LECTURE # 1

ANEMIC SYNDROME

Time – 2h.
Lecturer-corresponding member.Academy of Sciences of the Republic of Tatarstan, Professor
N. Khamidov.

Lecture plan:
Introduction
Topicality of the topic
Etiopathogenetic features and their significance
Clinical features. Differential diagnosis
Value of additional research methods
Complications. Prevention
Basics of therapy. Differentiation of treatment.

Content:
 Iron deficiency anemia.
 At12-deficiency anemia.
 Hemolytic anemia.
 Hypo-and aplastic anemia.
 Agranulocytosis.
IRON DEFICIENCY ANEMIA
 Definition. Iron deficiency anemia (IDA) is a disease caused by a violation of
hemoglobin synthesis and red blood cell production, due to insufficient iron content in
the patient's body.
 Etiology. An adult needs 20-30 mg of iron daily.
 No more than 10% of the daily requirement of this element comes from food. The bulk of
the necessary iron is of endogenous origin. Endogenous iron appears as a result of the
reutilization of this element from decaying cells, primarily from red blood cells.
  A balanced human diet contains 15-20 mg of iron, of which no more than 5-10% is
absorbed in the intestines. Only when iron is deficient in the body, its intake into the
blood increases to 25% of what is taken with food.
 Heme iron in meat and fish dishes is absorbed by 20-50%. Products – dairy and vegetable
origin-give up no more than 5% of the iron contained in them.
 Daily physiological iron losses in men reach 1 mg, in women, taking into account
monthly periods-2 mg. During pregnancy, up to 3-4 mg of iron is additionally consumed
daily.
 The adult body contains 3-4 grams of iron. It takes 2-3 years to develop IDA.
 Iron deficiency in the body that occurs after childbirth is compensated in 2-2. 5 years.
In adults, the causes of insufficient iron intake are:
 chronic blood loss in dysmenorrhea, peptic ulcers of the duodenum, stomach, hiatal
hernia, ulcerative colitis, intestinal diverticula, hemorrhoids, hematuric nephritis,
hemoptysis in some lung diseases;
 increased iron consumption during pregnancy and lactation;
 congenital iron deficiency (juvenile chlorosis in girls whose mothers suffered from iron
deficiency during pregnancy);
 insufficient intake of iron in the body due to a violation of its absorption in chronic
intestinal diseases with malabsorption syndrome, after extensive intestinal resections,
stomach resections with duodenal shutdown;
 reduction of iron intake from food with strict vegetarianism, with prolonged fasting.
Clinical picture.
 ANEMIC SYNDROME (AS):
 it is not specific to the railway station. This is a mandatory and usually leading
component of the clinical picture of all anemia.
 Typical complaints are palpitations, tinnitus, shortness of breath with moderate physical
exertion, muscle weakness, dizziness, flickering of dark "flies" in the eyes.
 Tendency to arterial hypotension. Complaints of unmotivated weakness, reduced physical
and mental ability to work, loss of interest in learning, difficulties in volitional
concentration.
 Objectively, AS is manifested by pallor of the skin and mucous membranes, tachycardia,
and functional systolic murmur over all points of auscultation of the heart.
SIDEROPENIC SYNDROME:
 It is specific for railway transport. Iron deficiency leads to a deficiency of iron-containing
enzymes (cytochrome oxidase, etc.), which are necessary for the vital activity of
absolutely all cells of the body. First of all, the activity of intensively proliferating tissue
structures - epithelial integuments, hematopoietic tissue, exocrine and endocrine glands-is
disrupted
 Clinically, these shifts are manifested by thinning, lethargy, dry skin, brittleness and hair
loss. Nails become curved, spoon-shaped (coilonychia), thin, and brittle. Due to atrophy
of the mucous membrane, the tongue is smooth, shiny, and crimson in color. Patients
complain of burning, tingling in the tongue. There is an angular stomatitis - ulceration,
cracks in the corners of the mouth. Damage to the epithelium and pharynx causes
choking, difficulty swallowing dry food, painful spasm of the upper third of the
esophagus-sideropenic dysphagia Plummer-Vinson.
 Atrophy of the secretory epithelium of the stomach causes a decrease in the secretory
ability of the organ up to histamine-resistant achlorhydria.
 Dystrophic changes in the mucosa lead to disturbances in the processes of parietal
digestion, absorption, and maintenance of adequate microflora in the intestine. In
connection with the defeat of the epithelium and sphincters of the urinary system,
patients often complain of imperative urges to urinate, nocturnal enuresis, involuntary
urination when coughing, laughing.
  Sideropenic syndrome is characterized by perverted taste and olfactory sensations, the
desire to eat chalk, clay, lime.
 According to the value of the hemoglobin content in the blood, there are 3 degrees of
severity of IDA:
 light (hemoglobin 110-90 g / l);
 moderate severity (hemoglobin 90-70 g / l);
 severe (hemoglobin is below 70 g / l).
 However, these gradations are conditional, since the clinical manifestations of IDA are
not always identical to the level of a decrease in the concentration of hemoglobin in the
blood.
Diagnostics.
 General blood test: hypochromic normocytes and microcytes, poikilocytosis and
anisocytosis. Reduced Hb and red blood cell count.. The CPU can drop below 0.5.
 Bioh. blood test: a decrease in serum iron concentration of less than 12 mmol/l. The
norm is 30-13 mmol/l. Increased total iron binding capacity of serum. The norm is 45-72
mmol/l. In healthy people, serum iron accounts for 20-45% of the heart rate, while in
patients with IDA, it is less than 16%.
 Iron reserves in the body can be judged by the level of serum ferritin. Its normal content
is 125 ng / l in men and 55 ng/l in women. When IDA falls below 10 ng/l. In the bone
marrow, iron is deposited in hemosiderin inclusions in the plasma of macrophages-
sideroblasts. With iron deficiency, such cells are absent, with excessive accumulation of
iron in the body, the content of sideroblasts in the bone marrow increases.
 There is a certain sequence of changes in laboratory parameters. First, the concentration
of serum ferritin decreases, then the heart rate increases, then the level of serum iron
decreases, and only after that the level of Hb decreases. Initially, anemia is normocytic
and normochromic, but then microcytosis and hypochromia of red blood cells inevitably
develop.
 ECG: flattening or inversion of the T wave.
 EoCG: dilatation of the ventricular and atrial cavities, hypertrophy, hyperkinesis of the
myocardium of the ventricular walls and interventricular septum, valve prolapse are
recorded.
Treatment.
 According to their chemical structure, IDA replacement drugs are divided into 4 groups:
 simple, easily dissociating salts: sulfates (ferroplex), fumarates (ferro-fumarate),
gluconates (ferronal), dichloronicotinamides (feramide);
 ферроцены (металлорганика) - ферроцерон;
 chelated iron compounds - ferbitol, ferricitol, ferkovene;
 complex polynuclear iron hydroxide complexes-ferum-fol and ferum-lek.
 Simple salts and ferrocenes are intended for oral use only.
 Chelates and polynuclear iron hydroxide complexes can be used either orally or
intravenously and/or intravenously.
 In clinical practice, preparations of simple salts - sulfate, lactate, carbonate, and iron
fumarate-are most often used.
 Feroplex containing 50 mg of iron sulfate in combination with ascorbic acid is prescribed
1-2 tablets 3-4 times a day.
 Conferon, consisting of 200 mg of iron sulfate in combination with succinic acid, is
prescribed 1 capsule 3-4 times a day.
 Tardiferon-retard, a long-acting iron sulfate preparation. Contains 80 mg of elemental
iron. It is prescribed 1-2 tablets 1 time a day.
 Ferro-gradumet is a prolonged form containing 105 mg of elemental iron in the form of
sulfate. It is prescribed 1-2 tablets 1 time a day in the morning, 30 minutes before
breakfast.
  In 15-20% of patients, preparations of simple iron salts cause dyspeptic disorders.
Constipation may occur, as iron preparations bind hydrogen sulfide, which is a
physiological stimulator of peristalsis. To reduce the toxic effect of simple iron salts, you
can prescribe vitamins E, C, fructose diphosphate, succinic acid.
 The drug from the ferrocene group-ferroceron (300 mg tablets) is very well absorbed in
the intestines, practically does not cause side effects. Ferroceron has the ability to
selectively deposit in adipose tissue. This is a disadvantage of the drug, which limits its
clinical use.
MEGALOBLASTIC ANEMIA
 Definition. Megaloblastic anemia is a group of blood diseases, the common feature of
which is the suppression of normal hematopoiesis with the transition to the embryonic
megaloblastic type of erythropoiesis, which is caused by a deficiency in the body of
cyancobalamin (vitaminB12) and/or folic acid.
Etiology.
 VitaminB12 deficiency is caused by the following circumstances:
 Prolonged insufficient intake with food. It occurs in strict vegetarians, elderly low-
income people
 Violation of vitamin assimilation in the absence of its carrier - gastromucoprotein
secreted by the gastric mucosa in atrophic gastritis type A, stomach tumors, after
gastrectomy operations.
 Malabsorption of vitamin in the small intestine in chronic bowel diseases (terminal ileitis,
diverticulosis, tumors, condition after resections of the small intestine).
Excessive consumption of vitamin supplied with food at the stages of its transportation in case
of intestinal invasion by a wide tapeworm, hemoblastosis.
 Insufficient ability to accumulate and store vitamin in its main depositing organ-the liver
in patients with cirrhosis, liver fibrosis.
 Congenital defects in the mechanisms of transport and utilization of vitaminB12.
 The following causes lead to folic acid deficiency:
 Alimentary insufficiency (monotonous canned animal food - for sailors, participants of
long-term expeditions).
 Alcoholism.
 Pregnancy.
 Side effects of pharmacotherapy (in the treatment of folic acid antagonists,
anticonvulsants, sulfonamides, etc.).
 Chronic inflammatory diseases of the small intestine, resections of the small intestine.
Clinical picture.
 The anemic syndrome in megaloblastic anemia is basically the same as in other variants
of anemia. The severity of the clinical manifestations of anemic syndrome depends on the
degree and speed of development of anemia.
 The syndrome of gastrointestinal pathology is manifested by burning sensations in the
tongue, loss of taste sensations, poor appetite, a feeling of heaviness, pain in the
epigastric region, diarrhea. A typical lesion of the tongue is Gunter's glossitis. It is
characterized by the appearance of initially bright inflammatory areas, aphthous rashes,
cracks on the tip and on the side surfaces of the tongue. Then the tongue becomes
smooth, shiny ("varnished"), dark crimson in color. Dystrophic changes in the mucous
membrane of the stomach and intestines, symptoms of atrophic gastritis, enteritis. The
liver is constantly moderately enlarged, b / painful. Occasionally, a small splenomegaly is
detected.
 The syndrome of neurological disorders is associated with damage to the posterolateral
pillars of the spinal cord-funicular myelosis. It is characterized by parasthesia, violations
of vibration and deep sensitivity. Disorders of deep sensitivity appear earlier and are
more pronounced in the distal parts of the h / limbs. In this connection, ataxia develops.
 Movement disorders, weakness, paresis of the h/ extremities, decrease or disappearance
of tendon reflexes are observed. There are pathological symptoms of Babinsky,
Rossolimo. Sometimes there is ophthalmoplegia, atony of the bladder, retrobulbar
neuritis. Very rarely there are changes in the psyche with hallucinations, manic outbursts,
paranoid state, which quickly disappear with timely treatment.
Diagnostics.
 General blood test: normochromic or hyperchromic anemia, leukopenia,
thrombocytopenia. Pronounced macroovalocytosis, anisocytosis, poikilocytosis. Along
with irregular red blood cells (schizocytes), large megalocyte cells are detected. In red
blood cells, the content of Hb – hyperchromia is increased (CP is greater than 1). B / cell
inclusions are visible – Jolie bodies, Cabot rings, diffuse polychromatophilia of cells.
Hypersegmented neutrophils are detected.
 Bioh. issl. increase in the content of bilirubin in the blood plasma due to the unconjugated
fraction, a slight increase in the concentration of serum iron.
 Immunological examination: IgG-specific antibodies against cytoplasmic antigens of
gastric parietal cells and gastromucoprotein are detected.
 Sternal puncture: megaloblastic type of erythropoiesis is detected. The erythroid sprout
prevails (the leuco/erythro ratio becomes greater than 1/2, whereas in normal cases it is
3/1-4/1). There are signs of abnormal leukopoiesis – unusually large granulocytes of
different stages of maturation, giant hypersegmented neutrophils. Reduced number of
megakaryocytes. When treating sternal punctate with alizarin red , cell staining is observed in patients with
B12-deficient anemia, whereas in patients with folic acid deficiency, such staining does not
occur.
 According to laboratory diagnostics of gastric secretion, histamine-resistant achlorhydria
occurs, with no secretion of gastromucoprotein.
 FGD: signs of atrophic gastritis. In some cases, clinically latent stomach cancer is
diagnosed.
 X-ray examination: smoothness, flattening of mucosal folds, decreased tone, violation of
gastric motor function.
 Ultrasound: some patients show signs of liver cirrhosis, portal hemodynamic disorders.
 ECG: tachycardia, diffuse changes (dystrophy) of the ventricular myocardium.
 Echocardiography: dilation of the ventricular and atrial cavities, an increase in the
systolic index (with severe anemic syndrome).
Treatment.
 Treatment ofB12-deficient anemia can be initiated only after verification of the diagnosis
by morphological analysis of the sternal myelogram. Before sternal puncture, blindly
prescribe vit preparations and coenzymes.12Absolutely not at 12.
 Treatment is carried out by IV injections of vit.B12 400-500 mcg daily for 4-6 weeks.
Evidence of the transition of megaloblastic hematopoiesis to normoblastic is a
reticulocytic crisis (the appearance of a large number of young normal red blood cells in
the peripheral blood), usually developing after 4-6 days of treatment.
 Against this background, the drug continues to be administered in the same single doses,
but every other day, until the development of complete hematological remission. Fixing
treatment can be carried out in vitro.B12 400-500 mcg / m 2 times a week or
oxycobalamin 1 time a week 500 mcg / m for 3 months.
 The criterion of remission is normalization of peripheral blood composition, bone
marrow hematopoiesis, and vit level.At12 in the blood and urine. In the future, vit
maintenance therapy is carried out.B12 400 mcg 2 times a month or oxycobalamin 500
mcg 1 time a month throughout the patient's life.
 In cases of severe anemia and funicular myelosis vit.B12 is administered at a dose of
1000 mcg daily for 5-10 days. At the same time, it is necessary to introduce the
coenzyme of vitaminB12 cobamine 500 mcg 1 time a day in/m (it helps to quickly
 eliminate the toxic effect of methylmolonic acid on the spinal cord). In the future, if the
condition improves, the drugs continue to be administered 2 times a week until a stable
hematological remission is obtained. Consolidation of remission and lifelong
maintenance treatment is carried out according to the methods described above with vit
preparations.B12 or oxycobalamin.
With deep anemia and the threat of developing anemic coma, along with the introduction of at
least 1000 mcg of cyancobalamin and 500 mcg of cobamine per day, transfusions of red blood
cell mass and rheopolyglucine are performed. In cases of anemia resistance to vitamin B12 treatment,
when high titers of autoantibodies to gastric parietal cells and gastromucoprotein are detected,
glucocorticoid hormones are used in medium doses (prednisone up to 40-60 mg per day orally).
 Folic acid is prescribed orally only in cases of proven folate-deficient megaloblastic
anemia at a dose of 5-15 mg per day.12Folic acid is not included in the treatment program
for vitamin B12 - deficient anemia. At the same time, such patients should be prescribed
a diet that includes foods and dishes rich in folic acid of natural origin, exclude the use of
medications that have the properties of folic acid antagonists.
HEMOLYTIC ANEMIA
 Definition. Hemolytic anemia (HA) is a pathological decrease in the content of red
blood cells and Hb in the blood, caused by premature and excessive destruction of red
blood cells.
Classification.
 Congenital GA caused by:
 defect in the structure of the red blood cell membrane;
 deficiency of the enzyme G-6-PD (glucose-6-phosphate dehydrogenase);
 synthesis of abnormal Hb.
 violations of the synthesis of globin chains.
 Purchased HA:
 Immune systems.
 Paroxysmal nocturnal hemoglobinuria.
HEREDITARY MICROSPHEROCYTOSIS (MINKOWSKI SHAFFAR DISEASE
 Definition. Hereditary microspherocytosis (Minkowski Schaffar's disease) is an anemia
caused by a hereditary defect in the red blood cell membrane, leading to the appearance
of spherical red blood cells - spherocytes that prematurely completely or partially
(sequestration of part of the cell volume) collapse in the spleen.
Etiology.
 The disease is based on an autosomal dominant defect in the structure of the red blood
cell membrane. Genes responsible for the synthesis of erythrocyte membrane proteins –
spectrin and ankyrin-are affected.
Pathogenesis.
 Violation of the synthesis of spectrin and ankyrin leads to an increase in the permeability
of the erythrocyte membrane to sodium and water. Red blood cells overloaded with water
take on a spherical shape. Unlike normal ones, they are not able to deform, and when
passing through the narrow intersinus spaces of the spleen pulp, they undergo total or
partial hemolysis (sequestration).
 In the process of partial hemolysis-sequestration-a part of the body is detached from the
abnormal spherocyte. The red blood cell is reduced in size to a size that allows it to pass
freely, without deforming, through the intersinus slits of the spleen. These cells are called
microspherocytes.
 Excessive intake of Hb into the blood from destroyed spherocytes and sequestered
fragments of abnormal red blood cells causes unconjugated hyperbilirubinemia,
characteristic of hemolytic conditions, and icteric skin.
 Periodically, there are exacerbations of the disease, when the intensity of hemolysis, the
severity of anemia and hyperbilirubinemia increases.
  Due to the high concentration of bilirubin in the bile, patients with hereditary
microspherocytic HA often form calculi in the gallbladder and/or ducts.
 Bile stones consist of calcium bilirubinate (pigment stones). Stones in the bile ducts often
complicate the course of microspherocytic anemia with attacks of biliary colic. Possible
mechanical jaundice caused by calculous obstruction of the bile ducts.
Clinical picture.
 The disease is usually detected in adolescence, but is sometimes first diagnosed in adults.
 In mild cases, AS is not very pronounced. Complaints of general weakness, moderate
persistent or transient jaundice. Sometimes the reason for going to the doctor is bouts of
pain in the right hypochondrium caused by concomitant cholelithiasis.
 Objective examination of patients reveals a little pronounced pallor of the skin in
combination with obvious icteric sclera. As a result of compensatory hyperfunction of
CP, patients with hereditary microspherocytosis are not so much anemic as jaundiced.
 Moderate splenomegaly is detected in all patients. Palpation of the spleen is elastic, b /
painful.
 In many patients, the area of soreness in the right hypochondrium is determined, ( + )
symptoms of Kera, Murphy as evidence of complications of GI anemia, and often
calculous cholecystitis.
 Disorders of peripheral microcirculation caused by the inability of spherocytes to deform
when passing through capillaries can manifest as trophic ulcers on the lower legs.
 Compensatory hyperplasia of c / m causes the appearance of defects in the development
of the skeleton, primarily flat bones. Patients with hereditary microspherocytosis often
have a square tower skull, a protruding forehead, microphthalmia, and deformity of the
jaws.
 The disease usually proceeds in waves with periods of exacerbation, increased jaundice
and anemia, alternating with remissions, when the only manifestation of the disease may
be mild icteric sclera in combination with moderate splenomegaly.
Diagnostics.
 General blood test: normochromic anemia. The smear shows three populations of red
blood cells: microspherocytes, normocytes, and reticulocytes.
 Osmotic resistance of red blood cells is reduced.
 Spontaneous autohemolysis after two-day incubation at 37 0S, increased resistance of red
blood cells to the action of hydrochloric acid, ( - ) Coombs test are characteristic. Adding
ATP and glucose to the test tube reduces autohemolysis of red blood cells.
 Bioh. issl. increased bilirubin level due to the indirect fraction.
 General information.urinalysis: increased urobilin content.
 Sternal puncture: hyperplasia of erythrocyte line cells is observed in the c/m preparation.
 Ultrasound: splenomegaly while maintaining the normal structure of the spleen, the
absence of hepatomegaly, signs of impaired portal hemodynamics. Concretions are often
found in the gallbladder and ducts.
 ECG: tachycardia is often detected, a decrease in the amplitude of the T wave in all or
only in the left thoracic leads, which may indicate myocardial dystrophy.
Differential diagnosis.
 Differential diagnosis should be made primarily with IDA, which also has the appearance
of microcytes in the peripheral blood. However, unlike untreated IDA, patients with
microspherocytosis have hyperplasia of the erythrocyte germ in the CT punctate. Patients
with IDA do not have hyperbilirubinemia or jaundice.
 In contrast toB12-deficient anemia, in which there is moderate hyperbilirubinemia, icteric
skin caused by shunt hemolysis of megaloblasts in c / m, in microspherocytosis, the CP
does not exceed one, and in c/m there are no megaloblasts, hypersegmented neutrophils.
  For differential diagnosis with other types of anemia, including congenital and acquired
GA, it is important to identify the round shape and reduced osmotic resistance of red
blood cells.
Treatment.
 For patients with severe anemia, hyperbilirubinemia, and severe splenomegaly, a radical
method of treatment is splenectomy.
 With a mild, compensated clinical course of microspherocytosis, treatment is not
required. Patients with concomitant GI often require surgical treatment of cholelithiasis,
which is best performed by minimally invasive laparoscopic methods.
HEMOLYTIC ANEMIA WITH GLUCOSE-6-PHOSPHATE DEHYDROGENASE
DEFICIENCY
 Definition. Anemia with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency is a
hereditary defect of the enzyme systems of red blood cells, causing the inability of red
blood cells to resist the hemolytic action of endogenous and external substances with
oxidizing properties
 Etiology. Mostly men get sick, since the enzyme gene is linked to the sex X
chromosome.
Pathogenesis.
 G-6-PD deficiency disrupts the antioxidant metabolic systems of the cell. Therefore,
exposure to various agents with oxidative properties, including drugs, leads to the
degradation of Hb with the formation of Heinz bodies. There is a destruction of such red
blood cells in the vessels and spleen. It is characterized by a wave-like course of the
disease with periodic occurrence of hemolytic crises against the background of exposure
to oxidants.
 Antimalarial drugs, sulfonamides, salicylic acid derivatives, nitrofurans, antituberculous
agents, and vikasol have an oxidative hemolytic effect on the red blood cells of patients
with G-6-PD insufficiency.
 In some patients, intensive hemolysis occurs immediately after eating legumes (horse
beans), as well as after pollen from these plants enters the respiratory tract. This variant
of the disease is called "favism". It is caused by a combined genetic defect of G-6-PD and
the enzyme systems of hepatocytes responsible for neutralizing some of the oxidizing
toxins found in horse beans.
 Hemolytic crises often occur in viral and bacterial infections, as in fever, hydrogen
peroxide is released from the collapsing granulocytes. Under the influence of neutrophil
membrane peroxidase, hydrogen peroxide decomposes with the release of a highly active
oxidant-atomic oxygen, which can provoke a hemolytic crisis.
Clinical picture.
 The disease is paroxysmal. In the latent period, outside of the provoking factors, the
patient's state of health is quite satisfactory. Possible manifestations of a slight anemia in
the form of pallor of the skin, complaints of general weakness, reduced physical and
mental ability to work, palpitations.
 In some patients, a small permanent hemolysis is possible, which is manifested by a
weakly expressed icteric sclera, skin.
 In typical cases, when provoking circumstances occur, an acute hemolytic crisis occurs in
2-3 days. In some patients, acute hemolysis occurs without an obvious cause.
 During a crisis, the concentration of Hb and red blood cells in the peripheral blood
rapidly decreases simultaneously with an increase in the level of free Hb and
unconjugated bilirubin. The urine becomes intensely dark due to free Hb.
 If the provoking factor continues to act, the patient's condition becomes more severe.
Fever, shortness of breath, severe headache, pain in the extremities, and lumbar pain
appear and increase. Blood pressure decreases. The skin becomes pale, jaundiced. With
 favism, the clinical picture is supplemented by intense abdominal pain, enlarged liver,
spleen.
 During a hemolytic crisis, patients ' lives are threatened by the development of acute
renal failure, DIC syndrome, and anemic coma.
Diagnostics.
 General analysis: normochromic anemia. During a crisis, anemia worsens. There is a
pronounced reticulocytosis - up to 25-50%, depending on the severity of the hemolytic
crisis. Most red blood cells contain Heinz corpuscles (denatured Hb). Visible" bitten " red
blood cells-dehmacytes. Leukocytosis occurs with a pronounced, up to myelocytes, shift
of the formula to the left, eosinophilia. The platelet count does not change. ESR is
increased.
 Coombs test: negative.
 Osmotic resistance of red blood cells is normal or increased.
 Sternal puncture: c/m enrichment with basophilic nucleated cells of the erythromyeloid
series and eosinophils.
 Bioh. blood serum analysis: hyperbilirubinemia due to unconjugated fraction, free Hb.
With the development of DIC, the content of consumed blood clotting factors
(prothrombin, fibrinogen, etc.) decreases, and fibrin degradation products appear. Acute
renal failure is accompanied by an increase in urea, creatinine, and potassium levels.
 General urinalysis: urobilin, free Hb, hemosiderin are detected.
Differential diagnosis.
 The diagnosis is based on the identification of such a typical symptom for this disease as
the appearance in the peripheral blood during a hemolytic crisis of red blood cells
containing inclusions from the denatured HbHeinz Hb – body.
 For a reliable differential diagnosis with other types of HA, the activity of glucose-6-
phosphate dehydrogenase in the patient's red blood cells is determined.
Treatment.
 First of all, drugs, food products that can cause a hemolytic crisis are canceled. Prescribe
vitamins with antioxidant properties: tocopherol, riboflavin.
 In order to prevent favism, legumes are excluded from food consumption. During a
hemolytic crisis, plasmapheresis is performed.
 With deep anemia, transfusion of washed red blood cells is necessary. If symptoms of
DIC appear, heparin and fresh frozen plasma are administered. Acute renal failure is an
indication for hemodialysis.
SICKLE CELL HEMOLYTIC ANEMIA
 Definition. Sickle cell anemia - HA caused by a genetic defect, when instead of normal,
abnormal Hb is synthesized, which has a reduced solubility under hypoxemia, which
causes violations of the structure of red blood cells and their destruction.
Etiology.
 As a result of a genetically determined defect, abnormal HBS hemoglobin is
synthesizedHbS.
 Pathogenesis. HbS is not able to remain in a dissolved state during hypoxemia or the
action of chemicals that have the properties of a reducing agent. It falls out in a gel-like
precipitate, changes the cellular configuration of red blood cells, giving them a
characteristic crescent-shaped or meniscoid shape.
 Red blood cells deformed by deposited Hb are unable to maintain tissue microcirculation
and undergo intra-vascular hemolysis. The breakdown products of red blood cells
activate the blood coagulation system, causing thrombosis in various vascular pools.
 Excessive formation and excretion of bilirubin through the bile ducts is a pathogenetic
factor in the formation of bile stones of pigmented composition.
Clinical picture.
  The homozygous variant of the disease is manifested by symptoms of severe GA, which
occurs already in the first year of life.
 The first hemolytic crises usually occur against the background of infections,
accompanied by painful swelling of the joints of the hands and feet.
 Patients are pale, jaundiced, suffer from mental retardation. Due to compensatory
hyperplasia of the c/m, most people have various disorders of skeletal development:
elongated limbs, a tower skull with thickened sutures of the frontal bones.
 Hemolytic crises occur with high fever. Crises are often accompanied by thrombosis of
the vessels of the extremities, mesenteric vessels, infarctions of the lungs, spleen, and
retinal hemorrhages. Ischemic or hemorrhagic strokes are possible.
 Aseptic necrosis of the femoral and humeral heads may occur.
 All patients have moderate hepatosplenomegaly. In the late stages of the disease, due to
frequent heart attacks, the spleen shrinks.
 Trophic ulcers of the lower legs often occur.
 Concretions in the bile ducts can cause attacks of hepatic colic.
Diagnostics.
 General blood test: normal or hypochromic anemia, reticulocytosis, leukocytosis with a
left shift to myelocytes, anisocytosis, poikilocytosis, anisochromia, basophilic granularity
of red blood cells. Meniscoid erythrocytes and normoblasts are often found.
 Sickle cell red blood cells are rarely detected. They can be detected after treating the
blood with sodium metabisulfite, which, acting as a reducing agent, causes a lack of
oxygen in red blood cells. This leads to the crystallization of HBS hemoglobin in red
blood cells with the formation of a crescent-shaped precipitate.
Bioh.analysis of sera. blood: increased bilirubin level due to unconjugated fraction, increased
iron content. During a crisis, free Hb is detected.
 When electrophoresis of Hb erythrocytes in homozygous patients, the content of
abnormal HBS hemoglobin can reach 90%.
 General analysis of urine: during a crisis, dark color due to a high concentration of
urobilin, free Hb, hemosiderin.
 Sternal puncture: hyperplasia of erythroid germ cells is detected in the bone marrow.
 X-ray examination: X-rays of the skull and other flat bones reveal the expansion of the
medullary zone, thinning of the cortical layer. Some patients show signs of aseptic
necrosis of the femoral or humeral heads. Often there are signs of osteoporosis,
compression deformity of the vertebrae.
Differential diagnosis.
 The disease must be differentiated from other HA variants. Essential help in differential
diagnosis is provided by tests for sickle cell disease with sodium metabisulfite, detection
by electrophoresis of the predominance of pathological hemoglobin HbSin red blood
cells.
Treatment.
 During the period of hemolytic crisis, the patient should be warmed up, since at low
temperatures the signs of sickle-shaped red blood cells are more pronounced.
 Prescribe folic acid 1 mg-1 time a day.
 To prevent hemosiderosis, patients with a high content of serum iron are prescribed
desferal 500 mg per day. In severe anemia, red blood cell mass is infused.
TALACSEMII
 Definition. Talcfamilies, in which the destruction of red blood cells is caused by
anomalies in the Hb structurecaused by inherited defects in transport RNA and regulatory
genes responsible for the synthesis of individual globin chains.
Etiology.
 The disease is caused by a genetic defect in transport RNA and regulatory genes
responsible for the synthesis of individual globin chains.
  Two forms of the disease are of clinical significance: beta - and alpha-thalasemia, in
which there is a depression in the synthesis of beta - and alpha - chains of globin,
respectively. Beta-thalasemia is more common.
Pathogenesis.
 Beta-thalasemia is characterized by ineffective erythropoiesis in combination with
intracerebral destruction of erythroid cells.
 Insufficient synthesis of globin beta chains causes a relative overabundance of alpha
chains. Unused alpha chains condense on the membrane of erythroid cells, causing their
damage and hemolysis, which occurs mainly in the spleen.
 Due to the lack of normal proportions in the amount of synthesized globin chains, the
total production of Hb in the patient's body decreases. Accordingly, iron consumption
decreases (sideroachresticheskoe state). This causes red blood cell hypochromia despite
normal or even elevated serum iron levels.
Due to the non-assimilation of iron by the hematopoietic system, its excessive content in the
blood, hemosiderosis and secondary hemochromatosis of internal organs may occur with the
development of cirrhosis of the liver, diabetes mellitus, adrenal insufficiency, secondary
restrictive cardiomyopathy with heart failure.
 Hemolysis is accompanied by compensatory activation of hematopoiesis. Hyperplasia of
c/m, in turn, leads to osteoporosis, skeletal deformity. It is possible to activate
extramedullary hematopoiesis in the liver and spleen, which is manifested by an increase
in the volume and impaired function of these organs.
 The constant release of a large amount of bilirubin through the biliary system causes the
formation of pigmented gallstones
 A distinction is made between heterozygous (low-grade) and homozygous (high-grade)
beta-thalasemia. The greatest clinical significance is greater beta-thalasemia – Cooley's
disease
Clinical picture.
 Heterozygous (poorly expressed) beta-thalasemia can occur with moderate hypochromic
anemia, slight pallor and mild icteric skin. Moderate splenomegaly is possible. The
general state of health of such patients is quite satisfactory.
 Large (homozygous) beta-thalasemia is characterized by symptoms of severe
hypochromic anemia, manifested from early childhood. There are severe, moderate and
mild forms of large beta-thalasemia. They survive to adulthood only with a mild form of
the disease. The severe form leads to the death of children within the first year of life.
 The early onset of hemolysis, accompanied by sharp bone marrow hyperplasia, leads to
such structural disorders of the skeleton as a tower skull, saddle nose, abnormal jaw with
an incorrect arrangement of teeth and malocclusion.
 Mentally retarded patients. They have pale, earthy-jaundiced skin. On the skin of the
scalp, around the eyes, on the back of the hands, they can find brown spots caused by
impaired porphyrin metabolism.
 The abdomen is enlarged due to hepatosplenomegaly. Patients with severe splenomegaly
often complain of pain in the left hypochondrium. Enlargement of the spleen can be
complicated by hypersplenism syndrome, when along with anemia, leukopenia and
thrombocytopenia occur and increase in patients.
 Many patients have microcirculation disorders in the form of trophic ulcers on the lower
legs, signs of circulatory insufficiency. Due to the formation of pigmented stones in the
gallbladder and ducts, patients often complain of bouts of intense pain in the right
hypochondrium.
 When the disease is complicated by secondary hemochromatosis, symptoms of diabetes
mellitus, cirrhosis of the liver, and heart failure appear.
Diagnostics.
  General blood test: reduced red blood cell count. Severe hypochromia, micro-and
anisocytosis of red blood cells. The Hb level is less than 30-60 g / l, the CP does not
exceed 0.4-0.5.There are target-like red blood cells. In these cells, instead of normal
illumination, a dark spot Hb is detected in the center, resembling the center of the target.
There is reticulosis, moderate leukocytosis.
 The life span of red blood cells and their osmotic resistance are reduced.
 Bioh.blood test: increased bilirubin content mainly due to unconjugated fraction,
increased serum iron concentration. Characteristic of thalasemia is an increased level of
serum iron, maximum iron saturation of transferrin.
 Electrophoretic examination of Hb erythrocytes reveals elevated levels of Hb HbF and
hba22.
 Sternal puncture: a pronounced hyperplasia of erythroid cells, a large number of
sideroblasts – macrophages containing the inclusion of hemosiderin-is determined by CT.
 General urinalysis: dark color, increased urobilin content.
 Myelogram (sternal punctate): hyperplasia of the erythroid germ.
 Ultrasound: splenomegaly, with secondary hemochromatosis signs of cirrhosis of the
liver, increased echogenicity, compaction of the pancreas, dilatation of the heart
chambers.
 Radiological examination: radiographs of the skull of patients with thalasemia on the
background of a thinned cortical layer of the arch show radial striation due to preserved
areas of bone tissue. This gives the X-ray image of the cranial vault a characteristic
"brush" appearance. In the tubular bones, the expansion of the medullary canal is
revealed, cyst-like lacunae appear in the metaphyses and epiphyses. These abnormalities
are evidence of severe hyperplasia of the hematopoietic tissue.
Differential diagnosis.
 The criterion of differential diagnosis that allows distinguishing beta-thalasemia from
other variants of anemia is the detection by electrophoresis of an increased content of
HBF and hba2 hemoglobin in red blood cells2.
Treatment.
 The heterozygous form of beta-thalasemia usually does not require treatment. In some
cases, folic acid preparations are prescribed to increase the effectiveness of
erythropoiesis.
 In the homozygous variant of the disease, infusions of washed red blood cells are used to
maintain the Hb level in the range of 80-100 g/l. For the prevention of hemosiderosis and
secondary hemochromatosis, desferal is used. The drug is administered intravenously at a
dose of 10 mg / kg / day for small children and 500 mg / day for adolescents.
 With the phenomena of hypersplenism, splenectomy is resorted to. Recently,
hydroxyurea and 5-azocytidine, cytostatic drugs that inhibit the synthesis of hemoglobin
Hb F, have been used with some success for the treatment of thalasemia.HbF.
HYPO-AND APLASTIC ANEMIA
 Definition. Hypo-and aplastic anemia (GiAA) is a disease of the hematopoietic system,
characterized by a decrease in the content of red blood cells, white blood cells, and
platelets in peripheral blood in combination with hypoplasia of all sprouts of
subcutaneous hematopoiesis, and a tendency to replace subcutaneous fat with adipose
tissue.
 GiAA with an isolated decrease in the content of red blood cells in the peripheral blood
and suppression of only the red blood cell growth of k / cerebral hematopoiesis are called
partial or pure red cell aplasias.
Etiology.
 There are congenital and acquired variants of GiAA. The most common forms of
congenital GiAA are:
 With the defeat of all sprouts of hematopoiesis:
  Fanconi anemia (with the presence of other congenital malformations);
 Estren-Dameshek anemia (without other congenital malformations).
 With only the erythropoietic line affected:
 pure (partial) Blackfen-Dayemond red cell HyAA.
 Acquired GiAA is divided into idiopathic (with unknown etiology) and caused by known
endogenous or exogenous effects. Endogenous factors include:
 Thymic tumors (thymoma, carcinoma).
 Immune lesion of c / m (graft-versus-host reaction).
 Eosinophilic fasciitis.
 Among the known exogenous causes that can cause acquired GiAA, the most important
are:
 Ionizing radiation.
 Chemicals (toxic chemicals used in everyday life and production, benzene, heavy metal
salts, etc.).
 Medicinal products: cytostatics (6-mercaptopurine, etc.), antithyroid drugs (mercazolil,
etc.), antibiotics (levamycetin, etc.), nonsteroidal anti-inflammatory drugs (analgin, etc.),
antidiabetic drugs (tolbutamide, etc.), antihypertensive drugs (captopril, etc.),
antiarrhythmic drugs (quinidine, etc.), etc.
 Infectious agents: Mycobacterium tuberculosis, fungi (Candida, Aspergillus, etc.), viruses
(hepatitis G, C, B; infectious mononucleosis; mumps, herpes; cytomegaloviruses, etc.).
 In the etiology of GiAA, an infectious disease caused by parvovirus B -19, which can cause
pure (partial) red cell aplasia with transient aplastic crises, is of particular importance.
From drugs, we can distinguish levomycetin (chloramphenicol), the ability of which to
suppress hematopoiesis is determined in the human genetic apparatus.
Pathogenesis.
 The following mechanisms play a leading role in the pathogenesis of suppression of
hematopoietic sprouts:
 Immune and/or toxic suppression of the mitotic capacity of polypotent stem cells and / or
erythropoietic progenitor cells in pure (partial) red cell aplasia.
 Immune and / or toxic suppression of the functional activity of the cellular
microenvironment of a stem cell in c/m.
 Genetically determined expression of apoptosis (suicide) genes in stem cells, progenitor
cells of the main lines of hematopoiesis.
 Reduction of the life span of red blood cells with their premature hemolysis in c / m
(shunt hemolysis) caused by immune or toxic effects on the activity of certain enzymes
of the red blood cell membrane.
Clinical picture
 Anemic syndrome пis characterized by general weakness, shortness of breath,
palpitations, dizziness, flickering of dark flies in the eyes, and inability to perform
prolonged physical and mental work.
 Patients have a pronounced pallor of the skin and mucous membranes. Pulse rate is high,
blood pressure may be normal or low. Percussion - defined borders of the heart are
moderately expanded, the tones are muted.
 A functional systolic murmur is heard over all auscultation points. Detection of an
enlarged liver is usually combined with other signs of congestive heart failure.
 Hemorrhagic syndrome is caused by thrombocytopenia caused by hypo-or aplasia of the
megakaryocytic germ in the subcutaneous space.
 Thrombocytopenia causes a tendency to bleeding with minor injuries to the oral mucosa,
is manifested by nosebleeds, menorrhagia, hematuria, bruising on the skin is noted with
minor physical exposure or for no obvious reason.
 On the abdomen, thighs, shins, and forearms, multiple hemorrhagic rashes and bruises of
various sizes are detected. Small hemorrhages are visible on the mucous membranes of
 the mouth, lips, and conjunctiva. At the injection sites, injuries occur hematomas, often
very extensive.
 Patients with severe exacerbation of the disease and deep thrombocytopenia often have
massive pulmonary, gastric, intestinal, and uterine bleeding, which significantly
aggravates AS. Intra-cranial hemorrhages are one of the causes of sudden death in
patients with GiAA.
 The syndrome of immune disorders is formed when the number of granulocytes in
peripheral blood and tissues decreases. It is characterized by a tendency of patients to
infectious diseases.
 Acute respiratory viral infections cause long - term and severe bronchitis, which is
complicated by pneumonia.
 Evidence of immune disorders should be considered pustular skin lesions. Very often,
fungal lesions of the skin and nail beds occur and spread quickly.
 With a severe exacerbation of GiAA, ulcerative-necrotic stomatitis and tonsillitis with
severe intoxication may develop.
 Hemolytic syndrome is caused by the occurrence in some cases of the phenomenon of
intracerebral hemolysis of red blood cells (shunt hemolysis)- a hemolytic form of GiAA.
This circumstance is associated with mild icteric, sometimes jaundice of the sclera and
skin, dark color of feces and urine due to the release of stercobilin and urobilin.
 With a prolonged course of the disease, pigmented concretions can form in the
gallbladder. The spleen is not enlarged in patients with GiAA, including in the hemolytic
form of the disease.
 The course of GiAA can be acute, subacute, or chronic, depending on the severity and
rate of increase in the clinical manifestations of the syndromes described above.
 The acute course is characterized by a rapid increase in pancytopenia. The clinical
picture is dominated by hemorrhagic syndrome. Within a few weeks, the number of red
blood cells, white blood cells, and platelets may fall to a critical level that is not
compatible with life.
 With a subacute course , the disease begins less violently. However, within a few
months, the pathological process leads to severe anemia, thrombocytopenia with
hemorrhagic manifestations, agranulocytosis with severe ulcerative-necrotic lesions of
the nasopharynx, destructive pneumonia, and other infectious complications.
 Without bone marrow transplantation, patients die in 4-12 months from the onset of the
first manifestations of the disease.
 The chronic course of GiAA is characterized by a gradual onset of the disease. The first
is anemic syndrome. Patients first go to the doctor in connection with the appearance of
feelings of general weakness, reduced mental and physical ability to work.
 Others notice the pale color of the skin. In the future, with the progression of bone
marrow damage, thrombocytopenic purpura and violations of anti-infectious immunity
appear.
 In the chronic course, spontaneous and treatment-induced remissions of the disease are
possible, but the duration of each subsequent remission decreases, and relapses become
more severe.
 The life expectancy of patients with a chronic course of GiAA when using adequate
treatment methods reaches several years. Recovery is possible with a successful bone
marrow transplant.
Diagnostics.
 General blood test: pancytopenia. The number of red blood cells is reduced, often to very
low values (less than 0.5x 10-12/l). Anemia is usually normochromic and normocytic.
Reticulocytes are absent, which indicates the aregenerative nature of anemia. The number
of granulocytes is sharply reduced. The platelet concentration may fall below the level of
5x109/l. ESR is increased to 40-60 mm / h.
  Biochemical blood test: in patients with a hemolytic form of GiAA, the concentration of
unconjugated bilirubin and serum iron is increased.
 General urinalysis: may be normal. With severe thrombocytopenia, micro-or
macrohematuria may occur. In the hemolytic form of GiAA, urobilin is detected in the
urine.
 Coprogram: a positive Gregersen reaction, which in patients with deep thrombocytopenia
may indicate the presence of gastrointestinal bleeding. Fresh red blood cells are detected
with hemorrhoidal bleeding. In the hemolytic form of the disease, an increased content of
stercobilin in the feces is determined.
 Sternal puncture and / or trepanobiopsy of the iliac wing: a pronounced decrease in the
number of cellular elements in the bone marrow is detected. In severe cases, histological
bone marrow samples appear drained.
 In the field of view, individual cells of the predominantly lymphoid series (lymphocytes,
plasma cells, single erythroblasts) are visible.
 There are macrophages overloaded with hemosiderin-sideroblasts, which indicates an
overflow of the bone marrow depot with iron that is not used for erythropoiesis.
 ECG: tachycardia, signs of myocardial dystrophy (reduced amplitude of QRScomplexes,
isoelectric T wave in the thoracic leads).
Differential diagnosis
 GiAA should be differentiated from acute leukemia, which can also cause anemia,
leukopenia, thrombocytopenia with hemorrhagic diathesis.
 A characteristic feature of acute leukemia is the appearance of blasts in the peripheral
blood and in the bone marrow, which does not happen with GiAA.
 Patients with megaloblastic anemia may also have moderate pancytopenia in the
peripheral blood, icteric skin as a result of intraosseous destruction of red blood cells.
 However, with megaloblastic anemia, hyperplasia of the hematopoietic tissue occurs,
megaloblasts and hypersegmented neutrophils are detected in the bone marrow, which is
not present in GiAA.
 In agranulocytosis, in contrast to GiAA, in which all hematopoietic sprouts, primarily the
erythropoietic line, are suppressed, only the myeloid sprout is suppressed, and the
erythroid and megakaryocytic sprouts are preserved.
 Agranulocytosis is not characterized by thrombocytopenia, hemorrhagic syndrome. The
clinical picture of agranulocytosis is formed mainly by infectious, septic complications
caused by deep immune disorders in this disease.
 In myelodysplastic syndrome, as well as in GiAA, the number of shaped elements in the
peripheral blood decreases, and the saturation of the bone marrow with cellular elements
decreases.
 At the same time, this disease in the bone marrow reveals signs of megaloblastic
erythropoiesis, defects in the maturation of red blood cells, an increase in the number of
blast cells, the structure of megakaryocytes is disturbed while maintaining their number.
All this does not happen with GiAA.
Treatment.
 Patients with GiAA need to eliminate the toxic effects of chemicals, drugs that have a
negative effect on hematopoiesis, and effective treatment of infectious diseases
(tuberculosis) that can cause suppression of hematopoietic tissue.
 With an exacerbation of GiAA, especially in cases where the content of granulocytes in
the blood falls below 0. 5x109/l, patients are placed in a specially designated sterile box.
The patient's skin is treated with antiseptic solutions, the oral cavity is sanitized. To avoid
blood loss during menstruation, women are given combined hormonal medications.
 With deep anemia, red blood cell mass is transfused. A drop in platelet levels below
20x109/l is the basis for platelet concentrate transfusion.
  To stop infectious complications, broad-spectrum antibiotics are prescribed. Choose
drugs that do not have a myelotoxic effect.
 If GiAA is caused by an autoimmune process, glucocorticoids can be used to treat it.
These drugs are particularly effective in pure (partial) red cell GiAA. Prescribe from 80
to 120 mg of prednisone per day until signs of remission appear. Then they gradually
switch to maintenance treatment with 15-20 mg of the drug per day.
 If there is a clinical effect, hormone therapy is continued for 3-4 months. If there is no
effect within 4 weeks, prednisone therapy is discontinued.
 In the absence of positive results from glucocorticoid therapy, splenectomy is indicated
for patients with a mild form of anemia. This eliminates the cytotoxic function of the
spleen. A positive clinical effect of splenectomy is observed in 70-80% of patients with
GiAA.
 If there is no effect from splenectomy, you can conduct a course of treatment with anti-
lymphocytic globulin. The drug is administered intravenously in drops of 120-160 mg
once a day for two weeks.
 Cyclosporin A (sandimmune) is an effective treatment for GiAA. It is dosed based on the
calculation of 4 mg per kilogram of the patient's weight per day. The drug is taken 2
times a day for 2-3 months. Hematological remission occurs in almost half of patients.
 Combined therapy of GiAA is possible with parenteral administration of anti-lymphocyte
globulin, oral administration of cyclosporin A, parenteral administration of colony-
stimulating factor preparations (filgrastim, lenograstim, nartograstim, neupogen) and oral
administration of methylprednisolone.
 The main and most promising method of treating GiAA is bone marrow transplantation.
For this purpose, a donor is selected that is compatible with the HLAsystem (human
leukocyte antigens). Before transplantation, the recipient's own bone marrow is destroyed
by total irradiation of the body at a dose of 10-11 Gray and the introduction of large
doses of cyclophosphamide (50 mg/kg 1 time a day for 3 consecutive days).

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Moiseev, A. S. Glyavich. - 3rd ed., ispr. - Moscow: GEOTAR-Media, 2015
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