Sickle Cell Genetic Markers: Geographic Distribution and Relation to Pain Outcomes in Multicenter Study of Hydroxyurea in Sickle Cell Anemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2582-2582 ◽  
Author(s):  
Samir K. Ballas ◽  
William F. McCarthy ◽  
Robert L Bauserman ◽  
Oswaldo L Castro ◽  
Myron A Waclawiw ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Genetic Markers ◽  
Sickle Cell ◽  
Multicenter Study ◽  
Globin Genes ◽  
Cell Disease ◽  
X Linkage ◽  
Medical Visits ◽  
Pain Outcomes ◽  
At Home

Abstract Abstract 2582 Poster Board II-559 Introduction: Genetic markers related to the severity of outcomes in sickle cell disease include β-globin cluster haplotypes; X-chromosome-linked F-cell production loci; and the number of α-globin genes. Patients in the Multicenter Study of Hydroxyurea (MSH), a randomized, double-blind, placebo-controlled trial of hydroxyurea (HU) treatment in sickle cell anemia, provided samples for genotyping. We examined the relationship between these markers and demographic characteristics; geographic distribution across MSH sites; HU treatment response; and pain outcomes including rate of painful crises; pain intensity; frequency of pain at home; frequency of at-home analgesic usage; frequency of medical contacts; and equianalgesic dosing at home and during hospital contacts. Patients and Methods: Subjects were n=299 patients enrolled in MSH. Patients came from 21 sites across 14 U.S. states and 1 Canadian province, with 5 to 57 enrolled at each site. The sample was almost equally males and females, ages 18 to 57 (with an average of 30) at entry, with a minimum of 3 painful crises in the previous year and a diagnosis of sickle cellanemia.Genetic markers examined were β-goblin haplotype (Central African Republic/CAR, Benin/BEN, Sengal /SEN, Cameroon /CAM, and atypical), X-linked loci, and α-globin genes. Patients kept two-week diaries in which they recorded daily pain levels on a 0-9 scale; whether or not they used opioids that day; and whether or not any unscheduled medical contacts took place. The use of specific opioids and the doses taken were recorded by providers at biweekly follow-up visits and also during medical contacts; these were converted into equianalgesic doses, which were used to obtain total and average daily doses for the two-week follow-ups and average daily doses for those medical contacts involving ER utilization or in-patient admission. Fetal hemoglobin (Hb F) was measured at baseline and again at 18-21 months after treatment initiation; ‘responders' were defined as patients with Hb F levels below 15% at baseline but above 15% at 18-21 months (the 15% level was selected based on prior research and treatment recommendations). Results: The only sex difference found in relation to genetic markers was higher values for x-linkage in females (p=.002). Geographically, sites were clustered into 2 regions (Northern/Southern) based on climate. The number of α-globin genes was higher in Northern sites than Southern (p=.039); β-haplotypes and X-linkage did not differ across regions.HU treatment responders, shown elsewhere to have better outcomes in terms of painful crisis rates and other pain variables, differed significantly from nonresponders only in X-linkage (p=.006), with stronger X-linkage associated with being a responder. For pain outcomes, there were no significant relationships between β-haplotypes or α-globin genes and rate of painful crises, average pain scores at home, the frequency of days with pain, days with analgesic use, or unscheduled medical visits. X-linkage was marginally (p=.06) associated with medical visits; stronger x-linkage was associated with fewer medical visits. For equianalgesic dosing, significant associations were found with α-globin genes and the CAM haplotype. More α-globin genes were associated were lower at-home total and daily dosing and with lower daily doses of both oral and parenteral analgesics in hospital; however, further exploration by sex indicated that all of these associations were significant for males only (all p's<.05 for males, >.05 for females). The presence of the CAM haplotype was associated with higher in-hospital oral and parenteral dosing and higher at-home total and daily dosing, but all associations were again significant for males only (p's<.05). Conclusions: Some genetic markers known to play a role in sickle cell disease were associated with classification as a treatment responder, pain-related outcomes, and equianalgesic dosing in the MSH cohort. However, when examined by sex, associations with equianalgesic dosing were statistically significant for males only. There is a need for further in-depth exploration of the role that genetic markers play in sickle cell pain outcomes, and in particular examination of possible sex differences and testing of potential explanations for those differences. Disclosures: No relevant conflicts of interest to declare.

The Effect of Sickle Cell Genetic Markers on Geographic Distribution and Relation to Pain Outcomes in the Multicenter Study of Hydroxyurea in Sickle Cell Anemia

2011 ◽  
Vol 07 (01) ◽  
pp. 64
Author(s):  
Samir K Ballas ◽  
Robert L Bauserman ◽  
William F McCarthy ◽  
Myron A Waclawiw ◽  
◽  
...  
Keyword(s):  
Genetic Markers ◽  
Sickle Cell ◽  
Multicenter Study ◽  
Fetal Hemoglobin ◽  
Hemoglobin Level ◽  
Future Research ◽  
Cell Disease ◽  
Pain Outcomes ◽  
Treatment Responder ◽  
Fetal Hemoglobin Level

Some genetic markers known to play a role in sickle cell disease were associated with classification as a treatment responder, pain-related outcomes, and equi-analgesic dosing in the Multicenter Study of Hydroxurea (MSH) cohort. However, when examined by sex, associations with equi-analgesic dosing were statistically significant for males only. Factors that increase the hemoglobin/hematocrit levels seem not to be beneficial. Future research should focus on factors that increase fetal hemoglobin level.

scholarly journals Engineering, Generation and Preliminary Characterization of a Humanized Porcine Sickle Cell Disease Animal Model

2020 ◽  
Author(s):  
Tobias M. Franks ◽  
Sharie J. Haugabook ◽  
Elizabeth A. Ottinger ◽  
Meghan S. Vermillion ◽  
Kevin M. Pawlik ◽  
...  
Keyword(s):  
Animal Model ◽  
Sickle Cell Disease ◽  
Mouse Models ◽  
Sickle Cell ◽  
Cell Model ◽  
Globin Genes ◽  
Cell Disease ◽  
Small Vessels

AbstractMouse models of sickle cell disease (SCD) that faithfully switch from fetal to adult hemoglobin (Hb) have been important research tools that accelerated advancement towards treatments and cures for SCD. Red blood cells (RBCs) in these animals sickled in vivo, occluded small vessels in many organs and resulted in severe anemia like in human patients. SCD mouse models have been valuable in advancing clinical translation of some therapeutics and providing a better understanding of the pathophysiology of SCD. However, mouse models vary greatly from humans in their anatomy and physiology and therefore have limited application for certain translational efforts to transition from the bench to bedside. These differences create the need for a higher order animal model to continue the advancement of efforts in not only understanding relevant underlying pathophysiology, but also the translational aspects necessary for the development of better therapeutics to treat or cure SCD. Here we describe the development of a humanized porcine sickle cell model that like the SCD mice, expresses human ɑ-, β− and γ-globin genes under the control of the respective endogenous porcine locus control regions (LCR). We also describe our initial characterization of the SCD pigs and plans to make this model available to the broader research community.

scholarly journals COVID Symptoms and COVID Anxiety in Sickle Cell Disease

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 16-17
Author(s):  
Wally R Smith ◽  
Benjamin Jaworowski ◽  
Shirley Johnson ◽  
Thokozeni Lipato ◽  
Daniel M Sop
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Research Funding ◽  
Telephone Survey ◽  
Cell Disease ◽  
Weighted Mean ◽  
The Us ◽  
Associated Symptoms ◽  
At Home

Background Even before the US upswing of the current COVID pandemic, the number of sickle cell disease (SCD) patients coming to hospitals and EDs appeared to fall drastically. This happened despite SCD patients having often been heavy utilizers of the ED and hospital for their iconic vaso-occlusive crises (VOC). Though ambulatory SCD clinics quick converted largely to telehealth in order to comply with stay-at-home orders designed to suppress person-to-person transmission, some SCD patients appeared to avoid care, delay care, or refuse doctors' invitations for care. Presumably patients did so out of COVID fears, but this has not been confirmed in the literature. Further, whether these patients had COVID symptoms but stayed at home has not been studied. As part of quality improvement (QI) to conduct COVID surveillance in an adult sickle cell program, we sought to explain and predict SCD health care utilization patterns we were observing, as well as to determine urgent physical and mental health needs of patients who appeared to be avoiding care. Methods Fifteen staff in the Adult Sickle Cell Medical Home at Virginia Commonwealth University, a large urban academic medical center, conducted a telephone survey ("wellness check"was used when we talked to patients) of all known adults with SCD over 19 days in 2020. A staff member confirmed the patient had SCD, asked permission to proceed, then asked about symptoms consistent with COVID-19. At the end of the telephone survey, respondents wer invited to complete an email survey of sickle cell and COVID-19 utilization attitudes (19-33 items, depending on the response pattern, either drawn from the National Health Interview Survey, from the Adult Sickle Cell Quality of Life Measurement quality of care survey, or drafted by the authors), the Sickle Cell Stress Survey-Adult (SCSS-A, a 10-item previously validated survey), and anxiety and depression (PHQ9 of the PRIME-MD). Results Of 622 adults approached by phone call, 353 responded to the following yes/no screening questions regarding the prior 14 days: fever over 100 F 0/353 (0.00%); cough 3/353(0.01%); difficulty breathing 0/353(0.00%); unexplained shortness of breath 2/353(0.01%); sore throat 2/353 (0.01%); unexplained muscle soreness 2/353(0.01%);contact with anyone who tested positive for COVID-19 2/353(0.01%); testing for COVID 19 6/353(0.02%). For QI purposes, we set a threshold of three or more COVID-associated symptoms or the presence of fever as criteria requiring intense telephone or in-person staff monitoring for the following week. Only three patients met criteria. A total of 219/353 had email surveys sent. Of 63 patients (28.8%) who returned email surveys by June 10, 2020, 35.9% had already managed a "pain attack" at home 4 or more times in the prior 12 months, and 45.5% of these said their bad ER experiences were very or somewhat important in that decision. In the prior 14 days, although 30/64 reported a crisis for at least one day, only 4/64 had visited the Emergency Department for pain. On a 0-10 scale, 21/61 patients endorsed "0" for worry that they would be COVID-infected by going for medical care (weighted mean 3.9), but 18/59 endorsed "10" for worry they were more at risk of COVID because of SCD (weighted mean 6.31), and 22/60 endorsed "10" for worry they would fare worse than others if COVID infected (weighted mean 6.97). Many patients forwent "needed" care (16/62) or delayed "needed" care by at least a day (36/61). Eleven patients met criteria for moderately severe to severe depression on the PHQ-9, and 28/63 somewhat or strongly agreed with the statement "death is always on the back of my mind" on the SCSS-A. Conclusions In adolescents and adults with SCD, many were already reticent to come to the ED for pain, but a significant portion reported delays or avoidance of needed care during the early stages of the US COVID pandemic, and few reported using the ED despite over half reporting at least one crisis day in 14. Patients nonetheless reported very few COVID-associated symptoms. Fears of COVID infection/susceptibility may limit visits for needed sickle cell care among adults. Acknowledgements: Mica Ferlis RN, FNP, Caitlin McManus, RN, FNP, Emily Sushko, RN, FNP, Justin West, RN, Kate Osborne, RN, Stefani Vaughan-Sams, Marla Brannon, BS, Nakeiya Williams, BS Disclosures Smith: GlycoMimetics, Inc.: Consultancy; Emmaeus Pharmaceuticals, Inc.: Consultancy; Novartis, Inc.: Consultancy, Other: Investigator, Research Funding; Global Blood Therapeutics, Inc.: Consultancy, Research Funding; Shire, Inc.: Other: Investigator, Research Funding; NHLBI: Research Funding; Patient-Centered Outcomes Research Institute: Other: Investigator, Research Funding; Health Resources and Services Administration: Other: Investigator, Research Funding; Incyte: Other: Investigator; Pfizer: Consultancy; Ironwood: Consultancy; Novo Nordisk: Consultancy; Imara: Research Funding; Shire: Research Funding.

Haemoglobinopathies

2013 ◽  
pp. 1466-1470
Author(s):  
David Rees
Keyword(s):  
Bone Marrow ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Lupus Erythematosus ◽  
Single Gene ◽  
Globin Genes ◽  
Globin Chain ◽  
Cell Disease ◽  
Chain Synthesis ◽  
Marrow Expansion

Inherited abnormalities of the globin genes are the commonest single-gene disorders in the world and fall into two main groups: thalassaemias and sickle cell disease. Thalassaemias are due to quantitative defects in globin chain synthesis which cause variable anaemia and ineffective erythropoiesis. Thalassaemia was initially thought to be a disease of the bones due to uncontrolled bone marrow expansion causing bony distortion, although this is now unusual with appropriate blood transfusions. Osteopenia, often severe, is a feature of most patients with thalassaemia major and intermedia, caused by bone marrow expansion, iron overload, endocrinopathy, and iron chelation. Treatment with bisphosphonates is generally recommended. Other rheumatological manifestations include arthropathy associated with the use of the iron chelator deferiprone. Sickle cell disease involves a group of conditions caused by polymerization of the abnormal -globin chain, resulting in abnormal erythrocytes which cause vaso-occlusion, vasculopathy, and ischaemic tissue damage. The characteristic symptom is acute bone pain caused by vaso-occlusion; typical episodes require treatment with opiate analgesia and resolve spontaneously by 5 days with no lasting bone damage. The frequency of acute episodes varies widely between patients. The incidence of osteomyelitis is increased, particularly with salmonella, although it is much rarer than acute vaso-occlusion. Avascular necrosis can affect the hips, and less commonly the shoulders and knees. Coincidental rheumatological disease sometimes complicates the condition, particularly systemic lupus erythematosus (SLE) which is more prevalent in populations at increased risk of sickle cell disease.

Haemoglobinopathies

2013 ◽  
Author(s):  
David Rees
Keyword(s):  
Bone Marrow ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Lupus Erythematosus ◽  
Single Gene ◽  
Globin Genes ◽  
Globin Chain ◽  
Cell Disease ◽  
Increased Risk ◽  
Marrow Expansion

Inherited abnormalities of the globin genes are the commonest single-gene disorders in the world and fall into two main groups: thalassaemias and sickle cell disease. Thalassaemias are due to quantitative defects in globin chain synthesis which cause variable anaemia and ineffective erythropoiesis. Thalassaemia was initially thought to be a disease of the bones due to uncontrolled bone marrow expansion causing bony distortion, although this is now unusual with appropriate blood transfusions. Osteopenia, often severe, is a feature of most patients with thalassaemia major and intermedia, caused by bone marrow expansion, iron overload, endocrinopathy, and iron chelation. Treatment with bisphosphonates is generally recommended. Other rheumatological manifestations include arthropathy associated with the use of the iron chelator deferiprone. Sickle cell disease involves a group of conditions caused by polymerization of the abnormal -globin chain, resulting in abnormal erythrocytes which cause vaso-occlusion, vasculopathy, and ischaemic tissue damage. The characteristic symptom is acute bone pain caused by vaso-occlusion; typical episodes require treatment with opiate analgesia and resolve spontaneously by 5 days with no lasting bone damage. The frequency of acute episodes varies widely between patients. The incidence of osteomyelitis is increased, particularly with salmonella, although it is much rarer than acute vaso-occlusion. Avascular necrosis can affect the hips, and less commonly the shoulders and knees. Coincidental rheumatological disease sometimes complicates the condition, particularly systemic lupus erythematosus (SLE) which is more prevalent in populations at increased risk of sickle cell disease.

French-Brazilian Survey On Pregnancy in Sickle Cell Disease A Study of the International Sickle Cell Disease Observatory

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3215-3215
Author(s):  
Jean-Antoine Ribeil ◽  
Patrícia Santos Ressende Cardoso ◽  
Aurelie Stanislas ◽  
Vanessa Maria Fenelon Costa ◽  
Benjamin Deloison ◽  
...  
Keyword(s):  
High Risk ◽  
Sickle Cell Disease ◽  
Caesarean Section ◽  
Pregnant Women ◽  
Sickle Cell ◽  
Infectious Complications ◽  
Transfusion Reaction ◽  
Cell Disease ◽  
Foetal Death ◽  
At Home

Abstract Abstract 3215 Introduction: The International Sickle Cell Disease Observatory (ISCDO) is an international group, established in 2011, including representatives from countries where sickle cell disease (SCD) is highly prevalent, in order to collect and share information of SCD patient's to improve patients care and quality of life, to define common guidelines, to develop advanced targeted approaches and transfer innovative practices worldwide. One of the first ISCDO study is a survey of pregnancy in SCD in France and Brazil. Context: Pregnancy in SCD has been associated with complications and adverse outcomes with an increased incidence of vaso-occlusive, infectious, obstetrical and neonatal complications. Recently, in Paris (France) and Belo Horizonte (BH) (Brazil), integrated care sickle-obstetric units were created, associating sickle cell haematologist, obstetrician and infectious disease specialists, experienced in the care of these high risk pregnancies. Our aim is to compare in two different geographic institutions the prognostic and evolution of SCD in pregnant women with the prospective goal to build up a clinical score in order to better determine appropriate treatment. Methods: We conducted a retrospective study on 253 pregnancies (120 Paris, 133 BH) characterized by 147 Hb SS, 91 Hb SC, 14 Hb SBeta, 2 Hb SD hemoglobinopathy. An e-crf was developed, to screen: the pre-pregnancy, the ante-partum rates of SCD-specific and infectious complications. We compared the obstetrical and the newborns health parameters and complications, the rate of Caesarean section, the perinatal and the maternal mortality in both countries. Results and Discussion: In both populations, 60% of women had a maternal age between 21–30 years old (yo). However, in Brazil there was a higher rate of young pregnant women (14–20 yo) (4% Paris; 20% BH) while in France, patients were older (>31 yo) (36% Paris; 18% BH). In the history of SCD women followed in Paris we noticed that: -Most of these patients had a severe form of SCD with 53% who had experienced an acute chest syndrome and 9% with a symptomatic cerebral vasculopathy, several infectious complications with 26% of pyelonephritis, -A high level of obstetrical complications with 35% of miscarriage and 10% of intrauterine foetal death. The patients followed in Paris during their pregnancy, were treated according to the French guidelines published in 2009. According to these guidelines 67% of patients were transfused and 17% patients were not transfused because of a post-transfusion reaction history. Caesarean section was performed in most cases in both populations (79% in Paris with 23% performed in emergency; 66% in BH). In both populations, there was 1 materno-foetal death. Furthermore, in BH, 15 perinatal deaths and 7 patient deaths were observed. In the Paris' group, there was no other perinatal death and 1 maternal death following a post-transfusional reaction after delivery. The key difference between the 2 study groups concerns the foetal/neonatal morbidity and mortality. These results lead us to compare the 2 health care structures to try to find out the medical guidelines to significantly reduce the frequency of these severe clinical events. In Paris, we introduce oxygenotherapy at home during pregnancy (2l/min) in patients who were transfused because of severe SCD symptomatology (33 patients) and who could not anymore be transfused because of a severe post-transfusion reaction history (11 patients). For these subgroups of patients, we found that 40% of them didn't experience any VOC complications, or preeclampsia. The introduction of oxygenotherapy at home during pregnancy might have a positive impact in reducing the occurrence of a number life threatening complications in these high risk pregnant woman especially when they cannot be appropriately transfused. This study is the first initial step of an international effort by the ISCDO to optimise the treatment of SCD pregnant women, to harmonize the guidelines in different countries and develop new methods of diagnosis and treatment. By improving care and the sharing knowledge of these pregnancies, we would like to increase worldwide access to the development of directed family cord blood banks in families with SCD and the access to hematopoietic stem cell transplant and other innovative therapies in developing and emerging countries where SCD is highly prevalent. Disclosures: No relevant conflicts of interest to declare.

Risky Behavior in Teens With Cystic Fibrosis or Sickle Cell Disease: A Multicenter Study

PEDIATRICS ◽  
1998 ◽  
Vol 101 (2) ◽  
pp. 250-256 ◽  
Author(s):  
M. T. Britto ◽  
J. M. Garrett ◽  
M. A. J. Dugliss ◽  
C. W. Daeschner Jr ◽  
C. A. Johnson ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Multicenter Study ◽  
Risky Behavior ◽  
Cell Disease

scholarly journals The Relationship between Mental Health, Educational Attainment, Employment Outcomes, and Pain in Sickle Cell Disease

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 419-419
Author(s):  
Kelly M Harris ◽  
Taniya Varughese ◽  
Anna Bauer ◽  
Seth Howdeshell ◽  
Cecelia Calhoun ◽  
...  
Keyword(s):  
Mental Health ◽  
Sickle Cell Disease ◽  
Educational Attainment ◽  
Sickle Cell ◽  
Employment Status ◽  
Severe Pain ◽  
Cell Disease ◽  
Annual Household Income ◽  
Significant Relationships ◽  
Pain Outcomes

Sickle cell disease (SCD) is the most common genetic condition in the world and disproportionately affects African Americans in families with lower household incomes. SCD is characterized by a variety of complications including episodes of severe pain, chronic anemia, and end-organ damage. Morbidity from SCD begins in infancy and increases in frequency and severity with age. Complications during childhood and adolescence, both critical learning periods for youth, substantially impact educational attainment and life outcomes. SCD-related hospitalizations are associated with social determinants of health, such as socioeconomic status (SES), depression, health literacy, and educational outcomes. In youth with SCD, family and neighborhood SES are predictors of pain level, pain frequency, and overall quality of life. In addition to the physiological impacts of SCD, individuals with SCD experience emotional and stress related effects of the disease that may impact daily quality of life and frequency and severity of pain. Studies have found that hospital admission frequency has limited or no impact on academic outcomes in youth with SCD. Few studies have explicitly examined the relationship between SCD-related pain and educational, socioeconomic, and mental health outcomes. This is a cross-sectional study of patient survey data from a single site in the Sickle Cell Disease Implementation Science Consortium (SCDIC). The primary objective was to identify a relationship between educational attainment, employment status, mental health, and the frequency, severity, or length of pain crises for individuals with SCD. Multivariate analysis was used to assess the impact of patients' educational attainment, employment status, annual household income (low = less than $25,000, high = $75,001 and above), and self-reported depression on the frequency, length, and severity of SCD-related pain. Our central hypothesis was that individuals with a history of depression, lower educational attainment, periods of unemployment, and lower incomes experience more frequent, more severe, and longer pain crises. A total of 307 participants were included. The mean age was 27.4 years (range 15 to 45), 58.3% were female, and 99% were African American. Sixty-two percent had Hgb SS, the most severe form of SCD. About half of all patients (50.5%) reported they take pain medication every day for SCD and majority were on some form of disease modification (64.2% on hydroxyurea (HU), 20.2% on chronic blood transfusion). Slightly less than half (48.9%) reported their highest level of education as a high school diploma or lower. Most were unemployed (15.3%), students (22.8%), or disabled (21.5%), and 59.2% reported an average annual household income less than $25,000. Univariate analysis revealed statistically significant associations between employment status as unemployed or disabled and frequency of pain (p &lt; .001), employment status as unemployed or disabled and severity of pain (p &lt; .001), and employment status as disabled and length of pain &gt; 4 days. Relationships between depression and frequency and severity of pain were statistically significant at the p &lt; .001 level, and between depression and length of pain &gt; 1 week at the p &lt; .01 level. Multivariate analysis revealed positive statistically significant relationships between depression and high pain frequency (p &lt; .001), employment status as disabled and severe pain (p &lt; .01), depression and severe pain (p &lt; .01), and employment status as disabled and length of pain &gt;4 days (p &lt; .05), Table 1. Educational attainment did not demonstrate statistically significant relationships with pain outcomes. No variables demonstrated statistically significant relationships with length of pain &gt; 1 week and length of pain &gt; 2 weeks. The only significant association with pain outcomes was that HU users were less likely to take daily opioids. Individuals with SCD who are disabled or have a history of depression are more likely to report more severe and frequent pain. No relationship emerged between educational attainment and pain outcomes. As the results are limited to the cross-sectional design, we cannot make statements of causality. For now, we know that people with SCD and these risk factors need further study for interventions. We plan to further assess study participants across all eight SCDIC sites in the next phase of this work. Disclosures King: Bioline: Consultancy; Amphivena Therapeutics: Research Funding; Incyte: Consultancy; Cell Works: Consultancy; Celgene: Consultancy; Magenta Therapeutics: Membership on an entity's Board of Directors or advisory committees; Novimmune: Research Funding; RiverVest: Consultancy; Tioma Therapeutics (formerly Vasculox, Inc.):: Consultancy; WUGEN: Equity Ownership.

Sickle Cell Disease

2017 ◽  
Author(s):  
Andrew Franklin
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Complex Disease ◽  
Perioperative Period ◽  
Multiple Organ ◽  
Acute Chest Syndrome ◽  
Globin Genes ◽  
Cell Disease ◽  
Organ Systems ◽  
Sickle Cell Crises

Sickle cell disease, a hemoglobinopathy that affects multiple organ systems, is a complex disease entity that presents unique challenges during the perioperative period. The hallmark of sickle cell disease, vaso-occlusion, results from sickling of erythrocytes containing hemoglobin of abnormal conformation due to genetically mutated beta globin genes. The perioperative clinician must properly care for acute sickle cell crises including acute painful episodes and acute chest syndrome, and safely care for the sickle cell patient through the preoperative, intraoperative, and postoperative phases of surgical treatment. Both acute painful episodes and acute chest syndrome result from vaso-occlusive crises, and early stabilization of these emergencies is crucial to ensuring a positive patient outcome. The singular perioperative objective for the care of sickle cell disease patients is both simple and daunting: to achieve physiologic homeostasis in patients with preexisting multiorgan dysfunction undergoing a series of physiologic insults during and after surgery.

Haemoglobinopathies

2016 ◽  
Author(s):  
David Rees
Keyword(s):  
Bone Marrow ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Lupus Erythematosus ◽  
Single Gene ◽  
Globin Genes ◽  
Globin Chain ◽  
Cell Disease ◽  
Increased Risk ◽  
Marrow Expansion

Inherited abnormalities of the globin genes are the commonest single-gene disorders in the world and fall into two main groups: thalassaemias and sickle cell disease. Thalassaemias are due to quantitative defects in globin chain synthesis which cause variable anaemia and ineffective erythropoiesis. Thalassaemia was initially thought to be a disease of the bones due to uncontrolled bone marrow expansion causing bony distortion, although this is now unusual with appropriate blood transfusions. Osteopenia, often severe, is a feature of most patients with thalassaemia major and intermedia, caused by bone marrow expansion, iron overload, endocrinopathy, and iron chelation. Treatment with bisphosphonates is generally recommended. Other rheumatological manifestations include arthropathy associated with the use of the iron chelator deferiprone. Sickle cell disease involves a group of conditions caused by polymerization of the abnormal -globin chain, resulting in abnormal erythrocytes which cause vaso-occlusion, vasculopathy, and ischaemic tissue damage. The characteristic symptom is acute bone pain caused by vaso-occlusion; typical episodes require treatment with opiate analgesia and resolve spontaneously by 5 days with no lasting bone damage. The frequency of acute episodes varies widely between patients. The incidence of osteomyelitis is increased, particularly with salmonella, although it is much rarer than acute vaso-occlusion. Avascular necrosis can affect the hips, and less commonly the shoulders and knees. Coincidental rheumatological disease sometimes complicates the condition, particularly systemic lupus erythematosus (SLE) which is more prevalent in populations at increased risk of sickle cell disease.

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