D55—D59 Anemia due to enzyme disorders. Hemolytic anemia What is autoimmune hemolytic anemia

Class III. Blood diseases hematopoietic organs and selected disorders involving the immune mechanism (D50-D89)

Excluded: 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 diseases, nutritional and metabolic disorders (E00-E90), disease caused by the human immunodeficiency virus [HIV] (B20-B24), injuries, poisoning and certain other consequences of exposure external reasons(S00-T98), neoplasms (C00-D48), symptoms, signs and abnormalities identified during clinical and laboratory research, not elsewhere classified (R00-R99)

This class contains the following blocks:
D50-D53 Anemia associated with nutrition
D55-D59 Hemolytic anemias
D60-D64 Aplastic and other anemias
D65-D69 Bleeding disorders, purpura and other hemorrhagic conditions
D70-D77 Other diseases of the blood and hematopoietic organs
D80-D89 Selected disorders involving the immune mechanism

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

NUTRITION-RELATED ANEMIA (D50-D53)

D50 Iron deficiency anemia

Included: anemia:
. sideropenic
. hypochromic
D50.0Iron-deficiency anemia secondary due 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 diet. Anemia of vegetarians
D51.8 Other vitamin B12 deficiency anemias
D51.9 Vitamin B12 deficiency anemia, unspecified

D52 Folate deficiency anemia

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

D53 Other diet-related anemias

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

D53.0 Anemia due to protein deficiency. Anemia due to amino acid deficiency.
Orotaciduric anemia
Excludes: Lesch-Nychen syndrome (E79.1)
D53.1 Other megaloblastic anemias, not elsewhere classified. Megaloblastic anemia NOS.
Excludes: DiGuglielmo disease (C94.0)
D53.2 Anemia due to scurvy.
Excludes: scurvy (E54)
D53.8 Other specified diet-related 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 Diet-related 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 glucose-6-phosphate dehydrogenase [G-6-PD] deficiency. Favism. G-6-PD deficiency anemia
D55.1 Anemia due to other disorders of glutathione metabolism.
Anemia due to deficiency of enzymes (except G-6-PD) associated with hexose monophosphate [HMP]
bypass of the metabolic pathway. 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 triosephosphate isomerase deficiency
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. Cooley's anemia. Severe beta thalassemia. Sickle cell beta thalassemia.
Thalassemia:
. intermediate
. big
D56.2 Delta beta thalassemia
D56.3 Carriage of thalassemia trait
D56.4 Hereditary persistence of fetal hemoglobin [HFH]
D56.8 Other thalassemias
D56.9 Thalassemia unspecified. Mediterranean anemia (with other hemoglobinopathy)
Thalassemia minor (mixed) (with other hemoglobinopathy)

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 crisis.
Sickle cell:
. anemia)
. disease) NOS
. violation )
D57.2 Double heterozygous sickle cell disorders
Disease:
. Hb-SC
. Hb-SD
. Hb-SE
D57.3 Carriage of 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 it is necessary to identify the drug, use an additional code for external causes (class XX).
D59.1 Other autoimmune hemolytic anemias. Autoimmune hemolytic disease(cold type) (thermal type). Chronic disease caused by cold hemagglutinins.
"Cold agglutinin":
. disease
. hemoglobinuria
Hemolytic anemia:
. cold type (secondary) (symptomatic)
. thermal type (secondary) (symptomatic)
Excludes: 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-induced enzyme deficiency anemia.
If it is necessary to identify the drug, use an additional code for 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. Chronic idiopathic hemolytic anemia

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

Excluded: agranulocytosis (D70)

D61.0 Constitutional aplastic anemia.
Aplasia (pure) red cell:
. congenital
. children's
. primary
Blackfan-Diamond syndrome. Familial hypoplastic anemia. Fanconi anemia. Pancytopenia with developmental defects
D61.1 Drug-induced aplastic anemia. If necessary, identify the drug
use an additional code for external causes (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 bone marrow. Panmyelophthisis

D62 Acute posthemorrhagic anemia

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

D63 Anemia in chronic diseases classified elsewhere

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

D64 Other anemias

Excluded: 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, an additional code is used to identify the disease.
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. Dyshematopoietic anemia (congenital).
Excludes: Blackfan-Diamond syndrome (D61.0)
DiGuglielmo disease (C94.0)
D64.8 Other specified anemias. Childhood pseudoleukemia. Leukoerythroblastic anemia
D64.9 Anemia, unspecified

BLOOD CLOTTING DISORDERS, PURPURA AND OTHERS

HEMORRHAGIC CONDITIONS (D65-D69)

D65 Disseminated intravascular coagulation [defibration syndrome]

Afibrinogenemia acquired. Consumptive coagulopathy
Diffuse or disseminated intravascular coagulation
Acquired fibrinolytic bleeding
Purpura:
. fibrinolytic
. lightning fast
Excluded: defibration syndrome (complicating):
. in a 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 disease
Shortage:
. factor IX (with functional impairment)
. thromboplastic plasma component
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 Von Willebrand's disease. Angiohemophilia. Factor VIII deficiency with vascular impairment. Vascular hemophilia.
Excludes: hereditary capillary fragility (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.
Shortage:
. AC globulin
. proaccelerin
Factor deficiency:
. I [fibrinogen]
. II [prothrombin]
. V [labile]
. VII [stable]
. X [Stuart-Prower]
. XII [Hageman]
. XIII [fibrin stabilizing agent]
Dysfibrinogenemia (congenital). Hypoproconvertinemia. Ovren's disease
D68.3 Hemorrhagic disorders caused by anticoagulants circulating in the blood. Hyperheparinemia.
Content enhancement:
. antithrombin
. anti-VIIIa
. anti-IXa
. anti-Xa
. anti-XIa
If necessary, identify the anticoagulant used, use an additional external cause code.
(Class XX).
D68.4 Acquired coagulation factor deficiency.
Coagulation factor deficiency due to:
. liver diseases
. vitamin K deficiency
Excludes: vitamin K deficiency in the newborn (P53)
D68.8 Other specified bleeding disorders. Presence of systemic lupus erythematosus inhibitor
D68.9 Bleeding disorder, unspecified

D69 Purpura and other hemorrhagic conditions

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

D69.0 Allergic purpura.
Purpura:
. anaphylactoid
. Henoch(-Schönlein)
. non-thrombocytopenic:
. hemorrhagic
. idiopathic
. vascular
Allergic vasculitis
D69.1 Qualitative platelet defects. Bernard-Soulier syndrome [giant platelets].
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.
Excluded: thrombocytopenia with absence 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. Capillary fragility (hereditary). Vascular pseudohemophilia
D69.9 Hemorrhagic condition, unspecified

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

D70 Agranulocytosis

Agranulocytic tonsillitis. Children's genetic agranulocytosis. Kostmann's disease
Neutropenia:
. NOS
. congenital
. cyclic
. medicinal
. periodic
. splenic (primary)
. toxic
Neutropenic splenomegaly
If it is necessary to identify the drug causing the neutropenia, use an additional external cause code (class XX).
Excludes: transient neonatal neutropenia (P61.5)

D71 Functional disorders of polymorphonuclear neutrophils

Defect of the cell membrane receptor complex. 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-Hegglina
. Pelguera-Huet
Hereditary:
. leukocyte
. hypersegmentation
. hyposegmentation
. leukomelanopathy
Excluded: Chediak-Higashi (-Steinbrink) syndrome (E70.3)
D72.1 Eosinophilia.
Eosinophilia:
. allergic
. hereditary
D72.8 Other specified white blood cell disorders.
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. Postoperative asplenia. Atrophy of the spleen.
Excludes: asplenia (congenital) (Q89.0)
D73.1 Hypersplenism
Excluded: splenomegaly:
. NOS (R16.1)
.congenital (Q89.0)
D73.2 Chronic congestive splenomegaly
D73.3 Spleen abscess
D73.4 Spleen cyst
D73.5 Splenic infarction. Splenic rupture is non-traumatic. Torsion of the spleen.
Excludes: traumatic splenic rupture (S36.0)
D73.8 Other diseases of the spleen. Splenic fibrosis NOS. Perisplenitis. Splenitis 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 hematopoietic organs

Excluded: increase lymph nodes(R59.-)
hypergammaglobulinemia NOS (D89.2)
lymphadenitis:
. NOS (I88.9)
. spicy (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
. decreased plasma volume
. height
. stress
. emotional
. hypoxemic
. nephrogenic
. relative
Excluded: 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 hematopoietic organs. Basophilia
D75.9 Disease of the blood and hematopoietic organs, unspecified

D76 Selected diseases involving lymphoreticular tissue and the reticulohistiocytic system

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

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

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

Splenic fibrosis in schistosomiasis [bilharzia] (B65. -)

SELECTED DISORDERS INVOLVING THE IMMUNE MECHANISM (D80-D89)

Includes: defects in the complement system, immunodeficiency disorders, excluding disease,
caused by human immunodeficiency virus [HIV] sarcoidosis
Excludes: autoimmune diseases (systemic) NOS (M35.9)
functional disorders 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] (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. Biotin-dependent carboxylase deficiency
D81.9 Combined immunodeficiency, unspecified. Severe combined immunodeficiency disorder NOS

D82 Immunodeficiencies associated with other significant defects

Excludes: ataxic telangiectasia [Louis-Bart] (G11.3)

D82.0 Wiskott-Aldrich syndrome. Immunodeficiency with thrombocytopenia and eczema
D82.1 DiGeorge syndrome. Pharyngeal diverticulum syndrome.
Thymus gland:
. 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 significant defects
D 82.9 Immunodeficiency associated with significant defect, unspecified

D83 Common variable immunodeficiency

D83.0 General variable immunodeficiency with predominant abnormalities in the number and functional activity of B cells
D83.1 General 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 Lymphocyte functional antigen-1 defect
D84.1 Defect in the complement system. C1 esterase inhibitor deficiency
D84.8 Other specified immunodeficiency disorders
D84.9 Immunodeficiency, unspecified

D86 Sarcoidosis

D86.0 Pulmonary sarcoidosis
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:
. arthropathy (M14.8)
. myocarditis (I41.8)
. myositis(M63.3)
Uveoparotitic 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)
non-engraftment and graft 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

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 significant amounts of indirect bilirubin. More than ten percent of all anemias are of the hemolytic form. Absolutely all people are susceptible to this disorder, and therefore it is necessary to know the main symptoms, causes and methods of treating this disorder.

The etiology of hemolytic anemia may be hereditary or 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. Penetration of various toxic substances and poisonous chemicals into the blood, including bites from poisonous animals.
2. With mechanical destruction of red blood cells.
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. Extensive injuries, 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 consists in the manifestation of the following signs: pale shade of the skin and mucous membranes, increased fatigue, frequent dizziness, shortness of breath even with minor exertion, rapid heartbeat. The picture of symptoms with hemolytic factor has the following manifestations: yellowish-pale tint skin, dark brown urine, enlarged spleen, painful discomfort in the left hypochondrium.

All subsequent periods of disease progression are manifested by the following symptoms: there is an increase in weakness throughout the body and headache, painful sensations may appear in other parts of the body, fever and vomiting appear. A dark red tint to the urine is also recorded. Severe hemolytic anemia is manifested by an increase in body temperature.

Pathogenesis of hemolytic anemia

The mechanism of 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 of a toxic substance and a direct effect on all the main components of the membrane. The hemolytic effect is carried out by the ability to produce pathological oxidation, which contributes to the accumulation of peroxide compounds in large quantities.

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

It can be precisely noted that a disturbance in the structural membrane of erythrocytes, as well as functional disorders, lead to changes in the vital processes of erythrocytes, which also affects the duration of their existence. Basically, hemolytic anemia occurs due to non-occupational factors, particularly in women.

Hemolytic anemia in children

Pathological blood disease in children differs from adults in the characteristic course of anemia and cyclical features - in children there is a change in periods of exacerbation and remission. In children, hemolytic anemia poses a great danger to the nervous system, and more precisely to the brain. Young children often have a jaundiced skin color.

Newborns and children preschool age suffer from this type of anemia due to several reasons. The most common and common cause There is a hereditary factor that manifests itself especially in newborns. The second common problem is blood transfusion when it is incompatible. Anemia occurs in children even if the mother took certain medications during pregnancy.

Other triggers include toxic lead poisoning, a poisonous insect or snake bite, autoimmune disorders that lead to the destruction of the red blood cell membrane, various diseases infectious nature, severe burns, traumatic situations, prolonged hypothermia. As the disease progresses, new signs of pathology and other symptoms appear. severe symptoms. ICD 10 code for hemolytic anemia has two designations: D58 - other hereditary hemolytic anemia, and code D59 - acquired hemolytic anemia.

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 that 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 recorded in the following forms: acute and chronic. Acute form appears as a result of illness of the newborn, infectious disease due to blood transfusion. Chronic form observed due to autoimmune diseases or other chronic diseases.

Acquired hemolytic anemia

Depending on the provocateur of the disease, there are two groups of hemolysis: congenital anemia or acquired. To better understand the mechanisms of formation and development of the acquired form of hemolytic anemia, it is necessary to better understand the causes, main symptoms and therapeutic tactics for treating this type. This form of anemia in childhood is accompanied by a more severe 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 red blood cell. IN early age It is quite problematic to establish an accurate diagnosis in a child. This is due to the fact that the blood of a newborn does not yet have stable properties and some physiological characteristics. It is also worth noting that some experts do not recognize that an acquired form of anemia exists.

Immune hemolytic anemia

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

A hematologist is involved in determining the form of hemolytic anemia based on blood tests, causes, and studying symptoms. During the initial examination and conversation, an anamnesis is determined. Then the color of the skin and visible mucous membranes is assessed. The diagnostic process involves examining the level of bilirubin.

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

Treatment of hemolytic anemia

Symptoms and treatment of hemolytic anemia are determined by the severity of the disease. All forms are different in treatment tactics, as they have their own characteristics. However, one thing remains the same in any form of this disease - the first thing that needs to be done is to eliminate the negative influence of hemolyzing factors. All patients are prescribed blood plasma, essential vitamins, in some cases – hormone therapy, taking antibiotics. Splenectomy is considered the only effective way elimination of hemolysis during microspherocytosis.

The autoimmune form of this disease is treated with glucocorticoid hormonal drugs, which lead to a reduction or complete cessation of hemolysis. In some cases mandatory part drug therapy is the prescription of immunosuppressants and antimalarials. Toxic hemolytic anemia involves treatment with intensive therapy: detoxification, diuresis, and antidotes. In case of renal failure an unfavorable prognosis for life is recorded.

D50- D53- diet-related anemias:

D50 - iron deficiency;

D51 - vitamin B 12 – deficient;

D52 - folate deficiency;

D53 - other diet-related 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 anemia;

D62 - acute aplastic anemia;

D63-anemia of chronic diseases;

D64 - other anemias.

Pathogenesis

The supply of oxygen to tissues is provided by red blood cells - the formed elements of blood that do not contain a nucleus; the main volume of the red blood cell is occupied by hemoglobin - a protein that binds oxygen. The lifespan of red blood cells is about 100 days. When the hemoglobin concentration is below 100-120 g/l, oxygen delivery to the kidneys decreases, this stimulates the production of erythropoietin by the interstitial cells of the kidneys, which leads to the proliferation of erythroid cells of the bone marrow. For normal erythropoiesis it is necessary:

healthy bone marrow

healthy kidneys that produce 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 red blood cell formation. (T.R. Harrison).

Clinical picture

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

When the Hb concentration is below 70-80 g/l, fatigue, shortness of breath during exercise, palpitations, headache pulsating in nature.

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

Acute blood loss leads to a rapid decrease in the number of red blood cells and blood volume. It is necessary, first of all, to assess the state of hemodynamics. Redistribution of blood flow and venous spasm cannot compensate for acute blood loss of more than 30%. Such patients lie down and have severe orthostatic hypotension and 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 sticky sweat, and decreased blood pressure. Emergency restoration of the central circulation is necessary.

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

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

Severity of anemia(by Hb level):

slight decrease in Hb 90-120 g/l

average Hb 70-90 g/l

heavy Hb<70 г/л

extremely heavy Hb<40 г/л

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

Are there any signs of bleeding or has it already occurred?

Are there signs of excessive hemolysis?

Are there signs of suppression of bone marrow hematopoiesis?

Are there any signs of iron metabolism disorders?

Are there signs of vitamin B12 or folic acid deficiency?

• D55 Anemia due to enzyme disorders.
  • Excluded: enzyme deficiency anemia caused by drugs (059.2)
  • D55.0 Anemia due to glucose-6-phosphate dehydrogenase [G-6-PD] deficiency, Favism, G-6-PD deficiency anemia
  • D55.1 Anemia due to other disorders of glutathione metabolism. Anemia due to enzyme deficiency (except for G-6-PD) associated with the hexose monophosphate [HMP] metabolic pathway shunt. 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 triosephosphate 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 Carriage of thalassemia trait
  • D56.4 Hereditary persistence of fetal hemoglobin [HFH]
  • D56.8 Other thalassemias
  • D56.9 Thalassemia, unspecified. Mediterranean anemia (with other hemoglobinopathy). Thalassemia minor (mixed) (with other hemoglobinopathy)
• D57 Sickle cell disorders.
  • Excluded: 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 crisis. Sickle cell: anemia, disease, disorder.
  • D57.2 Double heterozygous sickle cell disorders. Disease. Hb-SC. Hb-SD. Hb-SE.
  • D57.3 Carriage of 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. Elliptocytosis (congenital). Ovalocytosis (congenital) (hereditary)
  • D58.2 Other hemoglobinopathies. Abnormal hemoglobin NOS. Congenital anemia with Heinz bodies - Disease: H-C, H-D, H-E. Hemoglobinopathy NOS. Hemolytic disease caused by unstable hemoglobin.
  • Excluded: familial polycythemia (D75.0), Hb-M disease (D74.0), hereditary persistence of fetal hemoglobin (D56.4), altitude-associated 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) (warm type). Chronic disease caused by cold hemagglutinins. “Cold agglutinin”: disease, hemoglobinuria. Hemoltic anemia: cold type (secondary) (symptomatic), warm type (secondary) (symptomatic). Excluded: 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-induced 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 (Marchiafava - Micheli).
  • Excluded: hemoglobinuria NOS (R82.3)
  • D59.6 Hemoglobinuria due to hemolysis caused by other external causes. Hemoglobinuria: from exertion, marching, paroxysmal cold.
  • Excluded: hemoglobinuria NOS (R82.3)
• D59.8 Other acquired hemolytic anemias
• D59.9 Acquired hemolytic anemia, unspecified. Chronic idiopathic hemolytic anemia.

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

Orphan diseases

general information

Short description

Approved
Joint Commission on Quality medical services
Ministry of Health and Social Development of the Republic of Kazakhstan
dated September 15, 2016
Protocol No. 11

Autoimmune hemolytic anemia (AIHA)- a heterogeneous group of auto-aggressive 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 of 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 AIHA cases, hemolysis is caused by various medications. 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 dividing 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 biphasic cold hemolysins Donath-Landsteiner (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)

DIAGNOSTICS AT OUTPATIENT LEVEL (UD - B)

Diagnostic criteria:

Complaints and anamnesis:
The main syndromes with 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, there are 3 degrees of severity of anemia:
· 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 severe symptoms than chronic anemia, in which there is time for organs and tissues to adapt. Elderly patients tolerate anemia worse than younger ones, since the compensatory capabilities of their cardiovascular system are usually reduced.

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

Hemolysis syndrome, which may manifest itself as complaints of:
· icterus of the skin and visible mucous membranes (jaundice);
· darkening of urine.
· with intravascular hemolysis, the color of urine can range from pink to almost black. The color depends on the concentration of hemoglobin and 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 porphyria, myoglobinuria, which develops under certain conditions (massive traumatic muscle damage, 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, the degree of enlargement of the spleen is slight or moderate.

In more than 50% of patients, the development of AIHA is secondary, and therefore the clinical picture may be dominated by symptoms of the underlying disease (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 subicterus of the 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.

During a hemolytic crisis:
· moderate or severe condition;
· pallor of the skin and mucous membranes;
· expansion of the borders of the heart, dullness of sounds, 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, disturbances of consciousness, convulsions;
· with intracellular hemolysis: hepatosplenomegaly;
· with mixed and intravascular hemolysis: changes in urine due to hemoglobinuria.

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


· hemosiderin in urine - exclusion of intravascular hemolysis;
· general analysis urine (visual assessment of urine color is required);
· determination of copper in daily urine, ceruloplasmin in blood serum - exclusion of Wilson-Konovalov disease;
· bone marrow puncture (hyperplasia and morphology of the erythroid germ, the number and morphology of lymphocytes, complexes of metastatic cells);
· trephine biopsy (if necessary) - exclusion of secondary AIHA;
· immunophenotyping of lymphocytes (with lymphocytosis of peripheral blood and removed 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;
· detailed coagulogram + lupus anticoagulant - assessment 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 to exclude secondary AIHA;
· determination of blood group according to the AB0 system, Rh factor;
· blood test for HIV - if transfusion is necessary;
· 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 the hepatitis C virus (HCV) in blood serum using ELISA - screening for hepatitis C.

Instrumental studies:
· X-ray of the lungs (if necessary, CT);
· FGDS;

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

Diagnostic algorithm (scheme 1):

Diagnostics (ambulance)

DIAGNOSIS AND TREATMENT AT THE EMERGENCY CARE STAGE

Diagnostic measures:
· collection of complaints and anamnesis;
· physical examination.

Drug treatment: No.

Diagnostics (hospital)

DIAGNOSTICS AT THE INPATIENT LEVEL

Diagnostic criteria: see outpatient level.

Diagnostic algorithm: see outpatient level.

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

List of additional diagnostic measures:
· determination of haptoglobin level;
· blood type and Rh factor;
· biochemical blood test (total protein, albumin, total bilirubin, direct bilirubin, creatinine, urea, ALaT, ACaT, glucose, LDH, GGTP, C-reactive protein, alkaline phosphatase);
· iron metabolism (determining the level of serum iron, total iron-binding capacity of serum and ferritin level);
· determination of the concentration of folic acid and vitamin B12;
· immunophenotyping of lymphocytes (for lymphocytosis, suspected lymphoproliferative disease, ineffectiveness of corticosteroid therapy);
· Electrophoresis of serum and urine proteins with immunofixation (for lymphocytosis, suspected lymphoproliferative disease, ineffectiveness 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 (determination of glomerular filtration rate);
cold agglutinin titer;
· indirect Coombs test (mandatory for intense hemolysis and previous red blood cell transfusions);
· determination of hemosiderin, copper and hemoglobin in urine;
· trepanobiopsy of 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 organs;
· esophagogastroduodenoscopy;
· irrigoscopy/sigmoidoscopy/colonoscopy;
· Ultrasound of the abdominal organs and intra-abdominal lymph nodes, pelvis, prostate, thyroid gland;
· Doppler ultrasound of arteries and veins;
· ECG;
· echocardiography;
· 24-hour blood pressure monitoring;
· 24-hour ECG monitoring.

Differential diagnosis

Differential diagnosis and rationale for additional studies:

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Treatment

Drugs (active ingredients) used in treatment

Groups of drugs according to ATC used in treatment

Treatment (outpatient clinic)

TREATMENT AT OUTPATIENT LEVEL (UD - B)

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

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

Drug treatment:

· Prednisolone;

· Rituximab concentrate for solution for infusion 100 mg;
· Cyclosporine;
· Amlodipine;
Lisinopril;
· atenolol;
torasemide;
· folic acid;
· alendronate;
· risedronate;
· zoledronate;
alfacalcidol;
· calcium carbonate;
· paracetamol;
· chloropyramine;
· omeprazole;
· enoxaparin;
· nadroparin;
amoxicillin/clavulanic acid;
· levofloxacin;
· sodium chloride solution.

Therapy for AIHA is currently not based solely on retrospective and several 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 level of evidence D.

First line of therapy.
Glucocorticosteroids.
The first line of treatment for patients with AIHA with warm antibodies is glucocorticosteroids. The starting dose of prednisolone or methylprednisolone is 1 mg/kg (orally or intravenously). Typically, within 1-3 weeks of initial therapy (carried out in a hospital), the hematocrit level increases by more than 30% or the hemoglobin level by 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 initiated. The reduction in the dose of prednisolone continues at the outpatient stage. A slow reduction in the dose of prednisolone is carried out if a therapeutic effect is achieved. Reduce the dose of prednisolone by 5-10 mg over 2-3 days and continue until daily dose will not reach 20-30 mg. Further, drug withdrawal is carried out much more slowly - 2.5 mg per 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 discontinue the drug. This tactic involves taking prednisolone for 3-4 months. The level of hemoglobin and reticulocytes is monitored. If remission persists for 3-4 months while taking prednisolone at a dose of 5 mg per day, an attempt should be made to completely discontinue the drug. The desire to quickly reduce the dose from the moment of normalization of hemoglobin due to side effect GC (Cushingoid, steroid ulcers, arterial hypertension, acne with the formation of pustules on the skin, bacterial infections, diabetes, osteoporosis, venous thrombosis) always leads to relapse of hemolysis. In fact, patients receiving low-dose corticosteroids for more than 6 months have a lower relapse rate and longer duration of remission compared to patients who discontinue therapy before 6 months of therapy. Accompanying therapy with steroids may include bisphosphonates, vitamin D, calcium, supportive care folic acid. Blood glucose levels are monitored and diabetes is actively treated, so diabetes is big factor risk of death due to infection. The risk of thromboembolism must be assessed pulmonary artery, especially in patients with AIHA and lupus anticoagulant or relapse of AIHA after splenectomy 38.

First-line GCS therapy 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 prednisolone. It is believed that GCS monotherapy is effective in less than 20% of patients. In patients who are resistant to first line therapy, the possibility of secondary AIHA should be re-evaluated, since AIHA with warm agglutinins is associated with malignant tumors, UC, ovarian teratoma or with IgM are often steroid-refractory.

Second line of therapy.
Splenectomy.
After splenectomy, the risk of severe infections associated with Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae increases. Patients are prescribed polyvalent pneumococcal, meningococcal, Haemophilus influenzae type b capsular polysaccharide (PRP) tetanus toxoid (TT) conjugate vaccines 2-4 weeks before splenectomy. In patients who have received rituximab in the past 6 months, vaccination may not be effective. After surgery - low dose thromboprophylaxis low molecular weight heparins; gradual withdrawal 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 to take antibiotics from the penicillin group or respiratory fluoroquinolones (levofloxacin) during any febrile episode; they should also be informed about the risk of venous thromboembolism.

Rituximab.


· refusal of splenectomy;
· elderly age With high degree risk of complications of 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 GCS therapy before starting rituximab therapy should continue to take GCS until the first signs of response to rituximab.

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

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

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

Table 2 - Immunosuppressive therapy for AIHA

Algorithm of action in emergency situations:
· if there is a suspicion of a hemolytic crisis (fever, pallor, yellowness of the skin, dark urine, splenomegaly, cardiovascular failure, anemic shock, anemic coma) - call an 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: frequency and nature of breathing, frequency and rhythm of pulse, systolic and diastolic blood pressure, amount and color of urine;
· if there are signs of disturbance of vital functions (acute heart failure, signs of shock, renal failure) - emergency care: provision of venous access, infusion of colloidal drugs, if intravascular hemolysis is suspected - prevention of renal failure (furosemide), oxygenation.

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

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

Patient monitoring:
To monitor the effectiveness of treatment, the outpatient card notes: the general condition of the patient, general blood count indicators, including reticulocytes and platelets, biochemical indicators - bilirubin level, LDH, enzyme immunoassay determination of the amount of immunoglobulins on the erythrocyte membrane, direct Coombs test.

Individual patient observation card

Treatment (inpatient)

INPATIENT TREATMENT

Treatment tactics (UD-T): Patients are hospitalized in the hematology department, and if vital functions are impaired - in the intensive care unit.

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

Drug treatment:

1 line of therapy.

Glucocorticosteroids.
The first line of treatment for patients with AIHA with warm antibodies is glucocorticosteroids. Corticosteroids, usually prednisolone, are prescribed at a starting dose of 1 mg/kg per day (50-80 mg/day) for 1-3 weeks until the hematocrit level increases more than 30% or the hemoglobin level exceeds 100 g/l. If this goal is not achieved within 3 weeks, a second line of therapy should be started, since GCS therapy is considered ineffective. Increasing the dose of prednisolone to 2 mg/kg/day (90-160 mg/day) does not improve treatment results, leading to the rapid development of characteristic severe complications. If the therapeutic goal is achieved, the dose of prednisolone is reduced to 20-30 mg per day. The dose of prednisolone begins to be reduced by 5-10 mg over 2-3 days and continues until the daily dose reaches 20-30 mg. Further, drug withdrawal is carried out much more slowly - 2.5 mg per 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 discontinue the drug. This tactic involves taking prednisolone for 3-4 months. The level of hemoglobin and reticulocytes is monitored. If remission persists for 3-4 months while taking prednisolone at a dose of 5 mg per day, an attempt should be made to completely discontinue 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 relapse of hemolysis. In fact, patients receiving low-dose corticosteroids for more than 6 months have a lower relapse rate and longer duration of remission compared to patients who discontinue therapy before 6 months of therapy.
An alternative to long-term use of cortocosteroids (up to 3-4 months) is short courses (up to 3 weeks) followed by a transition to second line therapy.

All patients on steroid therapy should receive bisphosphonates, vitamin D, calcium, and maintenance folic acid. Monitor blood glucose levels and actively treat diabetes, 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 recurrence of AIHA 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 GCS in the literature is presented mainly in the form of descriptions of clinical cases. 19.20

First-line GCS therapy 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 prednisolone. 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 are often steroid-refractory.

Second line of therapy
When choosing second-line therapy, there are several options, and each choice requires weighing the benefits/risks in each case (Fig. 2).

Splenectomy.
Splenectomy is generally agreed to be the most effective and appropriate second-line treatment for AIHA with warm antibodies.

Indications for splenectomy:
· Refractoriness or intolerance to corticosteroids;
· The need for ongoing maintenance therapy with prednisolone at a dose of more than 10 mg/day;
· Frequent relapses.
The advantages of splenectomy are its fairly 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 with idiopathic AIHA); a significant number of patients remain in remission without requiring drug intervention for 2 years or more; the chance 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 the outcome of splenectomy;
· Risk surgical complications(PE, intra-abdominal bleeding, abdominal abscess, hematoma) - 0.5-1.6% with laparoscopic splenectomy and 6% with conventional splenectomy);
· The risk of developing infection is 3.3-5% (pneumococcal septicemia is the most dangerous) with a mortality rate of up to 50%.
After splenectomy, the risk of severe infections associated with Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae increases. Patients are prescribed polyvalent pneumococcal, meningococcal, Haemophilus influenzae type b capsular polysaccharide (PRP) tetanus toxoid (TT) conjugate vaccines 2-4 weeks before 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 withdrawal 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 to take antibiotics from the penicillin group or respiratory fluoroquinolones (levofloxacin) during any febrile episode; they should also be informed about the risk of venous thromboembolism.

Figure 2. Treatment algorithm for steroid-refractoryWAIHA.

Rituximab.
Indications for the use of rituximab:
· resistant forms of AIHA with an increasing number of various complications;
· refusal of splenectomy;
· elderly people 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 use of rituximab:
drug intolerance;
· active hepatitis B and C;
Acute viral or bacterial infection.

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

Maintenance therapy.
Patients with AIHA may frequently require red blood cell transfusions to maintain clinically acceptable hemoglobin levels, at least until specific therapy is effective. The decision to perform a transfusion depends not only on the hemoglobin level, but to a greater extent on the clinical status of the patient and comorbidity (especially coronary artery disease, severe lung diseases), their exacerbation, the rate of development of anemia, the presence of hemoglobinuria or hemoglobinemia and other manifestations of severe hemolysis.1 The patient in In critical clinical situations, red blood cell transfusion should not be withheld, even in cases where a lack of individual compatibility is found, since warm autoantibodies are often pan-reactive. Red blood cell-containing components of the first blood group Rh-compatible can be safely prescribed in emergency cases if alloantibodies (occurring in 12-40% of patients with AIHA) are reasonably excluded based on a previous transfusion history and/or obstetric history (women without pregnancies and/or previous transfusions and men without a history of transfusion). In other patients, extended phenotyping is carried out to determine the Rh subgroups (C,c,E,e), Kell, Kidd, and S/s using monoclonal IgM antibodies and selection of compatible red blood cells 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 treatment algorithm for AIHA with warm antibodies is presented in Figure 3.
Figure 3. Treatment algorithm for 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 primary AIHA (Table 3).

Table 3 - Treatment of secondary AIHA

Hospitalization

Information

Sources and literature

1. Minutes of meetings of the Joint Commission on the Quality of Medical Services of the Ministry of Health of the Republic of Kazakhstan, 2016
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