This article needs additional citations for verification. (February 2016) (Learn how and when to remove this template message)
|Symptoms||pale skin, hematoma, fast heart rate|
|Risk factors||Smoking, family history, ionizing radiation, some chemicals, prior chemotherapy, Down syndrome.|
|Diagnostic method||bone marrow biopsy, chemotherapy, radiotherapy, targeted therapy|
|Treatment||bone marrow transplant|
|Prognosis||five-year survival rate 45%|
|Frequency||3.83 million (2015)|
Aplastic anemia is a disease in which the body fails to produce blood cells in sufficient numbers. Blood cells are produced in the bone marrow by stem cells that reside there. Aplastic anaemia causes a deficiency of all blood cell types: red blood cells, white blood cells, and platelets.
It is more frequent in people in their teens and twenties but is also common among the elderly. It can be caused by heredity, immune disease, or exposure to chemicals, drugs, or radiation. However, in about one-half of cases, the cause is unknown.
First-line treatment for aplastic anaemia consists of immunosuppressive drugs, typically either anti-lymphocyte globulin or anti-thymocyte globulin, combined with corticosteroids, chemotherapy and ciclosporin. Hematopoietic stem cell transplantation is also used, especially for patients under 30 years of age with a related matched marrow donor.
Signs and symptoms
Aplastic anemia can be caused by exposure to certain chemicals, drugs, radiation, infection, immune disease; in about half the cases, a definitive cause is unknown. It is not a familial line hereditary condition, nor is it contagious. It can be acquired due to exposure to other conditions but if a person develops the condition, their offspring would not develop it by virtue of their genetic relationship.
Aplastic anemia is also sometimes associated with exposure to toxins such as benzene, or with the use of certain drugs, including chloramphenicol, carbamazepine, felbamate, phenytoin, quinine, and phenylbutazone. Many drugs are associated with aplasia mainly according to case reports, but at a very low probability. As an example, chloramphenicol treatment associated with aplasia in less than one in 40,000 treatment courses, and carbamazepine aplasia is even rarer.
Exposure to ionizing radiation from radioactive materials or radiation-producing devices is also associated with the development of aplastic anemia. Marie Curie, famous for her pioneering work in the field of radioactivity, died of aplastic anemia after working unprotected with radioactive materials for a long period of time; the damaging effects of ionizing radiation were not then known.
One known cause is an autoimmune disorder in which white blood cells attack the bone marrow. Acquired aplastic anemia is a T-cell mediated autoimmune disease, in which regulatory T cells are decreased in patients, and T-bet, a transcription factor and key regulator of Th1 development and function, is upregulated in affected T-cells. As a result of active transcription of the IFN-gamma gene by T-bet, IFN-gamma levels are increased, which reduces colony formation of hematopoietic progenitor cells in vitro by inducing apoptosis of CD34+ cells of bone marrow.
Short-lived aplastic anemia can also be a result of parvovirus infection. In humans, the P antigen (also known as globoside), one of the many cellular receptors that contribute to a person's blood type, is the cellular receptor for parvovirus B19 virus that causes erythema infectiosum (fifth disease) in children. Because it infects red blood cells as a result of the affinity for the P antigen, parvovirus causes complete cessation of red blood cell production. In most cases, this goes unnoticed, as red blood cells live on average 120 days, and the drop in production does not significantly affect the total number of circulating red blood cells. In people with conditions where the cells die early (such as sickle cell disease), however, parvovirus infection can lead to severe anemia.
More frequently parvovirus B19 is associated with aplastic crisis which involves only the red blood cells (despite the name). Aplastic anemia involves all different cell lines.
In some animals, aplastic anemia may have other causes. For example, in the ferret (Mustela putorius furo), it is caused by estrogen toxicity, because female ferrets are induced ovulators, so mating is required to bring the female out of heat. Intact females, if not mated, will remain in heat, and after some time the high levels of estrogen will cause the bone marrow to stop producing red blood cells.
The condition needs to be differentiated from pure red cell aplasia. In aplastic anemia, the patient has pancytopenia (i.e., leukopenia and thrombocytopenia) resulting in decrease of all formed elements. In contrast, pure red cell aplasia is characterized by reduction in red cells only. The diagnosis can only be confirmed on bone marrow examination. Before this procedure is undertaken, a patient will generally have had other blood tests to find diagnostic clues, including a complete blood count, renal function and electrolytes, liver enzymes, thyroid function tests, vitamin B12 and folic acid levels.
The following tests aid in determining differential diagnosis for aplastic anemia:
- Bone marrow aspirate and biopsy: to rule out other causes of pancytopenia (i.e. neoplastic infiltration or significant myelofibrosis).
- History of iatrogenic exposure to cytotoxic chemotherapy: can cause transient bone marrow suppression
- X-rays, computed tomography (CT) scans, or ultrasound imaging tests: enlarged lymph nodes (sign of lymphoma), kidneys and bones in arms and hands (abnormal in Fanconi anemia)
- Chest X-ray: infections
- Liver tests: liver diseases
- Viral studies: viral infections
- Vitamin B12 and folate levels: vitamin deficiency
- Blood tests for paroxysmal nocturnal hemoglobinuria
- Test for antibodies: immune competency
Treating immune-mediated aplastic anemia involves suppression of the immune system, an effect achieved by daily medicine intake, or, in more severe cases, a bone marrow transplant, a potential cure. The transplanted bone marrow replaces the failing bone marrow cells with new ones from a matching donor. The multipotent stem cells in the bone marrow reconstitute all three blood cell lines, giving the patient a new immune system, red blood cells, and platelets. However, besides the risk of graft failure, there is also a risk that the newly created white blood cells may attack the rest of the body ("graft-versus-host disease"). In young patients with an HLA matched sibling donor, bone marrow transplant can be considered as first-line treatment, patients lacking a matched sibling donor typically pursue immunosuppression as a first-line treatment, and matched unrelated donor transplants are considered a second-line therapy.
Medical therapy of aplastic anemia often includes a course of antithymocyte globulin (ATG) and several months of treatment with cyclosporine to modulate the immune system. Chemotherapy with agents such as cyclophosphamide may also be effective but has more toxicity than ATG. Antibody therapy, such as ATG, targets T-cells, which are believed to attack the bone marrow. Corticosteroids are generally ineffective, though they are used to ameliorate serum sickness caused by ATG. Normally, success is judged by bone marrow biopsy 6 months after initial treatment with ATG.
In the past, before the above treatments became available, patients with low leukocyte counts were often confined to a sterile room or bubble (to reduce risk of infections), as in the case of Ted DeVita.
Full blood counts are required on a regular basis to determine whether the patient is still in a state of remission.
Many patients with aplastic anemia also have clones of cells characteristic of the rare disease paroxysmal nocturnal hemoglobinuria (PNH, anemia with thrombopenia and/or thrombosis), sometimes referred to as AA/PNH. Occasionally PNH dominates over time, with the major manifestation intravascular hemolysis. The overlap of AA and PNH has been speculated to be an escape mechanism by the bone marrow against destruction by the immune system. Flow cytometry testing is performed regularly in people with previous aplastic anemia to monitor for the development of PNH.
Untreated, severe aplastic anemia has a high risk of death. Modern treatment, by drugs or stem cell transplant, has a five-year survival rate that exceeds 45%, with younger age associated with higher survival.
Survival rates for stem cell transplant vary depending on age and availability of a well-matched donor. Five-year survival rates for patients who receive transplants have been shown to be 42% for patients under age 20, 32% for those 20–40 years old, and closer to 10% for patients over age 40. Success rates are better for patients who have donors that are matched siblings and worse for patients who receive their marrow from unrelated donors.
Older people (who are generally too frail to undergo bone marrow transplants), and people who are unable to find a good bone marrow match, undergoing immune suppression have five-year survival rates of up to 35%.
Relapses are common. Relapse following ATG/ciclosporin use can sometimes be treated with a repeated course of therapy. In addition, 10–15% of severe aplastic anemia cases evolve into myelodysplastic syndrome and leukemia. According to a study, for children who underwent immunosuppressive therapy, about 15.9% of children who responded to immunosuppressive therapy encountered relapse.
Milder disease can resolve on its own.
Aplastic is a combination of two ancient Greek elements: a- meaning "not", and -plasis "forming into a shape."  Anemia is a combination of the ancient Greek element an- meaning "not", and -emia from new Latin from Greek -(h)aimia "blood."
Aplastic anemia is a rare, non cancerous disorder where the blood marrow is unable to adequately produce blood cells required for survival. It is estimated that the incidence of aplastic anemia is 0.7-4.1 cases per million people worldwide with the prevalence between men and women being approximately equal. The incidence rate of aplastic anemia in Asia is 2-3 times higher than it is in the West, with the incidence of the disease in the United States is 300-900 cases per year. The disease most commonly affects adults aged 15–25 and over the age of 60, but the disease can be observed in all age groups. The majority of instances of this disease are acquired during life and not inherited. These acquired cases are often linked to environmental exposures such as chemicals, drugs, and infectious agents that damage the blood marrow and compromise the ability of the marrow to generate new blood cells. However, in many instances the underlying cause for the disease is not found. This is referred to as idiopathic aplastic anemia and accounts for 75% of cases. This compromises the effectiveness of treatment since treatment of the disease is often aimed at the underlying cause. Those with a higher risk for aplastic anemia include individuals that are exposed to high-dose radiation, exposed to toxic chemicals, take certain prescription drugs, have pre-existing autoimmune disorders or blood disease, or are pregnant. The five-year survival rate is higher than 75% among recipients of blood marrow transplantation. Other treatment strategies include medications and blood transfusions. Patients that are untreated will often die within a year as a result of the disease due to related complications, which are most commonly bleeding and infection due to deficiency of platelets and white blood cells, respectively. There is not a screening test that currently exists for early detection and diagnosis of aplastic anemia.
- Marie Curie
- Eleanor Roosevelt
- Donny Schmit
- Ted DeVita
- Demetrio Stratos
- John Dill (British Field Marshal)
- Young, Neal S. (2018-10-25). "Aplastic Anemia". The New England Journal of Medicine. 379 (17): 1643–1656. doi:10.1056/NEJMra1413485. ISSN 1533-4406. PMC 6467577. PMID 30354958.
- Acton, Ashton (22 July 2013). Aplastic Anemia. ScholarlyEditions. p. 36. ISBN 978-1-4816-5068-7.
Aplastic anaemia (AA) is a rare bone marrow failure disorder with high mortality rate, which is characterized by pancytopenia and an associated increase in the risk of hemorrhage, infection, organ dysfunction and death.
- Kasper, Dennis L; Braunwald, Eugene; Fauci, Anthony; et al. (2005). Harrison's Principles of Internal Medicine, 16th ed. New York: McGraw-Hill. ISBN 978-0-07-140235-4.
- Merck Manual, Professional Edition, Aplastic Anemia (Hypoplastic Anemia)
- Peinemann, F; Bartel, C; Grouven, U (23 July 2013). "First-line allogeneic hematopoietic stem cell transplantation of HLA-matched sibling donors compared with first-line ciclosporin and/or antithymocyte or antilymphocyte globulin for acquired severe aplastic anemia". The Cochrane Database of Systematic Reviews. 7 (7): CD006407. doi:10.1002/14651858.CD006407.pub2. PMC 6718216. PMID 23881658.
- Adias; Erhabor (2013-02-11). Haematology Made Easy. AuthorHouse. pp. 229–. ISBN 978-1-4772-4651-1.
- "Marie Curie - The Radium Institute (1919-1934): Part 3". American Institute of Physics.
- Clark, Michael; Kumar, Parveen, eds. (July 2011). Kumar & Clark's clinical medicine (7th ed.). Edinburgh: Saunders Elsevier. ISBN 978-0-7020-2992-9.
- Zeng, Y; Katsanis, E (June 2015). "The complex pathophysiology of acquired aplastic anaemia". Clinical and Experimental Immunology. 180 (3): 361–370. doi:10.1111/cei.12605. ISSN 0009-9104. PMC 4449765. PMID 25683099.
- Aplastic Anemia: New Insights for the Healthcare Professional. ScholarlyEditions. 22 July 2013. p. 39. ISBN 9781481663182.
- Locasciulli A, Oneto R, Bacigalupo A, et al. (2007). "Outcome of patients with acquired aplastic anemia given first line bone marrow transplantation or immunosuppressive treatment in the last decade: a report from the European Group for Blood and Marrow Transplantation (EBMT)". Haematologica. 92 (1): 11–8. doi:10.3324/haematol.10075. PMID 17229630.
- Gale, Robert Peter (1981-10-01). "Aplastic Anemia: Biology and Treatment". Annals of Internal Medicine. 95 (4): 477–94. doi:10.7326/0003-4819-95-4-477. ISSN 0003-4819. PMID 6116472.
- Tisdale JF, Maciejewski JP, Nunez O, et al. (2002). "Late complications following treatment for severe aplastic anemia (SAA) with high-dose cyclophosphamide (Cy): follow-up of a randomized trial". Blood. 100 (13): 4668–4670. doi:10.1182/blood-2002-02-0494. PMID 12393567.
- "NIH Clinical Center: Clinical Center News, NIH Clinical Center". Retrieved 2007-12-04.
- Gamper CJ (Nov 2016). "High-Dose Cyclophosphamide is Effective Therapy for Pediatric Severe Aplastic Anemia". Journal of Pediatric Hematology/Oncology. Journal of Pediatric Hematology Oncology. 38 (8): 627–635. doi:10.1097/MPH.0000000000000647. PMC 5074865. PMID 27467367.
- DeZern, Amy E; Brodsky, Robert A (10 January 2014). "Clinical management of aplastic anemia". Expert Review of Hematology. 4 (2): 221–230. doi:10.1586/ehm.11.11. PMC 3138728. PMID 21495931.
- Scheinberg, Phillip; Young, Neal S. (April 19, 2012). "How I treat acquired aplastic anemia". Blood. 120 (6): 1185–96. doi:10.1182/blood-2011-12-274019. PMC 3418715. PMID 22517900. Free Text
- Kamio, T.; Ito, E.; Ohara, A.; Kosaka, Y.; Tsuchida, M.; Yagasaki, H.; Mugishima, H.; Yabe, H.; Morimoto, A.; Ohga, S.; Muramatsu, H.; Hama, A.; Kaneko, T.; Nagasawa, M.; Kikuta, A.; Osugi, Y.; Bessho, F.; Nakahata, T.; Tsukimoto, I.; Kojima, S. (21 March 2011). "Relapse of aplastic anemia in children after immunosuppressive therapy: a report from the Japan Childhood Aplastic Anemia Study Group". Haematologica. 96 (6): 814–819. doi:10.3324/haematol.2010.035600. PMC 3105642. PMID 21422115.
In the present study, the cumulative incidence of relapse at 10 years was relatively low compared to that in other studies mainly involving adult patients. A multicenter prospective study is warranted to establish optimal therapy for children with aplastic anemia.
- Flexner, Stuart; Hauck, Leonore, eds. (1993). Random House Unabridged Dictionary (2nd ed.). New York City: Random House. p. 98. ISBN 0-679-42917-4.
- Flexner, Stuart; Hauck, Leonore, eds. (1993). Random House Unabridged Dictionary (2nd ed.). New York City: Random House. p. 78. ISBN 0-679-42917-4.
- "What is aplastic anaemia?".
- "December Is National Aplastic Anemia Awareness Month" (PDF).
- Issaragrisil, Surapol; Kaufman, David W.; Anderson, Theresa; Chansung, Kanchana; Leaverton, Paul E.; Shapiro, Samuel; Young, Neal S. (2006-02-15). "The epidemiology of aplastic anemia in Thailand". Blood. 107 (4): 1299–1307. doi:10.1182/blood-2005-01-0161. ISSN 0006-4971. PMC 1895423. PMID 16254144.
- Moore, Christine A.; Krishnan, Koyamangalath (2019), "Aplastic Anemia", StatPearls, StatPearls Publishing, PMID 30480951, retrieved 2019-12-05
- "Aplastic Anemia".
- Rollyson, Carl (2004). Marie Curie: Honesty In Science. iUniverse. p. x. ISBN 978-0-595-34059-0.
- "Health". in Beasley, Maurine Hoffman; Holly Cowan Shulman; Henry R. Beasley (2001). The Eleanor Roosevelt Encyclopedia. Greenwood Publishing Group. pp. 230–32. ISBN 978-0-313-30181-0. Retrieved December 10, 2012.
- "AMA Motorcycle Museum Hall of Fame | Donny Schmit". www.motorcyclemuseum.org.
- "Oncologist Discusses Advancements In Treatment And The Ongoing War On Cancer". NPR.org. October 28, 2015.
- Pavese, Antonella (22 October 2006). "The life and times of Demetrio Stratos". AntonellaPavese.com. Retrieved 19 August 2019.
- Danchev, Alex (1991). "The Strange Case of Field Marshal Sir John Dill" (PDF). cambridge.org.com. Retrieved 15 October 2019.