This is an extensive group of diseases that differ in etiology, pathogenesis, clinical presentation, and treatment methods. Common to them is the presence of signs of increased destruction of red blood cells – hemolysis.
The biological meaning of the increased destruction of erythrocytes is the shortening of their lifespan. Under physiological conditions, the life span of erythrocytes is 100-120 days. By this time, erythrocytes gradually become microcytes and are sequestered by macrophages in the sinuses of the spleen, as well as in the bone marrow. As a result of the physiological breakdown of red blood cells, the pigment bilirubin is formed, which circulates in the blood in the form of free bilirubin, which is transported from the blood to the liver cell, where it combines with glucuronic acid with the participation of enzymes. The resulting bilirubin-glucuronide penetrates from the liver cells into the bile ducts, along with bile, is excreted into the intestine.
With hemolytic anemia, the lifespan of red blood cells is significantly shortened.
There are two main sites of premature death of red blood cells:
intravascular hemolysis – the death of red blood cells in the bloodstream with the release of the contents directly into the plasma. conditioned
mechanical injury of erythrocytes,
complement fixation on their surface or exposure to exogenous toxins.
intracellular hemolysis – the destruction of red blood cells in the spleen and liver, where red blood cells are absorbed by macrophages (mononuclear-phagocytic system), in which they are destroyed and digested.
The mononuclear phagocytic system captures erythrocytes under two conditions:
1) changes in the surface properties of erythrocytes, for example, during the fixation of immunoglobulins, for which there are specific receptors on macrophages;
2) limiting the possibility of deforming erythrocytes, which makes it difficult for them to pass through the filtration bed of the spleen.
criteria for hemolysis.
Absolute criterion for hemolysis: Reducing the lifespan of erythrocytes is an absolute criterion for hemolysis. The life span of erythrocytes is determined by the radioisotope method. In general clinical practice, this study is usually not available, so it is necessary to focus on indirect criteria for hemolysis.
Indirect criteria for hemolysis.
Reticulocytosis greater than 2%.
Erythroid hyperplasia of the bone marrow.
An increase in the concentration of unbound or “indirect” bilirubin in the blood serum (Jaundice). The concentration of unconjugated bilirubin also increases with ineffective erythropoiesis, in which the destruction of erythrocyte precursors in the bone marrow is enhanced.
Hemosiderinuria. Hemosiderin in the urine, determined by the color of its sediment, indicates that a large amount of free plasma hemoglobin has been filtered through the renal glomeruli.
Hemoglobinuria. When the threshold of hemoglobin-binding capacity of haptoglobin is exceeded, free plasma hemoglobin passes through the renal glomeruli. Filtered hemoglobin is reabsorbed at the level of the proximal nephron, where it is catabolized in situ, while heme iron is included in the proteins that perform the functions of iron storage (ferritin and hemosiderin). When the absorbing capacity of the tubular cells is impaired, hemoglobinuria occurs. The presence of hemoglobin in the urine indicates severe intravascular hemolysis. Sometimes it becomes necessary to decide whether the benzidine-positive heme pigment in the urine is hemoglobin or myoglobin. The easiest way to determine this is by examining plasma after centrifugation of blood with an anticoagulant added to it. Due to its higher relative molecular weight, hemoglobin is more difficult than myoglobin to cross the renal barrier and is more slowly excreted through the kidneys. With hemoglobinuria, the plasma is red-brown in color, and with myoglobinuria, its color does not differ from the norm.
External factors of hemolysis – splenomegaly. An important function of the spleen is to capture and destroy red blood cells with minimal defects that are often not detectable on examination. Normally, the spleen does not have any effect on intact erythrocytes, but with its increase, their destruction increases.
There are three main causes of splenomegaly .
Firstly, these are infiltrative processes – myeloproliferative diseases; lymphomas; and storage diseases such as Gaucher’s disease.
Secondly, these are systemic inflammatory diseases , accompanied by hypertrophy of the spleen tissue, and,
thirdly, diseases accompanied by congestive splenomegaly . Hemolysis can occur with any enlargement of the spleen.
· The morphology of erythrocytes is the key to diagnosis. Most of the hemolytic anemias are accompanied by changes in the morphology of erythrocytes.
Spherocytes . Spherocytosis serves as a diagnostic sign of involvement in the pathological process of the spleen.
Spherocytes are found when:
– hereditary spherocytosis
– autoimmune hemolytic anemia caused by warm antibodies.
Fragments of erythrocytes (schizocytes) make it possible to suspect their traumatic injury:
– Mechanical hemolysis, including with artificial heart valves
– microangiopathic hemolytic anemias (for example, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, disseminated intravascular coagulation).
Target erythrocytes filled with hemoglobin:
– hemoglobinopathy C
– liver disease.
Acanthocytosis – erythrocytes covered with spikes, as an artifact, if they are located mainly at the edges of the smear. If they appear in a smear surrounded by intact erythrocytes, this serves as a clue to the diagnosis.
– kidney failure
– after removal of the spleen
– anorexia nervosa,
– spur cell hemolytic anemia.
Sickle or crescent shaped erythrocytes typical of sickle cell syndromes
1. Anti-erythrocyte antibodies.
Detection of anti-erythrocyte antibodies – serological diagnosis of hemolytic anemia – the basis for the diagnosis of acquired immune hemolytic anemia.
According to the mechanism of formation (ingestion into the body), there are:
– Isoimmune antibodies
Autoantibodies are classified into
Agglutinins – stick together red blood cells
hemolysins – directly destroy red blood cells
thermal – operate at temperatures above 37 Gy C.
cold – act at a temperature of 4-14 Gy C
Full – able to overcome the force of natural repulsion of negatively charged red blood cells.
Incomplete – unable to overcome the force of natural repulsion of red blood cells.