1. ANEMIA 1. Decrease in hemoglobin concentration and/or
erythrocytes in comparison to normal age values
2. Reduction in the hemoglobin concentration in
blood (corrected by age)
3. Decreased total circulating red cell mass

2. PHYSIOLOGICAL ANEMIA In 3 month of life – decrease of hemoglobin
(in prematures to 80 g/L)
concentration to 100 g/L
Temporary decrease in erythropoietin level,
due to better body oxygenation

3. Reticulocytes /%/ NORMAL VALUES FOR PERIPHERAL BLOOD Female Male
Erythrocytes /per l/
Hemoglobin /g/dl/
Hematocrit /%/
Reticulocytes /%/
4.8±0.6x106
14±2
42±5
1±0,5
5.4±0.8x106
16±2
47±5
1±0,5
Mean
corpuscular
corpuscular corpuscular
volume
/MCV; m3/
82-92
27-32
hemoglobin /MCH; pg/
hemoglobin
concentration /MCHC; % /
32-36

4. MORPHOLOGIC CLASSIFICATION OF ANEMIA
Type
MCV
MCHC
Common cause
Macrocytic anemia
increased
Normal
Vit B12 deficiency
Folic acid deficiency
Posthemorrhagic
Microcytic anemia
- hypochromic
Decreased
Decreased
Iron deficiency
Thalassemia
Spherocytosis
- normochromic
Decreased
or normal
Normal
Normocytic anemia
- normochromic
Normal
Normal
Aplastic anemia
Chronic renal failure
~Hemolytic anemia

5. ETIOLOGIC CLASSIFICATIONOF
ANEMIAS 1. 2.
Post-hemorrhagic
Impaired red cell production
(deficiency anemia, hypo- Increased rate of destruction
and
aplastic) 3.
(hemolytic
anemias)

6. POST-HAEMORRHAGIC ANEMIA I. Acute 2. Infants and older children:
A. Accidents
B. Coagulation disorders
C. Nose bleedings (epistaxis) D. Digestive tract haemorrhage E. Urinary tract
1. Peri-natal period:
A. Traumatic delivery
B. Intra-uterine bleedings
C. Internal bleedings
D. Melaena neonatorum
E. Coagulopathies
II. Chronic

7. TREATMENT OF POST-HEMORRHAGIC ANEMIA
Fluids
Red Packed Blood Cells (10 ml/kg bw)

8. ETIOLOGIC CLASSIFICATION OF ANEMIAS
AD 2. Impaired red cell production A.
Disturbance of proliferation and maturation of
erythrocytes: 1.
Defective Hb synthesis:
a) Deficient heme synthesis (iron deficiency)
Defective DNA synthesis (megaloblastic anemia)
Unknown or multiple mechanisms (anemia of inflammation) 2. 3. B.
Disturbance of proliferation and differentiation of
stem cells (aplastic anemia, pure red cell aplasia)

9. ANEMIA OF INFLAMMATION:
EXPLANATIONS (2015):
(1)
During infection, iron is moved to tissue compartments
– natural cytostatic mechanism against bacterias which
(particularly G- bacteria)
require iron
(2)
Infection causes release of IL-6
IL-6 upregulates HEPCIDIN
HEPCIDIN decreases IRON concentration

10. ETIOLOGY OF DEFICIENCY
ANEMIA I.
Iron deficiency
IA. Sideroblastic anemia Folic acid deficiency Vitamin B12 deficiency
II.
III.
IV. V.
VI.
Vitamin B2, B6, PP, C deficiency
Cu, Co, Mg, Zn deficiency
Protein and aminoacids deficiency

11. ETIOLOGY OF IRON DEFICIENCY ANEMIA
I. Inadequate iron uptake:
A. Inadequate iron supply in newborns 1. 2. 3.
Prematures, multiple pregnancy
Anemia during pregnancy
Uterine bleeding
B. Inadequate iron dietary
C. Iron malabsorption
intake
II. Iron loss:
1. Blood loss
2. Parasites
III. Increase in physiological requirement
1. Premature infants / infancy
2. Adolescence
for
iron:

12. LABORATORY TESTS 1. Peripheral blood count
(HGB, RBC, HTC, MCV, MCHC, MCH, microcytosis, hypochromia, anisocytosis, poikilocytosis).
Iron and FERRITIN blood concentration.
Transferrin (TIBC), serum iron curve 2. 3.
Other lab tests – with respect to clinical situation

13. PROPHYLACTIC IRON SUPPLEMENTATION
Absolute indications: 1. 2. 3. 4. 5.
Prematures
Infants from multiple pregnancy
Low HGB concentration on delivery
Children after delivery with uterine bleeding
Children of mother with anemia in pregnancy
Relative indications: 1. 2. 3. 4.
Frequent respiratory and alimantary tract infections
Growth spurt (infants, adolescents)
Dietary problems (meat, fruits, vegetables) Children with recurrent bleedings

14. PRINCIPLES OF TREATMENT IN IRON DEFICIENCY
* Determine the cause of iron deficiency and treat the underlying disease!
* ORAL replacement therapy.
* Dosage:
4.5-6 mg Fe / kg bw / day
50 mg in infants,
200 mg in older children
t.i.d.
- maximum daily dosage:
* Prophylactic dosage:
1-2 mg Fe / kg bw / day
* Better absorption when administered with ascorbic acid.
* Adequate diet (infants!).

15. IRON THERAPY (EXAMPLES)
Hemofer (drops)
44 mg Fe in 1 ml
i.e. In 30 drops
Hemofer prolongatum 105 mg Fe in 1 tablet

16. DAILY IRON REQUIREMENT
AGE
DAILY REQUIREMENT
6 – 12 m
7.8 – 12 mg
1 – 3 y
5.8 – 9 mg
4 – 8 y
6.1 – 10 mg
9 – 13 y
8 – 15 mg

17. PRINCIPLES OF TREATMENT IN IRON DEFICIENCY
* Symptoms of improvement:
- increase in reticulocyte over 2% after 10 days
- increase in HGB concentration: g/L after 10 days •
Length of therapy:
After HGB reaches g/l continue therapy for 4-6 weeks, in prematures up to 3 months
* Adverse effects:
- gastrointestinal irritation
- teeth (dental enamel)

18. Indications for parenteral iron therapy (i.m.):
PRINCIPLES OF TREATMENT IN IRON
DEFICIENCY:
Indications for parenteral iron therapy (i.m.):
- side effects of oral therapy
- inflammatory bowel disease, peptic ulcer
- malabsorption, alimentary tract diseases
- severe iron defficiency

19. PRINCIPLES OF TREATMENT IN IRON DEFICIENCY:
Intravenous
iron
therapy in children (2015):
PAST:
No iv iron therapy in children (risk of anaphylactic shock!)
PRESENT:
Clinical studies with iv Ferric carboxymaltose in children
(Ferrinject, Injectafer)
FUTURE:
Probably iv iron theapy in children will be routine practice

20. PRINCIPLES OF TREATMENT IN IRON DEFICIENCY:
Red Packed Blood Cells transfusion in iron deficiency anemia: -
HGB below g/l
cerebral symptoms coexisting severe infection before surgical procedure

21. SIDEROBLASTIC ANEMIA
Microcytic and hypochromic anemia related to inefficacy of heme
synthesis (= inefficacy to synthetise iron in hemoglobin)
Etiology:
1. congenital - genetic disorders (enzyme defficiences, porphyria)
2. acquired
- spontaneous or secondary
(lead intoxication, chronic renal disease)
Therapy:
congenital
acquired
- pyridoxine (vit. B6)
- chelating agents, vit. B6

22. HYPO- and APLASTIC ANEMIA (SAA, BMF)
1. Hypoplastic anemia
A. congenital: Blackfan-Diamond
anemia
B. acquired (e.g. PRCA)
2. Aplastic anemia
A. congenital: Fanconi anemia
B. acquired (primary, secondary)

23. CAUSES OF APLASTIC ANEMIA (1)
I. Primary (idiopathic? probably autoaggressive reaction of T-cells against BM
stroma)
II. Secondary – drugs / therapy 1.
Ionizing radiation 2.
Antineoplastic drugs: folic acid antagonists, alkylating agents,
anthracyclines, nitrosoureas, purine and pyrimidine analogous 3.
Unpredictable (idiosyncratic reaction) -
antiepileptic drugs (hydantoins)
oral antidiabetic agents (tolbutamide, chlorpropamide)
tranquillizers (chlorpromazine, chlordiazepoxide)
antirheumatic drugs (indomethacin, gold salts, phenylobutazone)
antibacterial agents (sulfonamides, isoniazid, steptomycin, tetracyclines, chloramphenicol) 4.
Unpredictable hypersensitivity (immune reaction): many drugs

24. CAUSES OF APLASTIC ANEMIA (2) III. Associated diseases 1. 2. 3. 4. 5.
Familiar hypoplastic anemia (Fanconi)
Infective hepatitis
CMV infections
EBV
With
infections
paroxysmal nocturnal hemoglobinuria
IV. Industrial
and household chemicals:
benzene, some organic solvents, trinitrotoluene,
certain insecticides

25. CLASSIFICATION OF APLASTIC ANEMIA1.
Severe aplastic anemia is defined if at last two of the following criteria
are present: -
absolute granulocyte count less than 0.5 x 109/L
platelet count less than 20 x 109/L
reticulocyte count less than 1%
BM hypoplastic and depleted of hematopoietic cells (less than 20%) 2.
Very severe aplastic anemia
- criteria as above but granulocyte count less than 0.2 x 109/L 3.
Non-severe aplastic anemia

26. APLASTIC ANEMIA: CRITERIA FOR DIAGNOSIS1. 2.
Cytopenia (Hb<6.6 mmol/l; ANC<1,5 G/L;
Bone marrow histology and cytology
PLT<100 G/L) -
loss of hematopoietic parenchyma,
increased fat cells component,
no extensive fibrosis,
no malignancy or storage disease 3. 4. 5. 6. No
No No No
preceding treatment with X-ray or antyproliferative drugs
lymphadenopathy or hepatosplenomegaly deficiencies or metabolic diseases evidence of extramedullary hematopoiesis

27. SYMPTOMS AND SIGNS OF APLASTIC ANEMIA 1. Clinical symptoms: - due
due due to
to to
decrease
decrease decrease of
of of
RBC
WBC PLT 2.
Laboratory findings:
- anemia, neutropenia, thrombocytopenia
- bone marrow: hypoplastic with fatty changes

28. CAUSES OF PANCYTOPENIA1. 2. 3. 4. 5. 6. 7. 8.
Aplastic anemia
Myelodysplastic syndromes
Multiple myeloma
Acute leukemias
Hipersplenism
Megaloblastic anemias
Paroxysmal nocturnal hemoglobinuria
Myelosuppression after irradiation or antiproliferative drugs

29. MANAGEMENT OF SEVERE APLASTIC ANEMIA1. 2.
Hematopoietic stem cell transplantation (HSCT)
Immunosuppressive treatment -
cyclosporine
antilymphocyte/antityhymocyte methyloprednisolone
globulin, 3. 4. 5.
Growth factors: G-CSF, EPO
Supportive therapy
Androgens

30. HSCT in SAA 1. Advantages - correction of hematopoietic defect,
long-term survival of the patients >80%,
majority of the patients appear to be cured. 2.
Restrictions -
young age
suitable donor available
risk of GVHD (graft-versus-host disease).

31. THERAPY OF NON-SEVERE APLASTIC ANEMIA1. 2.
„Watch and wait”
Supportive care: red blood cells, platelet concentrates,
antibiotics.
Immunosuppressive treatment in selected patients. Androgens 3. 4.

32. HEMOLYTIC ANEMIA Common feature: decrease in survival of red cells.
Classification:
A. Intracellular defects
B. Extracellular defects:

33. ETIOLOGIC CLASSIFICATION OF ANEMIAS
AD 3. Increased rate of destruction (hemolytic anemias) A.
Intrinsic abnormalities
Hereditary 1.
Red cell membrane disorder (hereditary spherocytosis,
hereditary eliptocytosis)
Red cell enzyne deficiencies
a) Glycolytic enzymes: pyruvate kinase, hexokinase
b) Other enzymes: G6PDH
Disorders of globin synthesis
a) Deficient globin synthesis (thalassemia)
b) Structurally abnormal globin synthesis
(sickle cell anemia, unstable hemoglobins) 2. 3.
Acquired
1. Membrane defect: paroxysmal nocturnal hemoglobinuria

34. ETIOLOGIC CLASSIFICATION OF ANEMIAS
AD 3. Increased rate of destruction (hemolytic anemias) B.
Extrinsic abnormalities 1.
Antibody mediated
a) Autoantibodies (idiopathic, drug-associated, SLE, malignancies)
b) Isohemagglutinins (transfusion reactions, erythroblastosis fetalis)
Mechanical trauma of RBC
a) Microangiopathic hemolytic anemias (TTP, DIC)
b) Cardiac traumatic hemolytic anemia
Chemicals and microorganisms
Sequestration in mononuclear phagocytic system - hypersplenism 2. 3. 4.

35. CONGENITAL SPHEROCYTOSIS
Pathology: erythrocyte membrane
defect
(spectrin or
ankyrin
defficiency).
Clinical and laboratory symptoms: 1. 2. 3. 4. 5. 6. 7. 8. 9.
Familiar history
Hyperbilirubinemia
Splenomegaly
High reticulocyte count
Microspherocytes in blood smear
Osmotic Fragility Test – abnormal
EMA assay
results
Hemolytic crisis, aplastic crisis and megaloblastic crisis
Direct antiglobulin test (Coombs) negative

36. TREATMENT IN CONGENITAL SPHEROCYTOSIS1. 2.
RPBC, fluids, glucose, witamins, folinic acid
Splenectomy = treatment of choice -
- After
usually not below age of 5-7 years
vaccination
still limited efficacy
splenectomy: prophylactic antibiotics, no TBC vaccination! 3.