Hemoglobinuria is a series of syndromes, which are based on intravascular damage to red blood cells with the release of hemoglobin outside the vascular bed and into the urine. The main symptom of hemoglobinuria is the dark color of the urine due to the presence of oxyhemoglobin in it. Possible arthralgia, fever, vomiting, pallor of the skin, jaundice. The diagnosis of hemoglobinuria requires confirmation with the help of a complete blood and urine test, myelogram, functional and laboratory tests. Taking into account the pathogenetic form of hemoglobinuria, erythrocyte transfusion, the use of hormones, anticoagulants, splenectomy, and TCM can be indicated.
The concept of "hemoglobinuria" combines some forms of hemolytic anemia, occurring with intravascular hemolysis of erythrocytes and the appearance of free hemoglobin in the urine. These include paroxysmal nocturnal hemoglobinuria (Marchiafava-Micheli disease), toxic, marching and cold paroxysmal hemoglobinuria. These conditions, different in etiology, are united by massive, acutely developed intravascular hemolysis, accompanied by the release of hemoglobin into the blood plasma and overcoming the renal barrier. In hematology, single (symptomatic) and recurrent (paroxysmal) hemoglobinuria are distinguished.
In healthy individuals, about 10% of erythrocytes decay in the vascular bed, and plasma contains 1-4 mg% of hemoglobin. In this case, excess hemoglobin is bound by a specific protein haptoglobin with the formation of a large molecular hemoglobin-haptoglobin complex that does not overcome the renal barrier. This mechanism prevents the occurrence of hemoglobinuria and hemosiderosis of the kidneys. However, with a sudden massive breakdown of red blood cells or hypohaptoglobinemia, leading to a decrease in the hemoglobin-binding capacity of plasma, hemoglobin overcomes the renal filter and ends up in the urine. With a normal content of haptoglobin, hemoglobinuria develops when the concentration of hemoglobin in plasma exceeds 125-135 mg%.
The various forms of hemoglobinuria are based on their own causal factors. Thus, paroxysmal nocturnal hemoglobinuria develops as a result of a defect in erythrocyte membranes, as a result of which the latter become vulnerable to serum complement and, under certain conditions, are easily destroyed. Since some of the leukocytes and platelets in this case also have defective membranes, it is believed that the primary link in paroxysmal nocturnal hemoglobinuria is the appearance of an abnormal clone of the common myelopoiesis precursor cell as a result of a somatic mutation.
Toxic hemoglobinuria can be the result of bites of poisonous insects and animals, as well as poisoning by various substances: chemical compounds, drugs (sulfonamides), inedible mushrooms. Hemoglobinuria may be a post-transfusion complication in transfusion of blood that is incompatible in terms of group or Rh-affiliation. Marching hemoglobinuria develops after many kilometers of transitions (marches) or running loads. This form of hemoglobinuria is usually diagnosed in physically healthy individuals, more often in soldiers, athletes, and travelers. In this case, the destruction of red blood cells is provoked by the load on the feet, but this phenomenon, discovered back in the First World War, still has no scientific explanation. Presumably
Cold paroxysmal hemoglobinuria can develop as a result of prolonged cooling of the body (bathing in cold water, exposure to cold air), as well as infectious diseases (flu, mumps, measles, infectious mononucleosis, malaria, syphilis, anaerobic sepsis). This form is characterized by the appearance in the blood of two-phase Donat-Landsteiner hemolysins, which cause complement activation and intravascular hemolysis.
Other forms of hemoglobinuria are known - alimentary-toxic paroxysmal myoglobinuria (Haff disease), traumatic hemoglobinuria in crush syndrome, etc. Transient hemoglobinuria occurs in patients taking iron-containing drugs.
A distinctive feature of paroxysmal nocturnal hemoglobinuria (Marchiafava-Micheli disease) are attacks of intravascular hemolysis (hemolytic crises), developing mainly at night. The disease is registered with a frequency of 1:500,000. Hemolytic crises can be provoked by hypothermia, infection, vaccination, blood transfusions, physical activity, and surgical interventions.
Paroxysms of hemolysis of erythrocytes are accompanied by fever, arthralgia, drowsiness, pain behind the sternum, in the abdomen and lower back. A sign of increasing iron deficiency anemia are general weakness, yellowness of the skin and mucous membranes. Enlargement of the liver and spleen is characteristic. Dark urine is observed in only a quarter of patients with paroxysmal nocturnal hemoglobinuria.
The most dangerous manifestations of paroxysmal nocturnal hemoglobinuria are thrombosis of the mesenteric vessels, renal vessels, and peripheral vessels. Thrombosis of the hepatic veins is accompanied by a sharp increase in the size of the liver, progressive ascites, varicose veins of the esophagus. Persistent hemosiderinuria often leads to tubular nephritis; at the height of the hemolytic crisis, acute renal failure may develop.
Paroxysmal nocturnal hemoglobinuria often develops in patients with aplastic anemia, preleukemia, or acute myeloid leukemia, and therefore requires a complete hematological examination of the patient.
Morning hematuria is found in the urine of patients with paroxysmal nocturnal hemoglobinuria.
Symptoms of marching hemoglobinuria are usually more blurred and develop gradually. Chills and fever are uncommon. Weakness is noted, which can also be a consequence of general physical fatigue from the forced march. However, the pathognomonic sign of this form of hemoglobinuria is the dark color of urine. After the termination of the marching load, the state of health returns to normal, the urine brightens.
It is noted that almost all persons who are faced with marching hemoglobinuria have a pronounced lumbar lordosis. This form of hemoglobinuria has no independent clinical significance.
A rare form of hemolytic anemia - paroxysmal cold hemoglobinuria occurs paroxysmal. Paroxysms of cold hemoglobinuria are usually provoked by hypothermia and are accompanied by hyperthermia (sometimes up to 40 ° C), tremendous chills, nausea and vomiting, and abdominal pain. Hepato- and splenomegaly, yellowish color of the skin and sclera, characteristic color of urine are revealed.
Paroxysmal cold hemoglobinuria caused by acute viral infections usually resolves with the underlying disease. With syphilis and malaria, the disease can last for years.
The main macroscopic sign of hemoglobinuria is a change in the color and structure of the collected urine. The color of the urine may be dark red, brown, or almost black. When settling, urine is clearly divided into 2 layers: the upper one is transparent and the lower one contains an admixture in the form of detritus. Laboratory tests confirming hemoglobinuria are an ammonium sulfate test, the detection of hemosiderin in the sediment, a urine test by electrophoresis or immunoelectrophoresis.
To clarify the overall picture of the blood, a hemogram is examined. In order to detect complement components or antibodies fixed on the surface of red blood cells, a Coombs test is performed. A study of the coagulogram, biochemical parameters of blood (bilirubin, urea, alkaline phosphatase, etc.) is shown. To assess the state of hematopoiesis, especially in the case of pancytopenia with paroxysmal nocturnal hemoglobinuria, a bone marrow puncture and a myelogram study are required.
Hemoglobinuria must be distinguished from hematuria and diseases for which it is characteristic (kidney stones, acute glomerulonephritis), porphyria, autoimmune hemolytic anemia, aplastic anemia.
Therapeutic tactics for various forms of hemoglobinuria is determined by a hematologist. Marching and paroxysmal cold hemoglobinuria usually resolve without special intervention. In the case of the development of chronic autoimmune cold hemoglobinuria, glucocorticoids and immunosuppressants (cyclophosphamide, azathioprine) are prescribed.
Therapy for paroxysmal nocturnal hemoglobinuria is mainly symptomatic: transfusion of erythrocytes, administration of indirect anticoagulants, iron supplementation. With hypoplasia of the red bone marrow, glucocorticosteroids (prednisolone), anabolic drugs (methandienone) or androgens, antithymocyte immunoglobulin are prescribed. With severe hypersplenism, splenectomy may be justified. In the absence of the effect of other methods of treatment of paroxysmal nocturnal hemoglobinuria, the issue of bone marrow transplantation from an HLA-compatible donor is decided.
In order to prevent the development of hemoglobinuria, it is recommended to avoid provoking factors: poisoning, intoxication, infectious diseases, excessive physical exertion, injuries, etc.