Practice EssentialsSickle cell disease (SCD) and its variants are genetic disorders resulting from the presence of a mutated form of hemoglobin, hemoglobin S (HbS) [1, 2] (see the image below). The most common form of SCD found in North America is homozygous HbS disease (HbSS), an autosomal recessive disorder first described by Herrick in 1910. SCD causes significant morbidity and mortality, particularly in people of African and Mediterranean ancestry (see Pathophysiology). Morbidity, frequency of crisis, degree of anemia, and the organ systems involved vary considerably from individual to individual. Show
 Signs and symptomsScreening for HbS at birth is currently mandatory in the United States. For the first 6 months of life, infants are protected largely by elevated levels of fetal hemoglobin (Hb F). SCD usually manifests early in childhood, in the following ways:
Approximately half the individuals with homozygous HbS disease experience vaso-occlusive crises. The frequency of crises is extremely variable. Some individuals have as many as 6 or more episodes annually, whereas others may have episodes only at great intervals or none at all. Each individual typically has a consistent pattern for crisis frequency. Triggers of vaso-occlusive crisis include the following:
Many individuals with HbSS experience chronic low-level pain, mainly in bones and joints. Intermittent vaso-occlusive crises may be superimposed, or chronic low-level pain may be the only expression of the disease. See Presentation for more detail. DiagnosisSCD is suggested by the typical clinical picture of chronic hemolytic anemia and vaso-occlusive crisis. Electrophoresis confirms the diagnosis with the presence of homozygous HbS and can also document other hemoglobinopathies (eg, HbSC, HbS-beta+ thalassemia). Laboratory tests used in patients with SCD include the following:
In one study of 38 asymptomatic children with SCD, investigators found that hypertension and abnormal blood pressure patterns were prevalent in children with SCD. [3] They suggested using 24-hour ambulatory blood pressure monitoring (ABPM) to identify these conditions in young patients. [3] In the study, 17 patients (43.6%) had ambulatory hypertension, whereas 4 (10.3%) had hypertension on the basis of their clinic blood pressure. Twenty-three patients (59%) had impaired systolic blood pressure dipping, 7 (18%) had impaired diastolic blood pressure dipping, and 5 (13%) had reversed dipping. [3] Imaging studies Imaging studies that aid in the diagnosis of sickle cell anemia in patients in whom the disease is suggested clinically include the following:
See Workup for more detail. ManagementThe goals of treatment in SCD are symptom control and management of disease complications. Treatment strategies include the following 7 goals:
Pharmacotherapy SCD may be treated with the following medications:
Non-pharmacologic therapy Other approaches to managing SCD include the following:
Combination pharmacotherapy and non-pharmacotherapy
See Treatment and Medication for more detail. BackgroundCarriers of the sickle cell trait (ie, heterozygotes who carry one HbS allele and one normal adult hemoglobin [HbA] allele) have some resistance to the often-fatal malaria caused by Plasmodium falciparum. This property explains the distribution and persistence of this gene in the population in malaria-endemic areas. [5, 6, 7] However, in areas such as the United States, where malaria is not a problem, the trait no longer provides a survival advantage. Instead, it poses the threat of SCD, which occurs in children of carriers who inherit the sickle cell gene from both parents (ie, HbSS). Although carriers of sickle cell trait do not suffer from SCD, individuals with one copy of HbS and one copy of a gene that codes for another abnormal variant of hemoglobin, such as HbC or Hb beta-thalassemia, have a less severe form of the disease. GeneticsSCD denotes all genotypes containing at least one sickle gene, in which HbS makes up at least half the hemoglobin present. Major sickle genotypes described so far include the following:
Sickle cell trait or the carrier state is the heterozygous form characterized by the presence of around 40% HbS, absence of anemia, inability to concentrate urine (isosthenuria), and hematuria. Under conditions leading to hypoxia, it may become a pathologic risk factor. SCD is the most severe and most common form. Affected individuals present with a wide range of clinical problems that result from vascular obstruction and ischemia. Although the disease can be diagnosed at birth, clinical abnormalities usually do not occur before age 6 months, when functional asplenia develops. Functional asplenia results in susceptibility to overwhelming infection with encapsulated bacteria. Subsequently, other organs are damaged. Typical manifestations include recurrent pain and progressive incremental infarction. Newborn screening for sickle hemoglobinopathies is mandated in 50 states. Therefore, most patients presenting to the ED have a known diagnosis. PathophysiologyHbS arises from a mutation substituting thymine for adenine in the sixth codon of the beta-chain gene, GAG to GTG. This causes coding of valine instead of glutamate in position 6 of the Hb beta chain. The resulting Hb has the physical properties of forming polymers under deoxy conditions. It also exhibits changes in solubility and molecular stability. These properties are responsible for the profound clinical expressions of the sickling syndromes. Under deoxy conditions, HbS undergoes marked decrease in solubility, increased viscosity, and polymer formation at concentrations exceeding 30 g/dL. It forms a gel-like substance containing Hb crystals called tactoids. The gel-like form of Hb is in equilibrium with its liquid-soluble form. A number of factors influence this equilibrium, including oxygen tension, concentration of Hb S, and the presence of other hemoglobins. Oxygen tension is a factor in that polymer formation occurs only in the deoxy state. If oxygen is present, the liquid state prevails. Concentration of Hb S is a factor in that gelation of HbS occurs at concentrations greater than 20.8 g/dL (the normal cellular Hb concentration is 30 g/dL). The presence of other hemoglobins is a factor in that normal adult hemoglobin (HbA) and fetal hemoglobin (HbF) have an inhibitory effect on gelation. These and other Hb interactions affect the severity of clinical syndromes. HbSS produces a more severe disease than sickle cell HbC (HbSC), HbSD, HbSO Arab, and Hb with one normal and one sickle allele (HbSA). When red blood cells (RBCs) containing homozygous HbS are exposed to deoxy conditions, the sickling process begins. A slow and gradual polymer formation ensues. Electron microscopy reveals a parallel array of filaments. Repeated and prolonged sickling involves the membrane; the RBC assumes the characteristic sickled shape. (See image below.) After recurrent episodes of sickling, membrane damage occurs and the cells are no longer capable of resuming the biconcave shape upon reoxygenation. Thus, they become irreversibly sickled cells (ISCs). From 5-50% of RBCs permanently remain in the sickled shape. When RBCs sickle, they gain Na+ and lose K+. Membrane permeability to Ca++ increases, possibly due, in part, to impairment in the Ca++ pump that depends on adenosine triphosphatase (ATPase). The intracellular Ca++ concentration rises to 4 times the reference level. The membrane becomes more rigid, possibly due to changes in cytoskeletal protein interactions; however, these changes are not found consistently. In addition, whether calcium is responsible for membrane rigidity is not clear. Membrane vesicle formation occurs, and the lipid bilayer is perturbed. The outer leaflet has increased amounts of phosphatidyl ethanolamine and contains phosphatidylserine. The latter may play a role as a contributor to thrombosis, acting as a catalyst for plasma clotting factors. Membrane rigidity can be reversed in vitro by replacing HbS with HbA, suggesting that HbS interacts with the cell membrane. Interactions with vascular endotheliumComplex multifactorial mechanisms involving endothelial dysfunction underlie the acute and chronic manifestations of SCD. [8] A current model proposes that vaso-occlusive crises in SCD result from adhesive interactions of sickle cell RBCs and leukocytes with the endothelium. [9] In this model, the endothelium becomes activated by sickle cell RBCs, either directly, through adhesion molecules on the RBC surface, or indirectly through plasma proteins (eg, thrombospondin, von Willebrand factor) that act as a soluble bridge molecule. This leads, sequentiallly, to recruitment of adherent leukocytes, activation of recruited neutrophils and of other leukocytes (eg, monocytes or natural killer T cells), interactions of RBCs with adherent neutrophils, and clogging of the vessel by cell aggregates composed of RBCs, adherent leukocytes, and possibly platelets. [9] Sickle cells express very late antigen–4 (VLA-4) on the surface. VLA-4 interacts with the endothelial cell adhesive molecule, vascular cell adhesive molecule–1 (VCAM-1). VCAM-1 is upregulated by hypoxia and inhibited by nitric oxide. Hypoxia also decreases nitric oxide production, thereby adding to the adhesion of sickle cells to the vascular endothelium. Nitric oxide is a vasodilator. Free Hb is an avid scavenger of nitric oxide. Because of the continuing active hemolysis, there is free Hb in the plasma, and it scavenges nitric oxide, thus contributing to vasoconstriction. In addition to leukocyte recruitment, inflammatory activation of endothelium may have an indispensable role in enhanced sickle RBC–endothelium interactions. Sickle RBC adhesion in postcapillary venules can cause increased microvascular transit times and initiate vaso-occlusion. Several studies have shown involvement of an array of adhesion molecules expressed on sickle RBCs, including CD36, a-4-ß-1 integrin, intercellular cell adhesion molecule–4 (ICAM-4), and basal cell adhesion molecule (B-CAM). [10] Adhesion molecules (ie, P-selectin, VCAM-1, a-V-ß-3 integrin) are also expressed on activated endothelium. Finally, plasma factors and adhesive proteins (ie, thrombospondin [TSP], von Willebrand factor [vWf], laminin) play an important role in this interaction. For example, the induction of VCAM-1 and P-selectin on activated endothelium is known to enhance sickle RBC interactions. In addition, a-V-ß-3 integrin is upregulated in activated endothelium in patients with sickle cell disease. a-V-ß-3 integrin binds to several adhesive proteins (TSP, vWf, red-cell ICAM-4, and, possibly, soluble laminin) involved in sickle RBC adhesion, and antibodies to this integrin dramatically inhibit sickle RBC adhesion. In addition, under inflammatory conditions, increased leukocyte recruitment in combination with adhesion of sickle RBCs may further contribute to stasis. Sickle RBCs adhere to endothelium because of increased stickiness. The endothelium participates in this process, as do neutrophils, which also express increased levels of adhesive molecules. Deformable sickle cells express CD18 and adhere abnormally to endothelium up to 10 times more than normal cells, while ISCs do not. As paradoxical as it might seem, individuals who produce large numbers of ISCs have fewer vaso-occlusive crises than those with more deformable RBCs. Other properties of sickle cellsSickle RBCs also adhere to macrophages. This property may contribute to erythrophagocytosis and the hemolytic process. The microvascular perfusion at the level of the pre-arterioles is influenced by RBCs containing Hb S polymers. This occurs at arterial oxygen saturation, before any morphologic change is apparent. Hemolysis is a constant finding in sickle cell syndromes. Approximately one third of RBCs undergo intravascular hemolysis, possibly due to loss of membrane filaments during oxygenation and deoxygenation. The remainder hemolyze by erythrophagocytosis by macrophages. This process can be partially modified by Fc (crystallizable fragment) blockade, suggesting that the process can be mediated by immune mechanisms. Sickle RBCs have increased immunoglobulin G (IgG) on the cell surface. Vaso-occlusive crisis is often triggered by infection. levels of fibrinogen, fibronectin, and D-dimer are elevated in these patients. Plasma clotting factors likely participate in the microthrombi in the pre-arterioles. Development of clinical diseaseAlthough hematologic changes indicative of SCD are evident as early as the age of 10 weeks, symptoms usually do not develop until the age of 6-12 months because of high levels of circulating fetal hemoglobin. After infancy, erythrocytes of patients with sickle cell anemia contain approximately 90% hemoglobin S (HbS), 2-10% hemoglobin F (HbF), and a normal amount of minor fraction of adult hemoglobin (HbA2). Adult hemoglobin (HbA), which usually gains prominence at the age of 3 months, is absent. The physiological changes in RBCs result in a disease with the following cardinal signs:
Silent cerebral infarcts are associated with cognitive impairment in SCD. These infarcts tend to be located in the deep white matter where cerebral blood flow is low. [11] However, cognitive impairment, particularly slower processing speed, may occur independent of the presence of infarction and may worsen with age. [12] Musculoskeletal manifestationsThe skeletal manifestations of sickle cell disease result from changes in bone and bone marrow caused by chronic tissue hypoxia, which is exacerbated by episodic occlusion of the microcirculation by the abnormal sickle cells. The main processes that lead to bone and joint destruction in sickle cell disease are as follows:
When the rigid erythrocytes jam in the arterial and venous sinusoids of skeletal tissue, the result is intravascular thrombosis, which leads to infarction of bone and bone marrow. Repeated episodes of these crises eventually lead to irreversible bone infarcts and osteonecrosis, especially in weight-bearing areas. These areas of osteonecrosis (avascular necrosis/aseptic necrosis) become radiographically visible as sclerosis of bone with secondary reparative reaction and eventually result in degenerative bone and joint destruction. Infarction tends to occur in the diaphyses of small tubular bones in children and in the metaphyses and subchondrium of long bones in adults. Because of the anatomic distribution of the blood vessels supplying the vertebrae, infarction affecting the central part of the vertebrae (fed by a spinal artery branch) results in the characteristic H vertebrae of sickle cell disease. The outer portions of the plates are spared because of the numerous apophyseal arteries. Osteonecrosis of the epiphysis of the femoral head is often bilateral and eventually progresses to collapse of the femoral heads. This same phenomenon is also seen in the humeral head, distal femur, and tibial condyles. Infarction of bone and bone marrow in patients with sickle cell disease can lead to the following changes (see images below):
The shortened survival time of the erythrocytes in sickle cell anemia (10-20 days) leads to a compensatory marrow hyperplasia throughout the skeleton. The bone marrow hyperplasia has the resultant effect of weakening the skeletal tissue by widening the medullary cavities, replacing trabecular bone and thinning cortices. Deossification due to marrow hyperplasia can bring about the following changes in bone:
Patients with sickle cell disease can have a variety of growth defects due to the abnormal maturation of bone. The following growth defects are often seen in sickle cell disease:
Go to Skeletal Sickle Cell Anemia for complete information on this topic. SCD can result in significant skeletal muscle remodeling and reduced muscle functional capacities, which contribute to exercise intolerance and poor quality of life. [13] In addition, changes in muscle and joints can result in altered posture and impaired balance control. [14] Renal manifestationsRenal manifestations of SCD range from various functional abnormalities to gross anatomic alterations of the kidneys. See Nephrologic Manifestations of Sickle Cell Disease for more information on this topic. Splenic manifestationsThe spleen enlarges in the latter part of the first year of life in children with SCD. Occasionally, the spleen undergoes a sudden very painful enlargement due to pooling of large numbers of sickled cells. This phenomenon is known as splenic sequestration crisis. The spleen undergoes repeated infarction, aided by low pH and low oxygen tension in the sinusoids and splenic cords. Despite being enlarged, its function is impaired, as evidenced by its failure to take up technetium during nuclear scanning. Over time, the spleen becomes fibrotic and shrinks. This is, in fact, an autosplenectomy. The nonfunctional spleen is a major contributor to the immune deficiency that exists in these individuals. Failure of opsonization and an inability to deal with infective encapsulated microorganisms, particularly Streptococcus pneumoniae, ensue, leading to an increased risk of sepsis in the future. Chronic hemolytic anemiaSCD is a form of hemolytic anemia, with red cell survival of around 10-20 days. Approximately one third of the hemolysis occurs intravascularly, releasing free hemoglobin (plasma free hemoglobin [PFH]) and arginase into plasma. PFH has been associated with endothelial injury including scavenging nitric oxide (NO), proinflammatory stress, and coagulopathy, resulting in vasomotor instability and proliferative vasculopathy. A hallmark of this proliferative vasculopathy is the development of pulmonary hypertension in adulthood. Plasma arginase degrades arginine, the substrate for NO synthesis, thereby limiting the expected compensatory increase in NO production and resulting in generation of oxygen radicals. Plasma arginase is also associated with pulmonary hypertension and risk of early mortality. InfectionLife-threatening bacterial infections are a major cause of morbidity and mortality in patients with SCD. Recurrent vaso-occlusion induces splenic infarctions and consequent autosplenectomy, predisposing to severe infections with encapsulated organisms (eg, Haemophilus influenzae, Streptococcus pneumoniae). Lower serum immunoglobulin M (IgM) levels, impaired opsonization, and sluggish alternative complement pathway activation further increase susceptibility to other common infectious agents, including Mycoplasma pneumoniae, Salmonella typhimurium, Staphylococcus aureus, and Escherichia coli. Common infections include pneumonia, bronchitis, cholecystitis, pyelonephritis, cystitis, osteomyelitis, meningitis, and sepsis. Pneumococcal sepsis continues to be a major cause of death in infants in some countries. Parvovirus B19 infection causes aplastic crises. EtiologySCD originated in West Africa, where it has the highest prevalence. It is also present to a lesser extent in India and the Mediterranean region. DNA polymorphism of the beta S gene suggests that it arose from five separate mutations: four in Africa and one in India and the Middle East. The most common of these is an allele found in Benin in West Africa. The other haplotypes are found in Senegal and Bantu, Africa, as well as in India and the Middle East. The HbS gene, when present in homozygous form, is an undesirable mutation, so a selective advantage in the heterozygous form must account for its high prevalence and persistence. Malaria is possibly the selecting agent because a concordance exists between the prevalence of malaria and Hb S. Sickling might protect a person from malaria by either (1) accelerating sickling so that parasitized cells are removed or (2) making it more difficult for the parasite to metabolize or to enter the sickled cell. While children with sickle cell trait Hb SA seem to have a milder form of falciparum malaria, those with homozygous Hb S have a severe form that is associated with a very high mortality rate. The sickling process that prompts a crisis may be precipitated by multiple factors. Local tissue hypoxia, dehydration secondary to a viral illness, or nausea and vomiting, all of which lead to hypertonicity of the plasma, may induce sickling. Any event that can lead to acidosis, such as infection or extreme dehydration, can cause sickling. More benign factors and environmental changes, such as fatigue, exposure to cold, and psychosocial stress, can elicit the sickling process. A specific cause is often not identified. Vaso-occlusive crises are often precipitated by the following:
Data also suggest a role for exertional stress, particularly when compounded with heat and hypovolemia. Aplastic crises are often preceded by the following:
Acute chest syndrome has been linked to the following:
EpidemiologySCD is present mostly in blacks. It also is found, with much less frequency, in eastern Mediterranean and Middle East populations. Individuals of Central African Republic descent are at an increased risk for overt renal failure. United States statisticsThe sickle gene is present in approximately 8% of black Americans. The expected prevalence of sickle cell anemia in the United States is 1 in 625 persons at birth. The actual prevalence is less because of early mortality. More than 2 million people in the United States, nearly all of them of African American ancestry, carry the sickle gene. More than 30,000 patients have homozygous HbS disease. The following statistics are available from the Centers for Disease Control and Prevention and the National Institutes of Health [16, 17] :
In the United States, SCD accounts for less than 1% of all new cases of end-stage renal disease (ESRD). [18] The following factors are known to portend a greater likelihood of progression to overt renal failure: hypertension, nephrotic-range proteinuria, hematuria, severe anemia, and a Central African Republic heritage. [19, 20, 21] In patients with SCD, 5-18% develop renal failure. [22] In one study cohort, the median age at the time of renal failure in patients with SCD was 23.1 years. International statisticsIn several sections of Africa, the prevalence of sickle cell trait (heterozygosity) is as high as 30%. Although the disease is most frequently found in sub-Saharan Africa, it is also found in some parts of Sicily, Greece, southern Turkey, and India, all of which have areas in which malaria is endemic. The mutation that results in HbS is believed to have originated in several locations in Africa and India. Its prevalence varies but is high in these countries because of the survival advantage to heterozygotes in regions of endemic malaria. As a result of migration, both forced and voluntary, it is now found worldwide. Sex distributionThe male-to-female ratio is 1:1. No sex predilection exists, since sickle cell anemia is not an X-linked disease. Although no particular gender predilection has been shown in most series, analysis of the data from the US Renal Data System demonstrated marked male predominance of sickle cell nephropathy in affected patients. [23] Clinical characteristics at different agesAlthough hematologic changes indicative of the disorder are evident as early as the age of 10 weeks, clinical characteristics of SCD generally do not appear until the second half of the first year of life, when fetal Hb levels decline sufficiently for abnormalities caused by HbS to manifest. SCD then persists for the entire lifespan. After age 10 years, rates of painful crises decrease, but rates of complications increase. The median age at the time of renal failure in patients with SCD is 23.1 years, the median survival time after the diagnosis of ESRD is about 4 years, and the median age of death is 27 years, despite dialysis treatment. [24] PrognosisBecause SCD is a lifelong disease, prognosis is guarded. The goal is to achieve a normal life span with minimal morbidity. As therapy improves, the prognosis also improves. Morbidity is highly variable in patients with SCD, partly depending on the level of HbF. Nearly all individuals with the condition are affected to some degree and experience multiple organ system involvement. Patients with Hb SA are heterozygous carriers and essentially are asymptomatic. Vaso-occlusive crisis and chronic pain are associated with considerable economic loss and disability. Repeated infarction of joints, bones, and growth plates leads to aseptic necrosis, especially in weightbearing areas such as the femur. This complication is associated with chronic pain and disability and may require changes in employment and lifestyle. Prognostic factors in SCDThe following prognostic factors have been identified as predictors of an adverse outcome [25] :
Hand-foot syndrome, which affects children younger than 5 years, has proved a strong predictor of overall severity (ie, death, risk of stroke, high pain rate, recurrent acute chest syndrome). Those that have an episode before age 1 year are at high risk of a severe clinical course. The risk is further increased if the child's baseline hemoglobin level is less than 7 g/dL or the baseline WBC count is elevated. Pregnancy in SCDPregnancy represents a special area of concern. The high rate of fetal loss is due to spontaneous abortion. Placenta previa and abruption are common due to hypoxia and placental infarction. At birth, the infant often is premature or has low birth weight. Mortality in SCDMortality is high, especially in the early childhood years. Since the introduction of widespread penicillin prophylaxis and pneumococcal vaccination, a marked reduction has been observed in childhood deaths. The leading cause of death is acute chest syndrome. Children have a higher incidence of acute chest syndrome but a lower mortality rate than adults; the overall death rate from acute chest syndrome is 1.8% and 4 times higher in adults than in children. Causes of death are pulmonary embolism and infection. In the Dallas newborn cohort, estimated survival at 18 years was 94%. In a recent neonatal United Kingdom cohort followed in a hospital and community-based program including modern therapy with transcranial Doppler ultrasonography (TCD) screening, the estimated survival of HbSS children at 16 years was 99%. Data from the 1995 cooperative study of SCD (CSSCD) suggested that the median survival for individuals with SCD was 48 years for women and 42 years for men. [26] This life expectancy was considerably lower than that for African Americans who do not have SCD. In Africa, available mortality data are sporadic and incomplete. Many children are not diagnosed, especially in rural areas, and death is often attributed to malaria or other comorbid conditions. Data from Quinn et al in 2004 suggest that mortality from SCD has improved over the past 30 years. [27] In earlier reports, approximately 50% of patients did not survive beyond age 20 years, and most did not survive to age 50 years. In one study, the median survival time in patients with SCD after the diagnosis of ESRD was about 4 years, and the median age of death after diagnosis was 27 years, despite dialysis treatment. [24] The cooperative study of SCD (CSSCD) estimated that the median survival for individuals with SS was 48 years for women and 42 years for men. [26] In the Dallas newborn cohort, estimated survival at 18 years was 94%. In a recent neonatal United Kingdom cohort followed in a hospital and community-based program including modern therapy with TCD screening, the estimated survival of HbSS children at 16 years was 99%. This significant increase in life expectancy and survival of patients with SCD has been achieved thanks to early detection and introduction of disease-modifying therapies. Neonatal screening, penicillin prophylaxis for children, pneumococcal immunization, red cell transfusion for selected patients and chelation therapy, hydroxyurea therapy, parental and patient education and, above all, treatment in comprehensive centers have all likely contributed to this effect on longevity. However, as the population of patients with SCD grows older, new chronic complications are appearing. Pulmonary hypertension is emerging as a relatively common complication and is one of the leading causes of morbidity and mortality in adults with SCD. [28] A study of 398 outpatients with SCD in France found that the prevalence of pulmonary hypertension confirmed by right heart catheterization was 6%; echocardiography alone had a low positive predictive value for pulmonary hypertension. [29] Patient EducationPatients must be educated about the nature of their disease. They must be able to recognize the earliest signs of a vaso-occlusive crisis and seek help, treat all febrile illness promptly, and identify environmental hazards that may precipitate a crisis. Reinforcement should occur incrementally during the course of ongoing care. Patients or parents should be instructed on how to palpate the abdomen to detect splenic enlargement, and the importance of observation for pallor, jaundice, and fever. Teach patients to seek medical care in certain situations, including the following:
Patients should avoid the following:
Families should be educated on the importance of hydration, diet, outpatient medications, and immunization protocol. Emphasize the importance of prophylactic penicillin. Patients on hydroxyurea must be educated on the importance of regular follow-up with blood counts. Patients (including asymptomatic heterozygous carriers) should understand the genetic basis of the disease, be educated about prenatal diagnosis, and know that genetic counseling is available. Genetic testing can identify parents at risk for having a child with sickle cell disease. If both parents have the sickle cell trait, the chance that a child will have sickle cell disease is 25%. If one parent is carrying the trait and the other actually has disease, the odds increase to 50% that their child will inherit the disease. Screening and genetic counseling theoretically have the potential to drastically reduce the prevalence of SCD. This promise has not been realized. Some authors have recommended emergency department screening or referral for patients unaware of their status as a possible heterozygote. [30] Families should be encouraged to contact community sickle cell agencies for follow-up information, new drug protocols, and psychosocial support. Families should also follow the advances of gene therapy, bone marrow transplantation, and the usage of cord blood stem cells. For patient education information, see the Sickle Cell Disease Directory.
Author Joseph E Maakaron, MD Research Fellow, Department of Internal Medicine, Division of Hematology/Oncology, American University of Beirut Medical Center, Lebanon Disclosure: Nothing to disclose. Coauthor(s) Ali T Taher, MD, PhD, FRCP Professor of Medicine, Associate Chair of Research, Department of Internal Medicine, Division of Hematology/Oncology, Director of Research, NK Basile Cancer Center, American University of Beirut Medical Center, Lebanon Disclosure: Nothing to disclose. Specialty Editor Board Jeanne Yu, PharmD Disclosure: Nothing to disclose. Chief Editor Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences Disclosure: Nothing to disclose. Additional Contributors Mark Ventocilla, OD, FAAO Chief Executive Officer, Elder Eye Care Group, PLC; Chief Executive Officer, Mark Ventocilla, OD, Inc; President, California Eye Wear, Oakwood Optical Mark Ventocilla, OD, FAAO is a member of the following medical societies: American Academy of Optometry, American Optometric Association Disclosure: Nothing to disclose. Acknowledgements Roy Alson, MD, PhD, FACEP, FAAEM Associate Professor, Department of Emergency Medicine, Wake Forest University School of Medicine; Medical Director, Forsyth County EMS; Deputy Medical Advisor, North Carolina Office of EMS; Associate Medical Director, North Carolina Baptist AirCare Roy Alson, MD, PhD, FACEP, FAAEM is a member of the following medical societies: Air Medical Physician Association, American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, National Association of EMS Physicians, North Carolina Medical Society, Society for Academic Emergency Medicine, and World Association for Disaster and Emergency Medicine Disclosure: Nothing to disclose. Jeffrey L Arnold, MD, FACEP Chairman, Department of Emergency Medicine, Santa Clara Valley Medical Center Jeffrey L Arnold, MD, FACEP is a member of the following medical societies: American Academy of Emergency Medicine and American College of Physicians Disclosure: Nothing to disclose. Robert J Arceci, MD, PhD King Fahd Professor of Pediatric Oncology, Professor of Pediatrics, Oncology and the Cellular and Molecular Medicine Graduate Program, Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine Robert J Arceci, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, and American Society of Pediatric Hematology/Oncology Disclosure: Nothing to disclose. Wadie F Bahou, MD Chief, Division of Hematology, Hematology/Oncology Fellowship Director, Professor, Department of Internal Medicine, State University of New York at Stony Brook Wadie F Bahou, MD is a member of the following medical societies: American Society of Hematology Disclosure: Nothing to disclose. Dvorah Balsam, MD Chief, Division of Pediatric Radiology, Nassau University Medical Center; Professor, Department of Clinical Radiology, State University of New York at Stony Brook Disclosure: Nothing to disclose. Salvatore Bertolone, MD Director, Division of Pediatric Hematology/Oncology, Department of Pediatrics, Kosair Children's Hospital; Professor, University of Louisville School of Medicine Salvatore Bertolone, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Education, American Association of Blood Banks, American Cancer Society, American Society of Hematology, American Society of Pediatric Hematology/Oncology, and Kentucky Medical Association Disclosure: Nothing to disclose. Barry E Brenner, MD, PhD, FACEP Professor of Emergency Medicine, Professor of Internal Medicine, Program Director, Emergency Medicine, Case Medical Center, University Hospitals, Case Western Reserve University School of Medicine Barry E Brenner, MD, PhD, FACEP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Chest Physicians, American College of Emergency Physicians, American College of Physicians, American Heart Association, American Thoracic Society, Arkansas Medical Society, New York Academy of Medicine, New York Academy of Sciences,and Society for Academic Emergency Medicine Disclosure: Nothing to disclose. Marcel E Conrad, MD Distinguished Professor of Medicine (Retired), University of South Alabama College of Medicine Marcel E Conrad, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Blood Banks, American Chemical Society, American College of Physicians, American Physiological Society, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Association of Military Surgeons of the US, International Society of Hematology, Society for Experimental Biology and Medicine, and Southwest Oncology Group Disclosure: No financial interests None None Nedra R Dodds, MD Medical Director, Opulence Aesthetic Medicine Nedra R Dodds, MD is a member of the following medical societies: American Academy of Anti-Aging Medicine, American Academy of Cosmetic Surgery, American College of Emergency Physicians, American Medical Association, National Medical Association, and Society for Academic Emergency Medicine Disclosure: Nothing to disclose. James L Harper, MD Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Assistant Clinical Professor, Department of Pediatrics, Creighton University School of Medicine; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center James L Harper, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Federation for Clinical Research, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Council on Medical Student Education in Pediatrics, and Hemophilia and Thrombosis Research Society Disclosure: Nothing to disclose. Adlette Inati, MD Head, Division of Pediatric Hematology-Oncology, Medical Director, Children's Center for Cancer and Blood Diseases, Rafik Hariri University Hospital; Research Associate, Balamand University; Head of Post Bone Marrow Transplant Clinic and Consultant Hematologist, Chronic Care Center; Founding Faculty, Lebanese American University School of Medicine, Lebanon Adlette Inati, MD is a member of the following medical societies: Alpha Omega Alpha, American Society of Hematology, European Hematology Association, and International Society of Hematology Disclosure: Nothing to disclose. Ziad N Kazzi, MD Assistant Professor, Department of Emergency Medicine, Emory University; Medical Toxicologist, Georgia Poison Center Ziad N Kazzi, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American College of Emergency Physicians, and American College of Medical Toxicology Disclosure: Nothing to disclose. Richard S Krause, MD Senior Clinical Faculty/Clinical Assistant Professor, Department of Emergency Medicine, University of Buffalo State University of New York School of Medicine and Biomedical Sciences Richard S Krause, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine Disclosure: Nothing to disclose. Ashok B Raj, MD Associate Professor, Section of Pediatric Hematology and Oncology, Department of Pediatrics, Kosair Children's Hospital, University of Louisville School of Medicine Ashok B Raj, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, and Kentucky Medical Association Disclosure: Nothing to disclose. Sharada A Sarnaik, MBBS Professor of Pediatrics, Wayne State University School of Medicine; Director, Sickle Cell Center, Attending Hematologist/Oncologist, Children's Hospital of Michigan Sharada A Sarnaik, MBBS is a member of the following medical societies: American Association of Blood Banks, American Association of University Professors, American Society of Hematology, American Society of Pediatric Hematology/Oncology, New York Academy of Sciences, and Society for Pediatric Research Disclosure: Nothing to disclose. Hosseinali Shahidi, MD, MPH Assistant Professor, Departments of Emergency Medicine and Pediatrics, State University of New York and Health Science Center at Brooklyn Hosseinali Shahidi, MD, MPH is a member of the following medical societies: American Academy of Pediatrics, American College of Emergency Physicians, and American Public Health Association Disclosure: Nothing to disclose. Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference Disclosure: Medscape Salary Employment Garry Wilkes MBBS, FACEM, Director of Emergency Medicine, Calvary Hospital, Canberra, ACT; Adjunct Associate Professor, Edith Cowan University; Clinical Associate Professor, Rural Clinical School, University of Western Australia Disclosure: Nothing to disclose. Mary L Windle, PharmD, Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference Disclosure: Nothing to disclose. Ulrich Josef Woermann, MD Consulting Staff, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland Disclosure: Nothing to disclose. Grace M Young, MD Associate Professor, Department of Pediatrics, University of Maryland Medical Center Grace M Young, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Emergency Physicians Disclosure: Nothing to disclose. Which theory specifically predicts that we will be more helpful to our relatives than to others?According to inclusive fitness theory, people are more willing to help those they are genetically related to because relatives share a kin altruism gene and are able to pass it along. We tested this theory by examining the effect of reproductive potential on altruism.
Which of the following theories specifically predicts that we will be more altruistic towards our relatives than towards close friends?Hamilton's rule predicts that individuals should be more likely to altruistically help closer kin and likewise, be more likely to receive help from closer kin ( Hamilton 1964 ).
What norm states that we should help only when others deserve help?The social responsibility norm tells us that we should try to help others who need assistance, even without any expectation of future paybacks. The social responsibility norm involves a sense of duty and obligation, in which people are expected to respond to others by giving help to those in need of assistance.
In which situation are people most likely to help out?Researchers suggest that people are most likely to help others in certain circumstances:. They have just seen others offering help.. They are not in a hurry.. They share some similarities with the person needing help.. They are in a small town or a rural setting.. They feel guilty.. Which of the following defines the reciprocity norm?Reciprocity norm is the rule of human interaction that says people need to reciprocate the action of another person. Simply, this means that when a person is given a gift (which can take any number of forms) by another, the person must repay the gift.
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The network of traits that predisposes a person to be helpful are all of the following EXCEPT
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