Anaemia

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Anaemia

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• Anaemia from greek meaning lack of blood
• Anaemia less than the normal quantity of
  hemoglobin in the blood
• Anaemic syndrome clinical syndrome caused by
  tissue hypoxia

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NORMAL VALUES OF RED BLOOD CELLS
men
women Haemoglobin (Hb) 136
176 120 - 168 g/l Haematocrite
(HTK) 0,38 0,49 0,35 0,46 No of
erythrocytes (RBC) 4,2 5,8 3,8
5,2 x1012/l Volume of erythrocyte (MCV) 80
95 fl Mass of Hb in erythrocyte 26 32
pg (MCH) Hb concentration in
erythrocyte 0,32 0,37
(MCHC)
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NORMAL VALUES OF RED BLOOD CELLS

men
women Haemoglobin (Hb) 136
176 120 - 168 g/l Haematocrite
(HTK) 0,38 0,49 0,35 0,46 No of
erythrocytes (RBC) 4,2 5,8 3,8 5,2
x1012/l Volume of erythrocyte (MCV) 80 95
fl Mass of Hb in erythrocyte 26 32
pg (MCH) Concentration of Hb in
erythrocyte 0,32 0,37
(MCHC)
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Anaemic syndrome - symptomsrom (AS)

• Tissue hypoxia pallor, fatigue, weakness,
  dyspnea
• Compensation and adaptation
• Hypercinetic circulation, palpitations, tinnitus
• Secondary
• Cardiovascular symptoms decompensation of
  ischemic heart disease, AP, IM, claudications

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Anemický syndrom (AS)

• Progress and severity of AS depends on
• 1. Absolute value of Hb
• Hgb 70-80 g/l most of patients suffer from
  symptoms
• 2. Speed of onset
• 3. Age and overall performance of the patient

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• IRON PROTOPORFYRIN
• HAEM GLOBIN
• 
  
• HAEMOGLOBIN

DNA B12 ,folic acid, EPO
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ANAEMIA - CLASSIFICATION

• Morfologic criteria
• According to MCV (80 95 fl)
• microcytic, normocytic, macrocytic
• According to MCH (27-32 pg)
• normochrome, hypochrome
• According to no of reticulocytes (0,7 2,8 )
• anaemia with lowered, normal or incresed no
  of reticulocytes

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• MICROCYTIC ANAEMIA
• Iron deficiency anaemia
• Chronic disease anaemia
• Thalasemia, sideroblastic anaemia
• MACROCYTIC ANAEMIA
• Megaloblaste anaemia(lack of B12, folic acid,
  MDS)
• Macrocytic non-megaloblaste anaemia (usually
  secondary)
• NORMOCYTIC ANAEMIA
• Primar impairment of blood marrow aplastic
  anaemia, MDS, PNH,
• myelofibrosis.
• Secondary impairment of blood marrow
  (infiltration, infection,
• endocrinological and systemic diseases,
  ACD)
• D. ANAEMIA WITH RETICULOSIS
• Haemolytic aneamia corpuscular
• Haemolytic anaemia extracorpuscular
• imunne and non-immune based

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Pathofysiological classification

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EPO
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EPO
TSH
Fe, Fol, B12
C, E
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Pathofysiological classification

• Proliferation and differentiation disorder
• Increased destruction of RBC
• Blood loss
• Combined etiology

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• IRON
  PROTOPORFYRIN
• Iron insufficiency
  sideroblastic anaemia
• ACD
• HEM GLOBIN
• 
  thalasemia
• HEMOGLOBIN

DNA B12, folic acid, EPO
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Iron defficiency

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Iron defficiency

• Most frequent cause of anemia
• (500 000 000 worldwide WHO)
• 80of all anaemia
• SA 10 of fertile women
• Sideropenia 35-58 of fertile women

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Iron defficiency CAVE influencing not just the
blod count!

• DNA synthesis impairement
• Tissue fosforylation impairement
• Purine metabolism impairement
• Colagen synthesis impairement
• Granulocyte function impairement
• Neurotransmiter function impairement

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Iron distribution in the organism

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Iron metabolism

• Food contents 15-20mg/den
• Absorption 1-2mg (duodenum, upper part of
  jejunum)
• Loss (epitel desqvamation) 1-2mg
• Pregnancy overall loss 500-1000mg
• Supply in the organism 3000-5000mg

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Hepcidine

• Acute phase reactant
• Source hepatic cells, heart,
• Iron stimulates Hepcidine
• Hepcidine inhibits iron absorption in the
  intestine, iron release from macrophages and iron
  transport via placenta
• ACD, hereditary hemochromatosis

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Iron defficiency

• Insufficient intake - malnutrition
• Absorption impairement
• maldigestion, malabsorption
• Increased loss
• Lowered intake

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Insufficient intake

• Malnutrition
• Imbalanced diet
• Vegetarians
• - Meat 25-30 of iron is absorbed
• - Vegetables 5 of iron is absorbed

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Iron absorption from various foods ()
Rice Spinach Beans Corn Lettuce Wheat Soya Ferriti
n Veal liver Fish meat Haemoglobin Veal meat

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Iron absorption from
various foods ()
Rice Spinach Beans Corn Lettuce Wheat Soya
beans Ferritin Veal liver Fish meat Haemoglobin Ve
al meat

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Absorption disorder

• Resection of stomach 65 patients
• Achlorhydria
• Coeliakia
• M. Crohn
• Infection H. Pylori with gastritis

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Loss

• GIT (h. hernia, gastritis, ulcerous disease,
  tumours, intestinal inflammmatory diseases,
  hemorhoids, parasites, diverticulitis)
• Respiratory tractus
• Urogenital tract
• Menses cca 3mg Fe / den
• NSAIDs, hemodialysis, blood testing, self -
  harming

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Increased need

• Gravidity
• Brest-feeding
• Growth

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Symptoms

• Anemic syndrome
• Cefalea, paresthesia, fatigue
• Tongue burning, angulitis
• Odyno-, dysfagia
• Sy Kelly-Patterson
• Brittle hair, nails
• (Pica, pagofagia)

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Physical examination

• Pallor skin, mucous membrane
• Blue sclerae
• Ulcers/ angulitis
• Smooth tongue
• Straight/(spoon-shaped) nails
• Achlorhydria, atrophic gastritis

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Laboratory findings

• RDW high
• Trombocytosis (over 50 of patients)
• BM staining for iron
• - lack of Fe in siderophages
• - sideroblasts lower then 10

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Laboratory findings

• MCV under 80fl
• MCH under 25ug
• MCHC late symptom
• Transferrin -increased
• S-ferritin lt20ug/l
• Transferrin satur. under15 (N 20-40)
• VKFe (TIBC) increased
• S-sTfR gt 8g/l

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DIFFERENTIAL DIAGNOSIS OF IRON INSUFFICIENCY
(mikrocytic anaemia)

Fe TIBC satTRF ferritin TRF

receptor
_______________________________________________ 
Iron insuf. ? ? ?
? ?     Chronic disease
associated anaemia ? ?
N N N
(ACD)     Thalasemia N or ? N or ? N
or ? N or ? ?    
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CAVE

• Ferritine
• Acute phase reactant
• Nespecific tumorous marker
• Level increases with age
• (75ug/l in old people ? iron defficiency)

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Iron defficiency

• Prelatent
• Latent
• Manifest - SA

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Typical patient with IDA

• Woman 20-45y, fatigue, sleepiness, ear buzzing,
  hairloss, brittle nails, hyper- polymenorhea or
  normal menses.
• 2. Man 50y or older, dysfagia, weightloss,
  treated with ASA for ICD, blood in stools or
  urine.

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Treatment of IDA

• Treatment of the cause of iron loss
• iron supply

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Ferrotherapy

• 150-200mg Fe / day
• Until enough supply is formed (ferritin 50ug/l)
• Use on an empty stomach
• CAVE polyphenols, milk, egg yolk
• Dyspepsia
• Parenteral forms (CAVE anaphylaxis x new forms
  are safer - karboxymaltose)

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Ferinject (Vifor, Francie)
inj. Fe3 karboxymaltóza
100mg, 500mg
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P.o. iron treatment control

• Reticulocyte crisis D 10-14
• Increase of haemoglobin
• Normalisation of MCV a RDW
• Iron supply forming
• Ineffective treatment
• Diagnosis checking BM examination, GIT
  examination aso. Cave self-harming
• Switch to i.v. therapy

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Thalassemia

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• IRON PROTOPORFYRIN
• Fe insufficiency
  sideroblastic anemia
• ACD
• HEM GLOBIN
• 
  
  thalasemia
• HEMOGLOBIN

DNA B12 , folic acid
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Thalassemia

• thalasemia, 0thalasemia
• Fetus - Hb F a2 ?2
• Adult - Hgb A a2 ß2
• - Hgb A2 a2 d2
• - Hgb F a2 ?2

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Thalassemia

• a thalasemia a disorder
• ß thalasemia ß disorder

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a - Thalassemia

• (Normal genotype a a / a a)
• - a/ a a silent carrier
• - a/- a , - - / a a carrier (mikrocytosis,
  erythrocytosis)
• 
  Thalassemia minor
• - - / - a HbH (ß4) (splenomegalia,
  mikrocytosis, bones)
• - - / - - hydrops fetalis, sy Hb Barts (?4)

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ß - Thalassemia

• More severe then athalassemia
• ß thalasemia minor (ß/ ß, ß0/ ß)
• Mikrocytosis, anaemia, erythrocytosis
• ß thalasemia intermedia (ß/ ß, ß0/ ß)
• ß thalasemia major (ß0/ ß0, ß/ ß)
• Severe anemia, anisopoikilocytosis, affected
  ERY, HbF, hepatosplenomegalia,bone
  deformities,permanent transfusion therapy, Fe
  overload, Tx, splenectomia, HU

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BETA THALASEMIA

• Pathogenesis
• ? chains formation impairement ? increased
  synthesis of ? and ?
• Alpha chains overdose low solubility,
  precipitation, agregates deform cell membranes
• Hb easy autooxidation, lower stability ?
  release of
• Fe ? cell destruction by peroxidative
  lipid cleavage.
• Inefective erythropoiesis, large numbers of
  erytrocytes decline as soon as the BM
  peripheral hemolysis shortened lifespan
• Significant compensatory erythropoiesis
  hyperplasia?
• corticalis usuration?bone deformities,
  fractures, extramedular
• hemopoiesis
• Relative Fe defficiency in BM because of
  hyperplastic
• erythropoiesis, at the same time increased
  Fe supply (coming from destroyed ery in monocyte-
  macrophage system) ? increased Fe resorption in
  the intestine? Fe overload of the organism
  (together with Fe coming from transfusions).

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MEGALOBLASTIC ANAEMIA

• Lack of B12of folic acid
• 1. Pernicious anaemia - B12 absorption in the
  distal intestine disorder due to lack of
  intrinsic factor (produced by parietal cells of
  gastric mucosa)
• 2. Dihydrofolat reductase inhibitors (MTX,
  ARA-C)

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MEGALOBLASTIC ANAEMIA -CAUSES

• Insufficient intake of B12 of folic
• Absorption impairement
• a) lack of intrinsic factor, intrinsic
  factor
• b) celiakia, Crohn disease, intestinal
  resection, diverticules, strictures,parasites
• c) resorption inhibitors (fenylhydantoin,PAS
  ,pyrimidin, neomycin)
• d) selective malabsorption B12 with
  proteinuria
• Transport disorders because of lack of
  transkobalamin I. and II.
• Increased demand (gravidity, growth, anaemia with
  hyperplasia of erythropoiesis
• Increased loss (hepatic laesions, bleeding)
• dihydrofolat reductase inhibitors
  (MTX,pyrimethamin)
• pyrimidin antagonists (ARA-C) / purin
  antagonists (6-MP)

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Megaloblastic anaemia

• Blood count macrocytes (?MCV, ?MCH,normal
• MCHC), ?RTC, megalocytes, megaloblasts,
• leukocytosis with left shift,
  thrombocytopenia.
• Bone marrow hyperplasia of erytropoiesis,
  megaloblasts,
• granulocyte macrocytosis, mgkc. polyploidia
• dif.dg. MDS (cytogenetics, cytochemistry)
• biochemistry ? B12, ?folic acid, ?direct and
  indirect
• bilirubin, intrinsic factor antibodies,
  antibodies against parietal cells, normal iron
  supplies

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Proteins binding VITAMIN B12 Intrinsic
factor B12 absorption in ileum, binding to
specific receptor (cubilin) Secerned by parietal
gastric cells In case of lack leads to B12
malabsorption TRANSCOBALAMIN I Binds B12 in
plasma,binds to B12 in stomach before binding to
intrinsic factor, produced by neutrofiles and
cells with exocrine secretion, his lack leads to
low serum B12 levels TRANSCOBALAMIN II Enables
B12 absorption by cells, receptor on all type of
cells, produced by endotelial cells, fibroblasts,
ileum cells.., his lack leads to severe B12
deficiency in cells
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Pernicious anaemia
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Megaloblastic anaemiaDiferential dg.

• atrofic gastritis / sprue/ inflamations,
  parasites/ medication/ liver laesions
• DNA synthesis impairement due to abnormal cell
  clone MDS
• (bone marrow biopsy,
• cytogenetics, cytochemistry, B12)

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Treatment

• Substitution - vitamin B12 300 1000 µg/d
• - maintainance dose
• 1 x za 6 8weeks
  all life long
• reticulocyte crisis 5.-7.d of
  treatment
• rise of reticulocyte count up to
  10-30.
• need of iron metabolism parameters,
  regular GSK and colonoscopy

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• Autoimmune disease
• Smooth tongue surface, vitiligo, grey hair
• Not just anaemia, but pancytopenia
• Parenteral substitution of B12
• Reticulocyte crisis
• GSK á 1-2years

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Anaemia with increased no of reticulocytes

• HEMOLYTIC ANAEMIA
• - corpuscular
• - estracorspuscular
• bleeding - acute

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CORPUSCULAR HEMOLYTIC ANAEMIA

• MEMBRANE DEFECTS
• ENZYMOPATIA
• HEMOGLOBINOPATIA

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NON-IMMUNE ACQUIRED HEMOLYTIC ANAEMIA

• MECHANICAL AND PHYSICAL CAUSES
• heart valve impairement
• hemoglobinuria
• microangiopatic hemolytic anemia
• widespread burns
• METABOLIC CAUSES
• liver disease, alcoholism
• hypofosfatemia
• hereditary abetalipoproteinemia
• malnutrition
• Cu overload
• Wilsons disease
• CHEMICAL SUBSTANCES
• oxidative agents, snake venon
• INFECTIONS

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Corpuscular Haemolytic anaemias

• Pathogenesis
• Lack of and defects in membrane proteins
  (ankyrin, spectrin, etc.)
• ?
• Decreasesd size of ery surface spherocyte
• increased cell membrane permeability ( Na )
  
• ?
• Increased need for eneregy -
• - (Na pump) increased rigidity and loss of
  flexibility
• ?
• passge through spleen sinusoid more
  difficult ?
• loss of membrane parts
  microspherocyte
• cell deth in the spleen
  ?
• EXTRAVASCULAR HAEMOLYSIS

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Hereditary spherocytosis

• Autosomal dominant ( rarely recesiive) disease
  with variable gene expressivity ? variable
  clinical symptoms (phenotype)
• ( anemia with icterus, splenomegaly,
  hemolytic crisis ).
• Diagnostics
• Anemia s reticulocytosis spherocytes in blood
  smear, Hyperpluasti erythropoiesis in bone
  marrow, increased level of both direct and
  indirect bilirubin, serum Fe a feritin not
  increased
• Osmotic resistance of erythrocytes decreased
• Autohemolýza ( upravuje se po podání glukózy i
  ATP ) increased
• PINK test
• Dif dg. other corpuscular anemias (HE,
  etc.)
• imunne hemolytic anemias
• non-immune
  extracorpuscular hemolytic anemias
• paroxysmal nocturnal
  hemoglobinuria
• sometimes MDS
• Lécba splenectomy

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• ERYTROCYTE ENZYMOPATHY
• Defects in enzymes of anaerobe glykolysis
• pyruvát kinázy defficiency (PKD)
  chronic
• haemolytick anemia, with little
  effect of splnectomia
• Defect in enzymes of pentos cycle
• glucose-6-phosphate dehydrogenase
  defficiency
• increased sensitivity to oxydazing
• agents chronic haemolysis
• or haemolytic crisis
• anemia with Heinz
  bodies

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ANAEROBE GLYKOLYSIS
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GLUCOSE-6-PHOSPHATE DEHYDROGENASE defficiency

• Results in lack of NADPH . Increased
  sensitivity to oxydating agents
• Gene for G6PDH X chromosome , wide
  physiologic variability of the enzyme
• Mutation mostly point mutation in 1 or to
  bases ?
• decreased enzyme production, production
  of the enzyme with decreased
• activity or production of the enzyme with
  decreased afinty to the substrate or
• with decreased stability
• Wide variability in clinical symptoms
• Silent carrier severe
  haemolytic crisis, neonatal icterus
• Diagnostics
• G-6-PD activity analysis
• Activity to substrate analysis, mobility in ELFO,
  stability
• Molecular genetics
• Other GSH stability test, Heinz body formation
  test
• Th

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HEMOGLOBINOPATHIES

• Abnormal Hb with mostly one aminoacid (AA)
  substitution in the globion chaine
• a/ sicle cell anemia HbS
• b/ Hb C, Hb D, Hb E chronic haemolytic
  anemias often in combination with Hb S or ? thal
• c/ instable haemoglobin diseases
• hydrofobe AA ? decreased binding
  activity of Hb or impaired secondary structure of
  Hb
• and contacts between subunits
• chronic hemolytic anemia with Heinz
  bodies( denaturation of nestable Hb )
• d/ methemglobinemia
• Fe3 stabilisation due to histidine
  tyrosine in proximity of hem group
  results in cynosis
• e/ hemoglobine with increased oxygen
  affinity
• tissue hypoxia, cyanosis,
  polycythaemia in blood count.

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SICLE CELL ANEMIA

• Substitution glutamate valin on 6.
  position ?
• chain Hb polymerisation, deformation of
  erythrocyte, tvaru sickle cell.
• hemolýza extravscular intravascular (small
  vessel obstruction)
• Autosomal dominant type
• homozygotic form both ? chains impaired
• 
  
• heterozygotic form one ? chain impaired
• 25-50 HbS
  sickle cell trait

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SRPKOVITÁ ANÉMIE

• Clinicaly
• Hemolytic aplastic crisis, splenomegaly,
  
• Diagnostics
• krevní obraz anemie s retikulocytozou a
• srpkovitými
  ery
• elfo hemoglobinu prítomnost Hb S
• identifikace Hb S peptickým štepením
  globinu
• molekul.genetika analýza DNA -
  v prenatální péci
• Treatment
• Crisis prevention, transfusions, SCT

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NEIMUNNÍ ZÍSKANÉ HEMOLYTICKÉ ANÉMIE

• MECHANICKÉ A FYZIKÁLNÍ PRÍCINY
• vadná srdecní chlopen
• pochodová hemoglobinurie
• mikroangiopatické hemolytické anémie
• rozsáhlé popáleniny
• METABOLICKÉ PRÍCINY
• jaterní choroby, alkoholismus
• hypofosfatémie
• hereditární abetalipoproteinemie
• podvýživa
• nadbytek medi, Wilsonova choroba
• CHEMICKÉ LÁTKY
• oxidacní cinidla, hadí jedy
• INFEKCE
• prímá infekce erytrocytu malárie aj.

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MIKROANGIOPATICKÁ HEMOLYTICKÁ ANÉMIE

• prícina rozrušení integrity membrány
  erytrocytu mechanickou prícinou v prusvitu cévy,
  nejcasteji depozity fibrinu v míste poškození
  endotelu cévní steny.
• Vaskulitidy, akutní glomerulonefritis, po
  SCT, nádory, operace chlopní, AV malformace, léky
  ticlopidin, infekce Shigatoxin.
• fragmentace krvinek schistocyty zvýšený zánik
  ve slezine, pri masivní hemolýze
  intravaskulární hemolýza pri soucasné aktivaci
  kaogulacního systému DIC s tvorbou mikrotrombu
  v cirkulaci.
• klinický obraz dán kombinací hemolytické
  anémie, trombocytopénie a prítomnosti mikrotrombu
  (CNS, ledviny )
• HUS, TTP, HELLP v gravidite hemolýza,
  poruchy jaterních funkcí, trombocytopenie, DIC.

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Patofyziologie HUS a diagnostika
toxin
aktivace endotelu
aktivace monocytu
zánik endotelií
sekrece cytokinu sekrece
vWF exprese adhezivních molekul
sekrece cytokinu
deskvamace endotelií
aktivace trombocytu
adheze a invaze neutrofilu
adheze trombocytu
trombocytopenie okluze glomerulu MAHA renální
selhání
aktivace neutrofilu
poškození endotelií
elastázy, proteázy, H2O2
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MIKROANGIOPATICKÁ HEMOLYTICKÁ ANÉMIE

• Laboratorní nález
• anémie s retikulocytózou, schistocyty,
  akantocyty, sférocyty,
• trombocytopenie se známkami DIC, nález
  multimeru pri elfo vWF pri TTP, molekulárne
  genetické vyšetrení.
• Zvýšen prímý i neprímý bilirubin v séru,
  zvýšení LDH,
• proteinurie, Hburie, zvýšen volný Hb,
  kreatinin, urea.
• Lécba
• lécba vyvolávající príciny, u TTP/HUS
  plasmaferéza se substitucí cerstvou zmrazenou
  plasmou, kortikoidy, antikoagulancia, transfuze
  erytrocytu.

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AUTOIMMUNE HEMOLYTIC ANAEMIA Clasification

• HEAT antibodies
• - idiopatic
• - secondary (lymfoproliferation, other
  type of tumours, autoimmune
• diseases, viral infections,
  immunodefficiency)
• -drug induced HA
• COLD antibodies
• - idiopatic
• - secondary (lymfoproliferation, viral
  inf., mykoplasma, autoimmune diseases
• - paroxysmal cold haemoglobinuria (lues
  )
• MIXED HEAT AND COLD antibodies

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Pathogenesis of AIHA

• Cooperation disorder among supresor T helper T
  lymphocytes and B lymphocytes responsible for
  immunity control
• Dysregulation of this system leads to
  insufficient supression of antibody formation
  against own antigens

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IgG monomér, Fc cást vazebné místo pro C1q
složku komplementu a Fc? receptor makrofágu.
IgM pentamér, Fc cást vazebné místo pro C1q
složku komplementu a Fc? receptor makrofágu.
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HEAT ANTIBODIES

• IgG character optimal at 370C
• Catch up of erythrocytes with binded antibody by
  spleen macrophages
• EXTRAVASCULAR HEMOLYSIS
• Activation of complement by high antibody titre
• INTRAVACULAR HEMOLYSIS

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COLD ANTIBODIES

• IgM character optimál at 40C
• Bound to erytrocytes in colder acral parts,
  possibility of complement activation, ery
  aglutination
• INTRAVASCULAR HEMOLYSIS
• EXTRAVASCULAR HEMOLYSIS

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Secondary AIHA with heat antibodies

• AUTOIMMUNE DISEASES
• systemic lupus erytematodes, revmatoid
  arthritis,
• sclerodermia, ulcerose colitis, syndrome of
  antiphospholipid antibodies
• HEMATOLOGIC TUMOURS
• chronic lymphadenosis,malign lymphomas, rarely
  acute
• leucaemia
• OTHER TUMOURS
• carcinoma, thymoma, Kaposi sarkoma, teratoma
• INFECTIONS
• EBV, HIV-1,2, HCV, vaccination
  (difteria-pertusis-tetanus)
• IMUNODEFICIENCY
• congenital and acquired hypogamaglobulinemia and
• dysgamaglobulinemia

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DRUG-INDUCED HEMOLYTIC ANAEMIA

• hapten type
• imunocomplex type
• De-novo antigen formation

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AIHA laboratory parameters

• Blood count
• makrocytic anaemia with reticulocytosis
• Biochemistry
• ? direct and indirect bilirubin,
• ? urobilinogen in urine
• Special tests
• Direct and indirect antiglobuline test (Coombs
• test)
• INTRAVASCULAR HEMOLYSIS PROOF
• ? free Hb in plasma,
• ? levels of haptoglobin and hemopexin in
  serum,
• hemoglobinuria

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DIRECT COOMBS TEST
We add anti IgG
Erytrocytes with bound Ab

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INDIRECT COOMBS TEST
Sérum with free antibodies
we add erythrocytes of particular blood group
we add anti IgG or anti C3b
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AIHA diferential diagnosis

• CORPUSCULAR HEMOLYTIC ANAEMIA
• negative Coombs test, positive special
  tests (autohemolysis, erytrocyte enzyme tests,
  elfo Hb, shortened lifespan of autologous, not
  donor erythrocytes) PAROXYSMÁL NIGHT
  HAEMOGLOBINURIA
• negative Coombs test, pancytopenia, CD59
  and CD55 antigen defficiency on erythrocytes,
  CD14 antigen def. on the surface of granulocytes
  and monocytes
• GILBERT DISEASE- negative hemolysis tests
• NON- IMMUNE HEMOLYTIC ANAEMA
• microangiopatic hemolytic anemia
  (schistocytes, kidney and CNS affection), anemia
  from physical and chemical causes
• MYELODYSPLASTIC SYNDROME - hemolytic form
• morfological dysplastic
  changes,chromosomal aberances,cytochemical
  changes, clonality.

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AIHA - treatment

• Light form ( Hb gt 80 g/l )
• PREDNISONE 1 mg/kg/d 2-3 weeks
• - in case of good effect decreasing dose
  every 2-3 days by 10mg until 20 mg/day.
• - slow reduction of dose (by 5mg in 7-10
  days) until 5-10mg every second day.
• - end of corticooid therapy when
  repeated direct Coombs test negativity
• When therapy is ineffective or relaps occurs
  combination with
• CYCLOPHOSPHAMIDE 100-150 mg/d or
• CYCLOSPORINE A 3 mg/kg/d.

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AIHA - treatment

• SEVERE form ( Hb lt 80 g/l )
• PREDNISONE 1-2 g i.v. daily 5 days, after
  that in case of good response fast decrese of
  dose to 1 mg/kg.
• - combination of corticoids with
• CYCLOPHOSPHAMIDE 200 mg i.v./d
• i.v. IMMUNOGLOBULINS 0,5g /kg/d
• PLASMAPHERESIS
• RITUXIMAB (anti CD20 monoclonal Ab)
• Transfusion together with corticoids ,
  monitored hospitalised patient, not more then 1
  TU/day (unless vital indication)

98

• Thank you