scholarly journals Microfluidics in Sickle Cell Disease Research: State of the Art and a Perspective Beyond the Flow Problem

2021 ◽  
Vol 7 ◽  
Author(s):  
Anupam Aich ◽  
Yann Lamarre ◽  
Daniel Pereira Sacomani ◽  
Simone Kashima ◽  
Dimas Tadeu Covas ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Flow Problem ◽  
Red Cells ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Intercellular Interaction ◽  
Blood Disorder ◽  
Resource Setting ◽  
Wide Range

Sickle cell disease (SCD) is the monogenic hemoglobinopathy where mutated sickle hemoglobin molecules polymerize to form long fibers under deoxygenated state and deform red blood cells (RBCs) into predominantly sickle form. Sickled RBCs stick to the vascular bed and obstruct blood flow in extreme conditions, leading to acute painful vaso-occlusion crises (VOCs) – the leading cause of mortality in SCD. Being a blood disorder of deformed RBCs, SCD manifests a wide-range of organ-specific clinical complications of life (in addition to chronic pain) such as stroke, acute chest syndrome (ACS) and pulmonary hypertension in the lung, nephropathy, auto-splenectomy, and splenomegaly, hand-foot syndrome, leg ulcer, stress erythropoiesis, osteonecrosis and osteoporosis. The physiological inception for VOC was initially thought to be only a fluid flow problem in microvascular space originated from increased viscosity due to aggregates of sickled RBCs; however, over the last three decades, multiple molecular and cellular mechanisms have been identified that aid the VOC in vivo. Activation of adhesion molecules in vascular endothelium and on RBC membranes, activated neutrophils and platelets, increased viscosity of the blood, and fluid physics driving sickled and deformed RBCs to the vascular wall (known as margination of flow) – all of these come together to orchestrate VOC. Microfluidic technology in sickle research was primarily adopted to benefit from mimicking the microvascular network to observe RBC flow under low oxygen conditions as models of VOC. However, over the last decade, microfluidics has evolved as a valuable tool to extract biophysical characteristics of sickle red cells, measure deformability of sickle red cells under simulated oxygen gradient and shear, drug testing, in vitro models of intercellular interaction on endothelialized or adhesion molecule-functionalized channels to understand adhesion in sickle microenvironment, characterizing biomechanics and microrheology, biomarker identification, and last but not least, for developing point-of-care diagnostic technologies for low resource setting. Several of these platforms have already demonstrated true potential to be translated from bench to bedside. Emerging microfluidics-based technologies for studying heterotypic cell–cell interactions, organ-on-chip application and drug dosage screening can be employed to sickle research field due to their wide-ranging advantages.

scholarly journals Iron Overload in Sickle Cell Disease

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Radha Raghupathy ◽  
Deepa Manwani ◽  
Jane A. Little
Keyword(s):  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Organ Damage ◽  
Endothelial Damage ◽  
Red Cells ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Treatment And Prevention ◽  
Oxygen Carrying Capacity

In sickle cell disease transfusions improve blood flow by reducing the proportion of red cells capable of forming sickle hemoglobin polymer. This limits hemolysis and the endothelial damage that result from high proportions of sickle polymer-containing red cells. Additionally, transfusions are used to increase blood oxygen carrying capacity in sickle cell patients with severe chronic anemia or with severe anemic episodes. Transfusion is well-defined as prophylaxis (stroke) and as therapy (acute chest syndrome and stroke) for major complications of sickle cell disease and has been instituted, based on less conclusive data, for a range of additional complications, such as priapism, vaso-occlusive crises, leg ulcers, pulmonary hypertension, and during complicated pregnancies. The major and unavoidable complication of transfusions in sickle cell disease is iron overload. This paper provides an overview of normal iron metabolism, iron overload in transfused patients with sickle cell disease, patterns of end organ damage, diagnosis, treatment, and prevention of iron overload.

Hemoglobin F or: How I Learned to Stop Wondering and Love the Flow Cytometer

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S15-S16
Author(s):  
Roger Fecher ◽  
Jui Choudhuri ◽  
Mohammad Barouqa ◽  
Seda Tolu ◽  
Caterina Minniti ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
The United States ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Hemoglobin F ◽  
Blood Disorder ◽  
Cellular Concentration ◽  
Hbf Level

Abstract Sickle cell disease (SCD) is the most common inherited blood disorder in the United States. It is a hemoglobinopathy that leads to red blood cell (RBC) sickling and a broad range of disease complications including vaso-occlusive crisis, acute chest syndrome, and retinopathy. Hydroxyurea, a drug used to treat SCD, is known to increase expression of hemoglobin F (HbF), a type of hemoglobin normally expressed in infancy; HbF levels between 10% and 20% are associated with decreased vaso-occlusive episodes and improved survival. Hereditary persistent hemoglobin F (HPHF), a typically asymptomatic hemoglobinopathy associated with sustained hemoglobin F (HbF) expression into adulthood (HbF >10%), in combination with SCD is associated with decreased complications. Laboratories typically determine the HbF level via high-performance liquid chromatography (HPLC). HbF levels approaching 30% on HPLC are thought to be protective against SCD complications. However, HbF may be found within a majority or minority of RBCs, pancellular (deletional HPHF) or heterocellular distribution (nondeletional HPHF), respectively. Additionally, the quantity of HbF within cells can range from low (<10 picograms/cell) to high (>35 picograms). We sought to determine the quantity and distribution of HbF required to protect against sickle cell disease symptoms both via traditional HPLC as well as flow cytometry. This retrospective study was conducted at a large academic medical center over a period of 2 months (January-February 2019). We collected blood from sickle cell patients that had a detectable HbF level on hemoglobin electrophoresis. We then stained RBCs from 16 of the patients for HbF and performed flow cytometry to examine the HbF distribution. We calculated the cellular concentration of HbF within each HbF+ cell using the formula (MHC × %HbF)/%F-cells. We performed a chart review to determine the native hemoglobin type, exposure to hydroxyurea, and clinical symptoms of sickle cell disease. We identified four patients over the age of 20 with HbS/HPHP and no exposure to hydroxyurea. Two of these patients experienced no sickle cell disease complications; the protected patients had heterocellular distribution of HbF, but had a high concentration of HbF per HbF+ cell (>35 picograms/cell). Notably, these asymptomatic patients both had HbF level by HPLC less than 30. One of the symptomatic HbS/HPHF patients had heterocellular expression of HbF with low cellular concentration (28 picograms/cell) while the other patient had pancellular HbF expression with very low cellular concentration (6.4 picograms/cell). Our study demonstrates that HPHF alone does not prevent sickle cell disease complications. Our study highlights the importance of quantifying the cellular concentration of HbF, which can provide useful information beyond that of HPLC. In addition, our study raises the potential of the clinical use of hydroxyurea in patients with sickle cell disease even in the presence of HPHF.

scholarly journals Efficacy and Safety of Manual Partial Red Cell Exchange in the Management of Severe Complications of Sickle Cell Disease in a Developing Country

2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
B. F. Faye ◽  
D. Sow ◽  
M. Seck ◽  
N. Dieng ◽  
S. A. Toure ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Blood Count ◽  
Acute Chest Syndrome ◽  
Red Cell ◽  
Efficacy And Safety ◽  
Cell Disease ◽  
Resource Setting ◽  
Low Resource Setting ◽  
The Mean

Introduction. The realization of red cell exchange (RCE) in Africa faces the lack of blood, transfusion safety, and equipment. We evaluated its efficacy and safety in severe complications of sickle cell disease. Patients and Method. Manual partial RCE was performed among sickle cell patients who had severe complications. Efficacy was evaluated by clinical evolution, blood count, and electrophoresis of hemoglobin. Safety was evaluated on adverse effects, infections, and alloimmunization. Results. We performed 166 partial RCE among 44 patients including 41 homozygous (SS) and 2 heterozygous composites SC and 1 S/β0-thalassemia. The mean age was 27.9 years. The sex ratio was 1.58. The regression of symptoms was complete in 100% of persistent vasoocclusive crisis and acute chest syndrome, 56.7% of intermittent priapism, and 30% of stroke. It was partial in 100% of leg ulcers and null in acute priapism. The mean variations of hemoglobin and hematocrit rate after one procedure were, respectively, +1.4 g/dL and +4.4%. That of hemoglobin S after 2 consecutive RCE was −60%. Neither alloimmunization nor viral seroconversion was observed. Conclusion. This work shows the feasibility of manual partial RCE in a low-resource setting and its efficacy and safety during complications of SCD outside of acute priapism.

scholarly journals Blood Transfusion Frequency and Indications in Yemeni Children with Sickle Cell Disease

Anemia ◽  
2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Abdul-Wahab M. Al-Saqladi ◽  
Dikra M. Maddi ◽  
Aida H. Al-Sadeeq
Keyword(s):  
Sickle Cell Disease ◽  
Blood Transfusion ◽  
Sickle Cell ◽  
Hospital Admissions ◽  
Limited Resource ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
Female Ratio ◽  
Resource Setting

Background. Blood transfusion is an essential component in the care of patients with sickle cell disease (SCD), but it might be associated with serious acute and delayed complications. This study was aimed to describe red cell transfusion patterns and indications among hospitalized SCD children in a low-resource setting. Patients and Methods. A retrospective, descriptive study of all children (≤16 years) with SCD who received blood transfusion therapy during their hospital admissions in the pediatric department at Al-Sadaqa Teaching Hospital in Aden, Yemen, for a period of one year. Results. Out of 217 hospitalized children with SCD, 169 (77.9%) were transfused and received 275 RBC transfusion episodes. The mean age of transfused children was 6.9 ± 4.6 years and 103 (60.9%) were males, with a male/female ratio of 1.6 : 1 (p=0.004). Hemoglobin (Hb) levels were significantly lower in the transfused than in the nontransfused (Hb 5.5 ± 1.5 vs. 7.7 ± 1.5 g/dL, p=0.03). Pretransfusion Hb levels were ˂7.0 g/dL in 86.2% and ˂5.0 g/dL in 39.3% of patients. Single transfusion was given to 122 (72.2%) and 5 or more transfusions in 9 (4.15%) of patients on different occasions. Simple (top-up) transfusion was used in all transfusion events. Commonest indications for transfusion were anemic crises (41.1%), vasoocclusive crises (VOC) (13.8%), VOC with anemic event (11.3%), acute chest syndrome (8.7%), and stroke (7.3%). Conclusion. Intermittent blood transfusion remains a common practice for the management of children with acute SCD complications. Main indications were acute anemic crises, severe pain crises, ACS, and stroke. In limited resource settings, such as Yemen, conservative transfusion policy appears to be appropriate.

Polymorphisms (Snps) in Multiple Genes of the Tgf-ß/Bmp Pathway Are Associated with a Global Measure of Sickle Cell Disease Severity.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 74-74
Author(s):  
Paola Sebastiani ◽  
Clinton T. Baldwin ◽  
Vikki Nolan ◽  
Diego F. Wyszynski ◽  
Qian-Li Ma ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Disease Severity ◽  
Sickle Cell ◽  
Early Death ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Bmp Receptors ◽  
Wide Range ◽  
Bmp Pathway ◽  
Laboratory Variables

Abstract A global estimation of sickle cell disease severity has been difficult to establish making the integration of clinical and laboratory abnormalities of into a predictive model of disease complications and death, an unrealized goal. A useful model might help us to understand the interactions among common clinical and laboratory abnormalities and allow patients at risk of certain complications and early death to be identified early so that targeted treatment, if available, could be provided. To approach this problem we first integrated clinical and laboratory data from nearly 3500 individuals from the Cooperative Study of Sickle Cell Disease and applied to this data advanced statistical machine learning techniques to identify the significant associations between selected complications of disease and laboratory variables. We looked for predictors of the risk for early death in three separate age groups. The resulting model revealed that complex networks of interactions between clinical and laboratory variables underlie common disease complications and ultimately death. Predictors of risk in this model were the HBA1, HBA2 genotype, stroke, sepsis and acute chest syndrome. While this model can predict the risk for early death, given the presence of other disease complications and variations among common laboratory variables, it did not provide an understanding of the genetic basis for our observations. Accordingly, in over 1000 patients with sickle cell disease we genotyped SNPs in genes chosen because of their possible link to the pathophysiology of disease. We then used our estimate of global disease severity to find associations of genotypes with severity. In the initial screening studies we identified several genes in the TGF-ß/BMP pathway that were associated with selected disease subphenotypes (Sebastiani et al Nature Genet37: 435, 2005; Baldwin et al. Blood106: 372, 2005). The TGF-b/BMP pathway regulates a wide range of biological functions including cell proliferation, cellular differentiation, extracellular matrix production, cell death, tissue repair and immune regulation. To expand our initial findings, we typed haplotype tagging SNPS in a more comprehensive fashion in 21 genes that are key members of this pathway. The genes included BMP6, BMP receptors, TGF-b receptors, SMADs, MAP kinases and their associated co-factors such as SARA, CDH1 and SMURF1. We used a Bayesian significance test to model the associations between the score of disease severity and individual SNPs, as well as a traditional association test with p-values computed using permutation tests. To reduce the problem of multiple comparisons, we selected as significantly associated with disease severity, only those SNPs that passed both tests with strong evidence of association. The most striking associations were found for BMP6, its receptors BMPR1 and BMPR2, several SMAD proteins and SARA1. Our results confirm the importance of the TGF-ß signaling pathway in sickle cell disease pathophysiology and suggest that subtle variation in this cell signaling network can be associated with the severity of disease.

scholarly journals Crisis in Sickle Cell Disease: Review Article

2021 ◽  
pp. 679-685
Author(s):  
Syed Athhar Saqqaf ◽  
Rajendra Borkar
Keyword(s):  
Sickle Cell Disease ◽  
Red Blood Cells ◽  
Sickle Cell ◽  
Blood Cells ◽  
Well Being ◽  
Review Article ◽  
The Body ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Wide Range

Sickle cell disease is a very common inherited disorder of the hemoglobin. It is inherited in an autosomal recessive manner. Most affected are the people of African, Indian and Arabian origin. It occurs due to change in the single base pair gene wherein thymine replaces adenine in the 6th codon of the beta-globin gene. This result in the sickling shape of the red blood cells. Sickle cell disease includes a variety of phenotypes like the SS, AS, Sickle-thal, SC patterns, etc. Sickle cell- SS pattern also termed as sickle cell anemia is the most common of form of the disorder and is also responsible for the morbidity and mortality caused by the disorder. The sickling pattern of the red blood cells occludes the blood vessels and leads to a wide range of complication in the affected individuals. These complications can be seen in number of different systems of the body and also multiple systems at the same time. These complications are termed as crisis, which then include the vaso-occlusive crisis, acute chest syndrome, splenic sequestration crisis, etc. These crises can negatively affect the quality of life to a large effect, but are also largely controllable or rather delayed and effectively managed as far as possible with reduced effect in the normal well being. Hence the knowledge about these crisis and their treatment is an important aspect of medical practice, especially in the countries where this disorder is commonly seen. Here in this review article we aim to highlight the major crises seen in sickle cell disease and their treatment in brief.

scholarly journals ECMO Therapy in Acute Chest Syndrome for Patients with Sickle Cell Disease: a Case Report and Literature Review

2021 ◽  
Author(s):  
Soi Avgeridou ◽  
Ilija Djordjevic ◽  
Anton Sabashnikov ◽  
Kaveh Eghbalzadeh ◽  
Laura Suhr ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Scientific Data ◽  
Acute Chest Syndrome ◽  
Data Sets ◽  
Limited Data ◽  
Cell Disease ◽  
Life Saving ◽  
Institutional Experience ◽  
Ecmo Therapy

AbstractExtracorporeal membrane oxygenation (ECMO) plays an important role as a life-saving tool for patients with therapy-refractory cardio-respiratory failure. Especially, for rare and infrequent indications, scientific data is scarce. The conducted paper focuses primarily on our institutional experience with a 19-year-old patient suffering an acute chest syndrome, a pathognomonic pulmonary condition presented by patients with sickle cell disease. After implementation of awake ECMO therapy, the patient was successfully weaned off support and discharged home 22 days after initiation of the extracorporeal circulation. In addition to limited data and current literature, further and larger data sets are necessary to determine the outcome after ECMO therapy for this rare indication.

scholarly journals Streptococcus pneumoniae and Its Virulence Factors H2O2 and Pneumolysin Are Potent Mediators of the Acute Chest Syndrome in Sickle Cell Disease

Toxins ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 157
Author(s):  
Joyce Gonzales ◽  
Trinad Chakraborty ◽  
Maritza Romero ◽  
Mobarak Abu Mraheil ◽  
Abdullah Kutlar ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Sickle Cell Disease ◽  
Virulence Factors ◽  
Sickle Cell ◽  
Biological Activities ◽  
Acute Chest Syndrome ◽  
Antibiotics Resistance ◽  
Cell Disease ◽  
Antibiotic Drug ◽  
Tract Infections

Sickle cell disease (SCD) is one of the most common autosomal recessive disorders in the world. Due to functional asplenia, a dysfunctional antibody response, antibiotic drug resistance and poor response to immunization, SCD patients have impaired immunity. A leading cause of hospitalization and death in SCD patients is the acute chest syndrome (ACS). This complication is especially manifested upon infection of SCD patients with Streptococcus pneumoniae (Spn)—a facultative anaerobic Gram-positive bacterium that causes lower respiratory tract infections. Spn has developed increased rates of antibiotics resistance and is particularly virulent in SCD patients. The primary defense against Spn is the generation of reactive oxygen species (ROS) during the oxidative burst of neutrophils and macrophages. Paradoxically, Spn itself produces high levels of the ROS hydrogen peroxide (H2O2) as a virulence strategy. Apart from H2O2, Spn also secretes another virulence factor, i.e., the pore-forming exotoxin pneumolysin (PLY), a potent mediator of lung injury in patients with pneumonia in general and particularly in those with SCD. PLY is released early on in infection either by autolysis or bacterial lysis following the treatment with antibiotics and has a broad range of biological activities. This review will discuss recent findings on the role of pneumococci in ACS pathogenesis and on strategies to counteract the devastating effects of its virulence factors on the lungs in SCD patients.

scholarly journals To Give or Not to Give: RhD Immunoglobulin for an RHD*39 Pregnant Woman with Sickle Cell Disease

2021 ◽  
pp. 1-5
Author(s):  
Justin E. Juskewitch ◽  
Craig D. Tauscher ◽  
Sheila K. Moldenhauer ◽  
Jennifer E. Schieber ◽  
Eapen K. Jacob ◽  
...  
Keyword(s):  
Pregnant Woman ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Pregnancy Termination ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Childbearing Age ◽  
Procedural Complications ◽  
History Of ◽  
Chronic Hemolysis

Introduction: Patients with sickle cell disease (SCD) have repeated episodes of red blood cell (RBC) sickling and microvascular occlusion that manifest as pain crises, acute chest syndrome, and chronic hemolysis. These clinical sequelae usually increase during pregnancy. Given the racial distribution of SCD, patients with SCD are also more likely to have rarer RBC antigen genotypes than RBC donor populations. We present the management and clinical outcome of a 21-year-old pregnant woman with SCD and an RHD*39 (RhD[S103P], G-negative) variant. Case Presentation: Ms. S is B positive with a reported history of anti-D, anti-C, and anti-E alloantibodies (anti-G testing unknown). Genetic testing revealed both an RHD*39 and homozygous partial RHCE*ceVS.02 genotype. Absorption/elution testing confirmed the presence of anti-G, anti-C, and anti-E alloantibodies but could not definitively determine the presence/absence of an anti-D alloantibody. Ms. S desired to undergo elective pregnancy termination and the need for postprocedural RhD immunoglobulin (RhIG) was posed. Given that only the G antigen site is changed in an RHD*39 genotype and the potential risk of RhIG triggering a hyperhemolytic episode in an SCD patient, RhIG was not administered. There were no procedural complications. Follow-up testing at 10 weeks showed no increase in RBC alloantibody strength. Discussion/Conclusion: Ms. S represents a rare RHD*39 and partial RHCE*ceVS.02 genotype which did not further alloimmunize in the absence of RhIG administration. Her case also highlights the importance of routine anti-G alloantibody testing in women of childbearing age with apparent anti-D and anti-C alloantibodies.

Acute chest syndrome in children with sickle cell disease

1995 ◽  
Vol 62 (2) ◽  
pp. 201-205 ◽  
Author(s):  
H. A. Srair ◽  
J. A. Owa ◽  
H. A. Aman ◽  
M. A. Madan
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Acute Chest Syndrome ◽  
Cell Disease
Sign in / Sign up

Export Citation Format

Share Document