Aplastic anemia is a disease in which the bone marrow, and the blood stem cells that
reside there, are damaged.
This causes a deficiency of all three blood cell types: red blood cells, white blood cells,
and platelets.
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.
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.
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.
In February 2014, the oral thrombopoietin analog eltrombopag was approved by the FDA
for the treatment of patients who are refractory to immunosuppression.
This additional treatment option is the first of its class, and represents a significant
advancement in the prognosis and treatment of patients with aplastic anemia.
Signs and symptoms Anemia with malaise, pallor and associated
symptoms such as palpitations Thrombocytopenia, leading to increased risk
of hemorrhage, bruising and petechiae Leukopenia, leading to increased risk of infection
Reticulocytopenia Causes
Aplastic anemia can be caused by exposure to chemicals, drugs, radiation, infection,
immune disease, and heredity; in about half the cases, the cause is unknown.
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.
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.
Aplastic anemia is present in up to 2% of patients with acute viral hepatitis.
One known cause is an autoimmune disorder in which white blood cells attack the bone
marrow.
Short-lived aplastic anemia can also be a result of parvovirus infection.
In humans, the P antigen is the cellular receptor for parvovirus B19 virus that causes erythema
infectiosum in children.
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, however, parvovirus infection can
lead to severe anemia.
In some animals, aplastic anemia may have other causes.
For example, in the ferret, 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.
Diagnosis The condition needs to be differentiated from
pure red cell aplasia.
In aplastic anemia, the patient has pancytopenia 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.
History of iatrogenic exposure to cytotoxic chemotherapy: can cause transient bone marrow
suppression X-rays, computed tomography scans, or ultrasound
imaging tests: enlarged lymph nodes, kidneys and bones in arms and hands
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
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.
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.
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 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 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.
New treatment options include eltrombopag, which has shown promise as treatment for both
moderate aplastic anemia, as well as severe aplastic anemia that's refractory to traditional
immunosuppression.
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.
In the past, before the above treatments became available, patients with low leukocyte counts
were often confined to a sterile room or bubble, as in the case of Ted DeVita.
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, 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 5-year survival 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 has been shown to be 82%
for patients underneath the age of 20, 72% for those 20–40 years of age and closer
to 50% for patients over the age of 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 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%.
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.
Milder disease can resolve on its own.
See also Fanconi anemia
Acquired pure red cell aplasia References
External links Aplastic Anemia & MDS International Foundation
Mayo Clinic University of Texas
MedlinePlus Encyclopedia 000554—Idiopathic aplastic anemia
MedlinePlus Encyclopedia 000529—Secondary aplastic anemia
The Aplastic Anaemia Trust Shannon's Trust, support for people with aplastic
anemia