Transcript Document

Anaemia
• 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
NORMAL VALUES OF RED BLOOD CELLS
male
female
Hemoglobin
(Hb)
136 – 176
120 - 168 g/l
Hematokrit
(HTK)
0,38 – 0,49
0,35 – 0,46
Erythrocyte count (RBC)
4,2 – 5,8
3,8 – 5,2 x1012/l
Reticulocytes
0,7 – 2,8 %
Mean corpuscular volume
(MCV)
Mean corpuscular hemoglobin (MCH)
(event. 50 -150 x109/l)
80 – 95 fl
26 – 32 pg
Mean corpuscular hemoglobin concentration (MCHC) 0,32 – 0,37
Red cell distribution with (RDW)
11 -15%
NORMAL VALUES OF RED BLOOD CELLS
male
female
Hemoglobin
(Hb)
136 – 176
120 - 168 g/l
Hematokrit
(HTK)
0,38 – 0,49
0,35 – 0,46
Erythrocyte count (RBC)
4,2 – 5,8
3,8 – 5,2 x1012/l
Reticulocytes
0,7 – 2,8 %
(event. 50 -150 x109/l)
Mean corpuscular volume
(MCV)
80 – 95 fl
Mean corpuscular hemoglobin (MCH)
26 – 32 pg
Mean corpuscular hemoglobin concentration (MCHC) 0,32 – 0,37
Red cell distribution with (RDW)
11 -15%
Anaemic syndrome symptoms
rom (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…
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
IRON
PROTOPORFYRIN
HAEM
+
GLOBIN
HAEMOGLOBIN
DNA – B12 ,folic acid, EPO
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
A.
MICROCYTIC ANAEMIA
Iron deficiency anaemia (IDA)
Chronic disease anaemia (ACD)
Thalassemia, congenital sideroblastic anaemia
B.
MACROCYTIC ANAEMIA
Megaloblastic anaemia(lack of B12, folic acid)
Macrocytic non-megaloblastic anaemia (usually secondary:
alcohol abuse, liver disesae, hypothyreosis, pregnancy, chemotherapy.. )
Myelodysplastic syndrome (MDS) – some
Chronic haemolytic anaemia (AIHA)
C. NORMOCYTIC ANAEMIA
Primary impairment of blood marrow: aplastic anaemia, MDS – some, PNH,
myelofibrosis.
Secondary impairment of blood marrow :(infiltration, infection,
endocrinological and systemic diseases, ACD)
Acute bleeding, acute haemolysis
Morphology based dif. diagnosis of
anaemia
MCV
RTC
RDW
Iron deficiency anaemia (IDA)
Megaloblastic anaemia (vit. B12 defficiency)
Thalassemia (heteroz.)
N
Chron. haemolytic anaemia (AIHA)
Anaemia in chronic diseases (ACD)
N,
N
Aplastic anaemia
N,
N
Myelodysplastic syndrome (MDS)
N,
N,
Pathofysiological classification
EPO
EPO
TSH
Fe,
Fol,
B12
C, E
Pathofysiological classification
•
•
•
•
Proliferation and differentiation disorder
Increased destruction of RBC
Blood loss
Combined etiology
IRON
PROTOPORFYRIN
Iron insufficiency
sideroblastic anaemia
ACD
HEM
+
GLOBIN
thalasemia
HEMOGLOBIN
DNA – B12, folic acid, EPO
Iron
deficiency
Iron deficiency
• Most frequent cause of anemia
(500 000 000 worldwide – WHO)
• 80%of all anaemia
• SA: 10% of fertile women
• Sideropenia: 35-58% of fertile women
Iron deficiency
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
Iron distribution in the organism
•
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
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
Iron deficiency
• Insufficient intake - malnutrition
• Absorption impairement
– maldigestion, malabsorption
• Increased loss
• Lowered intake
Insufficient intake
• Malnutrition
• Imbalanced diet
• Vegetarians
- Meat: 25-30% of iron is absorbed
- Vegetables: 5% of iron is absorbed
Iron absorption from various foods (%)
Rice
Spinach
•
Beans
Corn
Lettuce
Wheat
Soya
Ferritin
Veal liver
Fish meat
Haemoglo
bin
Veal meat
Iron absorption from various foods (%)
Rice
Spinach
•
Beans
Corn
Lettuce
Wheat
Soya beans
Ferritin
Veal liver
Fish meat
Haemoglobin
Veal meat
Absorption disorder
•
•
•
•
•
Resection of stomach – 65% patients
Achlorhydria
Coeliakia
M. Crohn
Infection H. Pylori with gastritis
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
Increased need
• Pregnancy
• Brest-feeding
• Growth
Symptoms
•
•
•
•
•
•
•
Anemic syndrome
Cefalea, paresthesia, fatigue
Tongue burning, angulitis
Odyno-, dysfagia
Sy Kelly-Patterson
Brittle hair, nails
(Pica, pagofagia)
Physical examination
•
•
•
•
•
•
Pallor – skin, mucous membrane
Blue sclerae
Ulcers/ angulitis
Smooth tongue
Straight/(spoon-shaped) nails
Achlorhydria, atrophic gastritis
Laboratory findings
• RDW: high
• Trombocytosis (over 50% of patients)
• BM –staining for iron
- lack of Fe in siderophages
- sideroblasts lower then 10%
Laboratory findings
•
•
•
•
•
•
•
•
MCV under 80fl
MCH under 25ug
MCHC – late symptom
Transferrin -increased
S-ferritin <20ug/l
Transferrin satur. – under15 % (N: 20-40%)
VKFe (TIBC): increased
S-sTfR > 8g/l
DIFFERENTIAL DIAGNOSIS OF IRON
INSUFFICIENCY (mikrocytic anaemia)
Fe
TRF
receptor
_______________________________________________
Iron insuf.





Chronic
disease
associated
anaemia
(ACD)
Thalasemia

TIBC
satTRF ferritin

N or  N or 
N
N
N or 
N or 
N

CAVE
Ferritine
• Acute phase reactant
• Nespecific tumorous marker
• Level increases with age
(75ug/l in old people = ? = iron defficiency)
Iron deficiency
• Prelatent
• Latent
• Manifest - SA
Typical patient with IDA
1. Woman 20-45y, fatigue, sleepiness, ear
buzzing, hairloss, brittle nails, hyperpolymenorhea or normal menses.
2. Man 50y or older, dysfagia, weightloss,
treated with ASA for ICD, blood in stools
or urine.
Treatment of IDA
=
Treatment of the cause of iron loss
+ iron supply
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)
PŘÍPRAVKY ŽELEZA
léková
forma
složení
Aktiferrin
(Merckle,SRN)
cps.
síran železnatý
serin
34 mg
Aktiferrin
(Merckle,SRN)
sir.
síran železnatý
serin
6,8 mg/ml
Aktiferrin
(Merckle,SRN)
gtt.
síran železnatý
serin
9,3 mg/ml
Ferrlecit
(Nattermann,SRN)
inj
Ferro-Gradumet
(Galenika,Jugoslávie)
tab
síran železnatý
105 mg
Ferronat
(Galena,ČR)
susp.
fumarát železnatý
10 mg/ml
Ferronat retard
(Léčiva,ČR)
tab
síran železnatý
105 mg
Ferrum lek i.m.
(Lek,Slovinsko)
inj
komplex hydroxidu
železitého se sacharózou
Maltofer
(Vifor,Švýcarsko)
sir.
Maltofer
(Vifor,Švýcarsko)
gtt.
komplex Fe
3+
s polymaltosou
komplex Fe
3+
s polymaltosou
Sorbifer durules
(Egis,Maďarsko)
tab
síran železnatý
kyselina askorbová
100 mg
Tardyferon
(Robapharm,Švýcarsko)
drg
síran železnatý
mukoproteáza
80 mg
Ferinject (Vifor, Francie)
inj.
název
(výrobce)
komplex Fe 3+ s glukonátem
sodným
Fe3+ karboxymaltóza
obsah látky v lékové
formě
62,5 mg
100 mg
10 mg/ml
50 mg/ml
100mg, 500mg
P.o. iron treatment control
- Reticulocyte crisis D 10-14
- Increase of haemoglobin
- Normalisation of MCV a RDW
- Iron supply forming
Ineffective treatment:
1. Diagnosis checking :BM examination, GIT examination aso…. Cave
self-harming
2.Switch to i.v. therapy
Thalassemia
IRON
PROTOPORFYRIN
Fe insufficiency
sideroblastic anemia
ACD
HEM
+
GLOBIN
thalasemia
HEMOGLOBIN
DNA – B12 , folic acid
Thalassemia
• + thalasemia, 0 thalassemia
• Fetus: - Hb F
α2 γ2
• Adult - Hgb A: α2 β2
- Hgb A2: α2 δ2
- Hgb F: α2 γ2
Thalassemia
• α –thalassemia = α disorder
• β – thalassemia = β disorder
α - Thalassemia
(Normal genotype: α α / α α)
• - α/ α α = silent carrier
• - α/- α , - - / α α = carrier (mikrocytosis, erythrocytosis):
= Thalassemia minor
• - - / - α = HbH (β4) (splenomegalia, mikrocytosis, bones)
• - - / - - = hydrops fetalis, sy Hb Bart´s (γ4)
β - Thalassemia
More severe then α–thalassemia
• β – thalassemia minor (β+/ β, β0/ β)
Mikrocytosis, anaemia, erythrocytosis
• β – thalassemia intermedia (β+/ β+, β0/ β+)
• β – thalassemia major (β0/ β0, β+/ β+)
Severe anemia, anisopoikilocytosis, affected ERY, HbF,
hepatosplenomegalia,bone deformities,permanent transfusion
therapy, Fe overload, Tx, splenectomia, HU
BETA THALASsEMIA
•
•
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).
MEGALOBLASTIC ANAEMIA
• Lack of B12of folic acid:
1. Pernicious anaemia - B12 absorption in the distal
ileum disorder due to lack of intrinsic factor (produced
by parietal cells of gastric mucosa)
Homocystein-methyl-reductase (methionine synthase)
2. Dihydrofolat reductase inhibitors (MTX, ARA-C)
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)
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
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
Pernicious anaemia
Megaloblastic anaemia
Diferential dg.:
• atrofic gastritis / sprue/ inflamations,
parasites/ medication/ liver laesions
• DNA synthesis impairement due to
abnormal cell clone– MDS
(bone marrow biopsy,
cytogenetics, cytochemistry, B12)
Treatment
• Substitution - vitamin B12 300 – 1000 μg/d
- maintainance dose
1 x za 6 – 8weeks all life long
reticulocyte crisis : Day 5 - 10 of treatment
rise of reticulocyte count up to 10-30%.
need of iron metabolism parameters, regular
gastroscopy
•
•
•
•
•
•
Autoimmune disease
Smooth tongue surface, vitiligo, grey hair
Not just anaemia, but pancytopenia
Parenteral substitution of B12
Reticulocyte crisis
GSK á 1-2years
HAEMOLYTIC ANAEMIA
- corpuscular: lot of them congenital
- extracorspuscular: majority acquired
CORPUSCULAR HEMOLYTIC
ANAEMIA
MEMBRANE DEFECTS
ENZYMOPATIA
HEMOGLOBINOPATIA
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
Hereditary spherocytosis
•
Autosomal dominant ( rarely recesiive) disease with variable gene
expressivity  variable clinical symptoms (phenotype)
( anemia with ićterus, splenomegaly, hemolytic crisis ).
•
Diagnostics:
•
•
•
•
Anemia + s reticulocytosis + spherocytes in blood smear, Hyperplůasti
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
•
Léčba:
splenectomy
ERYTROCYTE ENZYMOPATHY
• Defects in enzymes of anaerobe glykolysis
pyruvate kinase deficiency (PKD) – chronic:
haemolytic anemia, with little effect of splnectomia
• Defect in enzymes of pentose cycle
glucose-6-phosphate dehydrogenase deficiency
increased sensitivity to oxydazing agents –
chronic haemolysis or haemolytic crisis–
anemia with Heinz bodies
ANAEROBE
GLYKOLYSIS
GLUCOSE-6-PHOSPHATE DEHYDROGENASE
defficiency
•
Results in: lack of NADPH …. Increased sensitivity to oxydasing 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:
Prevention of exposure to oxydative agents (medication: antimalarics,
sulfonamides,. Food: vicia fava etc.) , splenectomy, stem cell transplant
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.
•
Diagnostics:
elfo Hb
isopropanol test, Heinz body tests,
methemoglobine tests, afinity to O2 tests
molekular genetics, DNA analysis
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
SICLE CELL ANEMIA
• Clinicaly:
Haemolytic + aplastic crisis, splenomegaly,
• Diagnostics
blood count– anaemi with s reticulocytosis
+ sicle erythrocytesery
elfo hemoglobin – presence of Hb S
identification of Hb S by peptic dissolv. of globin
molecul.genetics – DNA analysis- prenatal care
• Treatment:
Crisis prevention, transfusions, SCT
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
Wilsonś disease
CHEMICAL SUBSTANCES
oxidative agents, snake venon
INFECTIONS
Direct ery infection – malaria
septicemia ( clostridium perfringens aj. )
leptospira, borelia
Microiangiopathic haemolytic anaemia
•
Cause: erythrocytes destructed by going through network of fibrine
deposits at the small cell wall
schistocytes
Vasculitis, acute glomerulonephritis, after SCT, tumors, heart valve
surgery, AV malformations, drugs– ticlopidin, infection– Shigatoxin.
•
intravascular haemolysis + thrombi formation. Also: DIC may occur
and make the situation more complicated
•
Clinical course: haemolytic anaemia, thrombocytopenia, microtrombi
(CNS, kidneys)
Most prevalent diseases: HUS, TTP, HELLP , DIC
MICROANGIOPATIC HEMOLYTIC ANAEMIA:
diagnosis and treatment : TTP (thrombotic
thrombocytopenic purpura)
• Laboratory finding:
anaemia, reticulocytosis, schistocytes, akantocytes, spherocytes,
thrombocytopenia, vWF multimers in ELFO + ADAMTS 13
deficiency (vWF multimers cleavage enzyme),
Hyoperbilirubinemia, elevation of LDH (lactate dehydrogenase),
proteinuria, Hemoglobinuria, haptoglobin decreased, free Hb
increased, kreatinin and urea elevated.
• Léčba:
léčba vyvolávající příčiny, u TTP/HUS plasmaferéza se substitucí
čerstvou zmrazenou plasmou, kortikoidy, antikoagulancia,
transfuze erytrocytů.
MICROANGIOPATIC HEMOLYTIC ANAEMIA:
diagnosis and treatment : TTP (thrombotic
thrombocytopenic purpura)
• Laboratory finding:
anaemia, reticulocytosis, schistocytes, akantocytes, spherocytes,
thrombocytopenia, vWF multimers in ELFO + ADAMTS 13
deficiency (vWF multimers cleavage enzyme),
Hyoperbilirubinemia, elevation of LDH (lactate dehydrogenase),
proteinuria, Hemoglobinuria, haptoglobin decreased, free Hb
increased, kreatinin and urea elevated.
• Léčba:
léčba vyvolávající příčiny, u TTP/HUS plasmaferéza se substitucí
čerstvou zmrazenou plasmou, kortikoidy, antikoagulancia,
transfuze erytrocytů.
SCHISTOCYTES
SCHISTOCYTES
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
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
IgG – monomér, Fc část – vazebné místo pro C1q složku
komplementu a Fcγ receptor makrofágů.
IgM – pentamér, Fc část – vazebné místo pro C1q složku
komplementu a Fcγ receptor makrofágů.
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
COLD ANTIBODIES
• IgM character – optimál at 40C
• Bound to erytrocytes in colder acral
parts, possibility of complement
activation, ery aglutination
INTRAVASCULAR HEMOLYSIS
EXTRAVASCULAR HEMOLYSIS
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-pertusistetanus)
• IMUNODEFICIENCY
congenital and acquired hypogamaglobulinemia and
dysgamaglobulinemia
DRUG-INDUCED HEMOLYTIC
ANAEMIA
• hapten type
• imunocomplex type
• De-novo antigen formation
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
DIRECT COOMBS TEST
Erytrocytes with bound Ab
We add : anti IgG
INDIRECT COOMBS TEST
Sérum with free antibodies
we add: erythrocytes of particular blood
group
we add : anti IgG or anti C3b
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.
AIHA - treatment:
• Light form ( Hb > 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.
AIHA - treatment:
• SEVERE form ( Hb < 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)
Thank you