Hereditary spherocytosis (Minkowski-Schoffar's disease)

Hereditary spherocytosis (Minkowski-Schoffar's disease) is hemolytic anemia, which is based on structural or functional disorders of membrane proteins, which proceeds with intracellular hemolysis.

German therapist O. Minkowski (1900) was the first to describe family hemolytic anemia; M.A. Schoffar (1907), a French therapist, found in patients a decrease in erythrocyte resistance and the associated increase in hemolysis.

The disease is ubiquitous, with a frequency of 1: 5 000 in the population. Transmitted by autosomal dominant type; about 25% of cases are sporadic, caused by the emergence of a new mutation.

It is more common in the inhabitants of Northern Europe, where the prevalence of the disease is 1 per 5000 population.

An autosomal dominant type of inheritance occurs in about 75% of cases. In family members of the patient, the severity of anemia and the degree of spherocytosis can vary. In 25% of cases, there is no family history. In some patients, changes in laboratory parameters are minimal, suggesting an autosomal recessive type of inheritance, and the remaining cases are the result of spontaneous mutations.

How does the Minkowski-Schoffar disease develop?

It is associated with a hereditary defect of the erythrocyte membrane in the form of deficiency of certain structural proteins (spectrin, ankirin, actin). These proteins serve to maintain the biconcave form of erythrocytes and at the same time allow them to deform when passing through narrow capillaries. Isolated partial deficiency of spectrin, combined deficiency of spectrin and ankyrin (30-60% of cases), partial deficiency of protein of band 3 (15-40% of cases), deficiency of protein 4.2 and other less significant proteins. Deficiency of these proteins leads to destabilization of the lipid structure of the erythrocyte membrane, the work of the sodium-potassium membrane pump is disrupted. Increases the permeability of erythrocyte for sodium ions. Entering the cage, sodium pulls water behind it. Swelling, the erythrocyte acquires a spherical shape - the most energetically favorable. In this case, it decreases in diameter, but its thickness increases. Such an erythrocyte, due to the altered structure of the membrane, is incapable of transformation when passing through small intersexive spaces of the spleen, where the concentration of glucose and cholesterol is lowered, which contributes to an even greater swelling of the erythrocyte. This passage is accompanied by a detachment of lipid structures. The erythrocyte becomes increasingly defective and small. Such an erythrocyte is perceived by spleen macrophages as alien, captured and destroyed. Thus, intracellular hemolysis occurs. The lifespan of erythrocytes is sharply reduced (up to 12-14 days) due to their severe wear, since more energy is needed to remove sodium ions from the cell, in excess of the incoming cells. Compensatory in the bone marrow is increased erythrouosis. Due to hemolysis, the amount of indirect bilirubin increases in the blood, but there is no sudden increase in it, since the liver significantly increases its functional activity: it increases the formation of direct bilirubin, resulting in its concentration in the bile and its content in the galleries. In this case, often formed bilirubin stones in the gallbladder and ducts - develops cholelithiasis. As a consequence, mechanical jaundice may appear: the amount of sterocilinogen and the content of urobilin increase. After the age of 10 years, stones of the gallbladder occur in half of patients not subjected to splenectomy.

Pathogenesis of hereditary spherocytosis (Minkowski-Schoffar disease)

Symptoms of Minkowski-Schoffar disease

The severity and diversity of the clinical picture is due to the type of structural protein that is absent on the erythrocyte membrane (the deficiency of the a-chain of the spectra is inherited autosomal dominant and proceeds easily, and the beta-chain deficiency causes a serious disease inherited autosomally-recessively). In half the cases, hereditary spherocytosis appears already in the period of the newborn, simulating the picture of hemolytic disease of newborns or prolonged conjugation hyperbilirubinemia. The clinical picture of hemolytic crisis consists of a triad of symptoms: pallor, jaundice, splenomegaly. Crises can be triggered by infectious diseases, taking a number of medications, but can be spontaneous. In the intercreeping period, the patients do not complain, but the enlarged spleen is always palpable. The harder the disease, the more pronounced are the specific fendtic features, namely: the tower skull, the gothic palate, the broad bridge of the nose, the large distances between the teeth. These changes in bone tissue are associated with compensatory bone marrow hyperplasia (erythroid sprout), and, as a consequence, osteoporosis of flat bones. Depending on the severity of hereditary spherocytosis, the severity of clinical symptoms may be different. Sometimes jaundice can be the only symptom about which a patient consults a doctor. It is to these persons that the well-known expression of M.A. Shoffara: "They are more jaundiced than sick." Along with typical classical signs of the disease, there are forms of hereditary spherocytosis, when hemolytic anemia can be so well compensated that the patient learns of the disease only when conducting the appropriate examination.

Symptoms of hereditary spherocytosis (Minkowski-Schoffar disease)

Complications of Minkowski-Schoffar disease

The most common complication in hereditary spherocytosis is the development of cholelithiasis due to bilirubin metabolism. Often, the hemolytic crisis is the development of mechanical jaundice in cholelithiasis. In the presence of stones in the gallbladder, cholecystectomy with splenectomy is indicated. Performing only cholecystectomy is impractical, since ongoing hemolysis will sooner or later lead to the formation of stones in the bile ducts.

The formation of trophic ulcers is a fairly rare complication that occurs in children. Ulcers occur due to the destruction of red blood cells, resulting in thrombosis of the vessels, ischemia develops.

Very rarely there are so called aregenerator, or aplastic, crises, when elevated hemolysis for several days is not accompanied by enhanced erythropoiesis. As a result, reticulocytes disappear from the blood, anemia rapidly builds up, the level of indirect bilirubin decreases. Now the leading etiological role in this complication is assigned to parvovirus (B 19).

[1]

How to recognize hereditary spherocytosis?

Diagnosis of this disease is quite simple. Diagnosis of hereditary spherocytosis makes undoubted the following symptoms: jaundice, deformation of the facial skull, enlarged spleen, spherocytosis of erythrocytes, their decreased osmotic resistance, high reticulocytosis. Careful collection of anamnesis is a great help in the formulation of the correct diagnosis. Typically, similar symptoms can be found in one of the parents of the patient, although their severity may be different (eg, periodic icteric sclera). In rare cases, the parents are perfectly healthy. Difficulties in diagnosis are often caused by cholelithiasis, usually accompanying hereditary microspherocytosis (due to the formation of bilirubin stones in the ducts and gall bladder). The intrinsic hemolysis indirect bilirubinemia with cholelithiasis is replaced by a direct - there is mechanical jaundice. Soreness in the area of the gallbladder, some enlargement of the liver are common symptoms in hereditary microspherocytosis. Often, for many years, patients are mistakenly treated as those suffering from biliary tract or liver disease. One of the reasons for the erroneous diagnosis in this case is the lack of information about reticulocytes.

Laboratory diagnostics includes a number of studies.

Clinical analysis of blood - determined normochromic hyperregenerative anemia, microspherocytosis of erythrocytes. During the crisis, there may be neutrophilic leukocytosis with a shift to the left. Characteristic increase in ESR.

Biochemical analysis - blood marks the increase in indirect bilirubin, serum iron, LDH.

It is necessary to study the osmotic resistance of erythrocytes in solutions of sodium chloride of various concentrations. With hereditary spherocytosis, a decrease in minimum osmotic resistance is noted when hemolysis of the least persistent red blood cells begins already at a sodium chloride concentration of 0.6-0.7% (norm 0.44-0.48%). The maximum durability can be increased (norm 0,28-0,3%). Among patients with hereditary spherocytosis there are individuals who, in spite of obvious changes in the morphology of erythrocytes, under normal conditions, the osmotic resistance of erythrocytes is normal. In these cases, it is necessary to examine it after a preliminary daily incubation of red blood cells.

Morphological features of erythrocytes in hereditary spherocytosis include the spherical form (spherocytes), a decrease in diameter (mean erythrocyte diameter <6.4 μm), an increase in thickness (2.5-3 μm at a rate of 1.9-2.1 μm) at usually normal the average volume of erythrocytes. In connection with this, in most cells there is no visible central enlightenment, since the erythrocyte from the biconcave turns into a globular.

The hemoglobin content in erythrocytes remains within the physiological norm or somewhat higher. The color index is close to 1.0. The Price-Jones erythrocytometric curve is stretched, shifted to the left.

A bone marrow puncture is not necessary. It is conducted only in unclear cases. In the myelogram, there should be compensatory stimulation of the erythroid germ of the hematopoiesis.

To conduct differential diagnosis with immune hemolytic anemias, a Coombs test should be performed. With hereditary spherocytosis, it is negative.

A definitive and reliable confirmation of the diagnosis of hereditary spherocytosis allows the electrophoresis of the erythrocyte membrane proteins in combination with the quantitative determination of proteins.

Differential diagnosis

Spherocytosis of erythrocytes and other signs of hemolysis (jaundice, enlarged spleen, reticulocytosis) occur in autoimmune hemolytic anemia. However, unlike hereditary microspherocytosis, there are no changes in the bones of the skull in the latter, signs of hereditary microspherocytosis in one of the parents; at the first clinical manifestations of autoimmune hemolysis there is still no significant increase in spleen, pain in the area of the gallbladder, but anisocytosis and poikilocytosis of erythrocytes are more pronounced than with microspherocytosis. In doubtful cases, it is necessary to perform a Coombs test, which is positive (direct sample) in most cases of autoimmune hemolytic anemia and negative in hereditary microspherocytosis.

Diagnosis of hereditary spherocytosis (Minkowski-Schoffar disease)

[2], [3], [4], [5], [6], [7], [8]

Treatment of Minkowski-Schofar's disease

Treatment during the hemolytic crisis consists in conducting replacement therapy with erythrocyte mass with a decrease in hemoglobin below 70 g / l. In some cases, an infusion therapy with a detoxification purpose is required. At high bilirubin indices, treatment with albumin is indicated. In off-the-clock period, treatment with choleretic preparations should be carried out. In the case of a severe course of the disease in combination with a delay in physical development, accompanied by frequent crises, requiring continuous replacement therapy, splenectomy is indicated. In addition, the indication for splenectomy is the development of hypersplenism. Splenectomy does not lead to a cure for this pathology, but after removal of the spleen, the main bridgehead for the destruction of erythrocytes disappears and their longevity lengthens. As a rule, hemolytic crises are not repeated in children with a distant spleen. There are also negative aspects of splenectomy. Removal of the spleen adversely affects the immunological reactivity of the child's body, the phagocytic activity of leukocytes decreases, the susceptibility to parasitic, fungal and viral infections increases. There is an opinion that the removal of the spleen leads to the development of a syndrome of hyposplenism, manifested in a decrease in vitality, phenomena of mental lability, and impaired ability to work. Potential risk factors for splenectomy are technical difficulties during surgery in patients with large organ sizes, development of bleeding during and after surgery, and infectious-septic complications. Cases of death from bacterial infections in the late postoperative period in children who have undergone splenectomy before the age of 5 years are described. This is why it is not recommended to perform splenectomy before the age of 5 years. Preparation for splenectomy includes an introduction 2 weeks before the operation of pneumococcal, meningococcal vaccines, the appointment of glucocorticoids, IVIG. For the next 2 years, monthly administration of bicillin-5 is indicated. In recent years, laparoscopic splenectomy has been widely performed, which has significantly less operational and postoperative complications, leaves a minimal cosmetic defect, and reduces the patient's stay in the hospital. An alternative to splenectomy can be considered endovascular occlusion of the spleen - the introduction of spleen artery substances that cause its spasm and subsequently lead to the development of spleen infarction. 2-5% of tissue after occlusion of the organ retain blood supply through collaterals. This supports the immunological reactivity of the body, which is important for pediatric practice. This operation has a minimum number of complications. Abroad, to reduce the risk of complications after surgery, proximal embolization of the spleen is often used several days before splenectomy.

How is hereditary spherocytosis (Minkowski-Schoffar's disease) treated?

Exodus

At an easy or a light; a mild course of disease, and also at timely spent splenectomy an outcome favorable. The course of hereditary spherocytosis is undulating. Following the development of the crisis, clinical and laboratory indicators improve and remission occurs, which can last from several weeks to several years.