Hemoglobinuria

Hemoglobinuria is one of the forms of hemolytic anemia (hemoglobinemia), more precisely a symptom of the pathological intravascular damage of red blood cells (erythrocytes), when hemoglobin is massively released into the circulatory environment and urine. The presence of hemoglobin in the urine is a direct evidence of the intense disintegration of red blood cells, which can be caused by both an internal disease (influenza, pneumonia, acute infection) and an external factor - hypothermia, excessive physical exertion, trauma, intoxication.

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

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

Causes of the hemoglobinuria

Hemoglobinuria is observed in some blood diseases, transfusion of blood grouping, poisoning with some dyes (aniline) and poisons (carbolic acid, bertholets salt), extensive burns, when the majority of hemoglobin is in a bound state, and its small free fraction is formed due to destruction of the red blood cell wall . True hemoglobinuria does not exist without hemoglobinemia and jaundice associated with it. Hemoglobinuria is also observed with prolonged physical activity, running, walking, etc.

Mention should be made of those rarer observations when the color of urine can be caused by the intake of certain medicines or food (for example, beets). Urine can acquire a dark red shade as a result of hemoglobinuria caused by intravascular hemolysis and the subsequent release of free hemoglobin by the kidneys.

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

Symptoms of the hemoglobinuria

The first obvious sign that hemoglobinuria manifests itself is the coloration of urine in a dark red color, which is explained by the presence of a large amount of oxyhemoglobin in the urine. The urine collected for analysis is divided into layers over time, the upper becomes transparent, but retains color, particles of dead organic matter (detritus) are clearly visible in the lower layer. Symptomatic hemoglobinuria develops rapidly, accompanied by aches and pains in the joints, a febrile condition, a sharp rise in body temperature, nausea and vomiting, pain in the head.

[11], [12], [13], [14]

Forms

• Paroxysmal nocturnal hemoglobinuria of Marietaafa-Mikeli (or Strubbing-Marietaafa disease) is a acquired hemolytic pathology in which a permanent intravascular decay of defective erythrocytes occurs. 
• Toxic hemoglobinuria is a pathological mass hemolysis that develops as a result of severe poisoning with chemical or natural poisonous substances (sulfonamides, fungi, bites of poisonous animals and insects). 
• Marching hemoglobinuria, which is called "soldier" disease, since mechanical hemolysis of red blood cells is associated with an excessive, intense strain on the feet. 
• Cold paroxysmal hemoglobinuria is the rarest form of autoimmune hemolysis.
• Hemoglobinuria, the main signs and symptoms

Paroxysmal nocturnal hemoglobinuria of Marietaafa-Mikeli

Paroxysmal hemoglobinuria was first described by the Italian physician Marciafawa and his two colleagues - Mikeli and Strijbing, since this rare syndrome has become known in various countries as variable - nocturnal hemoglobinuria, paroxysmal nocturnal hemoglobinuria of Marietaafa-Mikeli and Striubing-Marietaafa disease.

Paroxysmal nocturnal hemoglobinuria is a form of acquired anemia, which is extremely rare. This hemolytic symptom is characterized by a permanent hemolysis of erythrocytes, which manifests paroxysmally (paroxysmally), is accompanied by thrombosis and leads to bone marrow hypoplasia. Hemoglobinuria of this type is diagnosed in young people of both sexes at the age of 20 to 40 years, less often in elderly patients.

Symptoms that show night hemoglobinuria may be multivariate and most often manifest in the early morning or evening. This is due to the characteristic feature of the syndrome - the decay of erythrocytes at night, when the pH of the blood is somewhat reduced. Symptoms are febrile condition, aches and joint pain, general weakness, lethargy and apathy. It is also possible to color the skin in icteric color, as paroxysmal nocturnal hemoglobinuria of Marietaafa-Micheli is accompanied by a significant increase in the liver (splenomegaly). Hemolysis paroxysms may be associated with excessive intensive physical exertion, severe infection, incorrect blood transfusion, and surgical operation. Also, one of the reasons may be the introduction of iron-containing drugs, in which case paroxysmal hemoglobinuria is considered a temporary, transient symptom.

[15], [16], [17], [18], [19]

Night hemoglobinuria, treatment

The main way to stop the intensity of hemolysis of red blood cells is a transfusion of thawed 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 indicators of the patient's condition, it is believed that transfusions should not be less than five.

Also paroxysmal nocturnal hemoglobinuria is treated with an anabolic drug - nerobol, which is a temporary symptomatic remedy. After discontinuing the drug, hemolysis may recur.

As additional measures are shown iron-containing drugs, anticoagulants and hepatoprotectors.

Prophylaxis of hemoglobinuria in this form does not exist, the forecast is considered unfavorable: with constant maintenance therapy, the patient's life expectancy does not exceed five years. 

Marching hemoglobinuria

For the first time it was described by the German physician Fleischer at the end of the XIXth century, who drew attention to the unusually dark, reddish color of urine from the soldier. After him, his colleague Voigl began to study the connection of the load in the form of a many kilometers walk and the appearance of traces of hemoglobin in the urine of soldiers during the First World War. It is interesting that when walking for a long time or running along soft ground or grass symptoms of march hemoglobinuria are not observed, this syndrome is characteristic only of those who move on a hard, stony or wooden surface.

Marching hemoglobinuria is always diagnosed in practically healthy, physically strong people, subject to prolonged running loads - sportsmen, soldiers, travelers. The syndrome remains unexplored until the end, because there is no intelligible explanation why it is exactly the load on the feet that provokes erythrocyte hemolysis, while almost all the muscles of the body are exposed to strain. According to one version, intensive mechanical aggression on the foot skin causes destruction of red blood cells in the capillary grid of the sole of the feet, then this process extends to the entire hematopoietic system.

Marching hemoglobinuria develops gradually and is rarely accompanied by chills, fever and fever. There is a slight weakness, which, however, can be explained by general physical fatigue from a long walk. The main symptom is the hemoglobin released in the urine and the characteristic color of the urine. As soon as the march load stops, the symptomatology subsides, the urine gradually becomes lighter. Laboratory blood tests also do not show significant deviations from the norms either from the ROE or from the leukocytes, only an increased level of neutrophils and an acceleration of the ROE is possible. Marching hemoglobinuria is not diagnosed often, due to the fact that the symptoms disappear together with physical stress. The syndrome is 100% favorable and is considered benign. 

Cold paroxysmal hemoglobinuria

The most rare form of hemoglobinuria, which was first described in the early XIX century as one of the types of erythrocyte hemolysis. The syndrome was initially thought to be a consequence of renal hemolysis, while Dr. Rosenbach's inquisitive mind did not come up with a completely exotic kind of diagnosis - cooling the hand or leg in icy water. Subsequently, the Rosenbach test was used in a gentle way - only one finger was cooled. It was also found that cold paroxysmal hemoglobinuria may 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 the rate of 1 / 100,000 of all patients. However, this form of hemolytic syndrome is more often detected among the total number of patients with hemoglobinuria, among people with cold hemoglobinuria, people with diagnosed syphilitic disease predominate. In the past twenty years, interest in UGS (paroxysmal cold hemoglobinuria) has increased significantly, it has been found out during the study of the syndrome that it has an idiopathic form, that is, not associated with either syphilis or any other disease.

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

The reasons for the development of paroxysmal cold hemoglobinuria have not been fully studied, but it has been established that the intensive dissolution of erythrocytes provokes the cold. At the same time in the blood plasma there are pathological biphasic autohemolysins, named in honor of the authors of the discovery - Donat and Landsteiner. Cooling can be any - strong or weak, sometimes it is enough for a 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 in the direction of warming. Symptoms that are typical for UGS are similar to those of other acute diseases, so most often paroxysmal cold hemoglobinuria is diagnosed at later stages of development. Hyperthermia, pain in the abdominal part of the abdomen, chills, yellowish skin color and sclera, hepatomegaly and splenomegaly are symptoms of gall bladder, hepatitis and so on.

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

[20], [21], [22], [23], [24]

Diagnostics of the hemoglobinuria

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

Despite the obvious color characteristics (urine staining), subjective and objective clinical symptoms, hemoglobinuria is confirmed with the help of ammonium sulfate samples, detection of detritus and hemosiderin in the urine sediment, also informative "paper" test with electrophoresis and immunoelectrophoresis determining the presence of protein in the urine.

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Treatment of the hemoglobinuria

• In severe forms, such as cold paroxysmal hemoglobinuria or paroxysmal nocturnal hemoglobinuria, transfusion of blood (erythrocytes) is indicated. 
• Purpose of anabolic drugs (anticomplementary action). 
• A long course of treatment with antioxidants to reduce the activity of peroxide oxidation of fats and their derivatives. 
• Antianemic therapy, including iron-containing drugs. 
• Anti-thrombotic therapy, the appointment of anticoagulants direct and indirect action.