Sickle Cell Disease and Pain

Sickle Cell Disease and Pain | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 13 August 2025 V1 Latest version Share on Sickle Cell Disease and Pain Author : Joe Ordia, MD, FACS. 0000-0001-9799-8679 [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.175510741.13642609/v1 188 views 103 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Sickle cell disease refers to a group of inherited disorders characterized by the presence of crescent shaped (sickle) red blood cells (HbS). It is one of the most common genetic disorders in the world, impacting over 20 million people. It primarily affects people of African, Mediterranean, Middle Eastern, Asian, and Latin American descent. 1 , 2 The most common form is sickle cell anemia. When only one sickle cell gene is inherited, the condition is called sickle cell trait (HbAS), which rarely causes any symptoms. Two sickle cell genes have to be inherited, one from each parent, for a child to have sickle cell anemia (HbSS), which has the most severe symptoms. Other forms of sickle cell disease include sickle hemoglobin-C disease (HbSC), and sickle cell beta thalassemia (HbS/ß-Th). 3 Pain and suffering are prominent features of sickle cell disease and this manuscript aims to raise awareness and promote better understanding of strategies that may alleviate symptoms and enhance the quality of life for those affected. Red blood cells contain hemoglobin which is rich in iron, and is involved in the transportation of oxygen from the lungs to the tissues of the body. Normal red blood cells are round in shape. In sickle cell disease some of the red blood cells become sickle or crescent shaped and rigid, and cannot efficiently transport oxygen. Healthy red blood cells have a lifespan of about 120 days. The abnormally shaped sickle cells are fragile and they frequently breakdown in 10 to 20 days, leading to a deficiency in red blood cell count, and anemia which is an inadequate amount of red blood cells or hemoglobin. Symptoms usually begin to appear between the ages of 4 and 6 months, and the child can look pale, tired, and less playful. The liver is unable to quickly filter out the rapidly disintegrating sickle cells which release bilirubin into the system, resulting in yellow discoloration of the skin, eyes, and the urine. Under normal circumstances, bilirubin is excreted in the bile and urine. When the sticky red cells block the flow of blood in small blood vessels, the consequences can include pain, both acute and chronic, swelling of the hands and feet, infections, growth retardation, problems with vision, and stroke. Periodic episodes of acute pain, sometimes referred to as vaso-occlusive crisis, 2 , 4 occur when sickle-shaped cells block the blood flow to the spleen, abdomen, chest, bones, and joints, thereby depriving the tissues of oxygen. The body reacts by producing more lactic acid which activates the pain receptors called nociceptors. The acute, severe pain of sickle cell disease is thought to be mostly nociceptive. The severe pain often requires hospitalization. Witnessing an innocent child suffer through the pain of a sickle cell crisis is heart-wrenching, not only for the parents and family, but also for the doctors, nurses, and other healthcare providers. It can last from one day to about one week. Some children will bounce back with so much bravery and begin to play and interact with others shortly after the acute pain is over. Patients also have chronic pain from persistent or ongoing tissue and bone damage, and leg ulcers. 4 There is evidence that a component of the chronic pain is neuropathic. Pain can be divided into two categories based on the tissue of origin, neuropathic and nociceptive. Neuropathic pain results from injury or damage to nerves. Both mechanisms have to be taken into account for effective pain management. There is an important takeaway that cannot be emphasized enough. When a child frequently complains of pain and is found to be anemic or jaundiced, a diagnosis of malaria alone, as some parents have reported, is not sufficient. Proper laboratory investigation is required to explore the possibility of sickle cell disease. 5 It is absolutely acceptable for a parent or guardian to ask the pediatrician, “Do you think that it could be sickle cell?” In the United States, newborns are routinely screened for sickle cell disease through a blood test. Preventive Measures There is presently no way to fully prevent the symptoms of sickle cell disease in individuals who already have the condition. However, various measures can be taken to prevent factors that trigger acute attacks, thereby alleviating symptoms and reducing complications and sickle cell crises. Good hydration should be maintained to avoid the death of red blood cells. The acute pain can be exacerbated by cold weather, so a warm but not hot temperature is ideal. High altitudes are associated with low atmospheric oxygen, and should be avoided because of the risk of further tissue damage. Exercising should be done with moderation to avoid depriving the tissues of oxygen. Good hygiene is essential to ward off infection. Antibiotics may be used for prophylaxis or to treat an infection. 3 Vaccinations, and blood transfusions are often important tools. An oral medication called hydroxyurea can reduce frequency of pain episodes by about half. It promotes the production of fetal hemoglobin (HbF), which helps to prevent red blood cells from sickling, leading to a reduction in the need for blood transfusions, and other complications. It is approved by the Food and Drug Administration (FDA) for use in severe sickle cell disease. 3 , 6 Promising Research While there is currently no cure for sickle cell disease and many challenges remain, some ongoing research is starting to show promising results. 6 Red blood cells are produced in the bone marrow. In sickle cell disease, the bone marrow cannot produce enough red blood cells to compensate for the rapid breakdown of the defective ones. One area of research is bone marrow transplant as a potential cure. It is also known as stem cell transplant because it involves replacing abnormal stem cells in the bone marrow with normal cells from a compatible donor. Research in gene therapy is still in its infancy. It aims at modifying the gene of the individual so that there can be more production of fetal hemoglobin (HbF) which has more oxygen carrying power than sickle red blood cells (HbS). There is also gene editing which is a cutting-edge biotechnological technique designed to modify the genetic code inside the cells to correct the problem in the gene that causes the production of hemoglobin S (HbS). 7 Many studies are in their early stages, and are beginning to yield encouraging outcomes with less pain crises, and improved quality of life. I am positive that with more funding and research, there is hope in the horizon. Conclusion This perspective underscores the need to recognize the severe pain and suffering caused by sickle cell disease, a genetic disorder affecting over 20 million people worldwide. The symptoms typically present by the age of 6 months. Early diagnosis, preventive interventions, and comprehensive management strategies are essential to reduce pain, prevent permanent organ damage, and improve the quality of life. While there is currently no cure, advances in gene editing and other promising research offer hope. It is vital for scientists and pediatricians across nations to lead the public discourse, educating communities about these emerging therapies and countering misinformation from sources that often reject scientific evidence. Once these treatments are validated, they should be made affordable and accessible locally, ensuring equitable care that is not limited to only those with resources for medical tourism. Audio Podcast Available at: FAQ 51-55 References 1. National Heart, Lung, and Blood Institute. Sickle cell disease—causes and risk factors [Internet]. Bethesda (MD): National Institutes of Health; [cited 2025 Aug 10]. Available from: https://www.nhlbi.nih.gov/health/sickle-cell-disease/causes 2. Kavanagh PL, Fasipe TA, Wun T. Sickle cell disease: a review. JAMA. 2022;328(1):57–68. doi:10.1001/jama.2022.10233. https://pubmed.ncbi.nlm.nih.gov/35788790/ 3. Hardouin G, Magrin E, Corsia A, Cavazzana M, Miccio A, Semeraro M. Sickle Cell Disease: From Genetics to Curative Approaches. Annu Rev Genomics Hum Genet. 2023;24:255–275. doi:10.1146/annurev-genom-120122-081037. https://pubmed.ncbi.nlm.nih.gov/37624668/ 4. National Heart, Lung, and Blood Institute. How Sickle Cell Disease May Affect Your Health [Internet]. Bethesda (MD): NHLBI; [cited 2025 Aug 10]. Available from: https://www.nhlbi.nih.gov/health/sickle-cell-disease/health-effects 5. NYU Langone Health. Diagnosing sickle cell disease in children [Internet]. New York (NY): NYU Langone Health; [cited 2025 Aug 10]. Available from: https://nyulangone.org/conditions/sickle-cell-disease-in-children/diagnosis 6. Centers for Disease Control and Prevention. Prevention and treatment of SCD complications [Internet]. Atlanta (GA): CDC; 2024 Oct 3 [cited 2025 Aug 10]. Available from: https://www.cdc.gov/sickle-cell/about/prevention-and-treatment.html 7. Ma L, Yang S, Peng Q, Zhang J, Zhang J. CRISPR/Cas9-based gene-editing technology for sickle cell disease. Gene . 2023;874:147480. https://doi.org/10.1016/j.gene.2023.147480 Information & Authors Information Version history V1 Version 1 13 August 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords beta thalassemia gene editing genetic disorders hemoglobin-c hydroxyurea red blood cell disorders sickle cell crisis sickle cell disease stem cells vaso-occlusive crisis Authors Affiliations Joe Ordia, MD, FACS. 0000-0001-9799-8679 [email protected] Neurosurgery and Behavioral Sciences. Private Practice, Massachusetts, USA. View all articles by this author Metrics & Citations Metrics Article Usage 188 views 103 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Joe Ordia, MD, FACS.. Sickle Cell Disease and Pain. Authorea . 13 August 2025. DOI: https://doi.org/10.22541/au.175510741.13642609/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . Format Please select one from the list RIS (ProCite, Reference Manager) EndNote BibTex Medlars RefWorks Direct import Tips for downloading citations document.getElementById('citMgrHelpLink').addEventListener('click', function() { popupHelp(this.href); return false; }); $(".js__slcInclude").on("change", function(e){ if ($(this).val() == 'refworks') $('#direct').prop("checked", false); $('#direct').prop("disabled", ($(this).val() == 'refworks')); }); View Options View options PDF View PDF Figures Tables Media Share Share Share article link Copy Link Copied! Copying failed. 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