymorphisms, located in four  KLF genes, namely KLF3, KLF4, KLF9 and KLF10, were analyzed in 110 β-thalassemia major patients (TDT), 18 nontransfusion dependent β-thalassemia patients (NTDT), 82 sickle cell disease/β-thalassemia compound heterozygous patients and 85 healthy individuals as controls. Results: Our findings show that a KLF4 genomic variant (rs2236599) is associated with HU treatment efficacy in sickle cell disease/β-thalassemia compound heterozygous patients and two KLF10 genomic variants (rs980112, rs3191333) are associated with persistent HbF levels in NTDT patients. Conclusion: Our findings provide evidence that genomic variants located in KLF10 gene may be considered as potential prognostic biomarkers of β-thalassemia clinical severity and an additional variant in KLF4 gene as a pharmacogenomic biomarker, predicting response to HU treatment.

scholarly journals Nocturnal Hypoxemia (not sleep apnea) May Drive Reticulocytosis in Sickle Cell Disease

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1384-1384
Author(s):  
Jane A. Little ◽  
Seth Rotz ◽  
Ceonne Kim ◽  
MaryAnn O'Riordan ◽  
Nathan Langer ◽  
...  
Keyword(s):  
Sleep Apnea ◽  
Sickle Cell Disease ◽  
Oxygen Saturation ◽  
Sickle Cell ◽  
Reticulocyte Count ◽  
Sleep Time ◽  
Compound Heterozygous ◽  
Cell Disease ◽  
Nocturnal Hypoxemia ◽  
Polymer Formation

Abstract Introduction: Obstructive sleep apnea is a ventilatory defect that affects up to 10% of children with sickle cell disease (SCD). Sleep apnea has been implicated in cardiovascular disease in non-SCD adults and in cerebrovascular disease in children with SCD. In addition, prolonged hemoglobin oxygen desaturation from sleep disorderedbreathing would be predicted to increase sickle polymer formation and, possibly, activity of disease. We evaluated symptomatic adults from our SCD clinic for sleep apnea, in an effort to identify treatable disease modifying conditions. Methods: 46 adults with SCD were evaluated by polysomnography (PSG) between 2012 and 2014. Subjects were referred for symptoms or signs suggestive of sleep disordered breathing, including nighttime pain, snoring, early morning headache, narrow hypo-pharynx, and/or excessive reticulocytosis. Clinical characteristics of homozygous (HbSS, n=34) and compound heterozygous (HbSC and HbSBeta+Thalassemia, n=12) subjects are shown in Table 1. Results: Sleep apnea was diagnosed if the apnea/hypopnea index (AHI) was elevated: 5-15 (mild), 15-30 (moderate), or >30 (severe). Over half of our patients had sleep apnea by these criteria (16/34 HbSS and 7/12 compound heterozygotes). An elevated 3% oxygen desaturation index , i.e. >15 episodes per hour during which oxygen saturation dropped by 3% or more, was seen in one-third (14/43) of all evaluable subjects, and was 17 (median, range 1.2- 192.4) in subjects with, compared with 4.6 (median, range 1-23.7) in subjects without, sleep apnea (P<.001). Sleep apnea was moderate or severe in 5/34 (14.7%) and 3/12 (25%) of screened HbSS and compound heterozygote patients, respectively. However, the presence of sleep apnea, compared with the absence of sleep apnea, was not associated with differences in measured clinical variables including WBC, Hgb, absolute reticulocyte count, LDH, urinary albumin-to-creatinine ratio, or tricuspid regurgitant jet velocity. We then examined 8 subjects (7 HbSS, 1 SBeta+ thal) whose PSG showed >10% of sleep time afflicted by nocturnal hypoxemia. A median of 33.75% (range 16-98.6%) of sleep time was spent at <90% oxygen saturation in these subjects. Only 3 of 8 subjects with nocturnal hypoxemia had sleep apnea, based on an AHI >5, which was not different than the group as a whole (P=0.7). These 8 subjects had strikingly increased reticulocyte counts, compared with 38 subjects without nocturnal hypoxemia (median 460, range 100-923 (x103)/μL compared with median 303, range 76-733 (x103)/μL respectively, p=0.04), as well as a trend toward a higher LDH (median 488, range 140-752, compared with median 318, range 139-823, P=.08). Of note, hemoglobin levels were not different between subjects with and without nocturnal hypoxemia (mean 8.4±1.5 g/dL compared to mean 9.5±2.2 g/dL, respectively, p=0.17). Conclusions & Discussion: These studies suggest that, while sleep apnea is common in adults with SCD, greater physiological relevance may arise instead from prolonged nocturnal hypoxemia and associated reticulocytosis. We speculate that significant nighttime hypoxemia and hemoglobin desaturation may stimulate both endogenous erythropoietin (and therefore reticulocyte) production and HbS polymer formation and, possibly, hemolysis. This condition, while identifiable by conventional PSG, is not coincident with sleep apnea, and may be modulated by nighttime oxygen supplementation. These findings deserve confirmation in a larger cohort of patients. Table I.Clinical Characteristics of adults with SCD who underwent PolysomnographyHbSS(n=34)Compound Heterozygous (HbSC, n=8, HbSβ+Thal, n=4)P ValueAge (years)27 (19-50)29.5 (19-51)n.s.Body Mass Index23.8 (17.8-37.6)27.2 (20.1-59.8)n.s.Hgb (g/dL, mean±std dev)8.7±1.910.9±2.0P=.003ARC* (x103/μL),350 (93-923)200 (71-398)P=.004LDH (IU/L)398 (149-823)200 (140-632)P<.001TRV**(m/s)2.5 (n.d.-3.51)1.9 (n.d.-2.64)P<.001*Absolute reticulocyte count **Tricuspid regurgitant jet velocity ¦Median with range, unless otherwise indicated. Disclosures No relevant conflicts of interest to declare.

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