Aplastic anemia (hypoplastic anemia): causes, symptoms, diagnosis, treatment

Aplastic anemia (hypoplastic anemia) is a normochromic-normocytic anemia that results from depletion of hematopoietic precursors, leading to bone marrow hypoplasia and decreased red blood cell, white blood cell, and platelet counts. Symptoms are caused by severe anemia, thrombocytopenia (petechiae, bleeding), or leukopenia (infections). Diagnosis requires peripheral pancytopenia and absence of hematopoietic precursors in the bone marrow. Treatment includes equine antithymocyte globulin and cyclosporine. Erythropoietin, granulocyte-macrophage colony-stimulating factor, and bone marrow transplantation may be effective.

The term aplastic anemia refers to bone marrow aplasia, which is associated with leukopenia and thrombocytopenia. Partial erythroid aplasia is limited to the erythroid series. Although these two diseases are rare, aplastic anemia is more common.

[ 1 ], [ 2 ]

Causes aplastic anemia

Typical aplastic anemia (most common in adolescents and young adults) is idiopathic in about 50% of cases. It is known to be caused by chemicals (e.g., benzene, inorganic arsenic), radiation, or drugs (e.g., cytostatics, antibiotics, nonsteroidal anti-inflammatory drugs, anticonvulsants, acetazolamide, gold salts, penicillamine, quinacrine). The mechanism is unknown, but manifestations of selective hypersensitivity (possibly genetic) are the basis for the development of the disease.

[ 3 ], [ 4 ], [ 5 ]

Symptoms aplastic anemia

Although the onset of aplastic anemia is gradual, often weeks or months after exposure to toxins, it can also be acute. Signs depend on the severity of pancytopenia. The severity of symptoms and complaints characteristic of anemia (e.g., pallor) is usually very high.

Severe pancytopenia causes petechiae, ecchymosis, and bleeding of the gums, retinal hemorrhage, and other tissues. Agranulocytosis is often accompanied by life-threatening infections. Splenomegaly is absent unless induced by transfusion hemosiderosis. Symptoms of partial erythroid aplasia are usually less intense than those of aplastic anemia and depend on the degree of anemia or associated diseases.

[ 6 ], [ 7 ]

Forms

A rare form of aplastic anemia is Fanconi anemia (a type of familial aplastic anemia with skeletal abnormalities, microcephaly, hypogonadism, and brown skin pigmentation), which occurs in children with chromosomal aberrations. Fanconi anemia is often latent until concomitant diseases (usually acute infectious or inflammatory diseases) occur, causing peripheral pancytopenia. With the elimination of concomitant diseases, peripheral blood counts return to normal, despite the decrease in bone marrow cellularity.

Partial erythroid aplasia may be acute or chronic. Acute erythroblastopenia is the disappearance of erythropoiesis precursors from the bone marrow during an acute viral infection (especially human parvovirus), more often occurring in children. The longer the acute infection, the longer the anemia lasts. Chronic partial erythroid aplasia is associated with hemolytic diseases, thymoma, autoimmune processes, and less commonly with medications (tranquilizers, anticonvulsants), toxins (organic phosphates), riboflavin deficiency, and chronic lymphocytic leukemia. A rare form of congenital Diamond-Blackfan anemia usually manifests itself in infancy, but may also occur in adulthood. This syndrome is accompanied by abnormalities of the finger bones and short stature.

[ 8 ], [ 9 ], [ 10 ], [ 11 ], [ 12 ], [ 13 ]

Diagnostics aplastic anemia

Aplastic anemia is suspected in patients with pancytopenia (eg, white blood cells < 1500/μl, platelets < 50,000/μl), particularly at a young age. Partial erythroid aplasia is suspected in patients with skeletal abnormalities and normocytic anemia. If anemia is suspected, bone marrow examination is necessary.

In aplastic anemia, the red blood cells are normochromic-normocytic (sometimes borderline macrocytic). The white blood cell count is reduced, predominantly granulocytes. The platelet count is often less than 50,000/μl. Reticulocytes are reduced or absent. Serum iron is increased. Bone marrow cellularity is sharply reduced. In partial erythroid aplasia, normocytic anemia, reticulocytopenia, and increased serum iron levels are determined, but with normal white blood cell and platelet counts. Bone marrow cellularity and maturation may be normal, except for the absence of erythroid precursors.

[ 14 ], [ 15 ], [ 16 ], [ 17 ]

Treatment aplastic anemia

In aplastic anemia, the therapy of choice is equine antithymocyte globulin (ATG) 10 to 20 mg/kg diluted in 500 ml saline and administered intravenously over 4 to 6 hours for 10 days. About 60% of patients respond to this therapy. Allergic reactions and serum sickness may occur. All patients should undergo a skin test (to determine allergy to horse serum), and glucocorticoids are additionally prescribed (prednisolone 40 mg/m2 ^orally daily for 7-10 days or until symptoms of complications subside). Effective therapy is the use of cyclosporine (5 to 10 mg/kg orally daily), which causes a response in 50% of patients who have not responded to ATG. The most effective is a combination of cyclosporine and ATG. In the presence of severe aplastic anemia and the absence of a response to a course of ATG/cyclosporine, bone marrow transplantation or treatment with cytokines (EPO, granulocyte or granulocyte-macrophage colony-stimulating factors) may be effective.

Stem cell or bone marrow transplantation may be effective in younger patients (especially those under 30 years of age), but requires an HLA-matched sibling or unrelated donor skin. HLA typing of siblings is necessary at diagnosis. Because transfusions impair the effectiveness of subsequent transplantation, blood products should be given only when absolutely necessary.

Cases of successful use of immunosuppressive therapy (prednisolone, cyclosporine or cyclophosphamide) in partial erythroid aplasia have been described, especially when an autoimmune mechanism of the disease is suspected. Since the condition of patients with partial erythroid aplasia against the background of thymoma improves after thymectomy, CT is performed to search for such a lesion and the question of surgical treatment is considered.