Hereditary spherocytosis (Minkowski-Choffard disease)

Anemia - what is it?

Anemia is characterized by a decrease in the level of red blood cells and hemoglobin in the blood. In some cases, not only the numerical composition of red blood cells falls below normal, but their shape also changes. As the disease progresses, the red blood cells are unable to perform their functions.

Anemia develops against the background of other disorders in the body; it does not manifest itself. Therefore, to get rid of the disease, it is necessary to establish the cause that led to the change in the composition of the blood.

What is the distinctive feature of hemolytic anemia?

Hemolytic anemia combines several diseases, but the reasons for their development are the same. Red blood cells in the blood are destroyed too quickly, so the red bone marrow begins to produce them intensively. As a result, their growth cycle is disrupted. As anemia progresses, red blood cells undergo massive death.

Hemolytic anemia can be transmitted from parents to children, and can develop throughout life. Minkowski-Choffard anemia is a hereditary pathology.

This disease is also called microspherocytic anemia and hereditary spherocytosis. However, the term “Minkowski-Choffard anemia” is most often used after the scientists who first discovered this pathology.

This type of anemia cannot be called rare; it affects every 5,000th person on the planet. Most often it affects people living in Northern Europe. Minkowski-Choffar anemia first makes itself felt in childhood. If this disorder is left untreated, the body as a whole will suffer.

Causes of Minkowski-Choffard anemia

With Minkowski-Choffard anemia, the structure of red blood cells undergoes pathological changes, which affects their functioning. Red blood cells become fragile and are destroyed much more easily. Hemoglobin comes out of them, which circulates in free form in the blood.

If normally red blood cells have the shape of a biconvex disk, then with Minkowski-Choffard anemia they become round, which does not allow them to penetrate small blood vessels. When attempting to do this, the red blood cells are severely damaged and destroyed. Their level in the blood decreases, which causes the development of anemia.

If one of the parents suffered from Minkowski-Choffard anemia, then this disease will be inherited by the child. Rarely sick children are born from completely healthy parents. If this happens, experts say the cause is damage to the DNA structure. Genes mutate while the baby is in the womb.

Pathogenic factors are:

• Exposure of a woman’s body to radioactive or x-ray radiation.
• Poisoning of a pregnant woman’s body with salts of heavy metals, drugs, and tobacco smoke.
• Transmitted viral diseases.

It should be taken into account that these pathogenic factors can provoke not only anemia, but also other serious disorders in the body of a growing fetus. Therefore, you need to treat your health very carefully.

Causes and mechanism of disease development

Minkowski-Choffar anemia is accompanied by a disruption of the structure and function of the erythrocyte cell membrane.
As a result of the processes taking place, they change their shape to round and become fragile. The first signs of hemolysis appear - the destruction of red blood cells with the simultaneous release of hemoglobin. In a healthy person, red blood cells are shaped like a biconcave disc, due to which they move freely through the vessels. With anemia in the membrane of these elements, protein synthesis is disrupted. This leads to the penetration of fluid into the cells. For this reason they change their shape. Passing through the vessels, red blood cells are greatly deformed, and after a while they begin to collapse. Against the background of the ongoing processes, the level of red blood elements drops sharply, and hemolytic anemia develops.

If one of the parents has already been diagnosed with this disease, it will certainly be inherited by the child. It is extremely rare that sick children are born to completely healthy mothers and fathers. In this case, anemia develops against the background of changes in DNA. The primary gene mutation occurs during fetal development. A prerequisite for the development of the disease is the impact on the mother’s body of the following factors:

• radiation, x-rays;
• intoxication with salts of heavy metals, narcotic substances, nicotine;
• virus attack.

Under the influence of these factors, not only Minkowski-Choffard anemia can occur, but also more serious pathologies. Therefore, during pregnancy, a woman should try to protect her body.

Symptoms of Minkowski-Choffard anemia

The lower the level of normal red blood cells in the blood, the stronger the symptoms of the disease will be. The first signs of pathology develop in a child in the preschool period or during early school age. Anemia has a wave-like course, periods of remission are followed by periods of exacerbation.

During a hemolytic crisis, massive death of red blood cells occurs. At the same time, all the symptoms gain strength. When the crisis is over, the person will feel satisfactory. Possible excessive pallor of the skin and mucous membranes.

Symptoms of a crisis are:

• High body temperature.
• Headache.
• General weakness and malaise.
• Yellowness of the skin.
• Cramps and pain in the abdomen.
• Enlargement of the liver.
• Inflammation of the spleen.

The disease can also develop in adulthood. The first sign that a person most often pays attention to is yellowing of the skin. Although in some cases, objective symptoms of the disorder may be completely absent. Often, anemia can be diagnosed only during a random examination, when a person donates blood for analysis.

Hereditary spherocytosis in children

05.11.2021

Hereditary microspherocytic anemia (Minkowski-Choffard disease) is the most common congenital hemolytic anemia. It is characterized by the spherical shape of red blood cells, which are easily destroyed in the spleen. The main clinical manifestations are hemolytic anemia, jaundice and enlarged spleen.

What is the cause of hereditary spherocytosis?

Hereditary spherocytosis is caused by a genetic defect of the eighth chromosome, which is inherited in an autosomal dominant manner. In about 20% of cases, the gene is missing, and it is a new mutation on chromosome 8. The defective gene codes for the synthesis of abnormal membrane proteins, resulting in defects in the red blood cell membrane. The most common abnormality is found in the structure of the spectrin protein. Its binding to other structural proteins is also impaired. As a result, red blood cells have less membrane stability and flexibility, and change their shape - from a double concave disk they turn into spheres. Spherical red blood cells are tough and easily destroyed in the spleen, shortening their life.

What are the symptoms of hereditary microspherocytic anemia?

Hereditary spherocytosis can occur after childbirth with more pronounced and prolonged jaundice, and then with the development of anemia. There are also very mild forms with the first manifestation after puberty. However, most often the disease manifests itself at the age of about 5 years, with complaints of mild anemia, a swollen and enlarged spleen. The relatively calm course of the disease can be interrupted by two types of crises - hemolytic (most often caused by infections, stress or exercise) and aplastic crisis.

Hereditary microspherocytic anemia is characterized by three main symptoms:

• hemolytic jaundice - varies from mild subcutaneous sclera to severe jaundice during a hemolytic crisis.
• hemolytic anemia - due to increased hemolysis (destruction) of red blood cells. In between periods, anemia is mild, and during a hemolytic crisis it intensifies. The complaints are the same as with any anemia - fatigue, apathy, shortness of breath, palpitations, headaches;
• splenomegaly (enlarged spleen) - slightly to moderately enlarged, sometimes very enlarged and causing heaviness in the left hypochondrium. The liver may also be enlarged – hepatomegaly.

Children with frequent and severe hemolytic crises experience growth retardation, a high hard palate, prominent cheekbones, a saddle nose, and an elongated skull—a “spherical skull.” In older children, bilirubin stones may form in the gall bladder .

How is hereditary spherocytosis diagnosed?

The following tests help diagnose hereditary microspherocytic anemia:

• anamnesis data - genetic predisposition is established;
• physical examination - jaundice, enlarged spleen;
• laboratory research.

Laboratory tests are critical for diagnosis. Microspherocytes are detected - these are red blood cells of a smaller size and without central clearing. Elevated reticulocytes are always detected, hemoglobin is reduced. The osmotic resistance of red blood cells is reduced due to their defective membrane. Typically, red blood cells begin to break down when the sodium chloride concentration is below 0.46%. With hereditary spherocytosis, hemolysis begins below 0.7%. Biochemical studies reveal an increase in indirect bilirubin, an increase in urobilinogen in the urine , an increase in the iron content in the blood , and an increase in LDH.

Hereditary microspherocytic anemia should be distinguished from other types of congenital hemolytic anemia, thalassemia, and leukemia. In newborns, it should be differentiated from hemolytic disease of the newborn, from Gilbert's syndrome.

What is the treatment for hereditary spherocytosis?

In many cases, folic acid supplementation is sufficient. Sometimes a blood during hemolytic and aplastic crises. Because red blood cells are destroyed primarily in the spleen, splenectomy is performed in more severe cases. After surgical removal of the spleen, rapid improvement is observed - hemoglobin gradually increases, indirect bilirubin normalizes, reticulocytes decrease, the life of erythrocytes is extended, but does not reach normal, microspherocytosis remains a defect in the erythrocyte membrane.

Splenectomy is performed after 6 years of age because children are at risk of developing severe infection after splenectomy, most often caused by pneumococci or Haemophilus influenzae. Therefore, it is recommended to vaccinate children against pneumococcus before surgery . Another postoperative complication is an increased tendency to thrombosis in the lungs and brain . Therefore, it is advisable to carry out antithrombotic therapy after splenectomy.

Published in Pediatrics Premium Clinic

Diagnosis of Minkowski-Choffard anemia

Identifying the disease is usually not difficult. The doctor will listen to the patient’s complaints and examine him. It is imperative to clarify whether the person’s closest blood relatives suffered from anemia. In addition to an external examination of the skin and mucous membranes, the doctor palpates the abdomen to determine whether the patient’s liver and spleen are enlarged in size. An ultrasound of these organs is mandatory.

Without laboratory tests, it will not be possible to confirm the diagnosis, so the doctor directs the patient to undergo the following tests:

• Analysis of urine. It can contain bilirubin, protein and urobilin in high concentrations.
• Blood for biochemical analysis. In this case, it will be possible to detect a decrease in cholesterol levels, an increase in the level of indirect bilirubin and lactate dehydrogenase.
• Blood for clinical analysis. In this case, an increase in the level of reticulocytes will be detected, the red blood cells themselves decrease in size. In addition, ESR increases, and a decrease in platelet and leukocyte levels may be observed. The blood color index will be below normal.

To confirm the diagnosis, it will be necessary to study the proteins of the red blood cell membranes using two-dimensional electrophoresis.

It is imperative to carry out a differential diagnosis of Minkowski-Choffard anemia with autoimmune diseases. First of all, it is necessary to carefully study the family history, since Minkowski-Choffard anemia is most often inherited. In addition, sick children have certain changes in the structure of the skull. If the doctor remains in doubt, the patient is given a Coombs test. When this test gives a negative result, the diagnosis is confirmed.

The article provides a review of the literature concerning clinical and laboratory manifestations, diagnosis, treatment and prognosis of hereditary microspherocytic anemia. The results of our own observations of two patients undergoing treatment in the oncohematology department of the Yoshkar-Ola Children's City Hospital are described.

Hereditary microspherocytosis (Minkowsky - Shauffard disease)

The paper presents a literature review of clinical and laboratory manifestations, diagnosis, treatment and prognosis of hereditary microspherocytic anemia. It is describes the results of his own observations of two patients treated in oncohematological office in Yoshkar-Ola City Children's Hospital.

Hereditary microspherocytosis was first described in 1900 by Minkowski, and later in more detail by Shoffar. The prevalence of this disease is 1:5000 of the population, most often found in residents of Northern Europe [1, 2].

Pathogenesis. Congenital microspherocytic hemolytic anemia is a familial disease inherited in an autosomal dominant manner. The disease is based on a genetic defect in the protein of the erythrocyte membrane, as a result of which its permeability to sodium ions increases, which leads to swelling of erythrocytes, disruption of the ability of erythrocytes to deform, detachment of part of their surface in the spleen, shortening of their life span and destruction by spleen macrophages [3, 4 ]. The pathology of erythrocytes is manifested by a morphological abnormality - microspherocytosis. The duration of stay of microspherocytes in the circulating blood is sharply reduced; the average period of their stay in the bloodstream can be 12-14 days (instead of the normal 120-125 days) [5].

Clinical picture. The central place in the clinical picture belongs to the hemolytic syndrome, which is manifested by three cardinal signs: jaundice, splenomegaly and anemia [5]. Signs of delayed development may be observed, as well as disturbances of the facial skeleton in the form of a “tower skull”, saddle nose, high palate, disturbance of the arrangement of teeth, and narrow eye sockets [6]. The severity of anemic syndrome varies. A moderate decrease in hemoglobin is often observed. Some patients have no anemia at all. The most dramatic anemization is observed during the hemolytic crisis. Microspherocytic hemolytic anemia has a chronic course and is accompanied by periodic crises and remissions. Hemolytic crisis occurs under the influence of provoking factors (infection, hypothermia, overwork, pregnancy and others) and is manifested by a sharp increase in symptoms against the background of continuously ongoing hemolysis [6]. At the same time, the temperature rises due to the massive breakdown of red blood cells, the intensity of jaundice increases, hepatomegaly is pronounced, the spleen is dense and smooth, often painful as a result of tension of the capsule during blood filling or perisplenitis. Hemolytic disease is often complicated by attacks of hepatic colic, due to the formation of pigment stones in the gall bladder and bile ducts. Due to attacks of hepatic colic and stagnation of bile in the liver, patients may experience symptoms of angiocholecystitis and parenchymal hepatitis with the appearance of direct bilirubin in the blood. With exacerbation of the disease, there is a tendency to nosebleeds [3, 7]. Despite its congenital nature, the disease only rarely manifests itself in the first days after birth; symptoms usually appear in childhood, usually at 3-10 years of age, or adulthood [8].

Laboratory diagnostics. Microscopic examination of peripheral blood preparations reveals spherocytes, characterized by a decrease in the average diameter (less than 7.2-7.0 µm) against the background of a normal average MCV volume and an increased MCHC value. The red blood cell size distribution curve (Price-Jones curve) on the graph is shifted to the left. Anemia is normochromic in nature. The RDW value exceeds 12% (anisocytosis). Reticulocytosis - 15%-30% [1, 10]. The white blood cell count is usually normal. In hemolytic crises, neutrophilic leukocytosis with a shift to the left is noted. The platelet count varies within normal limits. The content of indirect bilirubin in the blood is moderately increased and, as a rule, does not exceed 50-70 µmol/l [6, 7]. Autoantibodies are not detected on the erythrocyte membrane; the direct Coombs test is negative. A characteristic laboratory sign is a decrease in the osmotic resistance of red blood cells to hypotonic sodium chloride solutions. The beginning of hemolysis in hereditary microspherocytosis corresponds to 0.6-0.7%, and the end - 0.4% instead of 0.48-0.22% normally [1, 9]. A decrease in osmotic resistance indicates the predominance of spherical erythrocytes in the blood - spherocytes, which are less resistant to osmotic hemolysis than normal macroplanocytes (Fig. 1).

Figure 1. Morphology of microspherocytes in peripheral blood smears of a patient (left), healthy (right)

Differential diagnosis of hereditary microspherocytosis comes down to the diagnosis of hemolytic anemia in general. Many patients are mistakenly diagnosed with Gilbert's syndrome, chronic hepatitis or even cirrhosis of the liver, and anemia is considered a consequence of these diseases. In all cases of jaundice, a thorough examination of the patient is necessary, regardless of hemoglobin content. A predominant increase in the content of indirect bilirubin, reticulocytes, and microspherocytosis detected when viewing a smear provide the basis for the correct diagnosis. A differential diagnosis of autoimmune hemolytic anemia and microspherocytosis is then necessary, since autoimmune hemolytic anemias often produce symptomatic microspherocytosis [3]. In this situation, a thorough ascertainment of the medical history, duration of the disease, the presence of a similar disease in relatives, identification of skeletal changes, and testing to detect autoantibodies (direct Coombs test) help.

Treatment and prognosis. Treatment during a hemolytic crisis is aimed at eliminating anemia, hypoxia, and hyperbilirubinemia. The method of choice for the treatment of hereditary spherocytosis is splenectomy, optimal at the age of 4-5 years. Splenectomy provides practical recovery, despite the preservation of spherocytosis. Indications for splenectomy in microspherocytosis are persistent anemia or that occurs in the form of crises, significant hyperbilirubinemia, even without anemia, the appearance of pain in the right hypochondrium, and developmental delays in children [3]. Blood (packed red blood cell) transfusions are indicated in cases of severe hemolytic crisis [5]. The prognosis for hereditary microspherocytosis is favorable. The probability of developing the disease in children if one of the spouses has microspherocytosis is slightly lower than 50% [9].

Clinical case No. 1. Patient S., 1 year 10 months, from 06/01/09 to 06/09/09 was undergoing an inpatient examination in the oncohematology department of the Yoshkar-Ola Children's City Hospital. From the anamnesis it is known that the child from the first pregnancy was born premature, weighing 900 grams. He was nursed in the department of the second stage of nursing premature babies. Heredity is unknown, since he was adopted at the age of four months. From birth, a decrease in the level of hemoglobin in the blood test and icterus of the skin were noted. Since December 2008, he has been under observation by a hematologist for anemia of prematurity and has been taking iron supplements. Upon receipt of a complaint of lethargy, weakness, fever to febrile levels, pallor and icteric discoloration of the skin. On palpation, the liver protrudes from under the edge of the costal arch by 2.5 cm, the spleen by 2 cm, is soft and elastic.

General blood test dated 06/01/09: HGB - 106 g/l, RBC - 3.9×10¹²/l, WBC - 11.6×109/l, Ht - 26%, MCV - 68.8 fl, MCH — 25.8 pg, MSHC — 375 g/l, RDW — 20.5%, PLT — 434×109/l, ESR — 6 mm/h, in the leukocyte formula: eosinophils — 10%, neutrophils — 34 %, lymphocytes - 47%, monocytes - 9%.

Anemia is normochromic in nature. In blood smears, microspherocytes predominate, characterized by the absence of central clearing characteristic of normal erythrocytes, which is confirmed graphically on the Price-Jones curve, reflecting the quantitative ratios of erythrocytes of different diameters. The apex of the Price-Jones curve is stretched and shifted to the left towards microcytes. In addition, normocytes and single macrocytes are visible in blood smears, this confirms an increase in the RDW index - 20.5%. In many red blood cells, basophilic punctation and polychromatophilia are detected. Reticulocytosis - 27%. Osmotic resistance of erythrocytes: min - 0.52%, max - 0.34% (with a norm of 0.48-0.22%) - a decrease in resistance to hypotonic solutions of table salt is determined. Biochemical analysis dated 06/02/09: concentration of indirect bilirubin - 29.9 µmol/l, ALT - 15 U/l, AST - 26 U/l, al. phosphatase - 415 U/l, LDH - 273 U/l, indicators of iron metabolism are within normal limits: serum Fe - 14.4 µm/l, THC - 69.9 µm/l. A negative result of the direct Coombs test allowed us to exclude autoimmune hemolytic anemia.

In hereditary microspherocytosis, the blood picture is characterized by a pathological triad on the part of erythrocytes: 1) microspherocytosis; 2) reticulocytosis; 3) reduced osmatic resistance. In our case, all three factors are well expressed. The patient was diagnosed with hereditary microspherocytic hemolytic anemia.

The child was discharged in stable condition on 06/09/09 with recommendations: observation by a hematologist and pediatrician, general and biochemical blood tests once every 3 months.

On June 24, 2009, patient S. was re-admitted to the oncohematology department. Upon admission, the condition was serious, complaints of lethargy, lack of appetite, poor sleep, fever up to 39.6°C, pallor, yellowness of the skin, dark urine. The pharynx is hyperemic and loose. The lymph nodes of the cervical group are enlarged. The abdomen is enlarged in volume, the liver protrudes from under the edge of the costal arch by 3.5 cm, the spleen by 5 cm.

General blood test dated June 24, 2009: HGB - 89 g/l, RBC - 3.4×10¹²/l, WBC - 27.7×109/l, Ht - 21%, MCV - 68.6 fl, MCH -25.5 pg, MSHC - 381 g/l, RDW - 20.8%, PLT - 260×109/l, ESR - 12 mm/h, in the formula: eosinophils - 4%, basophils - 1%, p/ I neutrophils - 4%, s/I neutrophils - 15%, lymphocytes - 20%, monocytes - 1%, atypical mononuclear cells - 55%. Reticulocytosis - 46.7%. Blood smears contain up to 50% microspherocytes. Indirect bilirubin - 41 µmol/l, ALT - 19 U/l, AST - 45 U/l, al. phosphatase - 316 U/l, LDH - 295 U/l. An increased content of stercobilin in the feces is determined. In the urine, urobilinuria is noted, the release of urates and uric acid crystals, explained by the increased breakdown of red blood cells. ELISA for Epstein-Barr virus (infectious mononucleosis) - positive.

Taking into account the child's intoxication, fever, enlarged cervical lymph nodes, high leukocytosis in the blood, mononuclear cells up to 55%, positive ELISA, infectious mononucleosis was diagnosed, which in turn was the trigger for the development of a hemolytic crisis in the boy.

Treatment was carried out: diet, bed rest, infusion and antiviral therapy. As a result of therapy, the fever stopped, the size of the liver, spleen and lymph nodes decreased. General blood test dated 07/06/09: HGB - 104g/l, RBC - 3.9×10¹²/l, WBC - 10.7×109/l, Ht - 28%, MCV - 73.3 fl, MCH - 26.4 pg, MSHC - 360 g/l, RDW - 21.8%, PLT - 452×109/l, ESR - 2 mm/h, in the leukocyte formula: eosinophils - 5%, p/n neutrophils - 5% , neutrophils - 25%, lymphocytes - 47%, monocytes - 8%, atypical mononuclear cells - 10%. Reticulocytosis - 9.3%. The number of microspherocytes decreased to 23%. Indirect bilirubin - 18.8 µmol/l. Appetite and sleep normalized. In a stable condition, on July 09, 2009, the child was discharged home with recommendations: observation by a hematologist once every 3 months, a general blood test with reticulocytes and a biochemical blood test once every 3 months, monitoring by ultrasound of the abdominal cavity once a year.

Clinical case No. 2. Patient G., 12 years old, on September 22, 2009, was transferred to the oncohematology department of the Yoshkar-Ola Children's City Hospital from the infectious diseases hospital. Upon receipt of a complaint of nasal congestion, sore throat, general weakness, enlarged cervical and occipital lymph nodes, fever up to 39.2°C, icteric skin, hepatosplenomegaly with pronounced density of parenchymal organs. From the anamnesis it is known that the girl’s father suffers from Gilbert’s syndrome and since birth the girl has developed yellowness of the skin and sclera due to fever and ARVI.

General blood test dated September 23, 2009: HGB - 61g/l, RBC - 1.8×10¹²/l, WBC - 10.7×109/l, Ht - 16%, MCV - 85 fl, MCH - 32, 5 pg, MSHC - 382g/l, RDW - 20.3%, PLT - 162×109/l, ESR - 48 mm/h, in the leukocyte formula: myelocytes - 1%, metamyelocytes - 2%, p/n neutrophils - 29%, neutrophils - 9%, lymphocytes - 24%, monocytes - 4%, atypical mononuclear cells - 31%. Reticulocytosis - 82.5%. Blood smears contain a significant number of microspherocytes. Osmotic resistance of erythrocytes: min - 0.72%, max - 0.42%, a sharp decrease in resistance to hypotonic solutions of table salt is determined. Increased levels of urobilin in urine and stercobilin in feces. Biochemical blood test dated September 23, 2009: ALT - 71 U/l, AST - 78 U/l, LDH 1234 U/l, direct bilirubin - 5.68 µmol/l, indirect - 54.8 µmol/l. Direct Coombs test is negative.

Severe normochromic anemia, the detection of a significant number of microspherocytes in blood products, a pronounced reticulocyte crisis, a sharp decrease in the osmotic resistance of erythrocytes, hyperbilirubinemia, as well as the presence of similar symptoms in the father gave grounds to diagnose the girl with a hemolytic crisis of hereditary microspherocytic anemia, provoked by infectious mononucleosis (Epstein virus ELISA - Barr - positive). An examination by an infectious disease specialist confirms the diagnosis of infectious mononucleosis.

The patient was prescribed infusion, antibacterial and antiviral therapy, and vitamins. During treatment, the patient's condition stabilized. General blood test dated 10/12/09: HGB - 106g/l, RBC - 3.5×10¹²/l, WBC - 3.9×109/l, Ht - 29.3%, MCV - 83.8 fl, MCH - 30.4 pg, MCHC - 362 g/l, RDW - 217.8%, PLT - 170×109/l, ESR - 8 mm/h, in the formula: basophils - 1%, p/n neutrophils - 4 %, neutrophils - 62%, lymphocytes - 20%, monocytes - 4%, atypical mononuclear cells - 9%. Reticulocytosis - 13.1%. Biochemical blood test: ALT - 41 U/l, AST - 32 U/l, direct bilirubin - 2.75 µmol/l, indirect - 24.35 µmol/l. According to abdominal ultrasound, positive dynamics are noted in the form of a decrease in the size of the liver and spleen. The girl was discharged home on October 13, 2009 with recommendations: observation by a hematologist, infectious disease specialist and pediatrician, complete blood count with reticulocytes once every 3 months, monitoring by ultrasound of the abdominal cavity.

Both patients are being monitored by a hematologist.

The diagnosis of congenital microspherocytosis sometimes presents certain difficulties. The most typical manifestations of hemolysis - yellowness of the sclera and skin - are not always correctly assessed by the doctor. The clinical cases we described are direct confirmation of this. In both patients, icterus of the sclera and skin was determined from birth, but a detailed examination was not carried out on the patients before the development of a hemolytic crisis. The presence of similar symptoms in the girl’s father (Gilbert’s syndrome?) suggests that patient G. inherited the disease from her father. The heredity of patient S. is unknown.

In both cases, the provoking factor in the development of the hemolytic crisis was the Epstein-Barr virus. Children have suffered from viral infections before, but they did not cause the development of a hemolytic crisis. Perhaps not every, but only a certain group of viruses can cause crises. This question remains open, since based on the example of two cases it cannot be argued that the Epstein-Barr virus always provokes the development of a hemolytic crisis in patients with hereditary microspherocytosis.

E.V. Shirdanina, Z.S. Gordeeva

Yoshkar-Ola Children's City Hospital, Yoshkar-Ola

Shirdanina Ekaterina Valerievna – doctor of the clinical diagnostic laboratory

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Treatment of Minkowski-Choffard anemia

Depending on the severity of the disease, the methods of its medicinal correction will differ. During the period of remission of anemia, therapy is not carried out. During an exacerbation of the pathology, the patient must be hospitalized.

Treatment boils down to the following activities:

• When the hemoglobin level decreases to 70 g/l, the patient is transfused with red blood cells.
• If the level of bilirubin in the blood is high, the patient is given albumin.
• To remove intoxication from the body, the patient is given infusion therapy.
• Choleretic drugs can improve the patient’s well-being during a hemolytic crisis.

Severe Minkowski-Choffard anemia requires surgical intervention. To do this, the patient's spleen is removed. This will not make it possible to completely get rid of anemia, but the person’s condition improves, since the life cycle of red blood cells can be extended.

After removal of the spleen, the patient will no longer be at risk of hemolytic crises. However, this procedure is contraindicated under the age of 5 years, since splenectomy can be fatal in children. In addition, the absence of a spleen in the body contributes to a decrease in immunity. A person becomes susceptible to various infections.

Another surgical method for treating anemia is endovascular occlusion. This procedure is an alternative to splenectomy. During the procedure, the patient is given a drug that causes a splenic infarction. A certain part of it does not die, but continues to function, so the patient’s condition improves, but immunity does not decrease.

If the disease is mild and the patient receives high-quality and timely treatment, then the prognosis for life is favorable. Removing the spleen avoids crises. Without surgery, the average duration of remission between hemolytic crises is 2 years.

Hereditary spherocytosis (Minkowski-Choffard disease)

Hereditary spherocytosis can manifest itself from the neonatal period, but more pronounced symptoms are found towards the end of preschool and at the beginning of school age. Early manifestation of the disease predetermines a more severe course. Boys get sick more often. Hereditary spherocytosis is a hemolytic anemia with a predominantly intracellular type of hemolysis, which also causes the clinical manifestations of the disease - jaundice, enlarged spleen, a greater or lesser degree of anemia, and a tendency to form gallstones.

Complaints and clinical and laboratory symptoms are largely determined by the period of the disease. Outside of a hemolytic crisis, there may be no complaints. With the development of a hemolytic crisis, there are complaints of increased fatigue, lethargy, headache, dizziness, pallor, jaundice, decreased appetite, abdominal pain, a possible increase in temperature to high levels, nausea, vomiting, increased frequency of stools, and a terrible symptom - the appearance of convulsions.

The symptoms of a crisis are largely determined by anemia and depend on the degree of hemolysis. On objective examination, the skin and visible mucous membranes are pale or lemon yellow. In children with early manifestations of hereditary spherocytosis, deformations of the skeleton are possible, especially of the skull (tower, square skull, the position of the teeth changes, etc.); Genetic stigmas are not uncommon. Patients exhibit varying degrees of severity of changes in the cardiovascular system caused by anemia. Hepatolienal syndrome with a predominant enlargement of the spleen is characteristic. The spleen is dense, smooth, often painful, which is apparently explained by tension of the capsule due to blood filling or perisplenitis. The color of excrement at the time of crisis is intense. It should be noted that there are possible fluctuations in the size of the spleen: a significant increase during hemolytic crises and a decrease during periods of relative well-being.

Depending on the severity of hereditary spherocytosis, clinical symptoms may be mild. Sometimes jaundice may be the only symptom for which the patient consults a doctor. It is to these individuals that Shoffar’s famous expression applies: “They are more jaundiced than sick.” Along with the typical classical signs of the disease, there are forms of hereditary spherocytosis, when hemolytic anemia can be so well compensated that the patient learns about the disease only after undergoing an appropriate examination.

Along with the most typical hemolytic crises in severe hereditary spherocytosis, aregenerative crises with symptoms of hypoplasia of the predominantly red bone marrow are possible. Such crises can develop acutely with quite pronounced symptoms of anemia-hypoxia and are usually observed in children after 3 years of life. Aregenerative crises are short-term (1-2 weeks) and are reversible, unlike true aplasia.

Hereditary spherocytosis is complicated by the formation of pigment stones in the gallbladder and bile ducts; after 10 years, gallstones occur in half of patients who have not undergone splenectomy.

Complications of Minkowski-Choffard anemia

In childhood, Minkowski-Choffard anemia can cause mental and physical development delays. Most often this is observed when the child does not receive treatment, or it is started too late.

In adulthood, the most common complication of Minkowski-Choffard anemia is gallstone disease, which develops against the background of increased levels of bilirubin in the blood. Often, hemolytic crisis is confused with obstructive jaundice, so the patient is not given adequate therapy. If stones are found in the patient's gall bladder, it is removed along with the spleen.

Prevention measures

Minkowski-Choffard anemia is a disease that is inherited, so it is impossible to prevent its development. People suffering from this pathology need to be registered with a hematologist.

The probability of a child being born with hemolytic anemia in a sick mother is equal to 50%. Therefore, such children should be thoroughly examined from birth.

Author of the article:

Shutov Maxim Evgenievich |
Hematologist Education: Graduated from Kursk State Medical University in 2013 and received a diploma in General Medicine. After 2 years, he completed his residency in the specialty “Oncology”. In 2021, she completed postgraduate studies at the National Medical and Surgical Center named after N.I. Pirogov. Our authors