26.1.40. What is the essence of talassemia?

Talassemia is a hereditary hemolytic anemia, endoerythrocytory with intracellular hemolysis. It referres to quantative hemoglobinopathy as the synthesis of chains of hemoglobin molecules is damaged.

Normally a man has the following formule of hemoglobin: HbA₁ (ααββ) – 95-96%, HbA₂ (ααλλ), in a newborn – HbF (ααγγ). If the synthesis of α-chains is damaged then α-talassemia develops. Thus HbA₁, HbA₂ and HbF are not produced. Instead of α-chains red blood xells synthesize β- and γ-chains. That’s why at α-talassemia in erythrocytes pathological forms of hemoglobin appear – in adults – HbH (ββββ), in newborns – HbBart (γγγγ). HbH and HbBart are instable, thus very easily preticipate, consequently erythrocytes become of a target shape (one more name of λ-talassemia is target-cell anemia). Changed erythrocytes are phagocytized by macrophages – intracellular hemolysis develops.

At β-talassemia (Huli disease) synthesis of β-chains of hemoglobin molecules is impaired. That’s why HbA₁ is absent compensatorily the production of HbA₂ increases. In newborns synthesis of HbF is not damaged.

26.1.41. What are clinical syndromes of hemolytic anemia?

Besides hematological signs (the change of peripheral blood and red bone marrow) the following clinical signs are characteristic.

1. Hypoxy – mediated by anemia and manifestated by acute weakness, unpleasant feeling in the heart area, heart beat, dispnea.

2. Hemolytic jaundice

3. Enhanced production of bilic stones, particularly of bilirubin origin, because of considerable amount of bilirubin in bile and increase of its viscosity.

4. Hemoglobinuria develops at intravascular hemolysis. Hemoglobin which is released from impaired erythrocytes, links with blood plasma protein by gaptoglobin. 100 ml of plasma contain such amount of gaptoglobin that it can fix 125 g of hemoglobin. If the concentration of hemoglobin in blood plasma is over 125 mg %, then unfixed hemoglobin passes through renal filter and appears in the urine.

5. Splenomegaly – the enlargement of spleen, characteristic for intracellular mechanism of erythrocyte hemolysis. At the basis of it there is increase of functional activity of macrophages which causes their intense proliferation. Splenomegaly is often followed by the enlargement of liver (proliferation of hepatic macrophages).

6. Hemosiderosis – sedimentation of hemosiderin in macrophages. Hemosiderin is a partly denaturated and deproteinated ferritin, protein containing a lot of iron in nonhemous form (amount of Fe in hemosiderin – 25-30%).

7. Disorders of microcirculation often develop at intense intravascular hemolysis and mediated by the development of DBC-syndrome.

8. Fever develops as a result of acute activation of phagocytory function of macrophages which consequently excrete interleukin.

26.1-3. Anemias due to disorders of erythropoiesis.

26.1.42. How can anemia connected with the disorders of erythropoiesis?

1. Due to the origin of anemia connected with disorders of erythropoieses can be acquired and hereditary.

2. Due to the aetiology:

1. myelotoxic, developed as a result of impaired hemopoetic cells undergoing exogene factors (radiation, chemical agents, viruses) and endogene factors (immune factors, toxic products of metabolism).

2. deficient – the cause of its development is the deficiency of factors necessary for hematosis – deficiency of iron, proteins, vitamins B₆ and B₁₂, folic acid.

3. disregulatory, develop as result of disregulation of erythropoiesis (disorders of interrelation of erythropoietins and inhibitors of erythropoiesis at renal failure, impairment of stroma, composing microinvironment for hemopoietic cells).

4. connected with the decrease of erythropoiesis, is a result of replacement of hemopoietic tissue by leucemic cells, connective tissue (fibrosis), metastases of tumors.

3. Due to the essence of processes which are at the basis of the development of anemia:

1. disorders of erythrocyte production: deficiency of hemopoietic cells as a result of their impairment or replacement, disorders of reproduction hemopoietic cells, defects of maturation erythrocytes and their exit into the blood stream (ineffective erythropoiesis)

2. disorders of hemoglobin synthesis: deficiency of iron, disorders of porfirins synthesis (hereditary protein disorders, lead poisoning,deficiency of vitamin B₆, disfunctions of synthesis of protein chains of hemoglobin molecules).