Hypoplastic and aplastic anemias

Hypoplastic or aplastic anemias are total or partial inhibition of hemopoietic processes. Any hypo- and aplastic anemia is accompanied by leukoand thrombocytopenia. When speaking about anemia we only emphasize the main syndrome (anemic) which determines clinical manifestations.

There are congenital and developed anemias.

According to their course they are divided into acute, subacute, chronic hypo- and aplastic anemias.

The etiology is different. The factors causing it may be exogenic and endogenic.

Endogenic:

1. Endocrine (hypothyroidism, thymus tumors.

2. Genuine (Ehrlich's aplastic anemia).

3. Osteomyelosclerosis. Exogenic:

1. Radiation lesions (x-rays, radium radiation, atomic energy).

2. Chemical (benzene, cytostatic preparations, etc.

3. Toxicoallergic:

a) medicinal (pyramidon, barbiturates, sulfanilamides);

b) antibiotics (Chloromycetin).

4. Infectious.

Congenital hypo- and aplastic anemias include:

Family anemia. It develops in childhood and occurs against the background of clearly marked endocrine insufficiency (dwarfism, infantilism, undeveloped thumb phalanges, testis atrophy).

Pathology: Clearly marked oligemia of all organs, bone marrow aplasia, atrophy of testes, thyroid and pituitary glands. The etiology is unknown.

Ehrlich's aplastic anemia It is a rare condition, mainly occurring in the young people. It is characterized by progressive anemia, hemorrhages, necrotic

phenomena and sepsis. The disease has either acute or subacute course.

The etiology is unknown.

Osteosclerotic anemia. There are two forms:

a) Marble disease which develops in childhood and is accompanied by obliteration of the bone marrow cavity. The bone looks like a solid mass resembling marble.

The etiology and pathogenesis are unknown but is considered that the course is parathyroid gland dysfunction.

b) Osteomyelosclerosis is observed mainly in elderly people, it is chronic subleukemic myelosis. Anemia develops due to substitution of bone-marrow spaces by osseous and osteoid tissues, i.e. due to osteosclerosis.

Aplastic and hypoplastic anemias can occur at destruction of the bone marrow by cancer metastases.

Anemias due to increased destruction of blood (hemolysis)

This group includes the conditions which develop when hemolysis prevails over hemopoiesis. There are congenital (family) and developed types of the disease.

One forms are due to hereditary defects of erythrocytes (erythrocytopathy or hemoglobinopathy), the other occur in persons due to different extra-erythrocyte causes which cause hemolysis. Therefore, there are two groups of hemolytic anemias: erythrocyte and extra-erythrocyte. Erythrocyte (intracellular) are

characterized by extravascular hemolysis and splenomegaly (splenic hemolysis).

Extra-erythrocyte anemias develop due to intravascular hemolysis and are accompanied by hemoglobinuria (renal hemolysis).

Hemolytic anemias due to extravascular hemolysis are congenital, hereditary conditions.

Destruction of erythrocytes occurs mainly in macrophages of the spleen, in the bone marrow, liver and lymphatic nodes. Therefore, splenectomy is indicated in such patients. This group of anemias is characterized by three signs: jaundice, splenomegaly, anemia. It includes the following forms of the disease: congenital (family) spherical-cell anemia, sickle-cell anemia, thalassemia, or Cooley's anemia.

Spherical-cell anemia is characterized by congenital spherocytosis (erythrocytes are small, spherical, brightly colored, without light center, with decreased resistance. These abnormal erythrocytes are destroyed in cells of reticuloendothelial system (mainly in the spleen).

The first sign of the disease is jaundice, it is followed by splenomegaly and anemia.

Sickle-cell anemia and thalassemia are hemoglobinopathies (conditions due to abnornmal hemoglobin in the erythrocytes).

The cause of cickle-cell anemia is congenital insufficiency of erythrocytes due to presence of S-hemoglobin (S-corresponds to sickle). The condition is characterized by presence of sickle-like erythrocytes revealed during crisis, they cause stasis, hemorrhages,

infarctions. Siderofibrosis caused by hemosiderin accumulation develops due to increased decay of sickle-like erythrocytes in the spleen.

Thalassemia (target cell anemia, Cooley's anemia) was described in the USA in the emigrants from the Mediterranean basin. It occurs in children and is characterized by: 1) progressive anemia with erythroblastemia, 2) enlargement of the spleen and liver, 3) increased hemolysis, 4) osteoporosis causing changes in the facial bones.

Acute hemolytic anemia develops in poisoning with hemolytic poisons (those of snakes and mushrooms, phosphorus, etc.), in burns, sepsis, malaria, transfusion of incompatible blood, fetal erythroblastosis. The latter occurs due to rhesus incompatibility of the mother's and fetus's blood.

Fetal erythroblastosis is a reaction of the bone marrow to the blood decay caused by maternal anti-rhesus agglutinins. In fetus, there is jaundice, enlargement of liver, spleen and hemorrhagic diathesis. The blood is characterized by anemia with great amount of erythroblasts (up to 50%), leukocytosis.

There are 3 types of hemolytic disease of newborn: 1) edematous, 2) with jaundice, 3) without jaundice.

Favism is acute hemolytic anemia caused by eating beans (Vicia fava) or inhalation of their pollen. It may be observed in Italy. Hemosiderosis in favism is connected with congenital deficiency of enzymie system of erythrocytes with deficiency of glucoso-6-phosphate.

Recently, autoaggressive hemolytic anemia has

been described. Under the influence of a number of medicines, bacteria, viruses, autoantibodies with specific agglutinating properties develop in the organism.

Hemolytic anemias are characterized by jaundice, hemoglobinuria, hemosiderosis.

LEUKEMIAS

Leukemias are malignant neoplasms of the hematopoietic stem cells characterized by diffuse replacement of the bone marrow by neoplastic cells.

Hemoblastoses (tumors of blood system) are divided into 2 groups: 1) leukemias — systemic tumors diseases of hemopoietic tissue; 2) lymphomas — regional tumorous diseases of hemopoietic and/or lymphatic tissue. Etiology is not completely known. There is no doubt that leukemia is polyetiologic disease. It develops due to a number of mutagenic factors:

• viruses (retrovirus HTLV-1, HTLV-2, Epstein-Barr DNA virus);

• ionizing radiation;

• chemical substances (benspyren, diben-santracen);

• hereditary factors (in chronic myeloid leukoses, reduction of autosome of the 22nd pair of leukoses cell chromosome is observed).

Thus, mutation theory of leukoses pathogenesis may be the most probable.

Classification

1. Leukemias.

1.1. Acute leukemias: 1) undifferentiated, 2) myeloblast, 3) lymphoblast, 4) plasmoblast, 5) monoblast, 6) erythromyeloblast; 7) megacaryo-blast.

1.2. Chronic leukoses.

a) of myelocyte origin: 1) chronic myeloid, 2) chronic erythromyelosis, 3) erythremia, 4) true polycytemia (Vaquez-Osler syndrome).

b) of lymphocyte origin: 1) chronic lympho-leukosis, 20 skin lymphomatosis (Sezary's disease), 2) para-proteinemic leukoses: a) myeloma, b) primary macroglobulinemia (Valdenstrem's disease), c) heavy chain disease (Franklin's disease).

c) of monocyte origin: 1) chronic monocyte leukoses, 2) histiocytosis.

2. Lymphomas — regional tumors: 1) lymphosarcoma: lymphocyte, prolymphocyte, lymphoblast, immunoblast, lymphoplasmocyte, African lymphoma (Burkitt's); 2) mycosis fungoides; 3) Sezary's disease; 4) reticulosarcoma; 5) lymphogranulomatosis (Hodg-kin's disease).

The above classification is based on histogenetic principles, that is the type of the proliferating cell clone is taken into account.

The division into chronic and acute leukemia is based on the presence of blasts (immature) or cytic (mature) cells. If blasts are revealed, acute leukemia

is diagnosed, if mature cells are found, the disease is chronic. The type of acute and chronic leukemia is established on the basis of cytochemical peculiarities of tumor cells.

In addition to histogenetic classification, there is classification based on the number of leukoses cells in 1 microl of blood:

1) leukemic (tens and hundreds thousand leukosis cells per 1 microl);

2) subleukemic (not more that 15.000 — 25.000 per 1 microl);

3) leukopenic (leukocyte count is reduced but leukosis cells can be found);

4) aleukemic (leukosiscells in the blood are absent).

Acute and chronic leukemias are characterized by the following pathomorphological syndromes:

1. Pyoid bone marrow due to proliferation of the tumor cells (mature or immature, respectively) in the bone marrow with displacement of the red sprout. Macroscopically, bone marrow is grayish-whitish.

2. Leukoses infiltration of hemopoietic organs (bone marrow, spleen, lymphatic glands) at first, then of the other organs (mucous membranes, myocardium, kidneys, brain, etc., vessels).

3. The displacement of the red sprout of the bone marrow causes anemia.

4. Severe hemorrhagic syndrome in combination with anemia and destruction of the vascular walls with

leukoses infiltration develop as a manifestation of thrombocytes formation in the bone marrow.

5. Necrotic tonsillitis, gingivitis develop due to leukoses infiltration of the oral mucosa and tonsils against the background of immunogenesis inhibition.

6. Secondary infection often accompanies the process, sepsis may develop.

7. Foci of extramedullar hemopoiesis develop in the liver, spleen, kidneys, lymphatic glands as compensatory adaptation reaction directed to restoration of the red sprout.

Distinctive features of acute and chronic leukaemias are:

1. Bone marrow and blood picture (In acute leukoses the blasts are observed, in chronic leukoses the mature cells are found).

2. Leukemic failure (hiatus leucemicus) characterizes acute leukoses. It is sharp increase of blast count and single mature elements while transitional forms are absent.

3. Sharp enlargement of the spleen, liver, kidneys and lymphatic glands characterizes chronic leukoses while in chronic leukoses it is less marked. The spleen can weigh 6—8 kg, the liver 5—6 kg.

Complications and causes of death: 1) hemorrhage to vital organs (brain); 2) ulcerative necrotic and septic complications (sepsis).