Aplastic anemia

Aplastic anemia is a group of diseases, the main symptom of which is depression of bone marrow hematopoiesis according to bone marrow aspirate and biopsy data and peripheral pancytopenia (anemia of varying severity, thrombocytopenia, leukogranulocytopenia and reticulocytopenia) in the absence of diagnostic signs of leukemia, myelodysplastic syndrome, myelofibrosis and tumor metastases. In aplastic anemia, there is a loss of all hematopoietic germs (erythroid, myeloid, megakaryocytic) and replacement of hematopoietic bone marrow with fatty tissue.

The meaning of the term "aplastic anemia" is a combination of decreased hemoglobin and red blood cell counts in the peripheral blood with depleted, inactive bone marrow. It is obvious that this term, introduced at the end of the 19th century and reflecting only the external, most striking phenomenology of a group of quite diverse diseases, is not precise. Indeed, an equally important feature of acquired aplastic anemia is the damage to the granulocytic and megakaryocytic germs. On the other hand, terms such as "hematopoiesis depressions" or "bone marrow failure syndromes" are either imprecise in essence or are broader concepts. Thus, these groups include syndromes that have fundamental etiological and/or pathogenetic differences from aplastic anemia, for example, myelodysplastic syndromes or chronic lymphocytic leukemia from large granular lymphocytes.

It should be noted that in hematological practice the term "aplastic anemia" is used only to denote acquired trilinear aplasias. Syndromes of monolinear cytopenias in combination with aplasia or reduction of the corresponding germ in the bone marrow have other names.

Trilineage aplastic anemia was first described by Paul Ehrlich in 1888 in a pregnant woman who died from a fulminant disease manifested by severe anemia, fever and hemorrhages. Ehrlich emphasized the surprising discrepancy between anemia, leukopenia and depleted bone marrow, devoid of erythroid and myeloid precursors. In fact, these two signs - pancytopenia and poor bone marrow - currently serve as the main diagnostic criteria for aplastic anemia. The study of diseases that are also accompanied by pancytopenia, but have nothing (or have little) in common with aplastic anemia, led to the addition of several more signs to the necessary criteria for the diagnosis of aplastic anemia: the absence of liver and spleen enlargement, myelofibrosis, as well as clinical and morphological signs of myelodysplastic syndrome or acute leukemia.

Currently, the generally accepted term is "aplastic anemia", which includes all forms or stages of hypo- and aplastic anemia, previously identified by various authors. The frequency in children is 6-10 cases per 1,000,000 children per year.

[ 1 ], [ 2 ], [ 3 ]

Causes of Aplastic Anemia

The cause of aplastic anemia is still not fully understood. Exogenous and endogenous etiological factors of aplastic anemia development are distinguished. Exogenous factors play a priority role in the development of the disease, including physical effects, chemicals (primarily drugs), infectious agents (viruses, bacteria, fungi).

Causes of Aplastic Anemia

[ 4 ], [ 5 ], [ 6 ], [ 7 ], [ 8 ]

Pathogenesis of aplastic anemia

According to modern concepts based on numerous cultural, electron microscopic, histological, biochemical, and enzymatic research methods, three main mechanisms are important in the pathogenesis of aplastic anemia: direct damage to pluripotent stem cells (PSCs), changes in the microenvironment of the stem cell and, as a result, inhibition or disruption of its function; and an immunopathological condition.

Pathogenesis of aplastic anemia

Symptoms

Retrospective studies have established that the average interval from exposure to the etiologic agent to the onset of pancytopenia is 6-8 weeks.

Symptoms of aplastic anemia are directly related to the degree of reduction of 3 most important indicators of peripheral blood - hemoglobin, platelets and neutrophils. The vast majority of patients with aplastic anemia consult a doctor about bleeding, and life-threatening bleeding as the first clinical manifestation of the disease is very rare.

Symptoms of Aplastic Anemia

Classification of aplastic anemia

Depending on whether there is isolated suppression of the erythroid lineage or all lineages, partial and total forms of aplastic anemia are distinguished. They are accompanied by isolated anemia or pancytopenia, respectively. The following variants of the disease are distinguished.

Classification of aplastic anemia

[ 9 ], [ 10 ]

Examination plan for patients with aplastic anemia

1. Clinical blood test, with determination of the number of reticulocytes and DC.
2. Hematocrit.
3. Blood type and Rh factor.
4. Myelograms from 3 anatomically different points and trephine biopsy, determination of colony-forming properties and cytogenetic analysis in hereditary variants of the disease.
5. Immunological examination: determination of antibodies to erythrocytes, platelets, leukocytes, determination of immunoglobulins, typing according to the HLA system, RBTL.

Diagnosis of aplastic anemia

Treatment of aplastic anemia

Bone marrow transplantation from a fully histocompatible donor is considered the treatment of choice for newly diagnosed severe aplastic anemia and should be performed immediately, since this type of treatment is most effective in children.

The long-term survival rate in children who have undergone bone marrow transplantation at early stages of the disease from a fully HLA-compatible donor is 65-90%, according to the literature. The most common type of bone marrow transplant is allogeneic, which uses bone marrow from siblings, i.e. from full brothers or sisters who have the greatest antigenic proximity to the recipient. If it is impossible to obtain bone marrow from siblings, they try to use bone marrow from other relatives or HLA-compatible unrelated donors. Unfortunately, a suitable donor can be found for only 20-30% of patients. Transplantation of incompletely compatible stem cells from donor umbilical cord blood is possible.

How is aplastic anemia treated?