Hemolytic anemia combines a group of diseases that are hereditary or acquired. These diseases are characterized by accelerated destruction of red cells, resulting in the release of a significant amount of indirect bilirubin. More than ten percent of all anemias belong to the hemolytic form. Absolutely all people are subject to this disorder, and therefore it is necessary to know the main symptoms, causes and methods of treatment of this disorder.

The etiology of hemolytic anemia can be hereditary and acquired diseases. Therefore, the cause of the development of the disease should be sought not only in circulatory system but also in other body systems. Hemolytic anemia develops due to the following reasons:

1. The penetration of various toxic substances and poisonous chemicals into the blood, these also include the bites of poisonous animals.
2. With mechanical destruction of erythrocytes.
3. A genetic factor that influenced the anomaly in the structure of red blood cells.
4. Due to infection with an infectious disease.
5. Avitaminosis.
6. Major trauma, severe burns or surgery.

Unfortunately, even after determining the cause of hemolytic anemia, it is not always possible to prevent the progression of the disease in patients. Some provoking phenomena cannot always be eliminated, which becomes an aggravating factor in the symptoms.

Symptoms of hemolytic anemia

Signs of hemolytic anemia combine two main syndromes - anemic and hemolytic. Clinical picture anemic syndrome is the manifestation of the following symptoms: pale skin tone and mucous membranes, increased fatigue, frequent dizziness, shortness of breath even with minor exertion, palpitations. The picture of symptoms with hemolytic factor has following manifestations: yellowish-pale shade of the skin, dark brown urine, enlarged spleen, painful discomfort in the left hypochondrium.

All subsequent periods of disease progression are manifested the following signs: there is an increase in weakness throughout the body and headache, pain may appear in other parts of the body, there is fever and vomiting. A dark red shade of urine is also fixed. Severe hemolytic anemia is manifested by an increase in body temperature.

The pathogenesis of hemolytic anemia

The mechanism of the development of the disease is directly related to the accelerated destruction of red blood cells, which occurs due to a violation of the integrity of their membrane. The hemolytic effect is due to the influence toxic substance and direct influence on all the main components of the membrane. The hemolytic effect is carried out by the ability to exert pathological oxidation, which contributes to the accumulation of a peroxide compound in large quantities.

This pathological mechanism leads to the fact that there is a functional and structural change in the composition of hemoglobin, various shifts in the membrane composition of erythrocytes. Sometimes you can observe a secondary hemolytic effect, which is caused by certain chemicals. Prolonged negative exposure to these substances is quite capable of causing chronic course hemolytic anemia. The pathogenesis of this disease seems to be mixed and complex, which requires a detailed and in-depth study.

It can be precisely noted that a violation in the structural membrane of erythrocytes, as well as functional disorders lead to the fact that the life processes of erythrocytes change, which also affects the duration of their existence. Basically, hemolytic anemia occurs due to a non-professional factor, in particular in women.

Hemolytic anemia in children

Pathological blood disease in children differs from adults in the characteristic course of anemia and cyclic features - in children there is a change in the period of exacerbation and remission. In children, hemolytic anemia poses a great danger to the nervous system, and more specifically to the brain. In young children, an icteric color of the skin is often noted.

Newborns and children preschool age suffer from this kind of anemia due to some reasons. The most common and common cause there is a hereditary factor that manifests itself especially in a newborn. Second common problem becomes a blood transfusion when it is incompatible. In children, anemia occurs even if the mother took certain medications during pregnancy.

Other provocateurs include toxic lead poisoning, venomous bite insect or snake, autoimmune disorders that lead to the destruction of the erythrocyte membrane, various diseases infectious nature, severe burns, traumatic situations, prolonged hypothermia. As the disease progresses, new signs of pathology and other serious symptoms appear. The microbial code 10 of hemolytic anemia has two designations: D58 - other hereditary hemolytic anemia, and code D59 - these are acquired hemolytic anemias.

Classification of hemolytic anemias

Congenital hemolytic anemias are divided into the following forms: erythrocytopathies and hemoglobinopathies. The first form combines congenital spherocytic and non-spherocytic anemia, as well as an acute form, which is caused by drug factors or viruses. This also includes chronic hemolytic anemia. The second form includes thalassemia and sickle cell anemia.

The acquired type of anemia is fixed in the following forms: acute and chronic. The acute form appears as a result of an illness of a newborn, an infectious disease, due to a blood transfusion. Chronic form observed due to autoimmune diseases or other chronic illnesses.

Acquired hemolytic anemia

Depending on the provocateur of the disease, two groups of hemolysis are distinguished: congenital anemia or acquired. In order to better understand the mechanisms of formation and development of the acquired form of hemolytic anemia, it is necessary to better understand the causes, the main symptoms and treatment tactics for treating this variety. This form of anemia childhood accompanied by a more pronounced course of the disease.

This form of anemia is characterized by development under the influence of external or internal provocateurs, which are completely unrelated to the structure of the erythrocyte. At an early age in a child, it is quite problematic to establish an accurate diagnosis. This is due to the fact that the blood of a newborn does not yet have stable properties and some physiological features. It is also worth noting that some experts do not recognize that there is an acquired form of anemia.

Immune hemolytic anemia

Drug-induced hemolytic anemia accounts for almost twenty percent of all cases of hemolytic anemia. In the case of this disease, the manifestation of hemolysis is noted only during a certain medicinal product, which often stops after discontinuation of this drug. Clinical signs are such manifestations: pale color, yellowness, increase in size internal organs, pain, shortness of breath.

The hematologist is engaged in determining the form of hemolytic anemia based on blood tests, causes, and the study of symptoms. During the initial examination and conversation, an anamnesis is determined. Then an assessment is made of the color of the skin, visible mucous membranes. The diagnostic process consists in examining the level of bilirubin.

The Coombs test is carried out to determine the clinical and hematological signs of hemolysis, as well as to detect autoantibodies on the surface of erythrocytes. In some cases, a blood test of hemolytic anemia shows the presence of microspherocytes, sometimes it is required laboratory diagnostics hemolytic anemia. The level of ESR also increases significantly, platelets are often within the normal range. Tests for hemolytic anemia show an increase in bilirubin in the blood.

Treatment of hemolytic anemia

Symptoms, treatment of hemolytic anemia are determined by the severity of the course of the disease. All forms are different in terms of treatment tactics, since they have their own characteristics. However, one thing remains unchanged in any form of this disease - the first thing to do is to eliminate the negative influence of hemolyzing factors. All patients are prescribed blood plasma, necessary vitamins, in some cases - hormonal therapy, antibiotics. Splenectomy is considered the only effective way elimination of hemolysis in microspherocytosis.

The autoimmune form of this disease is treated with glucocorticoids. hormonal drugs, which lead to a reduction or complete cessation of hemolysis. In some cases, an obligatory part of drug therapy is the appointment of immunosuppressants and antimalarials. Toxic hemolytic anemia involves treatment with intensive therapy: detoxification, diuresis, antidotes are carried out. In case of kidney failure fixed unfavorable prognosis for life.

• D55 Anemia due to enzyme disorders.
  • Excluded: enzyme-deficient drug-induced anemia (059.2)
  • D55.0 Anemia due to deficiency of glucose-6-phosphate dehydrogenase [G-6-PD], Favism, G-6-PD deficiency anemia
  • D55.1 Anemia due to other disorders of glutathione metabolism. Anemia due to deficiency of enzymes (with the exception of G-6-PD) associated with the hexose monophosphate [HMP] shunt of the metabolic pathway. Hemolytic nonspherocytic anemia (hereditary) type I.
  • D55.2 Anemia due to disorders of glycolytic enzymes. Anemia: hemolytic non-spherocytic (hereditary) type II, due to hexokinase deficiency, due to pyruvate kinase deficiency, due to triose phosphate isomerase deficiency
  • D55.3 Anemia due to disorders of nucleotide metabolism
  • D55.8 Other anemia due to enzyme disorders
  • D55.9 Anemia due to enzyme disorder, unspecified
• D56 Thalassemia
  • D56.0 Alpha thalassemia.
  • Excluded: hydrops fetalis due to hemolytic disease (P56.-)
  • D56.1 Beta-thalassemia Cooley's anemia. Severe beta thalassemia. Sickle cell beta thalassemia. Thalassemia: intermediate, major
  • D56.2 Delta beta thalassemia
  • D56.3 Thalassemia trait
  • D56.4 Hereditary persistence of fetal hemoglobin [NPPH]
  • D56.8 Other thalassemias
  • D56.9 Thalassemia, unspecified Mediterranean anemia (with other hemoglobinopathies). Thalassemia (minor) (mixed) (with other hemoglobinopathies)
• D57 Sickle cell disorders.
  • Excluded: other hemoglobinopathies (D58.-) sickle cell beta-thalassemia (D56.1)
  • D57.0 Sickle cell disease with crisis, Hb-SS disease with crisis
  • D57.1 Sickle cell anemia without crisis. Sickle cell(s): anemia, disease, disorder.
  • D57.2 Double heterozygous sickle cell disorders. Disease. Hb-SC. Hb SD. Hb-SE.
  • D57.3 Sickle cell carrier. Carriage of hemoglobin S. Heterozygous hemoglobin S
  • D57.8 Other sickle cell disorders
• D58 Other hereditary hemolytic anemias
  • D58.0 Hereditary spherocytosis. Acholuric (familial) jaundice. Congenital (spherocytic) hemolytic jaundice. Minkowski-Choffard syndrome
  • D58.1 Hereditary elliptocytosis. Elliptocytosis (congenital). Ovalocytosis (congenital) (hereditary)
  • D58.2 Other hemoglobinopathies. Abnormal hemoglobin NOS. Congenital anemia with Heinz bodies - Disease: Hb-C, Hb-D, Hb-E. Hemoglobinopathy NOS. Hemolytic disease caused by unstable hemoglobin.
  • Excluded Key words: familial polycythemia (D75.0), Hb-M disease (D74.0), hereditary persistence of fetal hemoglobin (D56.4), altitude-related polycythemia (D75.1), methemoglobinemia (D74.-)
  • D58.8 Other specified hereditary hemolytic anemias stomatocytosis
  • D58.9 Hereditary hemolytic anemia, unspecified
• D59 Acquired hemolytic anemia
  • D59.0 Drug-induced autoimmune hemolytic anemia
  • D59.1 Other autoimmune hemolytic anemias. Autoimmune hemolytic disease (cold type) (heat type). Chronic disease caused by cold hemagglutinins. "Cold agglutinin": disease, hemoglobinuria. Hemolytic anemia: cold type (secondary) (symptomatic), heat type (secondary) (symptomatic). Excluded Key words: Evans syndrome (D69.3), hemolytic disease of the fetus and newborn (P55.-), paroxysmal cold hemoglobinuria (D59.6)
  • D59.2 Drug-induced non-autoimmune hemolytic anemia. Drug Enzyme Deficiency Anemia
  • D59.3 Hemolytic uremic syndrome
  • D59.4 Other non-autoimmune hemolytic anemias. Hemolytic anemia: mechanical, microangiopathic, toxic
  • D59.5 Paroxysmal nocturnal hemoglobinuria(Marchiafavy - Micheli).
  • Excluded: hemoglobinuria NOS (R82.3)
  • D59.6 Hemoglobinuria due to hemolysis caused by other external causes. Hemoglobinuria: from the load, marching, paroxysmal cold.
  • Excluded: hemoglobinuria NOS (R82.3)
• D59.8 Other acquired hemolytic anemias
• D59.9 Acquired hemolytic anemia, unspecified Chronic idiopathic hemolytic anemia.

D50- D53- nutritional anemias:

D50 - iron deficiency;

D51 - vitamin B 12 - deficient;

D52 - folic acid deficiency;

D53 - other nutritional anemias.

D55- D59- hemolytic anemia:

D55 - associated with enzymatic disorders;

D56 - thalassemia;

D57 - sickle cell;

D58 - other hereditary hemolytic anemias;

D59-acute acquired hemolytic.

D60- D64- aplastic and other anemias:

D60 - acquired red cell aplasia (erythroblastopenia);

D61 - other aplastic anemias;

D62 - acute aplastic anemia;

D63-anemia of chronic diseases;

D64 - other anemias.

Pathogenesis

The supply of tissues with oxygen is provided by erythrocytes - blood cells that do not contain a nucleus, the main volume of an erythrocyte is occupied by hemoglobin - an oxygen-binding protein. The life span of erythrocytes is about 100 days. At a hemoglobin concentration below 100-120 g/l, oxygen delivery to the kidneys decreases, this is a stimulus for the production of erythropoietin by the interstitial cells of the kidneys, which leads to the proliferation of erythroid germ cells bone marrow. For normal erythropoiesis, it is necessary:

healthy bone marrow

healthy kidneys producing enough erythropoietin

sufficient content of substrate elements necessary for hematopoiesis (primarily iron).

Violation of one of these conditions leads to the development of anemia.

Figure 1. Scheme of erythrocyte formation. (T..R. Harrison).

Clinical picture

Clinical manifestations of anemia are determined by its severity, the rate of development, and the age of the patient. Under normal conditions, oxyhemoglobin gives tissues only a small part of the oxygen associated with it, the possibilities of this compensatory mechanism are great, and with a decrease in Hb by 20-30 g / l, the release of oxygen to tissues increases and there may be no clinical manifestations of anemia, anemia is often detected by a random blood test.

When the concentration of Hb is below 70-80g/l, fatigue, shortness of breath on exertion, palpitations, headache pulsating character.

In elderly patients with cardiovascular diseases, there is an increase in pain in the heart, an increase in signs of heart failure.

Acute blood loss leads to rapid decline number of erythrocytes and BCC. It is necessary, first of all, to assess the state of hemodynamics. Redistribution of blood flow and spasm of the veins cannot compensate for acute blood loss of more than 30%. Such patients lie down, marked orthostatic hypotension, tachycardia. Loss of more than 40% of blood (2000 ml) leads to shock, the signs of which are tachypnea and tachycardia at rest, stupor, cold clammy sweat, and a decrease in blood pressure. An urgent restoration of the BCC is needed.

With chronic bleeding, the bcc has time to recover on its own, a compensatory increase in the bcc develops and cardiac output. As a result, an increased apex beat, a high pulse, an increase in pulse pressure appear, due to the accelerated flow of blood through the valve, a systolic murmur is heard during auscultation.

The pallor of the skin and mucous membranes becomes noticeable when the concentration of Hb decreases to 80-100 g/l. Jaundice can also be a sign of anemia. When examining a patient, attention is drawn to the state of the lymphatic system, the size of the spleen, liver is determined, ossalgia is detected (pain when bones are beaten, especially the sternum), petechiae, ecchymosis and other signs of coagulation disorders or bleeding should attract attention.

Severity of anemia(by Hb level):

slight decrease in Hb 90-120 g/l

average Hb 70-90 g/l

severe Hb<70 г/л

extremely severe Hb<40 г/л

When making a diagnosis of anemia, you need to answer the following questions:

Are there signs of bleeding or has it already taken place?

Are there signs of excessive hemolysis?

Are there signs of suppression of bone marrow hematopoiesis?

Are there signs of iron metabolism disorders?

Are there signs of vitamin B 12 or folic acid deficiency?

Class III. Diseases of the blood, hematopoietic organs and certain disorders involving the immune mechanism (D50-D89)

Excludes: autoimmune disease (systemic) NOS (M35.9), certain conditions arising in the perinatal period (P00-P96), complications of pregnancy, childbirth and the puerperium (O00-O99), congenital anomalies, deformities and chromosomal disorders (Q00- Q99), endocrine, nutritional and metabolic disorders (E00-E90), human immunodeficiency virus [HIV] disease (B20-B24), injury, poisoning and certain other effects of external causes (S00-T98), neoplasms (C00-D48), symptoms, signs and abnormal clinical and laboratory findings, not elsewhere classified (R00-R99)

This class contains the following blocks:
D50-D53 Dietary anemia
D55-D59 Hemolytic anemias
D60-D64 Aplastic and other anemias
D65-D69 Coagulation disorders, purpura and other hemorrhagic conditions
D70-D77 Other diseases of the blood and blood-forming organs
D80-D89 Selected disorders involving the immune mechanism

The following categories are marked with an asterisk:
D77 Other disorders of the blood and blood-forming organs in diseases classified elsewhere

NUTRITIONAL ANEMIA (D50-D53)

D50 Iron deficiency anemia

Inclusions: anemia:
. sideropenic
. hypochromic
D50.0 Iron deficiency anemia secondary to blood loss (chronic). Posthemorrhagic (chronic) anemia.
Excludes: acute posthemorrhagic anemia (D62) congenital anemia due to fetal blood loss (P61.3)
D50.1 Sideropenic dysphagia. Kelly-Paterson syndrome. Plummer-Vinson Syndrome
D50.8 Other iron deficiency anemias
D50.9 Iron deficiency anemia, unspecified

D51 Vitamin B12 deficiency anemia

Excludes: vitamin B12 deficiency (E53.8)

D51.0 Vitamin B12 deficiency anemia due to intrinsic factor deficiency.
Anemia:
. Addison
. birmera
. pernicious (congenital)
Congenital intrinsic factor deficiency
D51.1 Vitamin B12 deficiency anemia due to selective malabsorption of vitamin B12 with proteinuria.
Imerslund (-Gresbeck) syndrome. Megaloblastic hereditary anemia
D51.2 Transcobalamin II deficiency
D51.3 Other vitamin B12-deficiency anemias associated with nutrition. Vegetarian anemia
D51.8 Other vitamin B12-deficiency anemias
D51.9 Vitamin B12 deficiency anemia, unspecified

D52 Folate deficiency anemia

D52.0 Folate deficiency anemia associated with nutrition. Megaloblastic nutritional anemia
D52.1 Folate deficiency anemia drug-induced. If necessary, identify the drug
use additional external cause code (class XX)
D52.8 Other folate deficiency anemias
D52.9 Folate deficiency anemia, unspecified. Anemia due to inadequate intake of folic acid, NOS

D53 Other nutritional anemias

Includes: megaloblastic anemia not responding to vitamin therapy
nom B12 or folates

D53.0 Anemia due to protein deficiency. Anemia due to lack of amino acids.
Orotaciduric anemia
Excludes: Lesch-Nychen syndrome (E79.1)
D53.1 Other megaloblastic anemias, not elsewhere classified. Megaloblastic anemia NOS.
Excludes: Di Guglielmo's disease (C94.0)
D53.2 Anemia due to scurvy.
Excludes: scurvy (E54)
D53.8 Other specified nutritional anemias.
Anemia associated with deficiency:
. copper
. molybdenum
. zinc
Excludes: malnutrition without mention of
anemia such as:
. copper deficiency (E61.0)
. molybdenum deficiency (E61.5)
. zinc deficiency (E60)
D53.9 Dietary anemia, unspecified. Simple chronic anemia.
Excludes: anemia NOS (D64.9)

HEMOLYTIC ANEMIA (D55-D59)

D55 Anemia due to enzyme disorders

Excludes: drug-induced enzyme deficiency anemia (D59.2)

D55.0 Anemia due to deficiency of glucose-6-phosphate dehydrogenase [G-6-PD]. Favism. G-6-PD-deficiency anemia
D55.1 Anemia due to other disorders of glutathione metabolism.
Anemia due to deficiency of enzymes (with the exception of G-6-PD) associated with hexose monophosphate [HMP]
metabolic pathway shunt. Hemolytic nonspherocytic anemia (hereditary) type 1
D55.2 Anemia due to disorders of glycolytic enzymes.
Anemia:
. hemolytic non-spherocytic (hereditary) type II
. due to hexokinase deficiency
. due to pyruvate kinase deficiency
. due to deficiency of triose phosphate isomerase
D55.3 Anemia due to disorders of nucleotide metabolism
D55.8 Other anemias due to enzyme disorders
D55.9 Anemia due to enzyme disorder, unspecified

D56 Thalassemia

D56.0 Alpha thalassemia.
Excludes: hydrops fetalis due to hemolytic disease (P56.-)
D56.1 Beta thalassemia. Anemia Cooley. Severe beta thalassemia. Sickle cell beta thalassemia.
Thalassemia:
. intermediate
. big
D56.2 Delta beta thalassemia
D56.3 Carrying a sign of thalassemia
D56.4 Hereditary persistence of fetal hemoglobin [NPPH]
D56.8 Other thalassemias
D56.9 Thalassemia, unspecified. Mediterranean anemia (with other hemoglobinopathies)
Thalassemia (minor) (mixed) (with other hemoglobinopathies)

D57 Sickle cell disorders

Excludes: other hemoglobinopathies (D58.-)
sickle cell beta thalassemia (D56.1)

D57.0 Sickle cell anemia with crisis. Hb-SS disease with crisis
D57.1 Sickle cell anemia without a crisis.
Sickle cell(s):
. anemia)
. disease) NOS
. violation )
D57.2 Double heterozygous sickle cell disorders
Disease:
. Hb-SC
. Hb-SD
. Hb-SE
D57.3 Carrying the sickle cell trait. Carriage of hemoglobin S. Heterozygous hemoglobin S
D57.8 Other sickle cell disorders

D58 Other hereditary hemolytic anemias

D58.0 hereditary spherocytosis. Acholuric (familial) jaundice.
Congenital (spherocytic) hemolytic jaundice. Minkowski-Choffard syndrome
D58.1 hereditary elliptocytosis. Ellitocytosis (congenital). Ovalocytosis (congenital) (hereditary)
D58.2 Other hemoglobinopathies. Abnormal hemoglobin NOS. Congenital anemia with Heinz bodies.
Disease:
. Hb-C
. Hb-D
. Hb-E
Hemolytic disease caused by unstable hemoglobin. Hemoglobinopathy NOS.
Excludes: familial polycythemia (D75.0)
Hb-M disease (D74.0)
hereditary persistence of fetal hemoglobin (D56.4)
altitude-related polycythemia (D75.1)
methemoglobinemia (D74.-)
D58.8 Other specified hereditary hemolytic anemias. stomatocytosis
D58.9 Hereditary hemolytic anemia, unspecified

D59 Acquired hemolytic anemia

D59.0 Drug-induced autoimmune hemolytic anemia.
If necessary, to identify the medicinal product, use an additional external cause code (class XX).
D59.1 Other autoimmune hemolytic anemias. Autoimmune hemolytic disease (cold type) (heat type). Chronic disease caused by cold hemagglutinins.
"Cold agglutinin":
. disease
. hemoglobinuria
Hemolytic anemia:
. cold type (secondary) (symptomatic)
. heat type (secondary) (symptomatic)
Excludes: Evans syndrome (D69.3)
hemolytic disease of fetus and newborn (P55.-)
paroxysmal cold hemoglobinuria (D59.6)
D59.2 Drug-induced non-autoimmune hemolytic anemia. Drug-induced enzyme deficiency anemia.
If necessary, to identify the drug, use an additional code of external causes (class XX).
D59.3 Hemolytic uremic syndrome
D59.4 Other non-autoimmune hemolytic anemias.
Hemolytic anemia:
. mechanical
. microangiopathic
. toxic
If it is necessary to identify the cause, use an additional external cause code (class XX).
D59.5 Paroxysmal nocturnal hemoglobinuria [Marchiafava-Micheli].
D59.6 Hemoglobinuria due to hemolysis caused by other external causes.
Hemoglobinuria:
. from load
. marching
. paroxysmal cold
Excludes: hemoglobinuria NOS (R82.3)
D59.8 Other acquired hemolytic anemias
D59.9 Acquired hemolytic anemia, unspecified. Idiopathic hemolytic anemia, chronic

APLASTIC AND OTHER ANEMIA (D60-D64)

D60 Acquired pure red cell aplasia (erythroblastopenia)

Includes: red cell aplasia (acquired) (adults) (with thymoma)

D60.0 Chronic acquired pure red cell aplasia
D60.1 Transient acquired pure red cell aplasia
D60.8 Other acquired pure red cell aplasias
D60.9 Acquired pure red cell aplasia, unspecified

D61 Other aplastic anemias

Excludes: agranulocytosis (D70)

D61.0 Constitutional aplastic anemia.
Aplasia (pure) red cell:
. congenital
. children's
. primary
Blackfan-Diamond Syndrome. Familial hypoplastic anemia. Anemia Fanconi. Pancytopenia with malformations
D61.1 Drug-induced aplastic anemia. If necessary, identify the drug
use an additional external cause code (class XX).
D61.2 Aplastic anemia caused by other external agents.
If it is necessary to identify the cause, use an additional code of external causes (class XX).
D61.3 Idiopathic aplastic anemia
D61.8 Other specified aplastic anemias
D61.9 Aplastic anemia, unspecified. Hypoplastic anemia NOS. Hypoplasia of the bone marrow. Panmyeloftis

D62 Acute posthemorrhagic anemia

Excludes: congenital anemia due to fetal blood loss (P61.3)

D63 Anemia in chronic diseases classified elsewhere

D63.0 Anemia in neoplasms (C00-D48+)
D63.8 Anemia in other chronic diseases classified elsewhere

D64 Other anemias

Excludes: refractory anemia:
. NOS (D46.4)
. with excess blasts (D46.2)
. with transformation (D46.3)
. with sideroblasts (D46.1)
. without sideroblasts (D46.0)

D64.0 Hereditary sideroblastic anemia. Sex-linked hypochromic sideroblastic anemia
D64.1 Secondary sideroblastic anemia due to other diseases.
If necessary, to identify the disease, use an additional code.
D64.2 Secondary sideroblastic anemia caused by drugs or toxins.
If it is necessary to identify the cause, use an additional code of external causes (class XX).
D64.3 Other sideroblastic anemias.
Sideroblastic anemia:
. NOS
. pyridoxine-reactive, not elsewhere classified
D64.4 Congenital dyserythropoietic anemia. Dyshemopoietic anemia (congenital).
Excludes: Blackfan-Diamond syndrome (D61.0)
di Guglielmo's disease (C94.0)
D64.8 Other specified anemias. Pediatric pseudoleukemia. Leukoerythroblastic anemia
D64.9 Anemia, unspecified

BLOOD COAGULATION DISORDERS, PURPLE AND OTHERS

HEMORRHAGIC CONDITIONS (D65-D69)

D65 Disseminated intravascular coagulation [defibrination syndrome]

Afibrinogenemia acquired. Consumption coagulopathy
Diffuse or disseminated intravascular coagulation
Fibrinolytic bleeding acquired
Purpura:
. fibrinolytic
. lightning fast
Excludes: defibrination syndrome (complicating):
. newborn (P60)

D66 Hereditary factor VIII deficiency

Factor VIII deficiency (with functional impairment)
Hemophilia:
. NOS
. A
. classical
Excludes: factor VIII deficiency with vascular disorder (D68.0)

D67 Hereditary factor IX deficiency

Christmas sickness
Deficit:
. factor IX (with functional impairment)
. thromboplastic component of plasma
Hemophilia B

D68 Other bleeding disorders

Excluded: complicating:
. abortion, ectopic or molar pregnancy (O00-O07, O08.1)
. pregnancy, childbirth and the puerperium (O45.0, O46.0, O67.0, O72.3)

D68.0 Willebrand disease. Angiohemophilia. Factor VIII deficiency with vascular damage. Vascular hemophilia.
Excludes: fragility of capillaries hereditary (D69.8)
factor VIII deficiency:
. NOS (D66)
. with functional impairment (D66)
D68.1 Hereditary factor XI deficiency. Hemophilia C. Plasma thromboplastin precursor deficiency
D68.2 Hereditary deficiency of other coagulation factors. Congenital afibrinogenemia.
Deficit:
. AC-globulin
. proaccelerin
Factor Deficiency:
. I [fibrinogen]
. II [prothrombin]
. V [labile]
. VII [stable]
. X [Stuart-Prower]
. XII [Hageman]
. XIII [fibrin-stabilizing]
Dysfibrinogenemia (congenital). Hypoproconvertinemia. Ovren's disease
D68.3 Hemorrhagic disorders caused by circulating anticoagulants in the blood. Hyperheparinemia.
Content boost:
. antithrombin
. anti-VIIIa
. anti-IXa
. anti-Xa
. anti-XIa
If it is necessary to identify the anticoagulant used, use an additional external cause code.
(class XX).
D68.4 Acquired clotting factor deficiency.
Coagulation factor deficiency due to:
. liver disease
. vitamin K deficiency
Excludes: vitamin K deficiency in newborn (P53)
D68.8 Other specified coagulation disorders. Presence of an inhibitor of systemic lupus erythematosus
D68.9 Coagulation disorder, unspecified

D69 Purpura and other hemorrhagic conditions

Excludes: benign hypergammaglobulinemic purpura (D89.0)
cryoglobulinemic purpura (D89.1)
idiopathic (hemorrhagic) thrombocythemia (D47.3)
fulminant purpura (D65)
thrombotic thrombocytopenic purpura (M31.1)

D69.0 Allergic purpura.
Purpura:
. anaphylactoid
. Henoch(-Schönlein)
. non-thrombocytopenic:
. hemorrhagic
. idiopathic
. vascular
allergic vasculitis
D69.1 Qualitative defects of platelets. Bernard-Soulier [giant platelet] syndrome.
Glanzmann's disease. Gray platelet syndrome. Thrombasthenia (hemorrhagic) (hereditary). thrombocytopathy.
Excludes: von Willebrand disease (D68.0)
D69.2 Other non-thrombocytopenic purpura.
Purpura:
. NOS
. senile
. simple
D69.3 Idiopathic thrombocytopenic purpura. Evans syndrome
D69.4 Other primary thrombocytopenias.
Excl.: thrombocytopenia with absence of radius (Q87.2)
transient neonatal thrombocytopenia (P61.0)
Wiskott-Aldrich syndrome (D82.0)
D69.5 Secondary thrombocytopenia. If it is necessary to identify the cause, use an additional external cause code (class XX).
D69.6 Thrombocytopenia, unspecified
D69.8 Other specified hemorrhagic conditions. Fragility of capillaries (hereditary). Vascular pseudohemophilia
D69.9 Hemorrhagic condition, unspecified

OTHER DISEASES OF THE BLOOD AND BLOOD-MAKE ORGANS (D70-D77)

D70 Agranulocytosis

Agranulocytic angina. Children's genetic agranulocytosis. Kostmann disease
Neutropenia:
. NOS
. congenital
. cyclic
. medical
. periodical
. splenic (primary)
. toxic
Neutropenic splenomegaly
If necessary, to identify the drug that caused neutropenia, use an additional external cause code (class XX).
Excludes: transient neonatal neutropenia (P61.5)

D71 Functional disorders of polymorphonuclear neutrophils

Defect of the receptor complex of the cell membrane. Chronic (children's) granulomatosis. Congenital dysphagocytosis
Progressive septic granulomatosis

D72 Other white blood cell disorders

Excludes: basophilia (D75.8)
immune disorders (D80-D89)
neutropenia (D70)
preleukemia (syndrome) (D46.9)

D72.0 Genetic abnormalities of leukocytes.
Anomaly (granulation) (granulocyte) or syndrome:
. Aldera
. May-Hegglin
. Pelguera Huet
Hereditary:
. leukocyte
. hypersegmentation
. hyposegmentation
. leukomelanopathy
Excludes: Chediak-Higashi (-Steinbrink) syndrome (E70.3)
D72.1 Eosinophilia.
Eosinophilia:
. allergic
. hereditary
D72.8 Other specified disorders of white blood cells.
Leukemoid reaction:
. lymphocytic
. monocytic
. myelocytic
Leukocytosis. Lymphocytosis (symptomatic). Lymphopenia. Monocytosis (symptomatic). plasmacytosis
D72.9 White blood cell disorder, unspecified

D73 Diseases of the spleen

D73.0 Hyposplenism. Asplenia postoperative. Atrophy of the spleen.
Excludes: asplenia (congenital) (Q89.0)
D73.1 hypersplenism
Excludes: splenomegaly:
. NOS (R16.1)
.congenital (Q89.0)
D73.2 Chronic congestive splenomegaly
D73.3 Abscess of the spleen
D73.4 spleen cyst
D73.5 Spleen infarction. Rupture of the spleen is non-traumatic. Torsion of the spleen.
Excludes: traumatic rupture of spleen (S36.0)
D73.8 Other diseases of the spleen. Fibrosis of the spleen NOS. Perisplenit. Spell NOS
D73.9 Disease of the spleen, unspecified

D74 Methemoglobinemia

D74.0 Congenital methemoglobinemia. Congenital deficiency of NADH-methemoglobin reductase.
Hemoglobinosis M [Hb-M disease]. Hereditary methemoglobinemia
D74.8 Other methemoglobinemias. Acquired methemoglobinemia (with sulfhemoglobinemia).
Toxic methemoglobinemia. If it is necessary to identify the cause, use an additional external cause code (class XX).
D74.9 Methemoglobinemia, unspecified

D75 Other diseases of the blood and blood-forming organs

Excl.: swollen lymph nodes (R59.-)
hypergammaglobulinemia NOS (D89.2)
lymphadenitis:
. NOS (I88.9)
. acute (L04.-)
. chronic (I88.1)
. mesenteric (acute) (chronic) (I88.0)

D75.0 Familial erythrocytosis.
Polycythemia:
. benign
. family
Excludes: hereditary ovalocytosis (D58.1)
D75.1 Secondary polycythemia.
Polycythemia:
. acquired
. related to:
. erythropoietins
. decrease in plasma volume
. height
. stress
. emotional
. hypoxemic
. nephrogenic
. relative
Excludes: polycythemia:
. newborn (P61.1)
. true (D45)
D75.2 Essential thrombocytosis.
Excludes: essential (hemorrhagic) thrombocythemia (D47.3)
D75.8 Other specified diseases of the blood and blood-forming organs. Basophilia
D75.9 Disease of the blood and blood-forming organs, unspecified

D76 Certain diseases involving the lymphoreticular tissue and the reticulohistiocytic system

Excludes: Letterer-Siwe disease (C96.0)
malignant histiocytosis (C96.1)
reticuloendotheliosis or reticulosis:
. histiocytic medullary (C96.1)
. leukemic (C91.4)
. lipomelanotic (I89.8)
. malignant (C85.7)
. non-lipid (C96.0)

D76.0 Langerhans cell histiocytosis, not elsewhere classified. Eosinophilic granuloma.
Hand-Schuller-Chrisgen disease. Histiocytosis X (chronic)
D76.1 Hemophagocytic lymphohistiocytosis. Familial hemophagocytic reticulosis.
Histiocytosis from mononuclear phagocytes other than Langerhans cells, NOS
D76.2 Hemophagocytic syndrome associated with infection.
If necessary, to identify an infectious agent or disease, use an additional code.
D76.3 Other histiocytic syndromes. Reticulohistiocytoma (giant cell).
Sinus histiocytosis with massive lymphadenopathy. xanthogranuloma

D77 Other disorders of the blood and blood-forming organs in diseases classified elsewhere.

Fibrosis of the spleen in schistosomiasis [bilharzia] (B65.-)

SELECTED DISORDERS INVOLVING THE IMMUNE MECHANISM (D80-D89)

Includes: defects in the complement system, immunodeficiency disorders excluding disease,
human immunodeficiency virus [HIV] sarcoidosis
Excl.: autoimmune diseases (systemic) NOS (M35.9)
functional disorders of polymorphonuclear neutrophils (D71)
human immunodeficiency virus [HIV] disease (B20-B24)

D80 Immunodeficiencies with predominant antibody deficiency

D80.0 Hereditary hypogammaglobulinemia.
Autosomal recessive agammaglobulinemia (Swiss type).
X-linked agammaglobulinemia [Bruton's] (with growth hormone deficiency)
D80.1 Nonfamilial hypogammaglobulinemia. Agammaglobulinemia with the presence of B-lymphocytes carrying immunoglobulins. General agammaglobulinemia. Hypogammaglobulinemia NOS
D80.2 Selective immunoglobulin A deficiency
D80.3 Selective deficiency of immunoglobulin G subclasses
D80.4 Selective immunoglobulin M deficiency
D80.5 Immunodeficiency with elevated levels of immunoglobulin M
D80.6 Insufficiency of antibodies with close to normal levels of immunoglobulins or with hyperimmunoglobulinemia.
Antibody deficiency with hyperimmunoglobulinemia
D80.7 Transient hypogammaglobulinemia in children
D80.8 Other immunodeficiencies with a predominant antibody defect. Kappa light chain deficiency
D80.9 Immunodeficiency with predominant antibody defect, unspecified

D81 Combined immunodeficiencies

Excludes: autosomal recessive agammaglobulinemia (Swiss type) (D80.0)

D81.0 Severe combined immunodeficiency with reticular dysgenesis
D81.1 Severe combined immunodeficiency with low T and B cell counts
D81.2 Severe combined immunodeficiency with low or normal B-cell counts
D81.3 Adenosine deaminase deficiency
D81.4 Nezelof syndrome
D81.5 Purine nucleoside phosphorylase deficiency
D81.6 Deficiency of class I molecules of the major histocompatibility complex. Naked lymphocyte syndrome
D81.7 Deficiency of class II molecules of the major histocompatibility complex
D81.8 Other combined immunodeficiencies. Deficiency of biotin-dependent carboxylase
D81.9 Combined immunodeficiency, unspecified. Severe combined immunodeficiency disorder NOS

D82 Immunodeficiencies associated with other significant defects

Excludes: atactic telangiectasia [Louis Bar] (G11.3)

D82.0 Wiskott-Aldrich Syndrome. Immunodeficiency with thrombocytopenia and eczema
D82.1 Di George Syndrome. Syndrome of the diverticulum of the pharynx.
Thymus:
. alymphoplasia
. aplasia or hypoplasia with immune deficiency
D82.2 Immunodeficiency with dwarfism due to short limbs
D82.3 Immunodeficiency due to a hereditary defect caused by the Epstein-Barr virus.
X-linked lymphoproliferative disease
D82.4 Hyperimmunoglobulin E syndrome
D82.8 Immunodeficiency associated with other specified major defects
D 82.9 Immunodeficiency associated with significant defect, unspecified

D83 Common variable immunodeficiency

D83.0 Common variable immunodeficiency with predominant abnormalities in the number and functional activity of B cells
D83.1 Common variable immunodeficiency with a predominance of disorders of immunoregulatory T-cells
D83.2 Common variable immunodeficiency with autoantibodies to B or T cells
D83.8 Other common variable immunodeficiencies
D83.9 Common variable immunodeficiency, unspecified

D84 Other immunodeficiencies

D84.0 Defect of functional antigen-1 of lymphocytes
D84.1 Defect in the complement system. Deficiency of C1 esterase inhibitor
D84.8 Other specified immunodeficiency disorders
D84.9 Immunodeficiency, unspecified

D86 Sarcoidosis

D86.0 Sarcoidosis of the lungs
D86.1 Sarcoidosis of the lymph nodes
D86.2 Sarcoidosis of the lungs with sarcoidosis of the lymph nodes
D86.3 Sarcoidosis of the skin
D86.8 Sarcoidosis of other specified and combined localizations. Iridocyclitis in sarcoidosis (H22.1).
Multiple cranial nerve palsies in sarcoidosis (G53.2)
Sarcoid(s):
. arthropathy (M14.8)
. myocarditis (I41.8)
. myositis (M63.3)
Uveoparotitis fever [Herfordt's disease]
D86.9 Sarcoidosis, unspecified

D89 Other disorders involving the immune mechanism, not elsewhere classified

Excludes: hyperglobulinemia NOS (R77.1)
monoclonal gammopathy (D47.2)
graft failure and rejection (T86.-)

D89.0 Polyclonal hypergammaglobulinemia. Hypergammaglobulinemic purpura. Polyclonal gammopathy NOS
D89.1 cryoglobulinemia.
Cryoglobulinemia:
. essential
. idiopathic
. mixed
. primary
. secondary
Cryoglobulinemic(s):
. purpura
. vasculitis
D89.2 Hypergammaglobulinemia, unspecified
D89.8 Other specified disorders involving the immune mechanism, not elsewhere classified
D89.9 Disorder involving the immune mechanism, unspecified. Immune disease NOS

RCHD (Republican Center for Health Development of the Ministry of Health of the Republic of Kazakhstan)
Version: Clinical Protocols of the Ministry of Health of the Republic of Kazakhstan - 2016

Other autoimmune hemolytic anemias (D59.1), Drug-induced autoimmune hemolytic anemia (D59.0)

Orphan diseases

general information

Short description

Approved
Joint Commission on the quality of medical services
Ministry of Health and Social Development of the Republic of Kazakhstan
dated September 15, 2016
Protocol #11

Autoimmune hemolytic anemias (AIHA)- a heterogeneous group of autoaggressive diseases and syndromes caused by the destruction of red blood cells, which is caused by the uncontrolled production of antibodies against one's own red blood cells.

Correlation between ICD-10 and ICD-9 codes:

Classification

Classification:
AIHA is divided into idiopathic (primary) and symptomatic (secondary). In more than 50% of patients, the development of AIHA is secondary (Table 1).
In 10% of cases of AIHA, various drugs are the cause of hemolysis. For a list of drugs that can cause the development of autoimmune hemolysis or lead to the detection of anti-erythrocyte antibodies, see Appendix 1.

The serological properties of autoantibodies formed the basis for the division of AIHA into four forms:
With incomplete thermal agglutinins (80% of all patients);
With complete cold agglutinins (12-15% of all cases);
with thermal hemolysins;
With two-phase cold Donat-Landsteiner hemolysins (extremely rare and, as a rule, a secondary form in syphilis and viral infections).

Table 1 - Frequency and types of antibodies in secondary AIHA

Diagnostics (outpatient clinic)

DIAGNOSIS AT OUTPATIENT LEVEL (LE - H)

Diagnostic criteria:

Complaints and anamnesis:
The main syndromes in hemolytic anemia are:
normocytic anemia with rapidly increasing weakness and poor adaptation to even a moderate decrease in hemoglobin.

Depending on the level of hemoglobin, 3 degrees of severity of anemia are distinguished:
I (mild degree) - Hb more than 90 g / l;
II (medium degree) - from 90 to 70 g / l;
III (severe degree) - less than 70 g / l.

Clinically, the severity of the patient's condition does not always correspond to the level of hemoglobin: acutely developed anemia is accompanied by much more pronounced symptoms than chronic, in which there is time for the adaptation of organs and tissues. Elderly patients tolerate anemia worse than younger ones, since the compensatory capabilities of the cardiovascular system are usually reduced in them.

In a hemolytic crisis, signs of severe anemia are pronounced against the background of an acute onset:
· fever;
· stomach ache;
· headache;
Vomiting
oliguria and anuria followed by the development of shock.

Hemolysis syndrome, which can be manifested by complaints of:
icterus of the skin and visible mucous membranes (jaundice);
darkening of the urine.
· With intravascular hemolysis, the color of urine can be from pink to almost black. The color depends on the concentration of hemoglobin, the degree of heme dissociation. The color of urine in hemoglobinuria must be distinguished from hematuria, when whole red blood cells are visible on microscopic examination. The color of urine can also be red due to taking medications (antipyrine), food (beets) or with porphyria, myoglobinuria, which develops under certain conditions (massive traumatic muscle injury, electric shock, arterial thrombosis, etc.).
The appearance of sensitivity to pressure, a feeling of heaviness or pain in the left hypochondrium associated with an enlarged spleen. More often degree of increase in a spleen has insignificant or moderate character.

In more than 50% of patients, the development of AIHA is secondary, and therefore the symptoms of the underlying disease may dominate in the clinical picture (Table 1).

Physical examination:
The results of a physical examination are determined by the rate and degree of hemolysis, the presence or absence of comorbidity, diseases that caused the development of AIHA. In the compensation stage, the condition is satisfactory, there may be slight subicteric skin, visible mucous membranes, slight splenomegaly, signs of the underlying disease, for example, SLE, lymphoproliferative disease, etc. In this situation, the presence of mild AIHA may not be diagnosed.

In a hemolytic crisis:
state of moderate or severe;
pallor of the skin and mucous membranes;
Expansion of the boundaries of the heart, deafness of tones, tachycardia, systolic murmur at the apex;
shortness of breath
· weakness;
· dizziness;
Bilirubin intoxication: icterus of the skin and mucous membranes, nausea, vomiting, abdominal pain, dizziness, headaches, fever, in some cases, disorders of consciousness, convulsions;
With intracellular hemolysis: hepatosplenomegaly;
With mixed and intravascular hemolysis: change in urine due to hemoglobinuria.

Laboratory research:
Complete blood count, including platelets and reticulocytes: normochromic anemia of varying severity; reticulocytosis, leukocytosis with a shift of the leukocyte formula to the left during the crisis; in a smear of peripheral blood, as a rule, microspherocytes;
· blood chemistry:
bilirubin with fractions (hyperbilirubinemia, indirect, non-conjugated fraction predominates),
LDH (an increase in serum LDH activity by 2-8 times, depending on the intensity of hemolysis),
haptoglobin - an indicator of hemolysis;
total protein, albumin, creatinine, urea, ALT, AST, GGTP, C-reactive protein, alkaline phosphatase - assessment of the state of the liver, kidneys
Glucose - exclusion of diabetes;
· direct Coombs' test in most cases is positive, but with massive hemolysis, as well as with cold and hemolysin forms of AIHA caused by IgA or IgM autoantibodies, it may be negative.


hemosiderin in the urine - the exclusion of intravascular hemolysis;
· general analysis urine (a visual assessment of the color of urine is required);
Determination of copper in daily urine, ceruloplasmin in blood serum - exclusion of Wilson-Konovalov's disease;
puncture of the bone marrow (hyperplasia and morphology of the erythroid germ, the number and morphology of lymphocytes, complexes of metastatic cells);
trepanobiopsy (if necessary) - exclusion of secondary AIHA;
Immunophenotyping of lymphocytes (with lymphocytosis of peripheral blood and remote spleen) - exclusion of secondary AIHA;
Vitamin B12, folate - exclusion of megaloblastic anemia;
· Indicators of iron metabolism (including transferrin, serum and erythrocyte ferritin) - exclusion of iron deficiency;
· extended coagulogram + lupus anticoagulant - assessment of the state of hemostasis, exclusion of APS;
Rheumatological tests (antibodies to native DNA, rheumatoid factor, antinuclear factor, antibodies to cardiolipin antigen) - exclusion of secondary AIHA;

if necessary, thyroid hormones, prostate specific antigen, tumor markers; exclusion of secondary AIHA;
Determination of the blood group according to the AB0 system, Rh factor;
blood test for HIV - if necessary, transfusion;
a blood test for syphilis - a standard examination at any level;
determination of HBsAg in blood serum by ELISA - screening for hepatitis B;
determination of total antibodies to hepatitis C virus (HCV) in blood serum by ELISA - screening for hepatitis C.

Instrumental research:
x-ray of the lungs (if necessary, CT);
FGDS;

Ultrasound of the organs abdominal cavity and intra-abdominal lymph nodes, small pelvis, prostate, thyroid gland.

Diagnostic algorithm (Scheme 1):

Diagnostics (ambulance)

DIAGNOSTICS AND TREATMENT AT THE EMERGENCY STAGE

Diagnostic measures:
collection of complaints, anamnesis;
physical examination.

Medical treatment: no.

Diagnostics (hospital)

DIAGNOSTICS AT THE STATIONARY LEVEL

Diagnostic criteria: see ambulatory level.

Diagnostic algorithm: see ambulatory level.

List of main diagnostic measures:
general blood test (calculation of leukoformula, platelets and reticulocytes in a smear);
biochemical blood test (total bilirubin, direct bilirubin, LDH);
direct Coombs test.

List of additional diagnostic measures:
determination of the level of haptoglobin;
blood type and Rh factor;
biochemical blood test (total protein, albumin, total bilirubin, direct bilirubin, creatinine, urea, ALaT, ASAT, glucose, LDH, GGTP, C-reactive protein, alkaline phosphatase);
iron metabolism (determination of the level of serum iron, the total iron-binding capacity of serum and the level of ferritin);
determination of the concentration of folic acid and vitamin B12;
Immunophenotyping of lymphocytes (with lymphocytosis, suspected lymphoproliferative disease, ineffectiveness of corticosteroid therapy);
Serum and urine protein electrophoresis with immunofixation (with lymphocytosis, suspected lymphoproliferative disease, failure of corticosteroid therapy);
myelogram;
ELISA for markers of viral hepatitis;
ELISA for HIV markers;
ELISA for markers of herpes group viruses;
coagulogram, lupus anticoagulant;
Reberg-Tareev test (glomerular filtration rate determination);
titer of cold agglutinins;
indirect Coombs test (required for intensive hemolysis and previous transfusions of erythrocytes);
determination of hemosiderin, copper and hemoglobin in urine;
trepanobiopsy of the bone marrow with histological examination;
vitamin B12, folate;
indicators of iron metabolism (including transferrin, serum and erythrocyte ferritin);
· coagulogram + lupus anticoagulant;
rheumatological tests (antibodies to native DNA, rheumatoid
factor, antinuclear factor, antibodies to cardiolipin antigen);
Serum immunoglobulins (G, A, M) + cryoglobulins;
thyroid hormones, prostate specific antigen, tumor markers;
· general urine analysis;
x-ray of the chest;
esophagogastroduodenoscopy;
irrigoscopy / sigmoidoscopy / colonoscopy;
Ultrasound of the abdominal organs and intra-abdominal lymph nodes, small pelvis, prostate, thyroid gland;
· Ultrasound of arteries and veins;
ECG;
echocardiography;
daily monitoring of blood pressure;
24-hour ECG monitoring.

Differential Diagnosis

Differential diagnosis and rationale for additional studies:

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Treatment

Drugs (active substances) used in the treatment

Groups of drugs according to ATC used in the treatment

Treatment (ambulatory)

OUTPATIENT TREATMENT (EL - H)

Treatment tactics: only in the absence of indications for hospitalization: at the outpatient stage, treatment started in the hospital often continues, monitoring of clinical and laboratory parameters with further correction of therapy.

Non-drug treatment:
ModeII. With long-term therapy with corticosteroids, regular exercise, elimination of risk factors for accidental loss of balance, falls (C), smoking cessation. In AIHA with cold antibodies avoid hypothermia.
Diet: to prevent glucocorticoid osteoporosis, adequate intake of calcium and vitamin D, limiting alcohol consumption (D).

Medical treatment:

Prednisolone;

Rituximab concentrate for solution for infusion 100 mg;
· Cyclosporine;
amlodipine;
lisinopril;
atenolol;
· torasemide;
· folic acid;
alendronate;
risedronate;
zolendronate;
alfacalcidol;
· calcium carbonate;
paracetamol;
chlorpyramine;
omeprazole;
enoxaparin;
Nadroparin;
amoxicillin/clavulanic acid;
Levofloxacin;
a solution of sodium chloride.

AIHA therapy is currently not based solely on retrospective and few prospective studies in the absence of randomized trials and does not have a high level of evidence. There is also no formal consensus on the definition of complete or partial remission. Thus, the recommendations for the treatment of AIHA described below have a level of evidence of D.

First line therapy.
Glucocorticosteroids.
Glucocorticosteroids are the first line of therapy for AIHA patients with warm antibodies. Starting dose of prednisolone or metiprednisolone 1 mg/kg (orally or intravenously). Usually within 1-3 weeks of starting therapy (conducted in a hospital), the hematocrit level increases by more than 30% or the hemoglobin level is more than 100 g / l (there is no need to normalize the hemoglobin level). If the therapeutic goal is achieved, the dose of prednisolone is reduced to 20-30 mg per day for several weeks. If these goals are not achieved by the end of the 3rd week, then second-line therapy is connected. Dose reduction of prednisolone continues at the outpatient stage. A slow decrease in the dose of prednisolone is carried out if a therapeutic effect is achieved. Reduce the dose of prednisolone start at 5-10 mg for 2-3 days and continue until daily dose will not reach 20-30 mg. Further, the withdrawal of the drug is carried out much more slowly - 2.5 mg for 5-7 days. After reaching a dose below 10-15 mg, the rate of withdrawal should be further slowed down: 2.5 mg every 2 weeks in order to completely cancel the drug. This tactic involves the duration of taking prednisolone for 3-4 months. The level of hemoglobin, reticulocytes is monitored. If within 3-4 months, when taking prednisolone at a dose of 5 mg per day, remission persists, an attempt should be made to completely cancel the drug. The desire for a rapid dose reduction since the normalization of hemoglobin due to side effects GC (cushingoid, steroid ulcers, arterial hypertension, acne with the formation of pustules on the skin, bacterial infections, diabetes, osteoporosis, venous thrombosis) always leads to recurrence of hemolysis. In fact, patients receiving low-dose corticosteroids for more than 6 months have a lower relapse rate and a longer duration of remission compared to patients who discontinue therapy before 6 months of therapy. Accompanying therapy during steroid treatment may include bisphosphonates, vitamin D, calcium, maintenance therapy folic acid. Blood glucose levels are monitored and diabetes is actively treated, as diabetes is a large risk factor for death due to infection. It is necessary to assess the risk of thromboembolism pulmonary artery especially in patients with AIHA and lupus anticoagulant or recurrent AIHA after splenectomy 38.

Therapy of the 1st line of corticosteroids is effective in 70-85% of patients; however, most patients require maintenance therapy with corticosteroids to maintain hemoglobin levels within 90-100 g / l, in 50% a dose of 15 mg / day or less is sufficient, and approximately 20-30% of patients require higher doses of prednisone. It is believed that GCS monotherapy is effective in less than 20% of patients. In patients with resistance to first-line therapy, the possibility of secondary AIHA should be re-evaluated, since AIHA with warm agglutinins associated with malignant tumors, UC, ovarian teratoma, or IgM is often steroid-refractory.

Second line therapy.
Splenectomy.
There is an increased risk after splenectomy severe infections associated with Streptococcus pneumoniae, Neisseria meningitidis, haemophilus influenzae. Patients are given polyvalent pneumococcal, meningococcal, Haemophilus influenzae type b capsular polysaccharide (PRP) tetanus toxoid (TT) conjugated vaccine 2 to 4 weeks prior to splenectomy. In patients who have received rituximab in the past 6 months, vaccination may not be effective. After surgery, thromboprophylaxis with low doses of low molecular weight heparins; gradual cancellation of GCS according to the scheme described above, pneumococcal vaccine every 5 years. Patients after splenectomy should be informed about the risk of infections and the need for any febrile episode to take antibiotics from the group of penicillins or respiratory fluoroquinolones (levofloxacin); they should also be informed about the risk of venous thromboembolism.

Rituximab.


refusal of splenectomy;
· elderly age With a high degree risk of complications of the first and second lines of therapy
contraindications to splenectomy, high risk of venous thromboembolism.


active hepatitis B and C;

Standard mode - 375 mg/m2 on days 1, 8, 15 and 22. Patients on glucocorticoid therapy prior to initiation of rituximab therapy should continue glucocorticosteroids until the first signs of response to rituximab.

Efficiency b rituximab at standard dose in AIHA with warm antibodies: overall response 83-87%, complete response 54-60, disease-free survival in 72% at 1 year and 56% at 2 years.
The response time varies from 1 month in 87.5% to 3 months in 12.5%. With a second course, the effectiveness of rituximab may be higher compared to the first course. The response to therapy is observed in mono mode or in combination with corticosteroids, immunosuppressants and interferon-α and does not depend on primary therapy.

Therapy toxicity: The drug has a good safety profile. Very rarely, usually after the first infusion, fever, chills, rash, or sore throat. More serious reactions include serum sickness and (very rarely) bronchospasm, anaphylactic shock, pulmonary embolism, retinal artery thrombosis, infections (episodes of infection in approximately 7%), and development of fulminant hepatitis due to reactivation of hepatitis B. In rare cases, progressive multifocal leukoencephalopathy.
Rituximab at a low dose (100 mg/week for 4 weeks) as first or second line therapy produces an overall response rate of 89% (complete response rate of 67%) and a relapse-free period of 36 months in 68%. Approximately 70% of patients treated with corticosteroids and rituximab had a remission of 36 months compared with 45% of patients who received steroids alone.

Immunosuppressive drugs.
The main factor in choosing an immunosuppressive drug should be patient safety, because the expected efficacy of all drugs is low and treatment may be more dangerous for the patient than treatment of the disease (Table 2). With long-term treatment, maintenance therapy can be carried out on an outpatient basis under the supervision of a specialist.

Table 2 - AIHA immunosuppressive therapy

Algorithm of actions in emergency situations:
if a hemolytic crisis is suspected (fever, pallor, yellowness of the skin, darkening of urine, splenomegaly, cardiovascular insufficiency, anemic shock, anemic coma) - call the ambulance team for emergency transportation of the patient to the hematology department or intensive care unit, depending on the severity of the condition;
monitoring of vital functions: the frequency and nature of breathing, the frequency and rhythm of the pulse, systolic and diastolic blood pressure, the amount and color of urine;
If there are signs of impaired vital functions (acute heart failure, signs of shock, renal failure) - emergency care: providing venous access, infusion of colloidal drugs, if intravascular hemolysis is suspected - prevention of renal failure (furosemide), oxygenation with oxygen.

· doctor's consultation on X-ray endovascular diagnostics and treatment - installation of a central venous catheter from a peripheral access (PICC);
consultation of a hepatologist - for the diagnosis and treatment of viral hepatitis;
consultation of a gynecologist - during pregnancy, metrorrhagia, menorrhagia, consultation when prescribing combined oral contraceptives;
consultation of a dermatovenereologist - in case of skin syndrome;
consultation of an infectious disease specialist - in case of suspected viral infections;
consultation with a cardiologist - in case of uncontrolled hypertension, chronic heart failure, cardiac arrhythmia and conduction disturbances;
consultation of a neuropathologist - in case of acute cerebrovascular accident, meningitis, encephalitis, neuroleukemia;
consultation of a neurosurgeon - in case of acute cerebrovascular accident, dislocation syndrome;
consultation of a nephrologist (efferentologist) - in case of renal insufficiency;
consultation of an oncologist - in case of suspicion of solid tumors;
· consultation of an otorhinolaryngologist - for the diagnosis and treatment of inflammatory diseases of the paranasal sinuses and middle ear;
consultation of an ophthalmologist - in case of visual impairment, inflammatory diseases of the eye and appendages;
consultation of a proctologist - with anal fissure, paraproctitis;
consultation of a psychiatrist - in case of psychoses;
· consultation of a psychologist - in case of depression, anorexia, etc.;
consultation of a resuscitator - in the treatment of severe sepsis, septic shock, acute lung injury syndrome in differentiation syndrome and terminal conditions, installation of central venous catheters.
consultation of a rheumatologist - with SLE;
consultation of a thoracic surgeon - with exudative pleurisy, pneumothorax, zygomycosis of the lungs;
consultation of a transfusiologist - for the selection of transfusion media in case of a positive indirect antiglobulin test, transfusion failure, acute massive hemolysis;
consultation of a urologist - in case of infectious and inflammatory diseases of the urinary system;
consultation of a phthisiatrician - in case of suspected tuberculosis;
consultation of a surgeon - in case of surgical complications (infectious, hemorrhagic);
consultation of a maxillofacial surgeon - in case of infectious and inflammatory diseases of the dentoalveolar system.

Preventive actions:
In secondary AIHA, adequate treatment of the underlying disease;
· in case of AIHA with cold antibodies - avoid hypothermia.

Patient Monitoring:
To monitor the effectiveness of treatment in the outpatient card, the following are noted: the general condition of the patient, indicators of a general blood test, including reticulocytes and platelets, biochemical parameters - the level of bilirubin, LDH, enzyme immunoglobulin determination of the amount of immunoglobulins on the erythrocyte membrane, direct Coombs test.

Patient's individual follow-up card

Treatment (hospital)

TREATMENT AT THE STATIONARY LEVEL

Treatment tactics (UD-B): patients are hospitalized in the hematology department, in case of violation of vital functions - in the intensive care unit.

Non-drug treatment: diet taking into account comorbidity, regimen - II.

Medical treatment:

1st line of therapy.

Glucocorticosteroids.
Glucocorticosteroids are the first line of therapy for AIHA patients with warm antibodies. Corticosteroids, usually prednisolone, are given at a starting dose of 1 mg/kg per day (50–80 mg/day) for 1 to 3 weeks until hematocrit increases by more than 30% or hemoglobin increases by more than 100 g/L. If this goal is not achieved within 3 weeks, a second line of therapy should be started, since corticosteroid therapy is considered ineffective. Increasing the dose of prednisolone to 2 mg/kg/day (90–160 mg/day) does not improve treatment outcomes, leading to rapid development typical severe complications. If the therapeutic goal is achieved, the dose of prednisolone is reduced to 20-30 mg per day. Reduce the dose of prednisolone start at 5-10 mg for 2-3 days and continue until the daily dose reaches 20-30 mg. Further, the withdrawal of the drug is carried out much more slowly - 2.5 mg for 5-7 days. After reaching a dose below 10-15 mg, the rate of withdrawal should be further slowed down: 2.5 mg every 2 weeks in order to completely cancel the drug. This tactic involves the duration of taking prednisolone for 3-4 months. The level of hemoglobin, reticulocytes is monitored. If within 3-4 months, when taking prednisolone at a dose of 5 mg per day, remission persists, an attempt should be made to completely cancel the drug. The desire to quickly reduce the dose from the moment of normalization of hemoglobin due to the side effects of GC (cushingoid, steroid ulcers, arterial hypertension, acne with the formation of pustules on the skin, bacterial infections, diabetes mellitus, osteoporosis, venous thrombosis) always leads to a relapse of hemolysis. In fact, patients receiving low-dose corticosteroids for more than 6 months have a lower relapse rate and a longer duration of remission compared to patients who discontinue therapy before 6 months of therapy.
An alternative to the long-term use of corticosteroids (up to 3-4 months) are short courses (up to 3 weeks) of the course, followed by a transition to the second line of therapy.

All patients on steroid therapy should receive bisphosphonates, vitamin D, calcium, and folic acid maintenance therapy. Blood glucose levels are monitored and diabetes is actively treated, as diabetes is a large risk factor for death due to infection. The risk of pulmonary embolism should be assessed, especially in patients with AIHA and lupus anticoagulant or AIHA recurrence after splenectomy.
Patients with particularly rapid hemolysis and very severe anemia or complex cases (Evans syndrome) are treated with methylprednisolone at a dose of 100-200 mg/day for 10-14 days or 250-1000 mg/day for 1-3 days. Therapy with high doses of corticosteroids in the literature is presented mainly in the form of a description of clinical cases. 19.20

Therapy of the 1st line of corticosteroids is effective in 70-85% of patients; however, most patients require maintenance therapy with corticosteroids to maintain hemoglobin levels within 90-100 g / l, in 50% a dose of 15 mg / day or less is sufficient, and approximately 20-30% of patients require higher doses of prednisone. It is believed that GCS monotherapy is effective in less than 20% of patients. In patients with resistance to first-line therapy, the possibility of secondary AIHA should be re-evaluated, since AIHA with warm agglutinins associated with malignant tumors, UC, ovarian teratoma, or IgM is often steroid-refractory.

Second line therapy
When choosing second-line therapy, there are several options, and when choosing each of them, it is necessary to weigh the benefit / risk in each case (Fig. 2).

Splenectomy.
Splenectomy is generally considered to be the most effective and appropriate 2nd line therapy for warm antibody AIHA.

Indications for splenectomy:
Refractoriness or intolerance to corticosteroids;
The need for continuous maintenance therapy with prednisolone at a dose of more than 10 mg / day;
Frequent relapses.
The advantages of splenectomy are quite high efficiency with the achievement of partial or complete remission in 2/3 of patients (38-82%, taking into account secondary forms of AIHA, in which the response is less than in idiopathic AIHA), a significant number of patients remain in remission without requiring medical intervention for 2 years or more ; the possibility of recovery is approximately 20%.
After splenectomy, patients with persistent or recurrent hemolysis often require lower doses of corticosteroids than before splenectomy.

Disadvantages of splenectomy:
Lack of reliable predictors of splenectomy outcome;
The risk of surgical complications (TELA, intra-abdominal bleeding, abdominal abscess, hematoma) - 0.5-1.6% with laparoscopic splenectomy and 6% with conventional splenectomy);
· The risk of infection is 3.3-5% (the most dangerous is pneumococcal septicemia) with a mortality rate of up to 50%.
Splenectomy increases the risk of severe infections associated with Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae. Patients are given polyvalent pneumococcal, meningococcal, Haemophilus influenzae type b capsular polysaccharide (PRP) tetanus toxoid (TT) conjugated vaccine 2 to 4 weeks prior to splenectomy. In patients who have received rituximab in the past 6 months, vaccination may not be effective.

After surgery, thromboprophylaxis with low doses of low molecular weight heparins; gradual cancellation of GCS according to the scheme described above, pneumococcal vaccine every 5 years. Patients after splenectomy should be informed about the risk of infections and the need for any febrile episode to take antibiotics from the group of penicillins or respiratory fluoroquinolones (levofloxacin); they should also be informed about the risk of venous thromboembolism.

Figure 2. Algorithm for the treatment of steroid-refractoryWAIHA.

Rituximab.
Indications for the appointment of rituximab:
resistant forms of AIHA with an increasing number of various complications;
refusal of splenectomy;
advanced age with a high risk of complications of the first and second lines of therapy;
Contraindications to splenectomy (massive obesity, technical problems), high risk of venous thromboembolism.

Contraindications to the appointment of rituximab:
drug intolerance;
active hepatitis B and C;
acute viral or bacterial infection.

Treatment "Last option” (Despair Therapy)
High-dose cyclophosphamide (50 mg/kg/day for 4 days) accompanied by a colony-stimulating factor was effective in 5 of 8 patients with highly refractory warm antibody AIHA.
Alemtuzumab has shown efficacy in the treatment of small groups of patients with refractory AIHA, however, due to its high toxicity, it is considered as a “last resort” in the treatment of severe idiopathic AIHA, refractory to all previous therapy options.
Hematopoietic stem cell transplantation. Information on the use of HSCT in AIHA with warm antibodies is limited to single cases or small groups, mainly in Evans syndrome with a complete remission of approximately 60% in allogeneic and 50% in autologous BMT.

supportive therapy.
Patients with AIHA may often require packed red cell transfusions to maintain clinically acceptable hemoglobin levels, at least until specific therapy is effective. The decision to conduct a transfusion depends not only on the level of hemoglobin, but to a greater extent on the clinical status of the patient and comorbidity (especially coronary artery disease, severe lung disease), their exacerbation, the rate of development of anemia, the presence of hemoglobinuria or hemoglobinemia, and other manifestations of severe hemolysis. RBC transfusion should not be withheld in a critical clinical situation, even in cases where a lack of individual compatibility is found, since warm autoantibodies are often panreactive. Rh-compatible erythrocyte-containing components of the first blood group Rh-compatible can be safely prescribed in emergency cases if alloantibodies (occur in 12-40% of patients with AIHA) are reasonably excluded on the basis of a previous transfusion history and/or obstetric history (women who are not pregnant and/or previous transfusions and men without a history of transfusions). In other patients, extended phenotyping is performed with the determination of Rh subgroups (C,c,E,e), Kell, Kidd, and S / s using monoclonal IgM antibodies and the selection of a compatible red blood cell mass for transfusion. In exceptional cases, thermal autoadsorption or allogeneic adsorption methods are used to determine alloantibodies. In any case, a biological test must be carried out.

The algorithm for the treatment of AIHA with warm antibodies is shown in Figure 3.
Figure 3. Algorithm for the treatment of AIHA with warm antibodies in adults




Treatment of secondary AIHA.
AIHA with warm antibodies in SLE.
The preferred first-line therapy is steroids, the order of administration is similar to that of primary AIHA (Table 3).

Table 3 - Treatment of secondary AIHA

Hospitalization

Information

Sources and literature

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