Aplastic anemia

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Aplastic anemia
Classification and external resources
ICD-10

D60.-D61.

ICD-9

284

OMIM

609135

DiseasesDB

866

MedlinePlus

000554

eMedicine

med/162

MeSH

D000741

Aplastic anemia is a condition where bone marrow does not produce sufficient new cells
to replenish blood cells.[1] The condition, per its name, involves both aplasia and anemia.
Typically, anemia refers to low red blood cell counts, but aplastic anemia patients have
lower counts of all three blood cell types: red blood cells, white blood cells, and platelets,
termed pancytopenia.

Contents
[hide]

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

[edit] 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 reticulocyte counts)

[edit] Causes
In many cases, the etiology is considered to be idiopathic (cannot be determined), but one
known cause is an autoimmune disorder in which white blood cells attack the bone
marrow.
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 1 in 40,000 treatment courses, and
carbamazepine aplasia is even more rare.
Exposure to ionizing radiation from radioactive materials or radiation-producing devices
is also associated with the development of aplastic anemia.
Aplastic anemia is present in up to 2% of patients with acute viral hepatitis[citation needed].
In some animals aplastic anemia may have other causes. For example, in the ferret
(Mustela putorius furo) aplastic anemia is caused by estrogen toxicity. This is 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.
Short-lived aplastic anemia can also be a result of parvovirus infection. In humans the P
antigen (also known as globoside) is the cellular receptor for parvovirus B19 virus that
causes erythema infectiosum (fifth disease) in children. Parvovirus causes complete
cessation of red blood cell production. In most cases, this goes unnoticed, as red blood
cells live for up to 180 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.

[edit] 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 (CBC), 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

[edit] 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.[2] 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 ("graftversus-host disease").
Medical therapy of aplastic anemia often includes a short course of anti-thymocyte
globulin (ATG) or anti-lymphocyte globulin (ALG) and several months of treatment with
ciclosporin to modulate the immune system. Mild chemotherapy with agents such as
cyclophosphamide and vincristine may also be effective. Antibody therapy, such as ATG,
targets T-cells, which are believed to attack the bone marrow. Steroids are generally
ineffective[citation needed], though are often used to combat serum sickness caused by ATG
use.

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.[3]
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 famed case of Ted DeVita.[4]

[edit] Follow-up
Regular full blood counts are required to determine whether the patient is still in a state of
remission.
10-33% of all patients develop the rare disease paroxysmal nocturnal hemoglobinuria
(PNH, anemia with thrombopenia and/or thrombosis), which has been explained as 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.

[edit] Prognosis
Untreated aplastic anemia is an illness that leads to rapid death, typically within six
months. If the disease is diagnosed correctly and initial treatment is begun promptly, then
the survival rate for the next five to ten years is substantially improved, and many
patients live well beyond that length of time.[citation needed]
Occasionally, milder cases of the disease resolve on their own. Relapses of previously
controlled disease are, however, much more common. Relapse following
ATG/ciclosporin use can sometimes be treated with a repeated course of therapy.
Well-matched bone marrow transplants from siblings have been successful in young,
otherwise healthy people, with a long-term survival rate of 80%-90%. Most successful
BMT recipients eventually reach a point where they consider themselves cured for all
practical purposes, although they need to be compliant with follow-up care permanently.
[citation needed]

Older people (who are generally too frail to undergo bone marrow transplants) and people
who are unable to find a good bone marrow match, who undergo immune suppression
have five year survival rates of up to 75%.

[edit] See also

Fanconi anemia
Acquired pure red cell aplasia

[edit] References

1.
2.

^ Aplastic anemia at Mount Sinai Hospital

^ 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.
3.
^ 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): 46684670. doi:10.1182/blood2002-02-0494. PMID 12393567.
4.
^ "NIH Clinical Center: Clinical Center News, NIH Clinical Center".
http://www.cc.nih.gov/about/news/newsletter/2004/aug04/index.shtml. Retrieved 200712-04.