The clinical value of bloodThe clinical value of blood. . . Allowance for doctors' Allowance for doctors'

(Institute of Pediatric Hematology, the drafters of the (Institute of Pediatric Hematology, the drafters of the A.G .Rumyantsev, E.B .Vladimirskaya), Moscow, 1999A.G .Rumyantsev, E.B .Vladimirskaya), Moscow, 1999

AutomaticAutomaticalal

CountingCounting

Units Units

Measure-Measure-mentment

Normal Normal LevelLevel

Short Short FormForm

HGB- Hemoglobin

G/Liter 120-160 HbHb

RBC - erythrocyte

1210 /L

3,9-5,9 ErEr

HCT -Hematocryte

%% 36,0-48,0 HtHt

MCV- average volume of erythrocyte

31 micron = 1 - femtoliter (fl)

80 - 9580 - 95

MCH – the average content of Hb in erythrocyte

Pikogram1 г =1012pikograms

27,0-31,02

Colour Index (0,85-1,0)

MCHC – average concentration of Hb in erythrocyte

G/dl или g %, less g/l

32,0-36,0

RDW – width of the distribution curve of erythrocyte by volume

%% 11,5-14,5 anisocytosis

RETICULOCYTERETICULOCYTE

Normal values:Normal values: The relative number of The relative number of

reticulocyte 0,5-1,2% reticulocyte 0,5-1,2% The absolute number of The absolute number of

reticulocyte 30-70 x 10 * 9 / Lreticulocyte 30-70 x 10 * 9 / L In cord blood of newborns 20-In cord blood of newborns 20-

60%.60%.

Аnemia – pathologic state,accompanied by decrease in the level of hemoglobin and the quantity of erythrocytes per unit of volume of the blood.

Erythrocytes - less informative index Erythrocytes - less informative index of anemia than the level of of anemia than the level of hemoglobin therefore, in the hemoglobin therefore, in the general practice the basic criterion general practice the basic criterion of severity is precisely Hb: of severity is precisely Hb:

Light degree of anemia - Hb 110-90 Light degree of anemia - Hb 110-90 g / l, g / l,

The average degree of severity - The average degree of severity - Hb 90-70 g / l, Hb 90-70 g / l,

Severe anemia - Hb below 70 g / Severe anemia - Hb below 70 g / literliter

In terms of number of In terms of number of reticulocyte, anemia are reticulocyte, anemia are

divided into:divided into: Regenerative- reticulocyte from 1.5 to Regenerative- reticulocyte from 1.5 to

5% (or 15 to 50 ppm) 5% (or 15 to 50 ppm)

Hyper-regenerative - reticulocyte more Hyper-regenerative - reticulocyte more than 5% (or more than 50 ppm) than 5% (or more than 50 ppm)

Aregenerative- Low reticulocyte (less Aregenerative- Low reticulocyte (less than 0.5%), not according to the than 0.5%), not according to the severity of anemia or lack of severity of anemia or lack of reticulocyte.reticulocyte.

Classification of AnemiaClassification of Anemia I. Anemias resulting from acute blood loss I. Anemias resulting from acute blood loss II. Anemias resulting from a deficit of erythropoesis II. Anemias resulting from a deficit of erythropoesis

1) At the expense of maturation (mainly microcyte): 1) At the expense of maturation (mainly microcyte):

violation of absorption and utilization of iron (iron) violation of absorption and utilization of iron (iron)

violation of transportation of iron (atransferrinemia) violation of transportation of iron (atransferrinemia)

violation of recycling iron (thalassemia, violation of recycling iron (thalassemia, sideroblastic anemia ) sideroblastic anemia )

violation of reutilization of iron (anemia of chronic violation of reutilization of iron (anemia of chronic disease);disease);

AnemiaAnemia ( (continuedcontinued))

2) At the expense of differentiation 2) At the expense of differentiation (essentially normal): (essentially normal):

aplastic anemia (congenital and aplastic anemia (congenital and acquired) acquired)

3) At the expense of proliferation 3) At the expense of proliferation (mainly macrocytes) (mainly macrocytes)

B12-DEFICIENCY anemia B12-DEFICIENCY anemia

Folic-DEFICIENCY anemia.Folic-DEFICIENCY anemia.

AnemiaAnemia ( (continuedcontinued)) Anemias resulting from increased Anemias resulting from increased

destruction of erythroid series cells - destruction of erythroid series cells - haemolytic: haemolytic:

1) caused by internal defects of 1) caused by internal defects of erythrocytes erythrocytes           membranopathy, enzimopathy,           membranopathy, enzimopathy, haemoglobinopathies; haemoglobinopathies;

2) the external (extracllular) effects: 2) the external (extracllular) effects: autoimmune, traumatic, etc. autoimmune, traumatic, etc.

Classification D. Nathan, F. Oski, 2003, (book «Anemias Classification D. Nathan, F. Oski, 2003, (book «Anemias in children», NA Finogenova et al, 2004.): in children», NA Finogenova et al, 2004.):

IRON DEFICIENCY ANEMIA IRON DEFICIENCY ANEMIA (IDA)(IDA)

IDIDА А recorded 20% of the world's recorded 20% of the world's population. population.       

83-90% of all anemia constitute IDA. 83-90% of all anemia constitute IDA.        

In children the first 2 years of life the In children the first 2 years of life the frequency of iron deficiency was 73%. frequency of iron deficiency was 73%.       

The second peak IDA development - The second peak IDA development - adolescence.adolescence.

CAUSES FOR CAUSES FOR DEVELOPMENT of IDADEVELOPMENT of IDA

Alimentary iron deficiency as a consequence of an Alimentary iron deficiency as a consequence of an unbalanced diet; unbalanced diet;

Increasing demand for iron and the reduction of the Increasing demand for iron and the reduction of the deposit (or the frequency of multiple pregnancies, deposit (or the frequency of multiple pregnancies, prematurity, lactation periods of rapid growth, sports) prematurity, lactation periods of rapid growth, sports)

Chronic blood loss (nasal bleeding, diaphragmatic Chronic blood loss (nasal bleeding, diaphragmatic hernia, and bleeding from GIT and diverticulitis, hernia, and bleeding from GIT and diverticulitis, menorrhagia, renal hemorrhage, idiopathic lung menorrhagia, renal hemorrhage, idiopathic lung hemosiderosis) hemosiderosis)

Reduction of iron absorption (malabsorption, chronic Reduction of iron absorption (malabsorption, chronic inflammatory diseases GIT, gastrectomy).inflammatory diseases GIT, gastrectomy).

The total content of iron in the body The total content of iron in the body - about 4.2 g.- about 4.2 g. From them: From them:- 75-80% belongs to the hemoglobin- 75-80% belongs to the hemoglobin

- 20 - 25% reserve- 20 - 25% reserve

- 5-10% part of the myoglobin- 5-10% part of the myoglobin

-1% is part of the enzyme for the -1% is part of the enzyme for the tissue respirationtissue respiration

Anemic SyndromeAnemic Syndrome - - Decrease amount of HemoglobinDecrease amount of Hemoglobin

Complaints: General weakness, reduction in Complaints: General weakness, reduction in the appetite, physical and mental fatigue, the appetite, physical and mental fatigue, shortness of breath, vertigo, noise in the shortness of breath, vertigo, noise in the ears, flashing “flies” before the eyes, ears, flashing “flies” before the eyes, unconscious states, in heavy cases – leads to unconscious states, in heavy cases – leads to coma. coma.

Symptoms: the pallor of the skin and Symptoms: the pallor of the skin and mucosa, tachycardia, hypotonia, the mucosa, tachycardia, hypotonia, the expansion of the boundaries of heart, muting expansion of the boundaries of heart, muting tones and systolic murmur. tones and systolic murmur.

Laboratory signs: a decrease in the level Hb Laboratory signs: a decrease in the level Hb and a drop in hematocrit (lower than 35% in and a drop in hematocrit (lower than 35% in children, 37% in girls and 42% in youths) children, 37% in girls and 42% in youths)

Sideropenic Syndrome (Deficit of Iron)Sideropenic Syndrome (Deficit of Iron)

dystrophic changes in the skin and its dystrophic changes in the skin and its appendages (shedding of hair, the brittleness appendages (shedding of hair, the brittleness of nails), the atrophy of the mucous of nails), the atrophy of the mucous membranes of nose, esophagus and stomach, membranes of nose, esophagus and stomach, gingivitis, glossitis, angular stomatitis); gingivitis, glossitis, angular stomatitis);

the distortion of taste and sense of smellthe distortion of taste and sense of smell muscular pain (deficit of myoglobin)muscular pain (deficit of myoglobin) muscular hypotoniamuscular hypotonia alteration in the nervous system: slowing alteration in the nervous system: slowing

down of conditioned reflexes, decrease down of conditioned reflexes, decrease attentiveness, worsening of memory, delay of attentiveness, worsening of memory, delay of intellectual development. intellectual development.

Laboratory Signs of Iron Deficit Laboratory Signs of Iron Deficit AnemiaAnemia A decrease MCV - less than 75A decrease MCV - less than 75

Reduction in the colored index - less than Reduction in the colored index - less than 0,85 0,85

Increase RDWIncrease RDW A decrease MCHC - less than 30.A decrease MCHC - less than 30. MorphologyMorphology of the erythrocytes - of the erythrocytes -

hypochromic, anisocytosis and poikilocytosis hypochromic, anisocytosis and poikilocytosis

BiochemicalBiochemical - - decrease level of serum decrease level of serum ferritinferritin

Decrease level of serum iron Decrease level of serum iron Increase Total Iron Binding Capacity (TIBC)Increase Total Iron Binding Capacity (TIBC) Increase level of serum transferrin Increase level of serum transferrin

Developmental Stages of Iron Deficiency Developmental Stages of Iron Deficiency Anemia (WHO, 1977)Anemia (WHO, 1977)

Pre-latentPre-latent (exhaustion of tissue reserve of (exhaustion of tissue reserve of iron; index of the blood within the standard; iron; index of the blood within the standard; there are no clinical manifestations)there are no clinical manifestations)

Latent (deficit of iron in the tissue and the Latent (deficit of iron in the tissue and the decrease of its reservoir transport; index of decrease of its reservoir transport; index of the blood within the standard; clinical the blood within the standard; clinical picture is caused by the sideropenic picture is caused by the sideropenic syndrome)syndrome)

Iron Deficiency Anemia (deviation from the Iron Deficiency Anemia (deviation from the standard index of the blood in dependence standard index of the blood in dependence on the degree of severity; the clinical on the degree of severity; the clinical manifestations in the form of sideropenic manifestations in the form of sideropenic syndrome and general anemic symptoms)syndrome and general anemic symptoms)

Differential Diagnosis of Iron Deficiency Differential Diagnosis of Iron Deficiency AnemiaAnemia

it is carried out with other forms of the hypochromic it is carried out with other forms of the hypochromic anemias: anemias:

Thalassemia - there are no signs of deficit of iron, Thalassemia - there are no signs of deficit of iron, the presence of pathologic hemoglobin with the the presence of pathologic hemoglobin with the electrophoresis. electrophoresis.

Sideroblastic Anemia - examination of the puncture Sideroblastic Anemia - examination of the puncture specimen of bone marrow. specimen of bone marrow.

Chronic poisoning by lead - specific starts in the Chronic poisoning by lead - specific starts in the erythrocytes. erythrocytes.

Against the background chronic infectious and Against the background chronic infectious and inflammatory diseases - hypochromic normocytic inflammatory diseases - hypochromic normocytic (thinner frequent microcytic) anemia, normal or (thinner frequent microcytic) anemia, normal or increased level of ferritin in combination with the increased level of ferritin in combination with the lowered content of serum iron and transferrin. lowered content of serum iron and transferrin.

FerritinFerritin water-soluble complex of iron water-soluble complex of iron

hydroxide with the protein hydroxide with the protein apoferritin.apoferritin.

It is located in cells of the liver, It is located in cells of the liver, spleen, bone marrow, in the spleen, bone marrow, in the reticulocytes. reticulocytes.

Ferritin is the basic protein in Ferritin is the basic protein in human which deposits iron and human which deposits iron and concentration of ferritin in the concentration of ferritin in the serum reflects the reserve of iron serum reflects the reserve of iron in the organism. in the organism.

Serum TransferrinSerum Transferrin((Beta-globulinBeta-globulin).).

Main function - transport of absorbed iron in the depot Main function - transport of absorbed iron in the depot (liver, spleen), into the medullary erythroid (liver, spleen), into the medullary erythroid predecessors and into the reticulocytes. predecessors and into the reticulocytes.

Basic place of synthesis - liver. Basic place of synthesis - liver. An increase in the content of transferrin with lowering An increase in the content of transferrin with lowering

in the level of iron of serum is characteristic for the in the level of iron of serum is characteristic for the iron-deficiency state. iron-deficiency state.

A decrease in the level of transferrin can be with the A decrease in the level of transferrin can be with the damage of the liver (different genesis) and with the damage of the liver (different genesis) and with the loss of protein (for example, in nephrotic syndrome). loss of protein (for example, in nephrotic syndrome).

The level of transferrin is increased in the last term of The level of transferrin is increased in the last term of pregnancy. pregnancy.

TransferrinTransferrinLIMITATION The concentration of TF is subjected to the The concentration of TF is subjected to the

daily variations daily variations Acute inflammation contributes to lowering Acute inflammation contributes to lowering

the TF levelthe TF levelCLINICAL SIGNIFICANCE Basic clinical index for the differentiation Basic clinical index for the differentiation

between the iron-deficiency ([TF]↑) and between the iron-deficiency ([TF]↑) and hemolytic anemia ([TF]↓) hemolytic anemia ([TF]↓)

More precise index than total iron binding More precise index than total iron binding capacity capacity

After the liberation of iron from the After the liberation of iron from the complex, TF ion of Fe3+ must be restored complex, TF ion of Fe3+ must be restored into Fe2+ into Fe2+

Treatment of Iron Deficiency Treatment of Iron Deficiency AnemiaAnemia

Diet: meat, liver, yeast, fishDiet: meat, liver, yeast, fish Oral preparations: recovery rate Hb Oral preparations: recovery rate Hb

does not differ from parenteral does not differ from parenteral introduction, side effects are less, introduction, side effects are less, excessive introduction does not lead excessive introduction does not lead to hemosiderosis. to hemosiderosis.

- Dosage : 1 hour prior to the meal- Dosage : 1 hour prior to the meal

in the evening time (absorption in the evening time (absorption increase in the second-half of a day) increase in the second-half of a day)

During first 3 days - half dose of the selected During first 3 days - half dose of the selected preparation. preparation.

Possibilities : dark colour of stool and transitory Possibilities : dark colour of stool and transitory dyspeptic disorders (nausea, diarrhea or dyspeptic disorders (nausea, diarrhea or watery stool) watery stool)

Check analysis of the blood: in 7-10 days – Check analysis of the blood: in 7-10 days – reticulocyte reaction; 4 weeks - increase Hb reticulocyte reaction; 4 weeks - increase Hb and Htand Ht

During the normalization of the indices of the During the normalization of the indices of the blood – reduce the dose of preparationblood – reduce the dose of preparation

Parenteral Introduction of IronParenteral Introduction of Iron

in exceptional casesin exceptional cases in severe iron deficiency anemiain severe iron deficiency anemia rendering to special aidrendering to special aid intolerance of oral preparations (after repeated intolerance of oral preparations (after repeated

replacement and reduction in the dose)replacement and reduction in the dose) diseases of gastro-intestinal tractdiseases of gastro-intestinal tract syndrome of the disrupted intestinal absorbtionsyndrome of the disrupted intestinal absorbtion after the extensive resection of the small after the extensive resection of the small

intestineintestine continuous blood losscontinuous blood loss not compensated by oral method not compensated by oral method

Complications of Parenteral Complications of Parenteral IntroductionIntroduction

Local reactions (pains, phlebitis)Local reactions (pains, phlebitis) General reactions (anaphylaxis, fever, General reactions (anaphylaxis, fever,

head and articulate pains, vomiting, head and articulate pains, vomiting, rash, bronchospasm). rash, bronchospasm).

Preparations: Preparations: Venofer - for the intravenous Venofer - for the intravenous

introduction,introduction,Maltofer, Ferrum-Lek - intramuscularMaltofer, Ferrum-Lek - intramuscular

Overdose of IronOverdose of Iron

In the first 6-8 hours - epigastral pains, In the first 6-8 hours - epigastral pains, nausea, vomiting (including with the blood), nausea, vomiting (including with the blood), diarrhea, pallor, sleepiness, acrocyanosis)diarrhea, pallor, sleepiness, acrocyanosis)

For 12-24 hours - metabolic acidosis, For 12-24 hours - metabolic acidosis, leukocytosis, there can be spasms, coma, leukocytosis, there can be spasms, coma, after 2-4 days - necroses of the liver and after 2-4 days - necroses of the liver and kidneys.kidneys.

Treatment: emetic means, stomach Treatment: emetic means, stomach lavage, the method of milk with the egg lavage, the method of milk with the egg white, Deferoksamin, Desferal, symptomatic white, Deferoksamin, Desferal, symptomatic therapy. therapy.

Iron Overload SyndromeIron Overload Syndrome ! ! Human does not have special mechanism of the Human does not have special mechanism of the

excretion of iron! Its excessive introduction leads to excretion of iron! Its excessive introduction leads to hemosiderosis. Clinical manifestations: Gradual hemosiderosis. Clinical manifestations: Gradual increase of the dimensions of the liver, spleen, increase of the dimensions of the liver, spleen, cardiopathy, suprarenal insufficiency, diabetes cardiopathy, suprarenal insufficiency, diabetes mellitus, eunuchoidism.mellitus, eunuchoidism.

Laboratory signs: Laboratory signs:

Increase in serum iron (more than 30 mmol/liter), Increase in serum iron (more than 30 mmol/liter), percentage of saturation transferrin by iron it is percentage of saturation transferrin by iron it is more than 45%, ferritin of serum it is more than more than 45%, ferritin of serum it is more than 1000 ng/ml; Test with desferalom; + the specific 1000 ng/ml; Test with desferalom; + the specific signs of the defect of internal organs (ECG, level signs of the defect of internal organs (ECG, level biochemical index of functions of the liver, the level biochemical index of functions of the liver, the level of hormones and others) of hormones and others)

Anemia due to the Anemia due to the disturbance of the disturbance of the

proliferation proliferation

B12 and Folate B12 and Folate Deficiency AnemiaDeficiency Anemia

MegaloblasticMegaloblastic

Causes of B12 Deficiency Causes of B12 Deficiency AnemiaAnemia

Deficiency of the internal factor of KastlaDeficiency of the internal factor of Kastla Atrophy of the mucous membrane of Atrophy of the mucous membrane of

stomach as the most frequent reason, stomach as the most frequent reason, gastrectomygastrectomy

Inflammatory or autoimmune diseases Inflammatory or autoimmune diseases of small intestine, the removal of its of small intestine, the removal of its specific sectionsspecific sections

Helminthic invasion Helminthic invasion (tapeworms),insufficiency of the vitamin (tapeworms),insufficiency of the vitamin B12 in the food (it is contained in the B12 in the food (it is contained in the meat, bean). meat, bean).

Causes of Folic Acid DeficiencyCauses of Folic Acid Deficiency

AlimentaryAlimentary Increase in need (prematurity birth, rapid Increase in need (prematurity birth, rapid

growth rate, pregnancy)growth rate, pregnancy) Feeding by the goat milk Feeding by the goat milk Disease of the small intestine Disease of the small intestine Comsumtion of folate antagonist with Comsumtion of folate antagonist with

metatreksatmetatreksat Anti-convulsant (diphenine),oral Anti-convulsant (diphenine),oral

contraceptives contraceptives Chronic hemolysisChronic hemolysis

ClinicalClinical

Anaemic syndromeAnaemic syndrome Skin is pale with the lemon shade Skin is pale with the lemon shade Slight jaundice of the sclerasSlight jaundice of the scleras Disturbance of the proliferation of Disturbance of the proliferation of

the epithelium of gastro-intestinal the epithelium of gastro-intestinal tract: dry-red tongue, loss of tract: dry-red tongue, loss of appetite, achylia, diarrhea, erosive appetite, achylia, diarrhea, erosive and ulcerous changes in the and ulcerous changes in the mucous membranes mucous membranes

Only for B12-Deficiency Only for B12-Deficiency AnemiaAnemia

Damage of CNS - funicular myelosis Damage of CNS - funicular myelosis (degeneration and the sclerosis of the (degeneration and the sclerosis of the posterior and lateral horn of spinal posterior and lateral horn of spinal cord), paresthesia, paralyses with the cord), paresthesia, paralyses with the disorder of the function of pelvic disorder of the function of pelvic organs. organs.

Diagnosis of B12 and Folate Diagnosis of B12 and Folate Deficiency AnemiaDeficiency Anemia

General Analysis of BloodGeneral Analysis of Blood: : reduction in the quantity of erythrocytes reduction in the quantity of erythrocytes

and hemoglobin hyperchromatic and hemoglobin hyperchromatic (macrocytic)(macrocytic)

anisocytosis of the erythrocytesanisocytosis of the erythrocytes hyper-segmentation of the neutrophilshyper-segmentation of the neutrophils Jolly body and Cabbots rings as the Jolly body and Cabbots rings as the

microscopical picture of the erythrocytes microscopical picture of the erythrocytes

ContinuationContinuation Reduced reticulocyte in blood countReduced reticulocyte in blood count Normoblasts in the smear of the Normoblasts in the smear of the

blood blood Leucopenia, thrombocytopenia Leucopenia, thrombocytopenia

Bone marrow:Bone marrow: Irritation in erythroid growth, Irritation in erythroid growth,

megaloblasts, the disintegration of megaloblasts, the disintegration of erithrokaryocytes.erithrokaryocytes.

Biochemical Analysis of Biochemical Analysis of BloodBlood

an increase in unconjugated an increase in unconjugated bilirubin bilirubin

an increase in serum iron an increase in serum iron

В12 – – decrease ordecrease or

Folate status ( (Folic acid in the Folic acid in the

bloodblood) – ) – decreasedecrease

Criteria of Effective TreatmentCriteria of Effective Treatment

Subjective improvement during the first Subjective improvement during the first days of treatment;days of treatment;

Reticulocytosis, maximally expressed (to Reticulocytosis, maximally expressed (to 20%) on 5-720%) on 5-7thth day of treatment; day of treatment;

Increase in hemoglobin and number of Increase in hemoglobin and number of erythrocytes, beginning from the 2nd erythrocytes, beginning from the 2nd week of treatment; week of treatment;

The normalization of the blood index, The normalization of the blood index, number of leukocytes and thrombocytes number of leukocytes and thrombocytes in 3-4 weeks of treatment. in 3-4 weeks of treatment.