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Proposal Requirement 4 Example: Sickle Cell Anemia Treatments

Writer: Natasha Matta

Instagram: @natashakmatta

Email: matta.natashak@gmail.com


Current Solutions and Their Insufficiencies

Current treatments for sickle cell anemia are primarily aimed at replacing sickled red blood cells with healthy ones from a donor or managing pain crises in which sickled red blood cells clog small blood vessels, slowing or blocking blood and oxygen flow and causing immense pain. The disease is primarily treated with medications L-glutamine oral powder (Endari), Hydroxyurea (Droxia, Sikios, Hydrea), Crizanlizumab (Adakveo), and Voxelotor (Oxybryta) that aim to reduce the frequency of these pain crises. Other treatment options include blood transfusion, erythrocytapheresis, bone marrow transplant, and stem cell therapy.

L-glutamine oral powder increases the number of the reduced form of nicotinamide adenine dinucleotides in sickle cell erythrocytes, a type of red blood cell. This likely reduces oxidative stress, an imbalance between free radicals and the antioxidants that detoxify them, which has been implicated in pathogenesis of sickle cell disease. However, more research is needed into if L-glutamine indeed counteracts oxidative stress and what its long term effects may be. Hydroxyurea increases fetal hemoglobin levels, which helps prevent gelation and sickling of red blood cells, and it decreases incidents of pain crises and the need for blood transfusions. However, it also increases risk of infection and may be harmful for pregnancy. Crizanlizumab inhibits P-selectin, a protein which binds to the surface of activated endothelium and platelet cells and blocks interactions between endothelial cells, platelets, red blood cells, and leukocytes. It is used to reduce the frequency of vaso-occlusive crisis (VOC) in adults but does not eliminate them entirely. Lastly, Voxelotor inhibits hemoglobin S (HbS) polymerization by binding to HbS and preferentially partitioning to red blood cells to improve anemia, the condition of not having enough healthy red blood cells to deliver oxygen throughout the body. However, the medication has many side effects like nausea, headache, diarrhea, rash, fever, and fatigue, one of the symptoms of anemia it is supposed to prevent. Although these medications may temporarily alleviate or decrease the frequency of pain crises, they are unable to eliminate these episodes completely.

Blood transfusions are another form of treatment for sickle cell anemia in which healthy red blood cells are removed from a donor’s blood and administered through a vein to a patient with sickle cell anemia. This increases the proportion of normal red blood cells to those that are sickled. However there is risk for alloimmunization, where minor differences in red cell antigens cause an immune response, infection, or excess iron, which can damage the heart, liver, and other vital organs.

A similar treatment, erythrocytapheresis, better known as automated red blood cell exchange, is a nonsurgical treatment that uses an apheresis machine to remove unhealthy red blood cells and replace them with saline, healthy red blood cells from a donor, and the patient’s plasma. It can be performed on both children as young as 2 years old and adults and takes less time and is more cost-effective than a simple blood transfusion. Automated red blood cell exchange can control iron accumulation in patients and regulate Hemoglobin and Hemoglobin S concentrations based on factors like height and weight through a computer in the apheresis machine, helping to mitigate complications.



Figure 1. Diagram explaining how the apheresis machine used in erythrocytapheresis works


The last form of treatment for sickle cell anemia is stem cell transplantations. The only curative procedure for the disease is a hematopoietic stem cell transplantation. A needle is inserted into the donor’s real pelvic bone, between one and two quarts of bone marrow and blood are harvested, and hematopoietic or blood-forming stem cells are collected from red bone marrow. In preparation for the treatment, patients undergo chemotherapy to weaken their bone marrow, and then hematopoietic stem cells are injected into the bloodstream and travel to the bone marrow. However, this is not always an option for patients as donors have to be human leukocyte antigen (HLA)-matched.

Another form of stem cell transplantation is a peripheral blood stem cell transplant, where a donor receives injections of a drug, filgrastim or plerixafor, for 4-5 days, blood is drawn from one arm then passed through a machine that separates the stem cells and returns the blood to the other arm, and the patient receives the isolated stem cells through a catheter connected to a blood vessel in their chest. Each stem cell collection takes between three and four hours, and one to three days are needed to collect enough stem cells for a transplant.

Stem cell transplants come with great risks: graft-versus-host disease (GVHD) in which graft cells from the donor recognize host cells from the patient as foreign and attack them, infection, infertility, graft failure where patients are not able to produce white blood cells, red blood cells, and platelets that are important for blood clotting, veno-occlusive disease (VOD) where the blood vessels that lead to or pass through the liver suffer damage after a bone marrow transplant, and nutrition problems. Because of the high risk associated with stem cell transplants, they are usually recommended for patients, generally children, who have significant complications and have not responded well to other safer treatments. Thus, the above treatments, although effective in some cases, pose too great of health risks to patients and can cost lives.


Analysis

The author of this piece methodically discusses each of the current treatment options for sickle cell anemia, addressing the methods, reasoning behind the treatment, and risks or side effects in detail. She used a diagram to explain the process of apheresis to help the reader visualize and better understand how the apheresis machine collects the healthy cells that will be transplanted to patients with sickle cell anemia. The writer successfully convinced the reader that although some treatments were effective in mitigating symptoms of sickle cell anemia like pain crises, they ultimately posed too great of risks to the patient’s health, could be life-threatening in cases, required intense preparation like radiation therapy, and were often painful for the patients to undergo. Thus, she proved that a new and safer treatment for sickle cell anemia is needed. The author used reputable sources from a combination of hospital and university websites and scholarly sources like science journals and wrote professionally, using third person, correct spelling, grammar, and formatting. One way to make the argument presented stronger would be to include statistics on morbidity of success rates of the treatment options listed.


Bibliography

“Sickle cell anemia.” Mayo Clinic, https://www.mayoclinic.org/diseases-conditions/sickle-cell-anemia/diagnosis-treatment/drc-20355882#:~:text=Management%20of%20sickle%20cell%20anemia,transplant%20might%20cure%20the%20disease.

“Sickle Cell Anemia Treatment & Management.” Medscape, https://www.mayoclinic.org/diseases-conditions/sickle-cell-anemia/diagnosis-treatment/drc-20355882#:~:text=Management%20of%20sickle%20cell%20anemia,transplant%20might%20cure%20the%20disease.

“Anemia.” Mayo Clinic, https://www.mayoclinic.org/diseases-conditions/anemia/symptoms-causes/syc-20351360#:~:text=Anemia%20is%20a%20condition%20in,range%20from%20mild%20to%20severe.

“Erythrocytapheresis.” Transfusion Medicine and Hemostasis, https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/erythrocytapheresis#:~:text=For%20chronic%20management%2C%20repeated%20erythrocytapheresis,the%20complications%20of%20RBC%20transfusion.

“Automated Red Blood Cell Exchange (Erythrocytapheresis).” Children’s Hospital of Philadelphia, https://www.chop.edu/services/automated-red-blood-cell-exchange-erythrocytapheresis

“What is Apheresis.” Federation of Bombay Blood Banks, http://www.fbbb.org.in/aphaeresis_donors.html

“Hematopoietic stem cell transplantation for sickle cell disease: The changing landscape.” Hematology/Oncology and Stem Cell Therapy, https://www.sciencedirect.com/science/article/pii/S1658387617300444#:~:text=Allogeneic%20hematopoietic%20stem%20cell%20transplantation,older%20patients%20with%20significant%20morbidity.

“Stem Cell Transplant for Sickle Cell Disease.” University of Michigan, https://www.uofmhealth.org/health-library/hw254074

“Peripheral blood stem cell transplant.” National Cancer Institute, https://www.cancer.gov/publications/dictionaries/cancer-terms/def/peripheral-blood-stem-cell-transplant

“Hematopoietic stem-cell transplantation for sickle cell disease: current evidence and opinions.” Therapeutic Advances in Hematology, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3766347/#:~:text=With%20rapidly%20expanding%20evidence%20of,the%20only%20curative%20therapy%20available.


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