Hemoglobinuria is a series of syndromes based on intravascular damage to erythrocytes with the release of hemoglobin outside the vascular bed and into the urine. The main symptom is the dark color of urine due to the oxyhemoglobin present in it. Arthralgia, fever, vomiting, pallor of the skin, jaundice are possible. The diagnosis requires confirmation by means of a general blood and urine test, a myelogram, functional and laboratory tests. Taking into account the pathogenetic form of hemoglobinuria, transfusion of erythrocytes, the use of hormones, anticoagulants, splenectomy, TCM may 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 (Markiafava-Mikeli 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, there are single (symptomatic) and recurrent (paroxysmal) hemoglobinuria.
In healthy individuals, approximately 10% of erythrocytes disintegrate in the vascular bed, and the plasma contains 1-4 mg% of hemoglobin. In this case, excess hemoglobin is bound by a specific protein haptoglobin to form a large-molecular complex hemoglobin-haptoglobin, which does not overcome the renal barrier. This mechanism prevents the occurrence and hemosiderosis of the kidneys. However, with a sudden massive breakdown of erythrocytes or hypogaptoglobinemia, leading to a decrease in the hemoglobin-binding ability of plasma, hemoglobin overcomes the renal filter and ends up in the urine. With a normal haptoglobin content, hemoglobinuria develops at a plasma hemoglobin concentration exceeding 125-135 mg%.
Causes and types of hemoglobinuria
Various forms are based on their causally significant factors. Thus, paroxysmal nocturnal hemoglobinuria develops due to a defect in the membranes of red blood cells, 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 of paroxysmal nocturnal hemoglobinuria is the appearance of an abnormal clone of a common myelopoiesis precursor cell as a result of somatic mutation.
Toxic hemoglobinuria can be the result of bites of poisonous insects and animals, as well as poisoning with various substances: chemical compounds, drugs (sulfonamides), inedible mushrooms. Hemoglobinuria can be a posttransfusion complication in blood transfusion that is incompatible by group or Rh affiliation. Marching hemoglobinuria develops after many kilometers of transitions (marches) or running loads. This form is usually diagnosed in physically healthy individuals, more often in soldiers, athletes, travelers. In this case, the destruction of red blood cells is provoked by the load on the feet, but this phenomenon, discovered during the First World War, still has no scientific explanation. Presumably, prolonged and severe mechanical irritation of the plantar part of the foot initially causes hemolysis of erythrocytes in the capillaries of this area, and then spreads to the entire vascular bed.
Cold paroxysmal hemoglobinuria can develop due to prolonged cooling of the body (bathing in cold water, staying in cold air), as well as infectious diseases (influenza, mumps, measles, infectious mononucleosis, malaria, syphilis, anaerobic sepsis). This form is characterized by the appearance of two-phase hemolysins Donat-Landsteiner in the blood, causing complement activation and intravascular hemolysis.
Other forms are known – alimentary-toxic paroxysmal myoglobinuria (Gaffa disease), traumatic hemoglobinuria in crash syndrome, etc. Transient hemoglobinuria occurs in patients taking iron-containing drugs.
Characteristics of forms
Paroxysmal nocturnal hemoglobinuria
A distinctive feature of paroxysmal nocturnal hemoglobinuria (Markiafava-Mikeli disease) are attacks of intravascular hemolysis (hemolytic crises), developing mainly at night. The disease is registered with a frequency of 1:500000. Hemolytic crises can be provoked by hypothermia, infection, vaccination, blood transfusions, physical exertion, surgical interventions.
Paroxysms of erythrocyte hemolysis are accompanied by fever, arthralgia, drowsiness, pain behind the sternum, in the abdomen and lower back. A sign of increasing iron deficiency anemia is general weakness, jaundice of the skin and mucous membranes. It is characterized by an increase in the liver and spleen. Dark-colored urine excretion is noted only in a quarter of patients with paroxysmal nocturnal hemoglobinuria.
The most dangerous manifestations of paroxysmal nocturnal hemoglobinuria are thrombosis of mesenteric vessels, renal vessels, peripheral vessels. Thrombosis of hepatic veins is accompanied by a sharp increase in the size of the liver, progressive ascites, varicose veins of the esophagus. Permanent hemosiderinuria often leads to the appearance of tubular nephritis; acute renal failure may develop at the height of a hemolytic crisis.
Paroxysmal nocturnal hemoglobinuria often develops in patients with aplastic anemia, preleukosis or acute myeloid leukemia, therefore requires a complete hematological examination of the patient.
The symptoms of marching hemoglobinuria are usually more erased and develop gradually. Chills and fever are uncharacteristic. Weakness is noted, which may also be a consequence of general physical fatigue from the march. At the same time, the pathognomonic sign of this form is the dark color of urine. After the termination of the marching load, well-being normalizes, urine brightens.
It has been noticed that almost all persons who have encountered marching hemoglobinuria have pronounced lumbar lordosis. This form has no independent clinical significance.
A rare form of hemolytic anemia – paroxysmal cold hemoglobinuria proceeds paroxysmally. Paroxysms of cold hemoglobinuria are usually provoked by hypothermia and are accompanied by hyperthermia (sometimes up to 40 ° C), terrific chills, nausea and vomiting, abdominal pain. Hepatomegaly and splenomegaly are detected, yellowish skin color and sclera, characteristic color of urine.
Paroxysmal cold hemoglobinuria caused by acute viral infections usually resolves together 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 can be dark red, brown or almost black. When settling, the urine is clearly divided into 2 layers: the upper one is transparent and the lower one contains an impurity in the form of detritus. Laboratory tests confirming hemoglobinuria are a sample with ammonium sulfate, detection of hemosiderin in sediment, urine examination by electrophoresis or immunoelectrophoresis.
To clarify the overall picture of the blood, a hemogram is examined. In order to identify complement components or antibodies fixed on the surface of red blood cells, a Coombs test is performed. The study of 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, bone marrow puncture and myelogram examination are required.
Hemoglobinuria must be distinguished from hematuria and the diseases for which it is characteristic (kidney stones, acute glomerulonephritis), porphyria, autoimmune hemolytic anemia, aplastic anemia.
Therapeutic tactics for various forms is determined by a hematologist. Marching and paroxysmal cold hemoglobinuria are usually resolved without special intervention. In the case of chronic autoimmune cold hemoglobinuria, glucocorticoids and immunosuppressants (cyclophosphamide, azathioprine) are prescribed.
Therapy of 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, antithymocytic immunoglobulin are prescribed. With severe hypersplenism, splenectomy may be justified. If there is no effect from other methods of treatment of paroxysmal nocturnal hemoglobinuria, the issue of bone marrow transplantation from an HLA-compatible donor is being resolved.
In order to prevent the development of hemoglobinuria, it is recommended to avoid provoking factors: poisoning, intoxication, infectious morbidity, excessive physical exertion, injuries, etc.