Hemoglobinuria

Hemoglobinuria is one of the forms of hemolytic anemia (hemoglobinemia), or more precisely, a symptom of pathological intravascular damage to red blood cells (erythrocytes), when hemoglobin is released en masse into the perivascular environment and urine. The presence of hemoglobin in urine is direct evidence of intensive breakdown of red blood cells, which can be caused by both an internal disease (flu, pneumonia, acute infection) and an external factor - hypothermia, excessive physical exertion, injuries, intoxication.

In a healthy state, blood plasma may also contain a small amount of hemoglobin - no more than 5% of the total plasma volume. An increase in hemoglobin levels to 20-25% may indicate congenital disorders of the structural composition of the protein (hemoglobinopathy) - beta-thalassemia, sickle cell anemia. Hemoglobinuria is characterized by a significant excess of all permissible norms, when during hemolysis the hemoglobin level reaches 200%. Such a volume of blood pigment cannot be adequately processed by the macrophage system (RES) and hemoglobin begins to enter the urine.

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Causes hemoglobinuria

Hemoglobinuria is observed in some blood diseases, transfusion of blood of a different group, poisoning with some dyes (aniline) and poisons (carbolic acid, potassium chlorate), extensive burns, when most of the hemoglobin is in a bound state, and its small free fraction is formed due to the destruction of the erythrocyte wall. True hemoglobinuria does not exist without hemoglobinemia and the associated jaundice. Hemoglobinuria is also observed during prolonged physical exertion, running, walking, etc.

It is worth mentioning those rarer observations when urine coloration may be caused by taking certain medications or foods (e.g. beets). Urine may acquire a dark red hue as a result of hemoglobinuria caused by intravascular hemolysis and subsequent release of free hemoglobin by the kidneys.

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Symptoms hemoglobinuria

The first obvious sign of hemoglobinuria is the dark red coloring of urine, which is explained by the presence of a large amount of oxyhemoglobin in the urine. Urine collected for analysis is divided into layers over time, the upper one becomes transparent but retains its color, and particles of dead organic matter (detritus) are clearly visible in the lower layer. Symptoms of hemoglobinuria develop rapidly, accompanied by aches and pains in the joints, fever, a sharp increase in body temperature, nausea and vomiting, and headache.

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Forms

• Paroxysmal nocturnal hemoglobinuria of Marchiafava-Micheli (or Strubing-Marchiafava disease) is an acquired hemolytic pathology in which there is a constant intravascular breakdown of defective red blood cells.
• Toxic hemoglobinuria is a pathological mass hemolysis that develops as a result of severe poisoning with chemical or natural toxic substances (sulfonamides, mushrooms, bites of poisonous animals and insects).
• March hemoglobinuria, which is called the “soldier’s disease” because mechanical hemolysis of red blood cells is associated with excessive, intense stress on the feet.
• Cold paroxysmal hemoglobinuria is the rarest form of autoimmune hemolysis.
• Hemoglobinuria, main signs and symptoms

Paroxysmal nocturnal hemoglobinuria of Marchiafava-Micheli

Paroxysmal hemoglobinuria was first described by the Italian physician Marchiafava and his two colleagues, Micheli and Strubing. Since then, this rare syndrome has been called differently in different countries: nocturnal hemoglobinuria, paroxysmal nocturnal hemoglobinuria of Marchiafava-Micheli, and Strubing-Marchiafava disease.

Paroxysmal nocturnal hemoglobinuria is a form of acquired anemia that is extremely rare. This hemolytic symptom is characterized by constant hemolysis of red blood cells, which manifests itself in attacks (paroxysmal), is accompanied by thrombosis and leads to bone marrow hypoplasia. Hemoglobinuria of this type is diagnosed in young people of both sexes aged 20 to 40 years, less often in elderly patients.

Symptoms of nocturnal hemoglobinuria can be multivariant and most often appear early in the morning or evening. This is due to a characteristic feature of the syndrome - the breakdown of red blood cells at night, when the blood pH is somewhat reduced. Symptoms are fever, aches and pains in the joints, general weakness, lethargy and apathy. It is also possible for the skin to turn yellow, since paroxysmal nocturnal hemoglobinuria of Marchiafava-Micheli is accompanied by a significant increase in the liver (splenomegaly). Paroxysms of hemolysis can be associated with excessive intense physical activity, severe infection, improper blood transfusion, surgery. Another cause may be the introduction of iron-containing drugs, in which case paroxysmal hemoglobinuria is considered a temporary, transient symptom.

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Nocturnal hemoglobinuria, treatment

The main method of stopping the intensity of erythrocyte hemolysis is the transfusion of defrosted red blood cells (transfusion), which, unlike the transfusion of fresh blood, gives a positive, stable result. The frequency of transfusions depends on the severity of hemoglobinuria, on the patient's condition indicators, it is believed that there should be no less than five transfusions.

Paroxysmal nocturnal hemoglobinuria is also treated with an anabolic drug, nerobol, which is a temporary symptomatic remedy. After the drug is discontinued, hemolysis may recur.

Iron-containing drugs, anticoagulants and hepatoprotectors are indicated as additional measures.

There is no prevention for hemoglobinuria in this form, the prognosis is considered unfavorable: with constant maintenance therapy, the patient's life expectancy does not exceed five years.

March hemoglobinuria

It was first described by the German doctor Fleischer at the end of the 19th century, who noticed an unusually dark, reddish color of the urine of a soldier. Following him, his colleague Voigl began to study the connection between the load in the form of many kilometers of walking and the appearance of traces of hemoglobin in the urine of soldiers during the First World War. Interestingly, during long walks or running on soft ground or grass, there are no symptoms of march hemoglobinuria; this syndrome is characteristic only of those who move on a hard, rocky or wooden surface.

March hemoglobinuria is always diagnosed in practically healthy, physically strong people exposed to long-term walking loads - in athletes, soldiers, travelers. The syndrome remains unexplored to the end, since there is no clear explanation why it is the load on the feet that provokes erythrocyte hemolysis, while almost all muscles of the body are subject to load. According to one version, intense mechanical aggression on the skin of the foot causes the destruction of erythrocytes in the capillary network of the sole of the foot, then this process spreads to the entire hematopoietic system.

March hemoglobinuria develops gradually and is rarely accompanied by chills, fever and elevated temperature. Slight weakness is noted, which, however, can be explained by general physical fatigue from long walking. The main symptom is hemoglobin excreted in the urine and the characteristic color of urine. As soon as the marching load stops, the symptoms subside, the urine gradually becomes lighter. Laboratory blood tests also do not show significant deviations from the norm either in ESR or leukocytes, only an increased level of neutrophils and an accelerated ESR are possible. March hemoglobinuria is not often diagnosed, due to the fact that the symptoms disappear along with physical activity. The syndrome has a 100% favorable prognosis and is considered benign.

Cold paroxysmal hemoglobinuria

The rarest form of hemoglobinuria, which was first described in the early 19th century as a type of erythrocyte hemolysis. The syndrome was initially considered a consequence of renal hemolysis, until the inquisitive mind of Dr. Rosenbach came up with a completely exotic type of diagnostics - cooling a hand or foot in ice water. Subsequently, Rosenbach's test began to be used in a gentle version - only one finger was cooled. It was also established that cold paroxysmal hemoglobinuria can be a consequence of the underlying disease - syphilis, which was later confirmed by two doctors - Landsteiner and Donat.

Paroxysmal cold hemoglobinuria is extremely rare, the number of diagnosed cases does not exceed 1/100,000 of all patients. However, this form of hemolytic syndrome is much more often detected among the total number of patients with hemoglobinuria, among patients with cold hemoglobinuria, people with diagnosed syphilitic disease predominate. In the last twenty years, interest in PCH (paroxysmal cold hemoglobinuria) has grown significantly, in the process of studying the syndrome, it was found that it also has an idiopathic form, that is, not associated with syphilis or any other disease.

If PCH is acute, then, as a rule, severe symptoms are explained by a viral or bacterial disease, such as influenza, measles, mumps, infectious mononucleosis. The Wasserman reaction in such cases can also be positive, but due to its low specificity, this method cannot be a diagnostic criterion against the background of paroxysmal cold hemoglobinuria.

The reasons for the development of paroxysmal cold hemoglobinuria are not fully understood, but it has been established that it is cold that provokes intensive disintegration of red blood cells. In this case, pathological two-phase autohemolysins appear in the blood plasma, named after the authors of the discovery - Donat and Landsteiner. Cooling can be any - strong or weak, sometimes it is enough for the patient to wash his hands under running water in order to start the pathological hemolysis of red blood cells after a slight change in temperature towards warming. The symptoms that are characteristic of PCH are similar to the signs of other diseases that occur in an acute form, so most often paroxysmal cold hemoglobinuria is diagnosed in the late stages of development. Hyperthermia, pain in the abdominal part of the abdomen, chills, yellowish color of the skin and sclera, hepatomegaly and splenomegaly - these are the symptoms of diseases of the gallbladder, hepatitis, and so on.

The main symptom of paroxysmal cold hemoglobinuria was and remains the characteristic color of urine and its structure - layers, in the lower of which methemoglobin and hemoglobin cylinders are detected. Treatment of paroxysmal cold hemoglobinuria consists of eliminating contact with cold provocateurs and treating the underlying disease, especially if it is syphilis. Paroxysmal cold hemoglobinuria, developing against the background of acute viral infections (flu), does not require specific treatment and passes along with general recovery. The chronic form of cold hemoglobinuria has a more severe course, often requiring blood transfusion, administration of antispasmodic drugs. In general, paroxysmal cold hemoglobinuria is characterized by complete clinical recovery and has a favorable prognosis.

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Diagnostics hemoglobinuria

Hemoglobinuria should be differentiated from another hemolytic syndrome – hematuria (the release of blood into the urine).

Despite obvious color signs (urine coloration), subjective and objective clinical symptoms, hemoglobinuria is confirmed using ammonium sulfate tests, detection of detritus and hemosiderin in urine sediment, and a “paper” test with electrophoresis and immunoelectrophoresis, which determines the presence of protein in the urine, are also informative.

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Treatment hemoglobinuria

• In severe forms, such as cold paroxysmal hemoglobinuria or paroxysmal nocturnal hemoglobinuria, blood transfusion (erythrocytes) is indicated.
• Prescription of anabolic drugs (anti-complementary action).
• Long-term treatment with antioxidants to reduce the activity of lipid peroxidation and its derivatives.
• Antianemic therapy including iron-containing drugs.
• Antithrombotic therapy, administration of direct and indirect anticoagulants.