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Aplastic Anaemia

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Aplastic anemia
Definition
Aplastic anemia is a condition where bone marrow does not produce sufficient new cells to replenish blood cells. 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.
Causes
Congenital or inherited causes
Congenital or inherited causes of aplastic anemia (20%) include the following:
• Patients usually have dysmorphic features or physical stigmata; on occasion, marrow failure may be the initial presenting feature.
• Fanconi anemia
• Dyskeratosis congenita
• Cartilage-hair hypoplasia
• Pearson syndrome
• Amegakaryocytic thrombocytopenia (thrombocytopenia-absent radius [TAR] syndrome)
• Shwachman-Diamond syndrome
• Dubowitz syndrome
• Diamond-Blackfan syndrome
• Familial aplastic anemia
Acquired causes
Acquired causes of aplastic anemia (80%) include the following:
• Idiopathic factors
• Infectious causes, such as hepatitis viruses, Epstein-Barr virus (EBV), human immunodeficiency virus (HIV), parvovirus, and mycobacteria
• Toxic exposure to radiation and chemicals, such as benzene
• Transfusional GVHD
• Orthotopic liver transplantation for fulminant hepatitis
• Pregnancy
• Eosinophilic fasciitis
Drugs and elements, such as chloramphenicol, phenylbutazone, and gold, may cause aplasia of the marrow.
Staging
Staging of aplastic anemia is based on the criteria of the International Aplastic Anemia Study Group, as follows:
• Blood - Neutrophils less than 0.5 X 109/L; platelets less than 20 X 109/L; reticulocytes less than 1% corrected (percentage of actual hematocrit [Hct] to normal Hct)
• Marrow - Severe hypocellularity; Moderate hypocellularity, with hematopoietic cells representing less than 30% of residual cells
Severe aplasia is defined as including any 2 or 3 peripheral blood criteria and either marrow criterion.
A further subclassification developed after the recognition that individuals with neutrophil counts lower than 0.2 X 109/L had very severe aplastic anemia (VSAA). This group is less likely than others to respond to immunosuppressive therapy.
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)
Diagnosis
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.
• 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").
• 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 cyclosporin 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, 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.
• 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.
• 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.
Complications
• infections and bleeding.
• Complications of bone marrow transplantation (BMT), used in the treatment of aplastic anemia, include graft versus host disease (GVHD) and graft failure.
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.
• 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
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%.
Patient education
Patients should maintain hygiene to reduce the risks of infection.
Clinicians must stress the need for compliance with therapy.
For patient education information, see the Blood and Lymphatic System Center, as well as Anemia.

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