1

NON-IMMUNE HEMOLYTIC

ANEMIAS

2

RED CELL MEMBRANE
DISORDERS

Hereditary spherocytosis (HS)

Hereditary elliptocytosis (HE)

Hereditary pyropoikilocytosis (HPP)

Herediatry stomatocytosis (HSt)

3

RED CELL MEMBRANE
DISORDERS

HS

spherical-shaped
erythrocytes lacking
central pallor

1:1000-2500

Northern European

HE

elliptical,
cigar-shaped
erythrocytes

1:2000- 4000

African (1:100),
Mediterranean

4

RED CELL MEMBRANE
DISORDERS

HS
HS
HS,HE
HS,HE
HS
HE
HE

Ankyrin
Band 3
α – spektrin
β – spektrin
Protein 4.2
Protein 4.1
Glycophorin C

DISORDER

GENE

5

RED CELL MEMBRANE
DISORDERS

6

RED CELL MEMBRANE
DISORDERS - DIAGNOSIS

positive family history

anemia

hemolysis (reticulocytosis, increase bilirubin,
LDH,decrease haptoglobin)

joundice

splenomegally

gallstones

peripheral blood sear –
spherocytes/elliptocytes

increased erythrocyte osmotic fragility

7

RED CELL MEMBRANE
DISORDERS - TRETMENT

splenectomy

folic acid

red cell transfusion

cholecystectomy, sphincterotomy,
extracorporal choletripsy

8

METABOLIC DEFICIENCIES

9

PYRUVATE KINASE (PK)
DEFICIENCY

95% hemolytic anemias – glycolytic
abnormalyties

decrease ATP concentration

autosomal recesive

manifestation :

early childhood

moderate hemolytic anemia

jaundice

splenomegaly

10

PYRUVATE KINASE (PK)
DEFICIENCY

xerocytes (echinocytes, acanthocytes,
spherocytes) in peripheral blood

diagnosis : enzyme activity

tretment:

avoidance of infections

splenectomy

11

G6PD DEFICIENCY

most common inherited abnormality

X chromosome

G6PDA (-)

12% of American black mels and more in West
Africa

moderately – severe, chronic hemolytic anemia

oxidative stress – drugs,diabetic ketoacidosis,
hepatitis, severe viral or bacterial infection

amemia, hemolisis, sometimes hemoglobinuria

12

G6PD DEFICIENCY

peripheral blood – „bite cells”, spherocytes,
polychromatophilia

Heinz bodies – cresyl vialet

quantitative of G6PD enzyme activity

G6PD-Mediterranean variant (3-5%)

”favism”

tretment

prevention of hemolzsis

transfusion

screening tests

13

PAROXYSMAL NOCTURNAL
HAEMOGLOBINURIA (PNH)

acquired clonal stem cell disorder

rare about 4/milion/year

14

PNH - BIOCHEMICAL AND
MOLECULAR BASIS

Xp22.1

15

PNH - BIOCHEMICAL AND
MOLECULAR BASIS

CD 59 – inhibits the
formation of the
membrane attack
complex

CD55 (DAF) –
inactivate protein of
complement et aerly
stage of the cascade

16

PNH – FAETURES AND
DIAGNOSIS

chronic hemolysis with exacebations

anemia

iron deficiency/overload by the transfiusion

hemosiderinuria, hemoglobinuria

thrombosis

cytopenia – AA

myelodysplasia, AML <5%

17

PNH – FAETURES AND
DIAGNOSIS

Ham test positive

flow cytometry

I normal red cells

II partially deficient

III completely deficient type

18

PNH - TRETMENT

most – supportive menagment

transfusions

folate supplemantation

iron status - proper tretment

thrombosis tretment and ptophilaxis

analgesia

AA progressive pancytopenia

immunossupresion

bone marrow transplantation