Medication
Management of sickle cell anemia is usually aimed at avoiding pain episodes, relieving symptoms and preventing complications. Treatments might include medications and blood transfusions.
Procedures
The FDA recently approved this drug for treatment of sickle cell anemia. It helps in reducing the frequency of pain crises. Crizanlizumab (Adakveo). This drug, given by injection, can help reduce the frequency of pain crises in adults and children older than 16. Side effects can include nausea, joint pain, back pain and fever. Voxelotor (Oxbryta).
Therapy
Sickle cell anemia (SCA) was first described in the Western literature more than 100 years ago. Elucidation of its molecular basis prompted numerous biochemical and genetic studies that have contributed to a better understanding of its pathophysiology.
Self-care
These are used to treat and prevent complications, such as stroke, in people with sickle cell disease. In a red blood cell transfusion, red blood cells are removed from a supply of donated blood, then given through a vein to a person with sickle cell anemia.
Nutrition
How is sickle cell anemia (SCA) treated?
What is the best drug for sickle cell anemia?
What is the history of sickle cell anemia (SCA)?
How are red blood cells used to treat sickle cell disease?
How to help sickle cell pain?
There are things you can do at home to help your sickle cell symptoms: Use heating pads for pain relief. Take folic acid supplements, as recommended by your doctor. Eat an adequate amount of fruits, vegetables, and whole-wheat grains.
What is sickle cell disease?
Sickle cell anemia, or sickle cell disease (SCD), is a genetic disease of the red blood cells (RBCs). Normally, RBCs are shaped like discs, which gives them the flexibility to travel through even the smallest blood vessels. However, with this disease, the RBCs have an abnormal crescent shape resembling a sickle.
How long do sickle cells live?
This breaking apart of RBCs is called chronic hemolysis. RBCs generally live for about 120 days. Sickle cells live for a maximum of 10 to 20 days.
What is the most common type of sickle cell disease?
Hemoglobin SS disease is the most common type of sickle cell disease. It occurs when you inherit copies of the hemoglobin S gene from both parents. This forms hemoglobin known as Hb SS. As the most severe form of SCD, individuals with this form also experience the worst symptoms at a higher rate.
Why is Hb electrophoresis needed?
Hb electrophoresis is always needed to confirm the diagnosis of sickle cell disease. It measures the different types of hemoglobin in the blood.
How many copies of SCD are needed?
This can cause pain and tissue damage. SCD is an autosomal recessive condition. You need two copies of the gene to have the disease. If you have only one copy of the gene, you are said to have sickle cell trait.
When do sickle cell anemia symptoms appear?
Symptoms of sickle cell anemia usually show up at a young age. They may appear in babies as early as 4 months old, but generally occur around the 6-month mark. While there are multiple types of SCD, they all have similar symptoms, which vary in severity. These include:
What Is the Standard Test for Sickle Cell Anemia?
There is one standard test for SCA that can be done in both adults and babies: hemoglobin electrophoresis.
What Is Sickle Cell Anemia?
Sickle cell anemia (SCA) is an inherited blood disorder, one of several types that fall under the larger umbrella of sickle cell disease (SCD). Its symptoms are many and varied, including severe pain, intense fatigue, frequent infections, and swelling. The disease also comes with an increased risk of stroke and other complications.
What Are the Symptoms and Complications of Sickle Cell Anemia?
This type of obstruction in the blood vessels can cause many symptoms because a blockage prevents oxygen from reaching tissue in areas throughout the body, leading to severe pain known as a pain crisis, vaso-occlusive crisis, or VOC (one of the main reasons for hospitalizations with SCA). SCA can rob the brain tissues of oxygen, causing a stroke. Or, it can pile up in the spleen, which filters infections from the body, and cause anemia , infections, and other issues.
Why do SCD and SCA occur?
The reason both SCD and SCA occur? Hemoglobin, a protein in your red blood cells that is responsible for transporting oxygen throughout the body, is flawed in folks with this disease. So instead of your red blood cells being shaped like smooth, flat discs, allowing for those cells to pass easily through your blood vessels, a design flaw makes your blood cells C-shaped, like a sickle (hence the name).
How to treat SCA?
Medication is one approach to treat SCA. Since drugs can affect every person differently, they might be used differently for different individuals, based on their SCA symptoms. Options for treating SCA with meds have increased in recent years, and research continues to increase the possibilities.
Why do you need a blood transfusion after a stroke?
Other reasons for this treatment might be for acute chest syndrome (with symptoms including chest pain, cough, fever, shortness of breath), multi-organ failure, and as a related procedure before surgery. Complications may include a negative immune response to donor blood, infection, and excess iron build-up (making additional treatment to reduce iron levels necessary).
When is SCA diagnosed?
It can be diagnosed at any time, from in utero to adulthood, but is most commonly diagnosed at birth in the U.S. That’s because since 2007, all 50 states (as well as Washington, D.C.) have given universal screenings for SCA via newborn testing in the hospital to catch the disease immediately. The U.S. is one of the only countries in the world with universal newborn screening.
What causes a sickle cell?
Sickle cell disease is caused by an abnormal HbS (α2βS2) in which glutamic acid at position 6 of the β-globin chain of hemoglobin is changed to valine. Goldstein et al. (1963)showed that this amino acid substitution arose from a single base change (A>T) at codon 6 (rs334). The genetic causes of SCD include homozygosity for the rs334mutation (HbSS, commonly referred as SCA) and compound heterozygosity between rs334and mutations that lead to either other structural variants of β-globin (such as HbC, causing HbSC) or reduced levels of β-globin production as in β-thalassemia (causing HbS/β-thalassemia). In patients of African ancestry, HbSS is the most common cause of SCD (65–70%), followed by HbSC (about 30%), with HbS/β-thalassemia being responsible for most of the rest (Steinberg et al., 2001). SCA in which the intracellular concentration of HbS is almost 100%, is by far the most severe and well described (Brittenham et al., 1985). The majority of the therapeutic developments and interventions have focused on this genotype, which is also the focus of this review, although they also impact the other SCD genotypes.
What is SCD in medical terms?
Sickle cell disease (SCD) is an inherited blood disorder that first appeared in the Western literature in 1910 when Dr. James Herrick described a case of severe malaise and anemia in a 20-year-old dental student from Grenada (Herrick, 1910). On examining his blood smear, he noticed many bizarrely shaped red blood cells, leading him to surmise that “…the cause of the disease may be some unrecognized change in the red corpuscle itself” (Herrick, 2014). More than 100 years later we recognize that the change in the red corpuscle is caused by a single base substitution in β-globin, and that the disease is not just present in the United States (US), but prevalent in regions where malaria was historically endemic, including sub-Saharan Africa, India, the Middle East, and the Mediterranean (Williams and Thein, 2018). Presence of SCD in the non-malarial regions is related to the recent migration patterns.
How many patients with MSD HSCT survived?
In an international, multicenter study, 59 patients had MSD HSCT, of which 50 survived and were cured of SCD. Of the nine patients that had a negative outcome, five had graft rejection and four intracranial hemorrhage. Thirteen patients developed mixed chimerism. Of those patients that developed mixed chimerism, there was no GVHD or disease recurrence/graft rejection. Patients with stable mixed chimerism did not have worse outcomes related to complications of SCD. Hsieh et al. (2009)developed a protocol for non-myeloablative HSCT with low dose total body radiation, alemtuzumab, and sirolimus. In the initial 10 patients with SCD, nine had long-term, stable, mixed donor chimerism and reversal of their sickle cell phenotype (Hsieh et al., 2009). An updated report showed that 87% of the 30 patients had long-term stable donor engraftment without acute or chronic graft-versus-host disease (Clinical trials [{"type":"clinical-trial","attrs":{"text":"NCT00061568","term_id":"NCT00061568"}}NCT00061568]) (Walters et al., 2001; Hsieh et al., 2014). More recent data reported at least 95% cure rate in 234 children and young adults (<30 years) with SCA after MSD with no increased mortality compared to SCA itself and better quality of life. The data also showed that myeloablative HSCT can be a safe option for patients <15 years old if a MSD is available unless there is a clear and strong recommendation not to undergo transplant (Bernaudin et al., 2020).
How many babies are affected by SCD?
Currently, an estimated 300,000 affected babies are born each year, more than 80% of whom are in Africa. Due to recent population migrations, increasing numbers of individuals affected by SCD are encountered in countries that are not historically endemic for malaria, such as the US. It is estimated that 100,000 Americans are affected with SCD, the majority of whom are of African descent (Hassell, 2010, 2016). The numbers affected with SCD are predicted to increase exponentially; Piel et al. (2013)estimated that between 2010 and 2050, the overall number of births affected by SCD will be 14,242,000; human migration and further globalization will continue to expand SCD throughout the world in the coming decades. While 75% or more of newborns with SCD in sub-Saharan Africa do not make their fifth birthday (McGann, 2014), in medium- to well-resourced countries almost all of affected babies can now expect to live to adulthood but overall survival still lags behind that of a non-SCD person by 20–30 years (Telfer et al., 2007; Quinn et al., 2010; Elmariah et al., 2014; Gardner et al., 2016; Serjeant et al., 2018). Despite these global prevalence figures, and the fact that SCD is by far the largest public health concern among the hemoglobinopathies, it was not until 2006 when the World Health Organization (WHO) recognized SCD as a global public health problem1.
What are the four categories of pathobiology for SCD?
Insight on the pathophysiology of SCD (Figure 2) has allowed different targets for interventions in patients with SCD summarized under four categories of its pathobiology – (1). Modifying the genotype, (2). Targeting HbS polymerization, (3). Targeting vasocclusion, and (4). Targeting inflammation.
What are the challenges of SCD?
One of the biggest challenges in managing SCD is the clinical complexity and extreme variable clinical course that cannot be explained by the specific disease genotype. Patients with identical sickle genotype still display extreme clinical course; both acquired and inherited factors contribute to this clinical complexity of SCD (Gardner and Thein, 2016). Although laboratory prognostic factors (HbF, hemoglobin, reticulocyte count, leukocytosis) and clinical phenotypes (such as stroke/TIA, acute chest syndrome/pulmonary hypertension, avascular necrosis, kidney injury, or skin ulcers) have been described and analyzed, classifying disease severity remains complex and should be assessed individually. Prediction of disease severity and clinical course of SCD has been the topic of many reviews and, to date there is no clear algorithm using genetic and/or imaging, and/or laboratory markers that can reliably predict mortality risk in SCD (Quinn, 2016).
Is hydroxyurea effective for fetal hemoglobin?
New therapeutic approaches that use drugs to ameliorate the downstream sequelae of HbS polymerization have not proved to be as effective as hydroxyurea (HU) which has an “anti-sickling” effect via induction of fetal hemoglobin (HbF, α2γ2) (Ware and Aygun, 2009). Other effects of HU include improvement of RBC hydration, reduction of neutrophil count, reduction of leucocyte adhesion, and reduction of pro-inflammatory markers, all of which add to the clinical efficacy of HU. In addition, HU also acts as NO donor, promoting vasodilation (Cokic et al., 2003). Increasing HbF is highly effective because it dilutes the intracellular HbS concentration, thereby increasing the delay time to HbS polymerization (Eaton and Bunn, 2017); in addition to which, the γ-chains also have an inhibitory effect on the polymerization process. Hydroxyurea, however, is only partially successful because the increase in fetal hemoglobin is uneven and not present in all cells. Nonetheless, the well-established clinical efficacy of HbF increase, substantiated by numerous clinical and epidemiological studies, has motivated both pharmacological and genetic approaches to induce HbF (Nevitt et al., 2017).
What causes sickle cell disease?
Sickle cell disease is caused by a specific point mutation in a gene that codes for the beta chain of hemoglobin. People with just one copy of this mutation have sickle cell trait and are generally healthy. But those who inherit two mutant copies of this gene suffer lifelong consequences of the presence of this abnormal protein. Their red blood cells—normally flexible and donut-shaped—assume the sickled shape that gives SCD its name. The sickled cells clump together and stick in small blood vessels, resulting in severe pain, anemia, stroke, pulmonary hypertension, organ failure, and far too often, early death.
What are red arrows in sickle cell?
Caption: Red blood cells from patient with sickle cell disease. The cells were differentiated from bone marrow with unedited and edited hematopoietic stem cells, and the red arrows show the sickled cells. Credit: Wu et al. Nature Medicine. March 25, 2019
What is the most frequent Cas9 edit in HSCs?
Their studies show that the most frequent Cas9 edits in HSCs are tiny insertions of a single DNA “letter.” With that slight edit to the BCL11A gene, HSCs reprogram themselves in a way that ensures long-term HbF production.
What protein is responsible for determining hemoglobin levels?
Eleven years ago, a team led by Vijay Sankaran and Stuart Orkin at Boston Children’s Hospital and the Dana-Farber Cancer Institute discovered that a protein called BCL11A seemed to determine HbF levels [2]. Subsequent work showed the protein actually works as a master mediator of the switch from fetal to adult hemoglobin, which normally occurs shortly after birth.
Why is BCL11A needed?
Because the BCL11A protein is required to turn off production of HbF in red cells. the researchers had another idea. They thought it might be possible to keep HbF on permanently by disrupting BCL11A in blood-forming hematopoietic stem cells (HSCs). The hope was that such a treatment might offer people with SCD a permanent supply of healthy red blood cells.
What cells did the CRISPR-edited human HSCs produce?
Then they transferred the editing cells into immune-compromised mice. Four months later, the mice continued to produce red blood cells that produced high levels of HbF and resisted sickling.
Who is leading the gene editing for SCD?
human clinical trials of such a gene-editing approach for SCD are already underway, led by CRISPR Therapeutics/Vertex Pharmaceuticals and Sangamo Therapeutics/Sanofi.
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