DISORDERS OF RED BLOOD CELL

ANAEMIA
HAEMOGLOBIN OPATHIES
THALASSEMIA
SICKLE CELL DISEASE

^
a
 At #*⇐ HHH#
Anaemia is the decrease belowthenormal time
defined .
as
Lineusfpectto aged six

ofan individual & also the pregnancy status) of the haemoglobin concentration,
-

eoiylhrocyle count oeehaematooict .

the blood → leading to

-

Functionally ,
decrease in the oxygen carrying capacity of
tissue hypoxia .

BJ RED CELL INDICES

absorbed in
mmmm mmmm
Iron
.

peu × tooo
④ Mean corpuscularVolm =

pnpgcwunfiumiuions .
duodenum .

82 -
98ft .

② Mean corpuscular =
tlbcgle)
haemoglobin RBC Cinmivionslgul)
27-52 pg .

③ Mean corpuscular Hb
31 35
gmldl
-

hb .

concentration =
Tv

@uantatinemeaseereofavusoeyfosnsIt .b
⑥ Red Cal distribution :

-
14.51 .

MACROCYTIC
µorµocyqc
NORMOTCHROMK -
large RBC
CLASSIFICATION OF ANAEMIA .

May > 1008L

Normal RBC
-

368M Idb
-

Mut cool -

Morphological classification Mev coz qgfcg

-

-
-

Vit Bkdif
Red cell size Mut Est 36g 1dB ,
-
-

→
-

FolicAcid def .

1) Methought -
Blood loss , trauma
2) Maerocyfic
D
Normocyfrc
→ Degree of Hb .

E) Norma chromic

2) Hypochromia .

DB MICROCYTICHYPOCH MIC
→ RBC smaller
→ MCV 280ft
→ MCH Lsogmldl
Iron defihrrhenieathhlleseeuie
 ETIOLOGICAL Ctttsslf KATON Rriowcyhc
-

.
M :

Mt : Macrocyclic
ANAEMIA H :
Hypochromia
N : Nornrochromic .

v
t t
Blood loss Impaired Red cell A Red cell Destruction
To Production
¢ →
lnkotud
Hereditary
Megaloblasticdu genetic spherocytosis
.
. .

Acute Chronic Nutritional def GGPD def

igonrdeficienq
-

- .

def Pyruvate kin def

.

anaemia
hexokinase def
.

def
.

Vit C .

I I -
Inherited 're
Thomsen → Hb Thhlllselnih
def abnormalities
Trauma Lesionof Fanconi anaemia sickle cuedisease
.

GIT gynaecological
,

disorders
-

Erythropoietin Renal Failure

.

def → Acquired Paroxysmal

genetic difmhaeduhomgeobinun.ae
-

immune AplasticAnaemia
mediated
Rh disease of
Infection of Parvovirus BH →Antibody
mediated
newborn

trsqyffmionreaet
-

RBCprogenitors infection
-

destruction

→ Mechanical Dlc , Purpure

trauma

Malesia
FILLE
'

µ
Babesiosis

' seeuestraeionieyperspieuism
IRON DEFICIENCY ANAEMIA
It is due to the deficiency of iron .
causing defective heme synthesis .

He
Pathogenesis
The
pathogenesis can be divided into 3.
stages
-

Stage 1 Iron depletion .

Iron adequate to maintain normal

hemoglobin level, but serum ferritin is
decreased .

Stage 2 Ikon deficient Erythropoiesis .

iron levels without anaemia@

Lowing of serum ,
and
transferrin ,
b

MCV and MCH) within normal

range . Bone shovel Iron deficient
erythropoiesis .
→
Stage 3 Iron deficiency anaemia

tow serum iron , serum foie Hint transferrin

. saturation I .
Impaired
Hb
production .

First reducer of size Cmioucyfic) → later

progresses to hypochromia RBIs .

Absent iron stares

Ikon Anaemia
causes
of def .
-

a
Decreased serum feritrw
Dz Dietary Def
.

I
Decreased serum Iron
-
Milk
feed Infants
-

Elderly withimproper diet a

-
Low socio -
economic sections .
Increased Tl BC

-
vegetarian . a
decreased Iron saturation
TB Impaired Absorption .

Total 1 Partial Anaemia

gastrectomy ti
-

-
.
M

sprue or steatorohoea.it chronic diarrhoea .

D8 Increased demand .

children and adolescents

Growing infants
.

-
,

-
Prig .

A lactation .

DB chronic Blood loss .

-
Gl tract carcinoma , hookworm infestation , ulcer , NSAIDs
-
,

-
UT Turnover
-
Genital tract tumour .

teaemoptysis .

TB Lab Findings .

→ tfb & Pcu : I I

→ Red cell Indices .

MW :
280ft (N : 82-98 HD
Mell :
czsrpg LN : 27 32 pg)
-

Mcteer .

227g 1dL Cool

-

36 gmldl)

RDW : TT d y ist .
. Earliest sign of Iron deficiency .

D8 Peripheral Blood Sunan

hypochromia RBC Shows ring or pessary

cues
RBC throweyfic &
.

Moderate anisoeyfosis or potkilocyton's ( pencil shaped cells)

NBC : Normal ; Eosinophilia in Hookworm infestation .

Platelets : Normal .
 IRON PROFILE
IDA LL 15481 et)
.

→ Sown ferritin : N CN -
soo peggy
IDAHO 15
ugldl)
Iron pig , de)
-

→ Sown N Coo 150

o -
.
.

→ Serum transferrin : Nooo -40T) LAA ( Litt)

saturation

BONE MARROW

cellularity :
Moderately hypercellular .

ME Ratio : 2: I -
l:2 LN 2 : l -

4 '
.
I)

erythropoiesis :
Hyperplasia and micro normalsCootie maturation)

Absence of
Bone marrow : Gold standard .

blue reader
Iron Negative Prussian
.

Reticulate Hb d :
Early feature of IDA .

CLINICAL FEATURES

- Insidious onset

Fatigue ,
Breathlessness, palpitations weakness ,

pharyngeal I euesophageal webs caused dysphagia

-

-
Patterson Kelly OR Plummer Winson syndrome
-

M H anaemia
stoop gastritis
Esophageal Aleks .

In severe Anaemia
Congestive HF : .

- unusual craving for substance of nutritious value chalk or fee no :

PagoPha'8°aC Ice) specific for ADA

.

-
Angular stomatitis glossitis ,

- chronic Atopic gastritis .

-
Kottomychin Csfoou mails ) .

③ causes of Micro cytic Hypochromia anaemia .

IDA
2)
4
Thallusenvier Major f. Minor
3) Anaemia of chronic disorder
4) Alcohol ,
lead poisoning .

5) Sideroblastie Anaemia (Rare) .

 MEGALOBLASTIC ANAEMIA .

Characterised
by defective ( impaired DNA synthesis and distinct
megoalo blasts in
the bone marrow .

⑤ causes .

Folic Acid deficiency .

Nit B12 Alcoholism, malnutrition

→ Deficiency -

•
Pure vegetarian - Nontropical or tropical spare

•
Def of pepsin on Intrinsic factor .
-
Drugs Anticonvulsant phenytoin
: ,

as
-
Pernicious Anaemia .

post gastrectomy .
-
teamadialysis

Prig infancy
, ,
lactation .

•
Intestinal
-
Malabsorption syndrome . -
folic acid antagonist ,

Lymphoma systemic sclerosis,

.

methotrexate
- Crohn's Disease .

Pregnancy ,
lactation, hyperthyroidism
DE Pathogenesis
Burpaired DNA synthesis
-

Impaired DNA synthesis due to def of 1312 (cyanocobalamin) on folicAcid .

Deficiency
to
abnormally large nucleated
Nuclear maturation lags behind & leads to
-

erythroid precursor rregaloblast

-

matures normally cells are large :

Macrocyte
cytoplasm
.

2 .
Infective Erythropoiesis : ohegaloblest precursor undergo inlttmedullany
destruction .

⑤ Laboratory Findings Peripheral Blood Sunan

tfb & PW lute

Paneyfopenia
:
-

Red cell Indices : TT

Diagnostic : macro ovalocylts
-
-

Mcv : A 100 fl taek central pallor

Mete : Normal (27-32 pg) -
marked anisopoikilocytosis
Meth : Normal CBI -36 gmfdl ) .

-
leucopenia
-
neutrophils
teypehsegmlntd
Leist and specific sign of Meganbestie
anaemia) Larger than normal
-

lmaoopolys)
Decreased platelets
.

-
 Dimorphic Anaemia .

Bath Bk and folic acid and iron deficiency

.

-
PBS shows : macro ovaloagets
and microcytes
- hypochromia RBCs

Bone marrow
eeveuelahity : Moderately to markedly hypercellular .

ME Ratio : Reversed 1 : l -
l: G LN : 2 : l -
4 : I)

Erythropoiesis : Nagatobeastietype
show
Large abnormal counterparts of normal normalslast megalob last .

asynehrony of nuclear
and cytoplasmic maturation .

Cytoplasm has normal

haemoglobingalion
.

bdntramedullahy hemolysis .

Adequate in
ihyelopousis
nos
BE : .

Granulocyte precursor display nuclear cytoplasmic asynchronism the form

of giant nretemyelocyee
and band forms
B12
^ Serum homocysteine Diagnostic tests
\ Serum Bilirubin levels are decreased Serum B12 .

u Shon d Ferri Ain Increased serum methyl malaria acid

Reasner LDH urinary Excretion of methylmalomc acid
Schilling test for B12 absorption
.

Folic Acid serum PA : It

Deoxy
uridine Suppression test :
pique in urine : TT

Sensitive measure
for both deft Evenly of 5 to methylene THF ,

which occurs both win

folic acid and Vit B12 deficiency .
 PERNICIOUS ANAEMIA .

Pernicious anaemia is autoimmune disease due to

an
deficiency of Intrinsic
factor causing impaired absorption Nit Br and megaeoblastic anaemia
of
PATHOGENESIS
An autoimmune disease due to the destruction
of gastric mucosa

infiltration of lymphocytes and plasma

edges
cell → Dense
Damage to parietal
Chronic
Failure of ←

production of Atrophic
Intrinsic
factor
.

gastritis
are 9
Antibodies present
Blocks the binding
A) Type I blocking antibody of Vit Biz to tf Present win
: .

50 -

751 .

of the cases

a) Type I binding : Attaches to the if uit By complex and prevents its

binding to the receptors in ileum
3) Parietal cell LTypelI ) antibody : Neither specific for PA
nor
for other autoimmune disorder . Found In 90 y of the patent
.

MORPHOLOGY

tf Alimentary canal
-

Tongue shiny georgy and beefy .

and intrinsic
- stomach gastritis with impaired
: secretion of tea pepsin ,

factor .

Loss
of Chief cells and parietal cells .

Nuclei
of mucosal all look similar to megaloblast
-

Infiltration of lymphocytes and plasma

cells .

-
Intestinal metaplasia
# ENS
lateral tracts sub acute combined
demyelination of dorsal and :
-

degeneration
a
p
.

-
Peripheral neuropathy .
 Laboratory findings .

Blood , Bone marrow and biochemical test are similar to those described
earlier

BE Specific test for PA : Pernicious Anaemia .

Radioactive wit Biz is used to asses the status of Intrinsic factor UF) and
wit B12
if deficiency ( Pernicious
Helps in megaloblastic anaemia
distinguishing causes
due to

anaemia from other Vit B12

of deficiency .

Serum antibodies specific for pernicious anaemia .

deficiency of Intrinsic factor

-

Severe

clinical features of Megalobiastic

anaemia
-
Insidious onset and
progresses slowly .

- Triad : weakness, sore throat and

paresthesias's
-
Tongue pain full red and beefy
, .

- Bilateral peripheral neuropathy : Gleave

and sock distribution
of numbness .

- club acute combined demyelination /

dorsal and labial tracts
degeneration of
-

ataxia , uncoordinated gait impairment of

,

vibration and position sense .

atherosclerosis
which tends to
aggravate
Atherosclerosis : Risk factor is homocysteine
and thrombosis .
 APLASTIC ANAEMIA
Aplastic anaemia can be defined as a chronic primary haumatopoietic stem cell
disorder characterised :

Paneytopema : (Anaemia , neutropenia to thrombocytopenia)

- Marked hypo cellular bone marrow3
Etiology .

# Acquired
Idiopathic :

in stem cells
-

Acquired defects
- Immune mediated .

Secondary antimetabolites
cytotoxic drugs Alkylating agents
.

,
:
-

Inorganic arsenical
.
-

Idiosyncratic
-
chloramphenicol
-
Peniullanune
-

GoldSalts

physical
-
Whole body Irradiation .

viral Infection .

Hepatitis is Epstein Barr v , cyfomegalov .

# Inherited
-
Fanconi Anaemia
-
Telomerase defect .

Pathogenesis .

- Damageto hematopoietic
Direct
stem cells and progenitor cells .

-
Immune mediated destruction
-

primary cell abnormality

it clinical features
-
Insidious
due to anaemia
-

Progressive weakness pallor dyspnea ,

frequent infections A fatal

due to
neutropenia .

-
Bleeding manifestations won the form of petechia , bruises and eehymoses
due to thrombocytopenia
 Go
>
Inherited
L
expressionof Abnormal
Direct vnhhen.gr Bag
damage
kqg.AE Jar
→
Abnormal
Stem cell
Expression
of Maadi

fmm÷olqgif
gens
.

Damaged net
stem cell .

µ
CENA
TNF
i v L

Aplastic Bone
Marrow

DB Laboratory findings
Hb
par
v
Reticulate Count markedly release : .

Peripheral Blood Linear .

Panagfopenia
RBC Nornrocyfic
: marmo chromic anaemia
WB e : The decreased , Neutrophil markedly decreased Indicates severity of
aplasia .

Platelets Decreased .

ABone Marrone

cellularity : Marked Hypocellular

HematopoiesisPaucity of All precursors

.

other cells Lymphocytes and plasma cues are prominent

.

other causes of Pancytopema

PROGNOSIS unpredictable :

myelodysplastic syndrome
.

- Bone marrow infiltration

Anaemia
-

crugaloblastie
-

Paroxysmal Nocturnal Haemoglobinnuria

-

chyetofrboosns Crary
* eeypersfdenism .
 HEMOLYTIC ANAEMIA
Anaemia that are caused due to increased destruction of RBC (Hemolysis) .

TB classification d causes .

I Inherited
Genetic defects
-
Red cell membrane disorders Hereditary gfheoocyfosis Hereditary Elliptocytosis
: ,

-
Enzyme deficiencies :
GGPD deficiencies PK deficiency teexokinase deficiencies
, ,

-
Hb abnormalities : Thhlleseuria, sickle cell Disease

it Acquired Genetic Defects .

-
Deficiency Glycoprotein :
Paroxysmal nocturnal
Haemoglobinn°a .

mediated destruction
e
Antibody .

-
Rh disease ofthe newborn ,
transfusion react
- SLE

a mechanical Trauma to RBC

-

Dlc ,
Thrombotic Thrombocytopenic purpurea
.

-
Defective cardiac values .

e Infection
- Malaria, Balderton's .

le snake venom ,
lead poisoning
ie thgpeesflenism .

Based on the location of hemolysis , hemolytic anaemia can be divided into

Extravascular & Intravascular -

EXTRAVASCULAR INTRAVASCULAR

- RE system Lslpleen , Bone Hemolysis within circulation .

manhood

-
usual splenomegaly uncommon .

-
AT serum Bilirubin in
Normal Seram leaptglobulin fo b
Wotton .

Hemoglobinunion tire

-
re tleamogeobinuria the
- ve teewweiderinusia .
the
Thalleseuria PNH
GGPD Dif ,
-

c. CA
DTELaboratory findings
Peripheral blood smear
RBC : Increased Reticulocyte count and appear as
large poly chrouretofhiuic
RBCs in peripheral blood .

blast)
Nucleated RBL's are present Clete Morino
.

present of
Neutrophillia ( more immature forms presence
are a
NBC :

metamyeloeyte & mydough's seen in active hemolysis .

Platelets : Thrombocytes's emay

be seen .

Bone Marrone

cellularity Increased
the hallmark
: .

is Characterised
erythropoiesis :
erythroid hyperplasia .

by
increased nos ofnoohroblast inthe marrow -

ME Ratio : l : I to l: IG (Reversed)

Dz Extramedullary tlaeuratopoiesis .

①wears when marrone erythroid Hyperplasia is not able to ameliorate

moderate to severe anaemia because of ineffective erythropoiesis

seen in SCD , thallusenvies . XRay shows
expansion of married Sfaee .

③ Increased Red cell Product .

Increased Red cell destruction .

A Erythropoietin Prod
h .

A conjugated Bilirubin th Rekkuloapir

T Erythroid Hyperplasia
in steecobiuinogen .

A urinobiuiougen .

T Iron stores

D8 Damaged RBCs
- Micro sfheroeytas, lelliptoeyles , Reed cell
Fragments
- RBC life shortened
 Hereditary Sfherocytosis .

Stds a rare inherited hemolytic anaemia resulting from the defect in red
cell membrane .

Pathogenesis
Red cue with Red with loss Slpherocyte
Young Red cell → → cell →
protrusions of membrane
fragments
Canfieldbled Tf v
PBS
Trapping in
-
Hero eyes ,
small dark
skiing hyper chromic spleen
RBL without central pallor
1
.

Poly chromatofhilia → dueto reticulescyton Phagocytosis

by macrophages
-

M UHC TT ( 735pm Idl)

-

Teeth MeV Id :
,

Reticulate count : xx

Bone marrow
→ Hyper cellulars Erythroid hyperplasia
spontaneous hemolysis Clo 157) N: ht
edutohemolysis test throwand in
-

coomb 's Test : - ne

Bilirubin in osmotic fragility : Carne shift to right -

Urolntinogen In
teaptoglobin T clinically
mild to moderate Anaemia
Tutunrithd Attack of Jaundice
moderate Splenomegaly
pigment Gall Horns .

Frt Inherited
Gb PD Deficiency .

Radicals X linked to full

to oxidative injury by free
-

RBL are susceptible

seen in males
expression .

Radical
Reduced Glutathione in normal RBC protects them against free
injury by -

the → tho .
GbPD regal for GSH -

presented as Sdf limited acute intravascular hemolytic anaemia -

has findings
Hbd Retiadoeyfetl
PBI → moderate and so poi kilocyton
's t poly chromatophiltiatmierosfhero
cute
+Bite cell
.

Heinz bodin seen in

active hemolysis with
vital stain
for todays causing
Haemogeobinuriov old RBCs
hem Ypg
usually
Test GG PD should be done after acute hemolytic episode
for
 SYNDROME
-

IHA LASSEMIA
Hb defects are either quantalive or
qualitative
-

Quantitative :
Genetic mutations lead to reduced production .

-
Qualitative Genetic mutations
: lead to production of abnormal hemoglobin

Thalleseuiras are
group of inherited disordersabsence
a dueto abnormality in

globin production Itis Hb

the decrease on complete
.
of either nor p
globin chain of adult
.

FB IBTHALLESEMIA
Itis an autosomal recessive hereditary disorder There is
.
diminished
synthesis of B globin chain & normal synthesis of a globin chain .

There are
point mutation heading to abkerant RNA stitching which are

the most common cause .

# Classification

B. Thallesemia major
-

Homozygous -
Severe
form Highest
,

level of Hbf in blood .

B thallusernie intermedia variable moderately severed not

-
-

transfusion dependent .

parallel envier whoa Heterozygous mild Anaemia and

asymptomatic
- -

B thalassemia major due to absence of synthesis of B globin chain of Hb .

Stig homozygous or double

Heterozygous .

Hair on end marrow

microcytes → Destruction
appearance qEee%TiF
Hypochromia ofRBC facies p
p
n

Abnormal Anaemia in spleen (

moundslast
→
Ineffective f Bone changes
erythropoiesis Anaemia
J

adessive detain
↳ T
in
Tissue Hypoxia
erythropoietin
→ Medullary &

hxegtyrahmfpdmu
.LY
insoluble
form
aggregates

* Secondary heaemosiderosis
Transfusion
Blood
f

w
t
)
Hepatospleno
-

megaly
-

andhaemoehromatosis '"

↳ L%ffion*°
"

¥mEu ftp.mdi.gg
.

,
e
:%
"

..

DEATH
 TB clinical features
anaemia won 6- 9 months
-
Infants dunlop secure to moderate
- untreated / untransformed child dice within 4 -
5
years of age .

- The bone shows distortion which won Inde

hair on end appearance
in the skull and face shows characteristic echipmurk) thalleseinic face .

- Splenomegaly due to hyperplasia to extramedullary haematopoiess's

's
had to iron overload A lead to haenrosideroen
-

Multiple transfusion
and secondary haemochromatosis .

Laboratory findings peaipheral Blood Simar

k d t
Hb : S -

gmfdl
8 - micro cyfie Hypochromia
anaemia
RBC count : T t Increased
Target cells Abnormal they
present RBC
RetiowFyte
- .

: Increased .
are basically
.

where only the central parks

MCV do I @5 70ft ) N 82 qgfh not
Hemoglobin sold periphery
:
-
: -

MUC : let 122

-

30gIde) N : si -

ssrgmyae .

resembling target a .

Mae I t ca 27-32 Pg
28
pg ) N
found in SCD post splenectomy
: -
:

-
,

Bs Bone marrow
ele .

Normals last (5 hot ) -

.

Markedly Hyper cellular

-

MIE ratio : l : I -
l: 5 Crewed) WBC : Leucotlyfosis .

Platelets Normal
Erythroid hyperplasia
:
Normoblastie with
.

- Iron bone marrow Increased .

D8 Biochemical Findings DE Special Test

.

S Bil T t Lunconjugated) Hbf 30-901 ; N : o It

- .

.
: :

TT pt Hts A t Hbf
'

U Unb :
Erythropoiesis : :
-

S .

Haptog : tu tu t Bo : tlbf only .

S Eron , S Feriltin
.
. : TTT HPLC : Hbf increased by so -907 .

Tranferrin (confirmatory test)

saturation
t d
Fofimation :pa l l CN)
TBC
:
:
of Globin :
chain lackof Bo : A
:

Thhlleseuiranniner is P
DB B more common

Heterozygous asymptomatic to mild anaemia ,

PB : chioweyfosis hypochromia target cells , , .

B. M : child Erythroid Hyperplasia .

 test)
NESTROF test (Naked Eye single Tube red cell osmotic fragility .
: the

HPLC : Esfimalth of HbAz : B -

8.1 .

A -
THAUESEMIA
Reduced or absence of a chain ,
Autosomal recessive disorder .

Deletion of a
gene
is the most common cause of d Thalleseuria
NOS OF A CLINICAL FEATURES
CUNICAL SYNDROME
DELETED

silent carrier 01
Asymptomatic -

A Thallesemia
Trait
02
Usually Asymptomatic

Hemoglobin H 03 Moderate miorocytio

disease hypochromia anaemia
Death
Hydrops foetal's 04 severe form t fatal .

is uterine life

character Iron Def .

Anaemia
-

B Thallesemia Major .

Red synthesis chain

Etiology Df of Iron .

of B
PBS
-
RBC microcytes Hypochromia Milroy tic Hypochromia
-

Anisopoikilocyt -

mild to Moderate severe

-

Target cells -
ve the

Bone Marrow Fe -
ve
Tve

Hbf
O -
It .
(Normal) 30-90.1 ( Abnormal)
.

growth t
Normal Retarded
Development

X Ray finding NIL Hair on End Appearance .

* check pthallesemia minor vs

Iron def Anaemia in
pg 287 .
 SICKLE CELL DISEASE
group of hereditary
characterised
SCD is a disorders of Hb , by production ofdefective
Hb chewed osickce Its Ltlbs)

low oxygen → Hbs leads to sicking of the RBC Produces .

a
qualitative defect
mutation in
in Hb production caused
by p globin gene
a Autosomal Recessive disorder .
constitutes about 70 I -

.
of Hb withno HBA

D8 Eli opathogenesis .

Hb A → Hbs

I Hbs in
+ Sol "
i s

)
.

bqugfmqqn.FI?on .
oxygenation .

- -
t t

v.
Reversible sickle
cell
Holly leaf
.

Ced d
de Vessell occlusion

Irreversible fickle fickle cell Anaemia sickle cell trait

date
Heterozygous date
cell
Homozygous
.

are abnormal
µ - Both p globin .

- one
gene
abnormal

Hemolysis while other gene is

normal Cbl8A)
Other sicking syndromes .

- Both p globin chains have

different abnormalities
each as Hbs -

p thatKleiner

substitution 6th
In Hbs there is a
of glutamic acid by valine in the

position ,
the p globin chain of tub . A-alters the solubility or
stahuty of Hb
and produces Hemolytic anaemia
TB Mechanism of RBC damage
.

-
Hbs polymerization .

of sicking leads to increased dehydration of

dehydration Repeated episodes and non
:

RBC They become more rigid

deformable
-

( IRREVERSIBLE) .
 -

Percentage of Ise
-
Impaired cation homeostasis .

DZ Pathogenesis of occlusions .

- Sickle rigid d tend to aggregate A block small

cells are blood vessel
- RBC cytoskeletal damage blow the movement of RBL through microvascular
beds
endothelium
-

High expression ofadhesion molecules : stick to the .

Hb binds with
Inactivation of nitric oxide : Lysed sickle cell liberate Hb .

This produces narrowing ofvessels and

-

nitric acid , which inactivates it .

microvascular stasis f tickling

produce
.

D8 Clinical features

Presence offlbf has protective role for 6 month Symptoms appear after .

-
6 months of age as the Hbf disappears .

Infants & children present with acute promblem such as severe int .

acute dust syndrome, splenic sequestration d stroke

.

Adults chronic
-
organ damage
lifelong hemolysis cmainly extravascular) and cause chronic hemolytic
anaemia which is of moderate degree .

Raised conjugated bit . → bilirubin

gallstones and cholecystitis

.
.

H types of crisis

D Stichting crisis
- Most common
cell RBC → Hypoxia & Infarction
-

Blockage of microcirculation by sicked

hand foot syndrome daily cities
Bones manifest
.

as ,
-

Acute chest syndrome of lung

.

-
Occlusion is spleen Repeated sfdeen
. occlusion leads to autosplenectomy .

Hemolytic crisis -
Rare , masked increase hemolysis .

s) Aplastic crisis
Associated with B 19
-

parvovirus
-

Reticulocytopenia
crisis
4) Sequestration .

Occur in children
Rapid Enlargement ofthe organ
.
-

-
sudden trapping ofblood
in line I spleen →

shock
drop in the haemato crit → thy pandemic
.

crisis
* Hypoplastic
crisis inadequate folate
Meg aloblastic
:

*
 There is an increased susceptibility to infection which are basically pneumonia due to

SfoeptPneumoniae .

osteomyelitis C. Bone infarcts are

- Pneumococcus .

-
Salmonella the cheese) .

the most for death in children

Septicaemia meningitis is and common cause
.

⑨nereased susceptibility is due to

Hypofunction of the spleen

.

poor blood flow

-

children :

autosplenectomy
Adults :
Infarcts →

-
Defective in alternate complement pathway .

Impairs opsonization of Encapsulated

-
bacteria .

D8 organ Damage
Chronic .

t lung
Seen in spleen bones kidneys heart
.

, , ,

children after Gmonths Splenomegaly .

red in size due to multiple infarcts

:→ Fibrosis of spleen
n

b- G
yrs
- ,

Gradual of splenic function

loss .

Bone :
Osteomyelitis (Salmonella)
skin ulcers in lower extremities .

TB Laboratory findings .

fl b de ESR de

peu d Reticuloeyfe : Ah 3- lot .

PBS
Nonnocyfdemormo chromic to mildly hypochromia
=

Moderate to secure anisopoikilocytosis

.

ends)
-

- characteristic sickle cell dong curved cell with pointed .

May show target cells 1 oval ought

-

NBC ! Mild Increase .

Platelets : Mild Increase .

TB Bone Marrow

Hypercellular
- .

-
compensatory normoblestie erythroid hyperplasia
a
Bone marrow expansion → Resorption .

- Iron stores AT
Lt
S Bil
'
: Tin Ser .

leapt :

Sf Tt u Urimob : TT
Iron
.

:
DE confirmatory Test
like 2T sodium metals sulphide
fickling test Induced by adding a
reducing agent .

to blood sample
to
Red cells withHbs show sicking or
Holly leaf appearance .

* Diagnostic of sickle cell anaemia .

Solubility test for Hbs

- Electrophoresis : Hbs is slow moving .

HPLC For confirmath

-

-
:

SICKLE CELL TRAIT

state of Hbs mutation and show both HBA & Hbs One defective
Heterozygous
.

& one normal .

But they may do

undergo polymerization
so
Hbs to
feb A prevents
.

in extreme condition Cflight deep sea) .

, .

-
Asymptomatic -

tlbs : 251 to hot .

Bonethhhrow :
Hypercellular due to compensatory noomoblestic erythroid
hyperplasia .

sicking Test : the

- HPLC