Clinical Manifestations of Sickle Cell Disease Across the Lifespan

2017 ◽  
pp. 3-39 ◽  
Author(s):  
Lydia H. Pecker ◽  
Jane Little
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Clinical Manifestations ◽  
Cell Disease

scholarly journals Predictors of musculoskeletal manifestations in paediatric patients presenting with sickle cell disease at a tertiary teaching hospital in Lusaka, Zambia

2020 ◽  
Vol 1 (6) ◽  
pp. 175-181
Author(s):  
Raymond Mpanjilwa Musowoya ◽  
Patrick Kaonga ◽  
Alick Bwanga ◽  
Catherine Chunda-Lyoka ◽  
Christopher Lavy ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Teaching Hospital ◽  
Clinical Manifestations ◽  
Classification Systems ◽  
University Teaching ◽  
Cell Disease ◽  
Tertiary Teaching ◽  
Musculoskeletal Manifestations

Aims Sickle cell disease (SCD) is an autosomal recessive inherited condition that presents with a number of clinical manifestations that include musculoskeletal manifestations (MM). MM may present differently in different individuals and settings and the predictors are not well known. Herein, we aimed at determining the predictors of MM in patients with SCD at the University Teaching Hospital, Lusaka, Zambia. Methods An unmatched case-control study was conducted between January and May 2019 in children below the age of 16 years. In all, 57 cases and 114 controls were obtained by systematic sampling method. A structured questionnaire was used to collect data. The different MM were identified, staged, and classified according to the Standard Orthopaedic Classification Systems using radiological and laboratory investigations. The data was entered in Epidata version 3.1 and exported to STATA 15 for analysis. Multiple logistic regression was used to determine predictors and predictive margins were used to determine the probability of MM. Results The cases were older median age 9.5 (interquartile range (IQR) 7 to 12) years compared to controls 7 (IQR 4 to 11) years; p = 0.003. After multivariate logistic regression, increase in age (adjusted odds ratio (AOR) = 1.2, 95% confidence interval (CI) 1.04 to 1.45; p = 0.043), increase in the frequency of vaso-occlusive crisis (VOC) (AOR = 1.3, 95% CI 1.09 to 1.52; p = 0.009) and increase in percentage of haemoglobin S (HbS) (AOR = 1.18, 95% CI 1.09 to 1.29; p < 0.001) were significant predictors of MM. Predictive margins showed that for a 16-year-old the average probability of having MM would be 51 percentage points higher than that of a two-year-old. Conclusion Increase in age, frequency of VOC, and an increase in the percentage of HbS were significant predictors of MM. These predictors maybe useful to clinicians in determining children who are at risk. Cite this article: Bone Joint Open 2020;1-6:175–181.

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 Variation in fetal hemoglobin parameters and predicted hemoglobin S polymerization in sickle cell children in the first two years of life: Parisian Prospective Study on Sickle Cell Disease

Blood ◽  
1994 ◽  
Vol 84 (9) ◽  
pp. 3182-3188 ◽  
Author(s):  
M Maier-Redelsperger ◽  
CT Noguchi ◽  
M de Montalembert ◽  
GP Rodgers ◽  
AN Schechter ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Oxygen Saturation ◽  
Cell Population ◽  
Sickle Cell ◽  
Clinical Manifestations ◽  
Fetal Hemoglobin ◽  
Cell Disease ◽  
Normal Children ◽  
Hemoglobin S ◽  
F Cells

Abstract Intracellular hemoglobin S (HbS) polymerization is most likely to be the primary determinant of the clinical and biologic manifestations of sickle cell disease (SCD). Fetal hemoglobin (HbF) does not enter the HbS polymer and its intracellular expression in sickle erythrocytes inhibits polymerization. HbF levels, high at birth but decreasing thereafter, protect the newborn from the clinical manifestations of this hemoglobinopathy. We have measured the sequential changes in HbF, F reticulocytes, and F cells in the first 2 years of life in 25 children with SCD and compared the results with those obtained in 30 normal children (AA). We have also calculated HbF per F cell (F/F cell), the preferential survival of F cells versus non-F cells, as measured by the ratio F cells versus F reticulocytes (FC/FR) and polymer tendency at 40% and 70% oxygen saturation. HbF levels decreased from about 80.4% +/- 4.0% at birth to 9.2% +/- 2.9% at 24 months. During this time, we observed a regular decrease of the F reticulocytes and the F cells. The kinetics of the decline of F/F cell was comparable with the decline of HbF, rapid from birth (mean, 27.0 +/- 3.6 pg) to 12 months of age (mean, 8.5 +/- 1.5 pg) and then slower from 12 to 24 months of age (mean, 6.2 +/- 1.0 pg) in the SCD children. In the AA children, the decrease in HbF, due to changes in both numbers of F cells and F/F cell, was more precipitous, reaching steady-state levels by 10 months of age. Calculated values for mean polymer tendency in the F-cell population showed that polymerization should begin to occur at 40% oxygen saturation at about 3 months and increase progressively with age, whereas polymerization at 70% oxygen saturation would not occur until about 24 months. These values correspond to HbF levels of 50.8% +/- 10.8% and 9.2% +/- 2.9%, respectively, and F/F cell levels of 15.6 +/- 4.5 pg and 6.2 +/- 1.0 pg, respectively. In the non--F-cell population, polymerization was expected at birth at both oxygen saturation values. Three individuals had significantly greater predicted polymerization tendency than the remainder of the group because of early decreases in HbF. These individuals in particular, the remainder of the cohort, as well as other recruited newborns, will be studied prospectively to ascertain the relationship among hematologic parameters, which determine polymerization tendency and the various clinical manifestations of SCD.

scholarly journals The Fc Receptor Polymorphisms and Expression of Neutrophil Activation Markers in Patients with Sickle Cell Disease from Western India

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Harshada K. Kangne ◽  
Farah F. Jijina ◽  
Yazdi M. Italia ◽  
Dipti L. Jain ◽  
Anita H. Nadkarni ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Clinical Manifestations ◽  
Western India ◽  
Genotypic Frequency ◽  
Cell Disease ◽  
Activation Markers ◽  
Initiation And Propagation ◽  
Significant Difference ◽  
The Common

Objective. Sickle cell disease has variable clinical manifestations. Activation of neutrophils plays an important role in the initiation and propagation of vaso occlusive crises which can be analysed by determining the expression of neutrophil antigens such as CD16, CD32, and CD62L. The common FcγR polymorphisms (FcγRIIA and FcγRIIIB) are considered to influence clinical presentation. This study focuses on distribution of FcγR polymorphisms and their association with neutrophil activity among the patients from western India.Methods. In this paper 127 sickle cell anemia patients and 58 patients with sickle-β-thalassemia (median age12±8.58 years) with variable clinical phenotypes along with 175 normals were investigated. FcγRs polymorphisms were analysed by RFLP and AS-PCR. Activation of neutrophils was measured by flow cytometry.Results. The genotypic frequency of the H/R genotype of FcγRIIA and the NA1/NA1 genotype of FcγRIIIB was significantly decreased in patients compared to normals (P-0.0074,P-0.0471, resp.). We found a significant difference in the expression of CD32 and CD62L among the patients as against normals. A significantly higher expression of CD32 was seen in the milder patients with the H/H genotype (P-0.0231), whereas the expression of CD16 was higher in severe patients with the NA2/NA2 genotype (P-0.0312).Conclusion. The two FcγR polymorphisms had significant association with variable phenotypes of sickle cell disease. The expression of CD62L decreased in our patients indicating activation of neutrophils.

scholarly journals Predictors of musculoskeletal manifestations in paediatric patients presenting with sickle cell disease at a tertiary teaching hospital in Lusaka, Zambia

2020 ◽  
Vol 1 (6) ◽  
pp. 175-181
Author(s):  
Raymond Mpanjilwa Musowoya ◽  
Patrick Kaonga ◽  
Alick Bwanga ◽  
Catherine Chunda-Lyoka ◽  
Christopher Lavy ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Teaching Hospital ◽  
Clinical Manifestations ◽  
Classification Systems ◽  
University Teaching ◽  
Cell Disease ◽  
Tertiary Teaching ◽  
Musculoskeletal Manifestations

Aims Sickle cell disease (SCD) is an autosomal recessive inherited condition that presents with a number of clinical manifestations that include musculoskeletal manifestations (MM). MM may present differently in different individuals and settings and the predictors are not well known. Herein, we aimed at determining the predictors of MM in patients with SCD at the University Teaching Hospital, Lusaka, Zambia. Methods An unmatched case-control study was conducted between January and May 2019 in children below the age of 16 years. In all, 57 cases and 114 controls were obtained by systematic sampling method. A structured questionnaire was used to collect data. The different MM were identified, staged, and classified according to the Standard Orthopaedic Classification Systems using radiological and laboratory investigations. The data was entered in Epidata version 3.1 and exported to STATA 15 for analysis. Multiple logistic regression was used to determine predictors and predictive margins were used to determine the probability of MM. Results The cases were older median age 9.5 (interquartile range (IQR) 7 to 12) years compared to controls 7 (IQR 4 to 11) years; p = 0.003. After multivariate logistic regression, increase in age (adjusted odds ratio (AOR) = 1.2, 95% confidence interval (CI) 1.04 to 1.45; p = 0.043), increase in the frequency of vaso-occlusive crisis (VOC) (AOR = 1.3, 95% CI 1.09 to 1.52; p = 0.009) and increase in percentage of haemoglobin S (HbS) (AOR = 1.18, 95% CI 1.09 to 1.29; p < 0.001) were significant predictors of MM. Predictive margins showed that for a 16-year-old the average probability of having MM would be 51 percentage points higher than that of a two-year-old. Conclusion Increase in age, frequency of VOC, and an increase in the percentage of HbS were significant predictors of MM. These predictors maybe useful to clinicians in determining children who are at risk. Cite this article: Bone Joint Open 2020;1-6:175–181.

Orthotropic Liver Transplantation for Acute Intrahepatic Cholestasis in Sickle Cell Disease: Clinical and Histopathologic Features of a Rare Case

2018 ◽  
Vol 27 (4) ◽  
pp. 411-417 ◽  
Author(s):  
Shu Kwun Lui ◽  
Alyssa Krasinskas ◽  
Rushikesh Shah ◽  
Jessica M. Tracht
Keyword(s):  
Liver Transplantation ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Hepatic Failure ◽  
Intrahepatic Cholestasis ◽  
Clinical Manifestations ◽  
Cell Disease ◽  
Explanted Liver ◽  
Wide Range ◽  
Histopathologic Features

Sickle cell disease has a wide range of hepatic manifestations, with acute intrahepatic cholestasis being one of the rarest and most fatal, often resulting in acute fulminant hepatic failure. Liver transplantation is an emerging but rarely utilized treatment for hepatic failure in the setting of sickle cell disease. Few such cases have been reported in the literature, with little emphasis on histopathologic correlation. We report a case of acute intrahepatic cholestasis in a patient with sickle cell disease who underwent orthotropic liver transplantation and describe novel correlating histopathologic features. The patient is a 29-year-old man who presented with hyperbilirubinemia, acute kidney injury, and coagulopathy. He was diagnosed clinically with acute intrahepatic cholestasis and received an orthotropic liver transplant. The explanted liver demonstrated marked sinusoidal expansion by sickled erythrocytes, hyperplastic Kupffer cells, and extramedullary hematopoiesis. There was extensive sinusoidal and centrizonal fibrosis with occlusion of central veins reminiscent of chronic sinusoidal obstructive syndrome, a previously undescribed pattern of injury. This case represents one of the few reported cases of sickle cell intrahepatic cholestasis treated by transplantation and demonstrates the rarely reported histopathologic features and gives insight to a potentially new mechanism of injury in these patients. Familiarity with the morphologic features of sickle cell hepatopathy and its clinical manifestations is important as transplantation in sickle cell–related liver injury increases in frequency.

scholarly journals Socio-demographic, economic and health profile of adults with sickle-cell disease

Rev Rene ◽  
2015 ◽  
Vol 16 (3) ◽  
Author(s):  
Júlia Lamese Amaral ◽  
Nívea Aparecida Almeida ◽  
Paula Silveira Santos ◽  
Patrícia Peres de Oliveira ◽  
Fernanda Moura Lanza
Keyword(s):  
Health Care ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Medical Records ◽  
Clinical Manifestations ◽  
Descriptive Study ◽  
Health Profile ◽  
Cell Disease ◽  
Analysis Software ◽  
Statistical Program

Objective: to describe socio-demographic and economic characteristics, lifestyle, clinical manifestations, use of medicationsand monitoring of adults with sickle-cell disease. Methods: a descriptive study with quantitative approach, made with 20adults, registered in a Hematology and Hemotherapy Center, using, for data collection, interviews in the participant’s homeand medical records. In order to have the database, the EpiDatae analysis software through statistical program was used.Results: most of the population consisted of women, married, with complete high school, which used exclusively the UnifiedHealth System. The average age was 30.6 years, and 90.0% (95% CI 68.3-98.8) were black. All of them reported painful crisesand fatigue. They used folic acid daily 35.0% (95% CI 15.4-59.2). Conclusion: the implications of sickle-cell disease could bemitigated through primary, secondary and tertiary health care, according to the needs of those adults.

Superoxide Inhibits ADAMTS-13 Activity and Regulates Sickle Cell Adhesion.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2342-2342
Author(s):  
Prasenjit Guchhait ◽  
Miguel A. Cruz ◽  
Jing-Fei Dong ◽  
José A. López
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Clinical Manifestations ◽  
Chronic Phase ◽  
Cell Disease ◽  
Ample Evidence ◽  
Enhanced Production ◽  
Sickle Erythrocytes ◽  
Erythrocyte Adhesion

Abstract The major clinical manifestations of sickle cell anemia are due to a vaso-occlusive process that leads to severe pain crises, tissue infarction, and in some instances, death. The pathophysiology of vaso-occlusion is extremely complex, the proximate cause appearing to be an increase in the adhesive interaction between sickle erythrocytes and vascular endothelium. There is ample evidence that it is the highest molecular weight forms of VWF, the ultra-large multimers (ULVWF), expressed on endothelium support sickle erythrocyte adhesion most potently. We postulate that variation in the activity of the plasma metalloprotease, ADAMTS-13, which processes ULVWF to the VWF form normally found in plasma will be an important determinant of the propensity for individuals with sickle cell anemia to develop vaso-occlusive crises. It has also been postulated that increased production of reactive oxygen species (ROS) also contributes to the pathology of sickle cell disease. ROS have been implicated in diverse cellular processes, acting through oxidation of cysteine residues. ADAMTS-13 is a cysteine-rich protein; we therefore hypothesized that its function could be affected by ROS. We measured ADAMTS-13 activity in the plasmas of sickle cell disease patients, both in the “steady state” and at various times during vaso-occlusive crises. We used three assays: a static assay that measures the ability of patient plasma to reduce the size of endothelial-derived ULVWF, a static assay that assesses the ability of patient plasma to cleave a recombinant VWF A2 fragment, and an assay performed under flow that evaluates the ability of patient plasma to cleave ULVWF attached to the surfaces of histamine-stimulated human umbilical vein endothelial cells (HUVECs). Five of nine patients with sickle cell anemia had significantly lower ADAMTS-13 activity than measured in normal controls during the chronic phase of the illness, some with activity measuring below 50% of normal levels. We also evaluated activity in two patients during acute vaso-occlusive crisis. Both patients had levels on the day of hospitalization that were indistinguishable from the levels found in patients with thrombotic thrombocytopenic purpura. Recovery of activity correlated with clinical recovery, to the point that in both cases activity was normal upon hospital discharge. We then compared superoxide generation facilitated by sickle erythrocytes with that generated by normal erythrocytes and found, as others have a significantly higher generation by sickle erythrocytes. We also found that superoxide (produced using a hypoxanthine-xanthine oxidase system) significantly decreased the activity of both plasma and recombinant ADAMTS-13 in vitro. Superoxide was also able to stimulate release of ULVWF and cell-membrane expression from cultured HUVEC. These results suggest that the enhanced production of superoxide in patients with sickle cell disease plays an important role in promoting erythrocyte adhesion to the endothelium by both stimulating release of ULVWF and inhibiting its cleavage by ADAMTS-13.

Association of Hemolysis with Clinical Manifestations of Sickle Cell Disease

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2482-2482
Author(s):  
Mehdi Nouraie ◽  
Caterina Minniti ◽  
Craig Sable ◽  
Andrew D. Campbell ◽  
Sohail R Rana ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Clinical Manifestations ◽  
Hemoglobin Concentration ◽  
Left Ventricular ◽  
P Value ◽  
Z Score ◽  
Cell Disease ◽  
History Of ◽  
Minute Walk

Abstract Background: Sickle cell disease shares common complications such as vasculopathy and organ dysfunction involving the heart, the lungs, the liver and the kidneys with other hemolytic conditions. We hypothesized that a hemolytic vasculopathy may underlie some of these complications. Distinguishing whether a complication is due to hemolysis or to the degree of anemia has been a challenge. Methods: A prospective, multicenter study of 310 children and adolescents with sickle cell disease in steady state was conducted. The associations of measures of hemolysis and of hemoglobin concentration with disease complications were assessed. Principle component analysis was used to develop a hemolytic index from the measurements of reticulocyte count, lactate dehydrogenase, aspartate aminotransfersae and total bilirubin. In order to determine the independent associations of hemolysis with the clinical manifestations of sickle cell disease, we computed correlation coefficient of the hemolytic index with these manifestations that controlled for hemoglobin concentration. P values were adjusted for multiple comparisons. Results: Hemolysis and hemoglobin had no significant correlation with number of the severe pain episodes, acute chest syndrome and priapism. The hemolytic index correlated with history of stroke (r= 0.19, p=0.026), white blood cell count (r=0.22, p&lt;0.001), tricuspid regurgitation velocity (r=0.25, p&lt;0.001), left ventricular mass index (r=0.33, 0&lt;0.001), left ventricular internal diastolic z score (r=0.30, p&lt;0.001) and hemoglobin oxygen desaturation (r=−0.30, p&lt;0.001) but not independently with platelet count and creatinine and six-minute-walk Correlation of clinical outcomes with hemolytic index and hemoglobin concentration in sickle cell cases N Hemolytic index (r and P value) Hemoglobin (r and P value) Hemolytic index adjusted for hemoglobin (partial r and P value) 1 Square roots 2Natural Log 3Adjusted for patient’s height p values are adjusted for 13 comparisons. Number of severe pain episodes in the last year 283 −0.05 (0.4) 0.06 (0.3) −0.02 (0.7) History of acute chest or pneumonia 278 0.11 (0.09) −0.63 (&lt;0.0001) 0.06 (0.3) History of priapism History of stroke 137 0.13 (0.1) −0.63 (&lt;0.0001) 0.06 (0.5) 277 0.14 (0.3) 0.003 (1.0) 0.19 (0.026) Platelet count 1 283 0.32 (&lt;0.0001) −0.35 (&lt;0.0001) 0.11 (0.07) White blood cells 2 283 0.46 (&lt;0.0001) −0.47 (&lt;0.0001) 0.22 (&lt;0.001) Creatinine 1 282 −0.34 (&lt;0.0001) 0.45 (&lt;0.0001) −0.07 (0.2) Systolic blood pressure 283 0.01 (0.8) 0.16 (0.07) 0.14 (0.2) Tricuspid regurgitant jet velocity 264 0.35 (&lt;0.0001) −0.27 (&lt;0.001) 0.25 (&lt;0.001) Left ventricular internal diastolic diameter z score 282 0.53 (&lt;0.0001) −0.50(&lt;0.001) 0.30 (&lt;0.001) Left ventricular mass index1 215 0.51 (&lt;0.0001) −0.44 (&lt;0.001) 0.33 (&lt;0.001) O2 saturation 273 −0.49 (&lt;0.0001) 0.42 (&lt;0.001) −0.30 (&lt;0.001) Six-minute-walk (m)3 228 −0.03 (0.6) 0.17 (0.1) 0.07 (0.3) Conclusion: These observations support the hypothesis that a hemolytic vasculopathy independent of the degree of anemia contributes to the pathogenesis of stroke and pulmonary hypertension and to the development of increased systemic vascular resistance. They also raise the possibility that leukocytosis may in part serve as a predictor of poor outcome by its association with hemolysis. Therapeutic interventions that reduce the rate of hemolysis need to be studied for their potential benefit in decreasing the risk and severity of vasculopathy and the resulting organ damage.

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