Aplastic Anemia – Causes, Symptoms, Diagnosis, Evolution, Prognosis And Treatment
Apalstic anemia is a syndrome of bone marrow failure which is characterized by pancytopenia (a reduction in the number of red and white blood cells, as well as platelets) with markedly hypocellular marrow. Incidence of aplastic anemia is 2 – 5 cases/million population/year. Criteria for diagnosis of severe aplastic anemia:
Aplastic Anemia Causes
The mechanism of pathogenesis in aplastic anemia is represented by:
- Intrinsic stem cell defect.
- Failure of stromal microenvironment.
- Absence or deficiency of growth factors.
- Immune suppression of hemopoietic marrow.
The main causes of aplastic anemia are:
- Chemicals (benzene and related compounds).
- Drugs ( chloramphenicol, gold salts, D-peniciline, phenylbutazone, carbamazepine, hydantoin and derived drugs, antineoplastic drugs and acetazolamide).
- Viruses (hepatitic C virus, parvovirus B19, Epstein-Barr virus, cytomegalovirus).
- Fanconi anemia.
- Dyskeratosis congenita may evolve into aplastic anemia.
- Schwachmann – Diamond syndrome (congenital granulocyte aplasia) may evolve into aplastic anemia.
- Idiopathic (in above 65% of cases).
- Other (connective tissue diseases, pregnancy).
Aplastic Anemia Symptoms
Patients with aplastic anemia will experience symptoms which are related to the decrease in bone marrow production of blood cells. The onset of this disease is insidious and the initial symptom can be represented by bleeding or by anemia, infections and fever can also represent symptoms of aplastic anemia.
The main symptoms are represented by fatigue, headaches, loss of apetite, weight loss, dyspneea, palpitations, bleeding (epistaxis, gingival bleeding, metrorrhagia, purpura, ecchymoses after minor trauma), recurrent infections which are secondary to cytopenias.
Physical examination is generally unrevealing.
Aplastic Anemia Diagnosis
- Low reticulocyte count and possible macrocytosis.
- Low absolute neutrophil count (if <200/ul, prognosis is extremely poor).
- Negative sucrose hemolysis test and HAM test (absence of hemolysis), to rule out paroxysmal nocturnal hemoglobinuria.
- Positive HAM test (hemolysis of patients erithrocytes by normal acidified serum) and sucrose hemolysis test associated with presence of hemosiderinuria are diagnostic findings for paroxysmal nocturnal hemoglobinuria in aplastic crisis.
- Markedly hypocellular marrow, due to replacement of hemopoietic marrow by adipous tissue (not fibrosis or neoplastic cells).
- Presence of cytogenetic abnormalities suggests hypoplastic myelodysplastic syndrome rather than aplastic anemia.
Positive diagnosis of aplastic anemia is sustained by the following criteria:
Bone marrow (one of the following criteria):
- Marrow cellularity less than 25% from normal or
- Marrow cellulatity less than 50% from normal with less than 30% hemopoietic cells.
Peripheral blood (at least two of the following criteria):
- Absolute neutrophil count less than 500/ul.
- Platelet count less than 20,000/ul.
- Anemia with corrected reticulocyte index of less than 1.
Aplastic Anemia Evolution And Prognosis
Median survival of untreated severe aplastic anemia is 3 to 6 months (20% survive longer than 1 year).
Aplastic anemia is having a poor prognosis, death will occur due to complications:
- Infectious: respiratory (Gramm negative microorganisms), cutaneous.
- Hemorrhagic: epistaxis, purpura, metrorrhagia, gastrointestinal bleeding, bleeding into the central nervous system.
- Malignant: acute leukemia and myelodysplastic syndrome.
Aplastic Anemia Treatment
Bone marrow transplantation represents the only curative option:
- Major indication in patients less than 40 years of age.
- Only one-third of patients have a HLA-identical or 1 antigen mismatched donor.
- With an appropiate donor cure is achieved in 75% – 85% of previously untransfused patients, whereas only 55-60% of multiply transfused patients achive cure.
Immunosuppressive therapy is not a curative option and is represented by:
- Antithymocyte globulin (ATG)
- Cyclosporine A (CSP-A)
Androgen hormones in the treatment of moderate or severe aplastic ane is controversed because recent studies showed no efficacy as primray therapy.
Hemopoietic growth factors have been used to treat neutropenia
- Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) resulted in temporary improvement in neutrophil counts in some patients treated with this cytokines.
- Interleukin-3 (IL-3) improved temporary the absolute neutrophil count in a few patients.
- Interleukin-1 (EL-l)was not effective in a study including a small group of patients.
Other therapeutic measures:
- HLA typing of patient and siblings (ideal is the existence of a normal twin) in order to identify a HLA matched donor, marrow transplantation beeing the therapy of choice in patients less than 40 years of age.
- Transfusions should be administered only when imperious needed. In potential transplant recipients there will not be used family donors and under no circumstances the HLA matched donor.
- Platelet transfusions are used only on assessement of risk of life-threatening bleeding (not solely on platelet count). Platelet transfusions from a single donor should be used to minimize sensitization and subsequent refractoriness. When the patient has become refractory to platelet transfusions, only HLA matched donors canprovide efficient platelets.
- Red blood cells (RBC’s) transfusions are indicated when hemoglobin level is less than 7-8 g/dl. In order to reduce subsequent sesitization packed RBC’s (irradiated or washed) are to be transfused, or leukocyte-depleted blood products.
- In severe neutropenic, hospitalised patients, measures in order to reduce risk of infections shouldbe undertaken (isolation in aseptic room, no visits allowed, gloves and mask for the medical care personell).
- Prompt institution of broad spectrum antibiotics, intravenously for fever after the appropiate cultures have been obtained.