Hemolytic anemias

Mechanisms and localization of hemolysis

The pathological process consists of the premature destruction of red blood cells with the release of hemoglobin into the environment. This process can occur in two compartments:

• Intracellular hemolysis. Occurs directly within the cells of the reticuloendothelial system (RES), primarily in the spleen. It can be either entirely physiological (natural cellular aging) or pathological.
• Intravascular hemolysis. Occurs directly within the bloodstream and is a sign of serious pathology in one hundred percent of cases.

The course of the syndrome can be acute or chronic. The body attempts to compensate for the loss by sharply increasing erythropoiesis. As a result, a massive number of young red blood cell forms enters the bloodstream—reticulocytosis develops. The anemia itself (decreased hemoglobin and erythrocyte levels) begins only when the rate of destruction irreversibly exceeds the regenerative capacity of the bone marrow.

Etiological Classification

Dividing these into two major groups is critically important for choosing treatment tactics. All pathologies are classified as inherited or acquired.

1. Hereditary hemolytic anemias:

• Membranopathies: defects in the protein skeleton of the membrane (a classic example is hereditary microspherocytosis).
• Hemoglobinopathies: abnormalities in the synthesis or structure of globin chains (thalassemia, sickle cell disease—common in the tropics).
• Enzymopathies: genetic deficiency of enzymes within erythrocytes (e.g., glucose-6-phosphate dehydrogenase deficiency).

2. Acquired hemolytic anemias:

• Immune: destruction of one's own cells by autoantibodies.
• Pathologies with somatic membrane mutation: Marchiafava–Micheli disease (paroxysmal nocturnal hemoglobinuria).
• Mechanical: physical trauma to the cell membrane (march hemoglobinuria, prosthetic heart valves, microangiopathic destruction).
• External factors: exposure to chemical agents, infections, and parasites (severe malaria).

Hereditary microspherocytosis (Minkowski–Chauffard disease)

The underlying mechanism of the disease is increased permeability of the cell membrane to sodium ions. Water follows sodium into the cell, causing the erythrocyte to swell, lose its biconcave disc shape, and become spherical (spherocyte) while decreasing in diameter. Such cells are extremely fragile under mechanical stress, leading to intracellular destruction.

The disease is chronic. Onset typically occurs in childhood, but may also happen in old age. The leading syndrome is suprahepatic jaundice.

Laboratory findings:

• Moderate decrease in erythrocyte count, microcytosis, hyperchromia, and reticulocytosis on the hemogram.
• Elevated unconjugated bilirubin up to 50–70 µmol/L.
• Erythroid hyperplasia in the bone marrow.
• Key marker: decreased osmotic fragility of erythrocytes.
• Negative Coombs test (distinguishes it from immune forms).

Splenectomy is the treatment of choice. After the spleen is removed, destruction ceases, although the spherical shape of the cells remains with the patient for life.

Enzymopathies: G6PD deficiency

Hereditary enzyme deficiency impairs the maintenance of reduced nucleotide levels. The most common variant is glucose-6-phosphate dehydrogenase deficiency. Morphologically, this is confirmed by the presence of specific intracellular inclusions—Heinz–Ehrlich bodies (precipitates of hemoglobin derivatives).

If the enzyme deficiency is mild (about 20% of normal), an acute hemolytic crisis occurs only after the administration of oxidative drugs. Triggers include antimalarials (primaquine), sulfonamides, nitrofurans, and certain analgesics. The risk of destruction increases manifold in renal or hepatic failure due to delayed toxin clearance. In marked deficiencies, neonatal jaundice or constant spontaneous chronic destruction occurs without drug provocation.

Autoimmune hemolytic anemia (AIHA)

In this form, red blood cell damage is caused by the patient's own autoantibodies. Cells coated with antibodies are engulfed and destroyed by splenic macrophages. The process is frequently triggered by medications.

Patients complain of typical general anemia symptoms (weakness, pallor, dyspnea). The hemolytic syndrome is accompanied by fever, jaundice, and hepatosplenomegaly. In severe acute cases, shock and epigastric pain may occur.

The blood test reveals normochromic anemia, spherocytosis, and reticulocytosis. Immunological diagnostics are critically important to confirm the diagnosis. The direct Coombs test becomes decisive: adding a special serum to erythrocytes causes them to clump together (agglutination), confirming the presence of plasma proteins (IgG) fixed to the membrane. It is important to remember that the indirect Coombs test is completely uninformative here. Glucocorticoids (prednisolone) form the basis of treatment.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Pathogenesis of intravascular and intracellular hemolysis
• Differential diagnosis of suprahepatic jaundices
• Paroxysmal nocturnal hemoglobinuria (Marchiafava–Micheli disease)
• Hemoglobinopathies (sickle cell anemia, thalassemia)
• Mechanical hemolytic anemias and microangiopathic hemolysis

Other topics in the "Blood System" section

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.