Hemolytic anemia in adults

At the end of their normal life (-120 days), red blood cells are removed from the bloodstream. Hemolysis prematurely destroys and as a result shortens the life span of erythrocytes (<120 days). If the hematopoiesis can not compensate for the shortening of the life of red blood cells, anemia develops, and this condition is called hemolytic anemia. If the bone marrow is able to compensate for anemia, this condition is defined as compensated hemolytic anemia.

[1], [2], [3], [4], [5]

Causes of hemolytic anemia

Hemolysis is the result of structural or metabolic abnormalities of erythrocytes or external influence on erythrocytes.

External effects on erythrocytes include factors such as the hyperactivity of the reticuloendothelial system (Hypersplenism), immune disorders (eg, autoimmune hemolytic anemia, isoimmune hemolytic anemia), mechanical damage (hemolytic anemia associated with mechanical trauma), and exposure to infectious agents. Infectious agents can lead to the development of hemolysis through direct exposure to toxins (eg, Clostridium perfringens - or b-hemolytic streptococci, meningococci) or by invasion and destruction of red blood cells by microorganisms (eg Plasmodium and Bartonella spp ). When hemolysis caused by external action, erythrocytes are normal, and both autologous and donor cells are destroyed.

In hemolysis caused by an internal erythrocyte abnormality, the process is caused by factors such as hereditary or acquired erythrocyte membrane damage (hypophosphatemia, paroxysmal nocturnal hemoglobinuria, dentocytosis), impaired erythrocyte metabolism (Defden metabolic pathway defect, glucose-6-phosphate dehydrogenase deficiency), and also hemoglobinopathies (sickle-cell anemia, thalassemia). The mechanism of hemolysis in the presence of quantitative and functional anomalies of certain membrane proteins of erythrocyte (a- and b-spectrin, protein 4.1, F-actin, ankyrin) remains unclear.

[6], [7], [8], [9], [10], [11]

Pathophysiology of hemolytic anemia

The membrane of aging erythrocytes undergoes gradual destruction, and they are purified from the bloodstream by phagocytic cells of the spleen, liver and bone marrow. The destruction of hemoglobin occurs in these cells and hepatocytes with the help of the oxygenation system, the subject with the retention (and subsequent reutilization) of iron, the degradation of heme to bilirubin through a series of enzymatic transformations with protein re-utilization.

The increase in unconjugated (indirect) bilirubin and jaundice is manifested when the conversion of hemoglobin into bilirubin exceeds the ability of the liver to form bilirubin glucuronide and its excretion with bile. The catabolism of bilirubin is the cause of the increase in stercobilin in the feces and urobi-linogen in the urine and sometimes the formation of gallstones.

Hemolytic anemia

Mechanism

Disease

Hemolytic anemia associated with internal erythrocyte anomaly

Hereditary hemolytic anemia associated with structural or functional disorders of the erythrocyte membrane	Congenital erythropoietic porphyria. Hereditary elliptocytosis. Hereditary spherocytosis
Acquired hemolytic anemia associated with structural or functional disorders of the erythrocyte membrane	Hypophosphatemia. Paroxysmal nocturnal hemoglobinuria. Stomatocytosis
Hemolytic anemia associated with impaired metabolism of erythrocytes	Defect enzymes path of Embden-Meyerhof. Deficiency G6FD
Anemia associated with impaired globin synthesis	The carrier of stable abnormal Hb (CS-CE). Sickle-cell anemia. Thalassemia

Hemolytic anemias associated with external exposure

Hyperactivity of the reticuloendothelial system	Hyperplenism
Hemolytic anemia associated with exposure to antibodies	Autoimmune hemolytic anemia: with thermal antibodies; with cold antibodies; paroxysmal cold hemoglobinuria
Hemolytic anemia associated with exposure to infectious agents	Plasmodium. Bartonella spp
Hemolytic anemia associated with mechanical trauma	Anemia caused by the destruction of red blood cells when they come into contact with a prosthetic valve of the heart. Anemia due to trauma. Marching hemoglobinuria

Hemolysis mainly occurs extravascularly in phagocytic cells of the spleen, liver and bone marrow. The spleen usually contributes to a decrease in the lifespan of red blood cells, destroying pathological red blood cells, as well as red blood cells that have thermal antibodies on the surface. The enlarged spleen is able to sequester even normal red blood cells. Erythrocytes with pronounced anomalies, as well as cold antibodies or complement (C3) present on the surface of the membrane are destroyed within the bloodstream or in the liver, where the destroyed cells can be effectively removed.

Intravascular hemolysis is rare and leads to hemoglobinuria in cases where the amount of hemoglobin released into the blood plasma exceeds the hemolobin-binding capacity of proteins (for example, haptoglobin, which is normally present in plasma at a concentration of about 1.0 g / L). Unbound hemoglobin is reabsorbed by the cells of the renal tubules, where iron is converted to hemosiderin, one part of which is assimilated for reutilization, and the other part is excreted by urine upon transplantation of tubule cells.

Hemolysis can be acute, chronic or episodic. Chronic hemolysis can be complicated by aplastic crisis (temporary failure of erythropoiesis), more often as a result of an infection usually caused by parvovirus.

Symptoms of hemolytic anemia

Systemic manifestations are similar to other anemias. Hemolytic crisis (acute expressed hemolysis) is a rare phenomenon. It can be accompanied by chills, fever, pain in the lumbar region and abdomen, severe weakness, shock. Severe hemolysis can be manifested by jaundice and splenomegaly.

Diagnosis of hemolytic anemia

Hemolysis is expected in patients with anemia and reticulocytosis, especially in the presence of splenomegaly, as well as other possible causes of hemolysis. If suspected of hemolysis, a smear of peripheral blood is studied, serum bilirubin, LDH, ALT are determined. If these studies do not work, hemosiderin, hemoglobin urine, also serum haptoglobin is determined.

When hemolysis can be assumed the presence of morphological changes in erythrocytes. The most typical for active hemolysis is the spherocytosis of erythrocytes. Fragments of erythrocytes (schistocytes) or erythrophagocytosis in blood smears suggest the presence of intravascular hemolysis. With spherocytosis, there is an increase in the ICSU index. The presence of hemolysis can be suspected with an increase in serum LDH and indirect bilirubin levels with a normal ALT value and the presence of urinary urobilinogen. Intravascular hemolysis is assumed when a low level of serum haptoglobin is detected, but this index can be lowered with liver dysfunction and increased in the presence of systemic inflammation. Intravascular hemolysis is also assumed when hemosiderin or hemoglobin is detected in the urine. The presence of hemoglobin in the urine, as well as hematuria and myoglobinuria, is determined by a positive benzidine test. Differential diagnosis of hemolysis and hematuria is possible on the basis of the absence of erythrocytes with microscopy of urine. Free hemoglobin, in contrast to myoglobin, can stain the plasma brown, which is manifested after centrifugation of the blood.

Morphological changes in erythrocytes in hemolytic anemia

Morphology	Causes
Spherocytes	Transfusable erythrocytes, hemolytic anemia with thermal antibodies, hereditary spherocytosis
Schistocytes	Microangiopathy, intravascular prosthesis
Targeted	Hemoglobinopathies (Hb S, C, thalassemia), liver pathology
Crescent-shaped	Sickle-cell anemia
Agglutinated cells	Disease of cold agglutinins
Taurus Heinz	Activation of peroxidation, unstable Hb (eg, G6PD deficiency)
Nuclear-containing red blood cells and basophilia	Large beta-thalassemia
Acanthocytes	Anemia with spike-like erythrocytes

G6PD - glucose-6-phosphate dehydrogenase.

Although the presence of hemolysis can be established with these simple tests, the decisive criterion is the determination of the life span of red blood cells through a radioactive label study, such as ⁵¹ Cr. The determination of the lifetime of labeled erythrocytes can reveal the presence of hemolysis and the location of their destruction. However, this study is rarely used.

When detecting hemolysis, it is necessary to establish the disease that provoked it. One way to limit differential search in hemolytic anemia is to analyze the patient's risk factors (for example, the geographical location of the country, heredity, existing diseases), identify splenomegaly, determine the direct antiglobulin test (Coombs), and study the blood smear. Most hemolytic anemias have deviations in one of these variants, which can direct a further search. Other laboratory tests that can help in determining the cause of hemolysis are quantitative hemoglobin electrophoresis, study of erythrocyte enzymes, floucytometry, determination of Cold agglutinins, osmotic resistance of erythrocytes, acid hemolysis, glucose test.

Although certain tests can help in the differential diagnosis of intra-vascular from extravascular hemolysis, it is difficult to establish these differences. During the intensive destruction of erythrocytes, both mechanisms take place, although to varying degrees.

[12], [13], [14]

Treatment of hemolytic anemia

Treatment depends on the specific mechanism of hemolysis. In hemoglobinuria and hemosiderinuria, it may be necessary to replace iron with iron. Long-term transfusion therapy leads to intense deposition of iron, which requires chelation therapy. Splenectomy can be effective in some cases, especially when sequestration in the spleen is the main cause of erythrocyte destruction. After the use of pneumococcal and meningococcal vaccines, as well as vaccines from Haemophilus influenzae, splenectomy is possibly delayed for 2 weeks if possible.