Classification by origin
Hemolytic anemias are divided into two large groups depending on the cause of occurrence:
- Primary (hereditary and congenital). Associated with genetic defects of the red blood cells themselves. The pathology may lie in the membrane, enzymes, or the hemoglobin molecule.
- Secondary (acquired). Occur when initially healthy red blood cells are destroyed under the influence of external factors: antibodies, mechanical obstacles, toxins, or parasites.
Hemolysis can be intravascular (directly in the bloodstream) or extravascular (in splenic macrophages).
Primary anemias: intraerythrocytic defects
This group is caused by flaws in the structure of red blood cells:
- Membranopathies. Defect of structural proteins (protein-dependent) or lipids (lipid-dependent). Because of this, the cell shape changes (poikilocytosis), osmotic resistance drops, and the red blood cell is destroyed outside the vessels. Examples: hereditary spherocytosis, elliptocytosis. The only exception is paroxysmal nocturnal hemoglobinuria (PNH), which is acquired.
- Enzymopathies. The most frequent form is glucose-6-phosphate dehydrogenase (G6PD) deficiency. Normally, this enzyme helps restore glutathione, which protects the cell from oxidative stress. In case of deficiency, free radicals destroy membrane lipids and denature proteins (a precipitate forms). Drugs or fava beans act as triggers for hemolysis.
- Hemoglobinopathies. The synthesis of hemoglobin protein components is impaired due to point mutations. In sickle cell anemia, the amino acid valine is replaced by glutamine. Abnormal hemoglobin S is formed, which polymerizes under oxygen deficiency. The red blood cell becomes rigid, acquires a sickle shape, is destroyed in the spleen, and blocks small vessels, causing organ infarctions.
Secondary anemias: external aggression
Here, red blood cells fall victim to adverse conditions in the body:
- Immunogenic. Cells are destroyed by cytotoxic immunoglobulins. They can be autoimmune (attack on own antigens), isoimmune (destruction of foreign red blood cells during transfusion or Rhesus incompatibility), heteroimmune (reaction to a drug-hapten deposited on the membrane), and transimmune (maternal antibodies penetrate to the fetus).
- Mechanical. Red blood cells literally smash against obstacles during turbulent blood flow. Causes: arterial hypertension, artificial heart valves, DIC syndrome.
- Infectious. Hemolysis is triggered by bacterial endotoxins or parasites (e.g., malaria plasmodium).
Pathogenesis of destruction and blood picture
The universal mechanism of red blood cell death looks like this: damaging factor $\rightarrow$ increased membrane permeability $\rightarrow$ accumulation of ions (Na⁺, Ca²⁺) $\rightarrow$ hyperosmolarity of the cytosol $\rightarrow$ cell swelling (spherocytosis) $\rightarrow$ rupture of the plasmalemma.
What we see in laboratory tests:
- In the bone marrow: compensatory hyperplasia of the erythroid lineage.
- In the blood: erythropenia (except for thalassemia), reticulocytosis, polychromatophilia, and poikilocytosis.
- In biochemistry: hyperbilirubinemia due to the indirect (unconjugated) fraction.
Principles of therapy
Treatment is based on three pillars:
- Etiological. Elimination of the hemolysis trigger or replacement therapy (administration of riboflavin, glutathione).
- Pathogenetic. Prevention of cell destruction (radically — splenectomy), combating iron deposition using chelators (drug Desferal), and elimination of hypoxia (red blood cell transfusion, antioxidants).
- Symptomatic. Administration of buffer solutions to correct the acid-base balance and support the function of the heart, kidneys, and liver.
Briefly: answers to topical questions
Which diseases belong to hereditary red blood cell membranopathies?
Hereditary red blood cell membranopathies include:
- Hereditary spherocytosis — associated with spectrin deficiency, plasmalemma instability, acquisition of a spherical shape by red blood cells, and loss of flexibility.
- Hereditary elliptocytosis / ovalocytosis — characterized by the appearance of ellipsoid or elongated red blood cells in the peripheral blood; the cause is spectrin damage.
- Hereditary forms of stomatocytosis.
- Hereditary forms of pyropoikilocytosis.
- Rh-null syndrome.
Main forms of hereditary red blood cell membrane defects: spherocytosis and ovalocytosis (elliptocytosis).
Which chelating agents are used to combat iron deposition in hemolysis?
To combat excess iron (hemosiderin) deposition in hemolytic anemias, iron-binding substances (chelators) are used.
Example of a drug indicated in the source: deferoxamine (Desferal).
To remember the types of immune hemolysis, use the acronym "AIHA": Autoimmune (own antibodies against own cells), Isoimmune (foreign red blood cells, e.g., from a donor), Heteroimmune (antibodies against a foreign hapten on the red blood cell), Transimmune (from mother to fetus).
Class and exam questions
Why does unconjugated bilirubin specifically rise during hemolysis?
Massive erythrocyte destruction leads to the release of a huge amount of heme. It is metabolized into unconjugated (indirect) bilirubin, and the liver simply cannot keep up with binding such volumes.
What is the molecular cause of sickle cell anemia?
It is based on a point mutation due to which the amino acid valine is replaced by glutamine in the globin molecule. This leads to the formation of unstable hemoglobin S.
Which membranopathy is acquired rather than hereditary?
Paroxysmal nocturnal hemoglobinuria (PNH). Unlike hereditary spherocytosis or elliptocytosis, this is an acquired form of pathology.
What else to study on this topic
- The role of the hexose monophosphate shunt and Fenton reaction in G6PD deficiency
- Mechanisms of formation of warm and cold agglutinins in autoimmune hemolysis
- Aplastic and hypoplastic anemias (including Fanconi anemia)
- Changes in leukocyte and platelet lineages upon stem cell damage
- Pathogenesis of microvascular obstruction and organ infarctions in sickle cell anemia
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