Aplastic anemia

From Wikipedia, the free encyclopedia

Aplastic anemia
Classification and external resources
Specialty

Oncology, hematology

ICD-10

D60-D61

ICD-9-CM

284

OMIM

609135

DiseasesDB

866

MedlinePlus

000554

eMedicine

med/162

MeSH

D000741

Aplastic anemia (AA) is a disease in which the bone marrow, and the blood stem
cells that reside there, are damaged.[1] This causes a deficiency of all three blood
cell types (pancytopenia): red blood cells (anemia), white blood cells (leukopenia),
and platelets (thrombocytopenia).[2][3] Aplastic refers to inability of the stem cells to
generate the mature blood cells.
It is most prevalent in people in their teens and twenties, but is also common
among the elderly. It can be caused by exposure to chemicals, drugs, radiation,
infection, immune disease, and heredity; in about half the cases, the cause is
unknown.[2][3]
The definitive diagnosis is by bone marrow biopsy; normal bone marrow has 30-70%
blood stem cells, but in aplastic anemia, these cells are mostly gone and replaced
by fat.[2][3]
First line treatment for aplastic anemia consists of immunosuppressive drugs,
typically either anti-lymphocyte globulin or anti-thymocyte globulin, combined with
corticosteroids and cyclosporine. Hematopoietic stem cell transplantation is also
used, especially for patients under 30 years of age with a related, matched marrow
donor.[2][3]
Contents

1 Signs and symptoms

2 Causes

3 Diagnosis

4 Treatment
o

4.1 Follow-up

5 Prognosis

6 See also

7 References

8 External links

Signs and symptoms

Anemia with malaise, pallor and associated symptoms such as palpitations

Thrombocytopenia (low platelet counts), leading to increased risk of

hemorrhage, bruising and petechiae

Leukopenia (low white blood cell count), leading to increased risk of infection

Reticulocytopenia (low counts of reticulocytes, that is, immature red blood

cells)

Causes
Aplastic anemia can be caused by exposure to certain chemicals, drugs, radiation,
infection, immune disease, and heredity; in about half the cases, the cause is
unknown.[2][3]
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 is followed by aplasia in less
than one in 40,000 treatment courses, and carbamazepine aplasia is even rarer.
[citation needed]

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. [4]
Aplastic anemia is present in up to 2% of patients with acute viral hepatitis.[5]

One known cause is an autoimmune disorder in which white blood cells attack the
bone marrow.[citation needed]
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. [citation needed]
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. [citation needed]
Diagnosis
The condition needs to be differentiated from pure red cell aplasia. In aplastic
anemia, the patient has pancytopenia (i.e., anemia, neutropenia 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:
1. Bone marrow aspirate and biopsy: to rule out other causes of pancytopenia
(i.e. neoplastic infiltration or significant myelofibrosis).
2. History of iatrogenic exposure to cytotoxic chemotherapy: can cause
transient bone marrow suppression
3. 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)
4. Chest X-ray: infections
5. Liver tests: liver diseases

6. Viral studies: viral infections

7. Vitamin B12 and folate levels: vitamin deficiency
8. Blood tests for paroxysmal nocturnal hemoglobinuria
9. Test for antibodies: immune competency
Treatment
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.[6] 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 a cyclosporin 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 Tcells, which are believed to attack the bone marrow. Corticosteroids are generally
ineffective,[citation needed] 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.[7]
One prospective study involving cyclophosphamide was terminated early due to a
high incidence of mortality, due to severe infections as a result of prolonged
neutropenia.[7]
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.[8]
Follow-up
Regular full blood counts are required 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.
Prognosis
Untreated, severe aplastic anemia has a high risk of death. Treatment, by drugs or
stem cell transplant, has a five-year survival rate of about 70%, 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 82% for patients underneath age 20, 72% for those 2040
years old, and closer to 50% 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. [9]
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 75%. [citation needed]
Relapses are common. Relapse following ATG/cyclosporin use can sometimes be
treated with a repeated course of therapy. In addition, 10-15% of severe aplastic
anemia cases evolve into MDS and leukemia. [citation needed]
Milder disease can resolve on its own.[citation needed]
See also

Fanconi anemia

Acquired pure red cell aplasia

Eleanor Roosevelt Cause of death.

References
1.
Acton, Ashton (22 July 2013). Aplastic Anemia. ScholarlyEditions. p. 36.
ISBN 978-1-4816-5068-7. Aplastic anemia (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 9780-07-140235-4.
Merck Manual, Professional Edition, Aplastic Anemia (Hypoplastic Anemia)
"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.
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): 118.
doi:10.3324/haematol.10075. PMID 17229630.
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.
Scheinberg, Phillip; Young, Neal S. (April 19, 2012). "How I treat acquired aplastic
anemia". Blood 120 (6): 118596. doi:10.1182/blood-2011-12-274019.
PMC 3418715. PMID 22517900. Free Text