What is Hereditary Microspherocytosis?
Hereditary microspherocytosis, also known as Minkowski – Chauffard disease, is a hereditarily determinable disease transmitted by an autosomal dominant type, characterized by a defect in the erythrocyte membrane proteins. As a result, in this process there is a violation of its permeability, an excess amount of sodium ions is supplied.
The disease is described more than 100 years ago. At the end of the XIX century. the inheritance of the disease was established (1885; Wilson, 1890; Minkowsky, 1900; Chauffard, 1907).
The disease is widespread in various countries of Europe (frequency 1: 5000). Much less often the disease is found in Japan and African countries.
Pathogenesis during Hereditary Microspherocytosis
The basis of violations in microspherocytosis is a defect in the structure of the erythrocyte membrane. Initially, scientists considered the main violation of the structure of lipids,
however, later it was proved that after removal of the spleen, the lipid content becomes normal. In 1970, research began on erythrocyte membrane proteins in hereditary microspherocytosis.
Apparently, microspherocytosis is not one, but several diseases with a similar clinical picture. Some changes in the structure of the membrane protein lead to increased permeability of the erythrocyte membrane, passive penetration of sodium ions through it into the cell. The active transport of sodium from the erythrocyte during microspherocytosis is increased, but the relative excess of sodium ions inside the cell still leads to an increased accumulation of water in it. The spherical shape of the erythrocytes and the peculiarities of the structure of the protein violate the ability of erythrocytes to deform in narrow parts of the blood flow.
The ability of the spleen to destroy red blood cells is associated with the peculiarity of the splenic circulation. Blood enters through the splenic artery, which immediately disintegrates into the trabecular arteries. They pass through trabeculae, and then enter the white pulp as the central artery. Then the blood enters the red pulp. Red pulp of the spleen consists of the sinuses of the oblong blood vessels and areas located between the sinuses, the so-called splenic ligaments. Most of the blood normally goes along the path of the “closed” blood circulation, and a certain part of it enters the intersinus spaces, but does not linger there. The splenic intersinus spaces and splenic ligaments are intersected by reticular fibers.
In microspherocytosis, a certain part of the blood penetrates into the intersinus spaces. There red blood cells are exposed to a number of adverse factors. In the intersinus spaces, the concentration of glucose and cholesterol is reduced, which contributes to an even greater erythrocyte swelling.
When passing through a narrow gap such red blood cells can not be deformed. In addition to swelling, impaired cell elasticity matters.
Losing a portion of the surface, red blood cells can not hemolyze. The edges of the broken shell are connected, the erythrocyte re-enters the bloodstream, the erythrocyte loses its nucleus, denatured protein particles, iron granules, without losing part of the shell. In microspherocytosis, the loss of part of the membrane and cell surface leads to a gradual decrease in the red blood cell.
Symptoms of Hereditary Microspherocytosis
In most cases, one of the parents of the sick child can detect microspherocytosis. Sometimes a child’s illness is severe, and in a father or mother the disease is detected only after seeing a blood smear. However, in parents of 20-25% of patients the most thorough analysis does not establish any signs of the disease. All described patients are heterozygous carriers of the disease gene.
The clinic depends on the severity of hemolysis. In most cases, the first signs are detected in adolescence or adulthood. In children, the disease is usually detected when examining for the disease of their relatives. Complaints without exacerbation of the disease may be missing. In the period of exacerbation marked weakness, dizziness, fever. One of the main clinical symptoms is jaundice, which for a long time may remain the only sign of the disease. The severity of jaundice depends, on the one hand, on the intensity of hemolysis, and on the other, on the ability of the liver to conjugate free bilirubin with glucuronic acid.
In the urine, bilirubin is not detected, since free bilirubin does not pass through the kidneys. The feces are intensely colored dark brown due to the increased content of stercobilin. In connection with the tendency to stone formation, patients may experience bouts of cholelithiasis, often accompanied by signs of cholecystitis. In case of blockage with a stone of the common bile duct, obstructive jaundice syndrome occurs (a significant increase in the bilirubin content, the presence of bile pigments in the urine, itching of the skin, etc.).
The cardinal symptom of hereditary microspherocytosis is an enlarged spleen, which usually protrudes 2 to 3 cm from under the hypochondrium. During long-term hemolysis, significant splenomegaly is observed, and therefore patients complain of heaviness in the left hypochondrium. The liver with an uncomplicated disease is usually of normal size, but sometimes in patients with long-term hemolytic anemia, an increase in it is found. There may be signs of delayed development, as well as violations of the facial skeleton in the form of a “tower skull”, a saddle nose, high standing of the sky, a violation of the location of the teeth, narrow eye sockets.
The severity of anemic syndrome is different. Often there is a moderate decrease in hemoglobin. Some patients have no anemia. The most severe anemization occurs during hemolytic crises. In middle-aged and elderly people, sometimes trophic ulcers of the lower legs are difficult to treat, associated with agglutination and the breakdown of red blood cells in small capillaries of the extremities.
The course of the disease is characterized by so-called hemolytic crises, manifested by a sharp increase in symptoms against the background of continuously ongoing hemolysis. This increases the temperature due to the massive breakdown of red blood cells, increases the intensity of jaundice, there is severe pain in the abdomen, vomiting. Hemolytic crises usually occur after intercurrent infections, hypothermia, in women due to pregnancy. The frequency of crises is different, in some patients they do not occur.
Diagnosis of Hereditary Microspherocytosis
The severity of anemia in microspherocytosis is different, in a significant proportion of patients it is small. The hemoglobin content of 90-100 g / l, during the crisis period is reduced to 40-50 g / l, especially in young children. Hemolytic crises in microspherocytosis are most often provoked by infection.
The number of microspherocytes in hereditary microspherocytosis is different. In some patients, the majority of erythrocytes are microspherocytes; they usually have pronounced signs of hemolysis. Relatives of patients with microspherocytosis who do not show complaints and in whom the disease is detected only with active examination, most often a small percentage of microspherocytes is detected. Most of the cells are transitional forms from disc-shaped cells to microspherocytes.
The number of leukocytes in microspherocytosis is more often normal; during crises, leukocytosis is observed, sometimes with a pronounced neutrophilic shift. The number of platelets remains in most cases normal.
As a rule, there is irritation of the red sprout of the bone marrow. Normally, the ratio is 3: 1. With microspherocytosis, as with many other types of hemolytic anemia, this ratio changes – the number of red nuclear elements becomes equal to or even exceeds the number of white.
The level of hyperbilirubinemia in patients with microspherocytosis depends on the severity of the disease and the period of examination of the patient. Outside of crises, the content of bilirubin can vary from normal numbers to 57-76 mmol / l, during the period of the crisis it greatly increases.
Under normal liver function and a relatively large increase in the breakdown of red blood cells, the bilirubin content may be normal.
Naturally, the level and type of bilirubin change with the complication of microspherocytic hemolytic anemia by obstructive jaundice. In these cases, the content of bilirubin increases (sometimes to high numbers). As a rule, bilirubin is not detected in patients with urine, but bilirubinuria is also possible with concrements in blocking the biliary tract. The content of urobilin in the urine, as in other forms of hemolytic anemia, may be elevated. Coombs’s test is usually negative. However, in rare cases, combinations of hereditary microspherocytic hemolytic anemia with autoimmune hemolytic anemia are possible. You can prove this combination only by detecting microspherocytosis in other family members suffering from hereditary microspherocytosis.
Cases of acute aplasia of the bone marrow in microspherocytosis are described.
Morphological changes in the organs during microspherocytosis are characteristic of hemolytic anemias — icteric staining of most organs, an increase in bone marrow structures in the flat and tubular bones, mainly due to the elements of the red row. At the same time, the cells of the white and megakaryocytic rows are well preserved.
Pronounced blood filling of the pulp of the spleen. Venous sinuses are narrow slits, compressed full-blooded pulp. In other areas, the sinuses are dilated, contain pale colored, with indistinct contours of red blood cells and their fragments. Marked hyperplasia of the endothelium of the sinuses. A large number of hemolyzed erythrocytes is found in the intersinus spaces. Hemosiderosis (excessive deposition of iron pigment hemosiderin) pulp was predominantly focal.
Differential diagnosis of microspherocytosis is primarily reduced to the diagnosis of hemolytic anemia in general.
In each of the cases of jaundice with an enlarged spleen, the doctor carefully examines the patient. It should be noted that the increase in the content of indirect bilirubin, reticulocytes, as well as microspherocytosis provide the basis for a correct diagnosis. The doctor then conducts a differential diagnosis of autoimmune hemolytic anemia and microspherocytosis, since autoimmune hemolytic anemia often gives symptomatic microspherocytosis. In this situation, a thorough clarification of the anamnesis, the duration of the disease, the presence of such a disease in relatives, and the production of samples to identify autoantibodies help. The patient makes a thorough examination of the skeletal system to identify characteristic deformities.
If a small number of microspherocytes is detected and a normal or insignificant increased content of reticulocytes is found, a sternal puncture is necessary to exclude hereditary dizerythropoietic anemia, in which binuclear erythrocyocytes are found in the bone marrow, and in peripheral blood – an unsharply expressed microsphereocytes.
Diagnostic difficulties arise in cases of a combination of hereditary microspherocytosis with acute viral hepatitis. In patients with microspherocytosis who develop acute hepatitis, the course of hepatitis is unusual: there is a marked violation of the flow of bile, very long-lasting jaundice without intoxication. The absence of a pronounced painful attack, changes in the activity of enzymes give grounds to suspect hepatitis.
Treatment of Hereditary Microspherocytosis
Unfortunately, a fairly common method of treating microspherocytosis is spleen removal. In microspherocytosis, the erythrocyte life span is sharply shortened. The destruction of red blood cells is carried out mainly in the spleen.
Indications for the need to remove the spleen in microspherocytosis are constant or arising anemia, severe hyperbilirubinemia.
It should be noted that the removal of the spleen in children under the age of 10 years is used in extreme cases when other methods of therapy are exhausted.
After removal of the spleen, almost all patients normalize the general condition and hemoglobin level. Bilirubin levels and reticulocyte levels are significantly reduced. It should be noted a clear correlation between the severity of red blood cell destruction before removal of the spleen and the content of bilirubin and reticulocytes after surgery.
The most serious, albeit rare, complications of the postoperative period that are not related to surgical technique are thrombosis of both pulmonary and mesenteric vessels. An increase in the platelet count in the postoperative period above 700-800 × 109 / l requires the prescription of drugs capable of reducing the aggregation of platelets (for example, chimes of 0.05 g 3 times a day); It is also advisable to prescribe heparin of 5000 IU, 2 times a day in the abdominal skin.
Characteristic is the disappearance of the smallest forms of microspherocytes.
Absolutely useless in patients with microspherocytosis without removal of the spleen is cholecystectomy (surgical operation for the treatment of hernia, calculous cholecystitis, performed through punctures of the abdominal wall). In many patients, gallstones are absent.
If you suspect the presence of stones, you must carefully examine the patient. Gallstones (rather than thick mucous mass) are indications for combined surgery (removal of the spleen and cholecystectomy).
If microspherocytosis is detected in pregnant women with moderate anemisation and a quiet course of the disease, pregnancy can be maintained and not be used in cesarean section.
Further, in such women, according to the indications, the spleen is removed. Blood transfusion should be carried out only for health reasons, with severe hemolytic or aplastic crises. Removal of the spleen in most cases is carried out without red blood cell transfusion.
Glucocorticosteroids should be used in aplastic crises.
Duodenal sensing, laxatives and antispasmodics are indicated for severe pain in the right hypochondrium.
In connection with the increased tendency to stone formation patients are recommended resort treatment.
The prognosis of the disease is almost always good, even in cases of spleen removal.