Aplastic anemia is a rare but dangerous blood disorder. If someone has the disease, the bone marrow does not have enough new blood cells. The causes are:
Exposed to toxic substances such as pesticides, arsenic, and benzene
Radiation therapy and chemotherapy for cancer
Some medications
Infections such as hepatitis, Epstein-Barr virus, or HIV
Autoimmune disorders
In many people, the cause is unknown.
Aplastic anemia is a disease that begins acutely and noisily, and the patient usually ends in cytopenia (decreased production of all blood cell lines, including hemoglobin below 10, platelets below 100,000, and neutrophil counts below 1500) and decreased Clearly the mother brain is a bone marrow. The disease was first described by Paul Erlich in 1888. Ehrlich discovered that an autopsy of bone marrow samples from a young woman who died of severe anemia and neutropy (neutrophil depletion) Were severely hypoplastic (reduced bone marrow cells). In patients with severe aplastic anemia, the number of multinucleated bone marrow stem cells is much lower than in normal individuals, even if the bone marrow tissue cells are active and even the level of stimulatory cytokines is increased.
Aplastic anemia is an uncommon disease with an incidence of one to five cases per million. The disease has two age types, one in young people 20 to 25 years old and one in the elderly (60 to 65 years old). Its prevalence is the same in men and women.
Its incidence in developing countries (Thailand, China) is 3 times that of Western industrialized countries (Europe and Israel). This difference can not be explained by differences in medication or radiation exposure.
Cause of aplastic anemia
The etiology of aplastic anemia can be divided into 2 categories:
- Acquired ((acquired
- Congenital ((constitutional
1) The known causes of acquired aplastic anemia are many. Which includes the following:
- Drugs (dose-dependent): Chemotherapy drugs, antibiotics (chloramphenicol, trimethoprim, sulfamethoxazole) idiosyncratic (many cases not proven): chloramphenicol, quinacarbon, nonsteroidal anti-inflammatory drugs, anticonvulsants, anticonvulsants, , Cimetidine, penicillamine
- Toxins: benzene and other hydrocarbons, insecticides
- Viral infections: hepatitis, Epstein-Barr virus (EBV), human immunodeficiency virus (HIV) and
- Immune disease: Transplant host disease in immunodeficiency, hypogammaglobulinemia, nocturnal hemoglobinuria and…
- Radiation
- Pregnancy
These factors directly damage the proliferation and differentiation of hematopoietic stem cells by damaging DNA. In contrast to treatments such as cytotoxic chemotherapy (especially alkylating drugs) or radiation therapy, they target all cells with a rapid growth cycle and often cause reversible bone marrow aplasia. Despite all these acquired causes, most cases of aplastic anemia are idiopathic.
2) A small percentage of cases of aplastic anemia occur in the context of congenital disorders of bone marrow failure. These disorders include Fanconi anemia, Men and I syndrome, and congenital dyskeratosis.
The most common congenital cause of aplastic anemia is Fanconi anemia, which is an autosomal recessive disorder whose DNA becomes sensitive to cross-linking and mutations in the genes of the DNA repair protein donors.
Acquired and congenital aplastic anemia appear to be etiologically related through abnormal maintenance of telomerase (an enzyme that retains long telomeres, stops growth, and increases cell life). .
In congenital dyskeratosis, which is an autosomal dominant disease, there are mutations in the telomerase complex gene that predispose them to premature aging and increased bone marrow failure due to accelerated telomere shortening.
One-third of patients with acquired aplastic anemia are also likely to have a combination of genetic, environmental, epigenetic, and environmental factors. They have short telomeres.
Clinical manifestations of aplastic anemia
Patients with aplastic anemia often have symptoms of complainant cytopia, including weakness, fatigue, shortness of breath or palpitations due to anemia, bleeding gums, epistaxis, palpitations due to low platelet count, and recurrent bacterial infection. Deficiency or inefficiency of neutrophils.
Their physical examination is often normal, except that those with congenital aplastic anemia may have a variety of abnormalities.
Patients with aplastic anemia are more likely to present with a symptom of bleeding (due to platelet depletion) and are more likely to present with bleeding in the front of the mucosa and are less likely to experience an infection because the disease has a rapid onset and does not allow the patient to Decreased neutrophils become infected.
Laboratory evaluation of aplastic anemia
To diagnose the disease, bone marrow biopsies must be taken and cells reduced (hypocellularity) observed, thus excluding other bone marrow processes.
Normal bone marrow cellularity reaches 30-30% by the age of 70 and then below 20%. But in aplastic anemia it goes below 20% (5-15%) and instead a lot of fat accumulates in the bone marrow and its hematopoietic cells are few if any, but mainly plasma cells and primary lymphocytes. In the bone marrow of these people, less than 1% of the progenitor cells are normal. Stem cells are significantly functional and their ability to differentiate in the laboratory is reduced.
In young patients, the diagnosis of Fanconi anemia is definitive if the cultured cells become sensitive to methidemycin or dipoxybutane and become chromosomally damaged.
Patients with aplastic anemia have a predominant reticulocyte count, few blood cells, and large red blood cells in the peripheral blood.
Treatment of aplastic anemia
Treatment of aplastic anemia depends on the severity of the disease. Patients with mild cytopenia can be expected to follow up. But patients with severe aplastic anemia are defined by peripheral blood cell counts (which are platelet counts less than 20,000 ml, neutrophil counts less than 500 ml anemia with corrected reticulocyte counts less than 1%, and bone marrow cellularity 5% to 10%. The average survival will be slightly moderate without treatment, which is between 12 and 6 months. Because most patients die from debilitating infections, supportive care with broad-spectrum antibiotics as well as antiviral and antifungal medications may be necessary in patients with severe neutropenia. In patients with severe symptoms, platelet and red blood cell injections are helpful.
The current therapeutic approach for aplastic anemia focuses on the replacement of defective stem cells through stem cell transplantation or the control of extreme immune responses. All young patients with severe aplastic anemia should have an allogeneic bone marrow transplant if a bone marrow donor is compatible with HLA. This is done with the aim of restoring stem cell function to normal, and is the only method that may lead to definitive healing.
However, the long life expectancy of patients younger than 3 years who are transplanted from a sibling is excellent. (75 to 95%), but the complications of transplantation and the control of long-term complications are a persistent problem that patients face. The outcome is disappointing in patients older than 4 years or those who have been transplanted without a suitable HLA donor.
The possible mechanism of drug-induced aplasia has led to the emergence of new methods for the treatment of aplastic anemia in older patients or patients for whom no suitable donor can be found. Treatment with a combination of anti-thymocyte globulin or anti-lymphocyte globin with cyclosporine (a specific inhibitor of T cells) has allowed bone marrow function to be restored in 70-80% of patients and has increased the 5-year survival rate to 90%. Side effects of ALG and ATG include anaphylaxis and serum sickness from horse and rabbit antigens present in the antiserum, which usually resolve on their own. Recurrence occurs in most patients and can be treated with ALG, ATG, new immunosuppressive drugs, androgens, and experimental drugs. Treatment with traditional chemotherapy drugs such as cyclophosphamide is usually too toxic. Because the production of endogenous cytokines is high in patients with aplastic anemia, the use of growth factors such as rhG-CST or erythropoietin or stem cell agents will not be effective. However, in refractory patients, long-term administration of cytokine compounds is somewhat effective in maintaining blood cell counts. Patients who survive after initial treatment are at risk for disorders such as myelodysplasia, leukemia, and invasive PNH’s nocturnal hemoglobinuria. The association between these clonal disorders and the pathogenesis of aplastic anemia is unclear.
