Nucleus & cell size ↓ )

Maturity disappear
C is when .

have Of RNA & Ribosome

they
Bcz more no . .

>

chromatin starts
→
dumping
.

C orthochromatic )
' '
> Reticular RNA
,
y ,
> Hb

ROMANSOKY STAIN
↓
Eosin
methylene Blue +
→ At the
stage
of
erythrocyte
contain
also
they
are not
mature RNA
they
as .

& that
through
removes
>
They pass spleen spleen
extra amount of
RNA
.

Whn Sp

Note 1-2
days BM
: -

1- 2
peripheral blood
days
_

2 the content of RNA

days depending upon
will
RBC
stay
in
spleen
.

formation of mature
days
4-5 for
RBC
.

◦ ◦

* There will be condition when BM will stimulated for

erythropoiesis .

count in blood µ a
Retieulocgte
increases

RETICULOCYTOS IS
to

~
×

hoses of RBC
anemia
Post
splenectomy
maturation
Hemolytic for
• C RBC were

spleen but
going
to now
• Blood loss
is absent )
spleen
Reticulocyte count : No .
or
reticuloeyte
⊕ in 100 RBC .

05 -
21 . in adults
2- 6% in cord blood / neonates

with anemia then

automatically
→
It a
person come
you
will count
culoeyte
of
more no
Reti
-

Note you think that Anemia

Reticulocytes
: means ( ↑ ) in
but how do
you know BM
responses
ornot .

so
count Hematocrit
Reliculocyte
'
corrected =
Nc ✗
N Hematocrit

Normal hematocrit
occupied by
→ rot RBC i. e , 45%

of total blood .

Or
[Hb] ✗3

Normal ttb hence hematocrit

isgmldl N
=

= 15 ✗ 3=45

have Hit 5
Eg → Let a = 15% RIC =

person ,

corrected
PYC ¥5
-

.
.
=
5✗ = t 7%

oho no
,
bi rest
you will see Rc = b- % → case of Reticule
cytosis →
Hemolytic anemia must have occurred .
9- Hb 6% Calculate CRC
gm
= b- Ric =
.
.

Ans -7 Cor .

pyc = 6✗
E5¥3 = 2%

Note : It anemic
a
person is severe means immature
Reticule cyte
very
present
having
are in blood more

amount of RNA so
spleen take moretime to
mature them .

So , to know about

BM we calculate
the
outiueloeyte produced
by
production
Retiadocyte Index

→ RPI =
12/2 = 6%

Count
* Absolute
Reticulocyte RIC ✗ No

+
.
of RBC

To cheer the
Aplastic anemia
severity
.
of
 Bluish chromate
cell
Poly
- -

phill
→ cell have central pallor
Red
of
Normoeytie
i. e ,
43rd Norm -

oehromie
RBC
.

Reticuloeytes
are
larger
than
RBC .

the Reti eulocytosis in stain

Romanosky
• we can see

but can't confirm it .

we have to see the RNA Reticulum

↓
we need
supravital dye
C stain live
RN A)

methylene
Blue
Eg → New

E-

↓ ☆
Immediately dye stain the collected specimen
they
as
,

live
retiuilocyte mature into
are so will

RBC 's you will not bound

any retiaeloeyte
.

→ other
dye 's line •

•
Brilliant
Azure B -
creeyl Blue .
*

✓
b.
↓

It is used to stain
Amyloidosis
.

*
seen in
a- Thaklhemill
→

also as
known HB.tl

inclusions .

*
There are not RNA Reticulum there
,

definitive inclusions
periphery
are
on

of
rgeticulocyte .

I
Heinz
Body → Denatured
in GGPD
Hb

deficiency
.
4:47 PM Mon 21 Mar 29%

APPROACH TO ANEMIA AND UNDERSTANDING

HEMATOCRIT ESR AND MCV (RED CELL I

PARAMETERS PART=

Classification of Anemia on
Etiology O0:00:05
Nutritional Anemia
i. Iron deficiency 7

ii. 312 & Folic acid

×

deficiencyAnemia
~

Nutritional
Anemia
Hemolytic Pian
teypoproliteratiue
Anemia
•
Iron Hemolytic Anemia
deb Anemia .

Roca
• i. Extravascular Hemolysis
B12 & folieaeid
" ~

Extra Intravascular
ii. intravascular
deb Anemia Hemolysis
vascular
hemolysis
.

pic @ or )
Hemolysis
I.ExtravascularHemolysis O0:01:54

#ÉÉoutside
→
i. Membrane defects Brute in liver &
spleen .

Detects
i. Membrane
Membrane
HS,HE

Globin
Qualitahire
Fig:

- Hereditary spherocytosis CHS )

- Hereditary elliptocytosis CHE )

i. Globin defects (Haemoglobinopathies)

a.Qualitative defects
Sickle cell anemia ( Hbs )

- Hemoglobin C

Approach to Anemia &

Understanding Hematocnit, ESR &
MCV(Red cell Parameters Part 1)
4.47 PM Mon 21 Mar
29%

b.Quantitative
- X - Thalassemia

B Thalassemia
iii.A
c. Enzyme defects
- G6PD deficiency

Pyruvate kinase deficiency

-

Pyrimidine 5 nucleosidase deficiency

- • Lead poisoning causes pyrimidine -
• S nucleosidase

deficiencies
i ☆
d. Antibody defects
-

Autoimmune hemolytic anemias -

IgG Cds
IgG
is not a complete
Ab it does not complete lysis
so
cause .
It opsonise ) .

l.Intravascular Hemolysis O0:09:00

a. Paroxysmal Nocturnal Hemoglobinuria (PNH)

-b
.Clinical feature complement activated
system
Hbemia
Hburia

PCT
PsHEMOSIDERIN

Hemosiderinuria Fig: 2 will also shed

AS PCT cells
.

>

Acquired Hemolytic Anemia,elderly Generally present

PNH C with
PNH )
b. Thrombotic microangiopathy FL
i. Hemolytic uremic

Shod
Syndromne
i. Hemolytic uremic syndrome
ii. Disseminated Intravascular coagulation
ii. Thrombotic Thrombocytopenic purpura
Approach to Anemia &
Understanding Hematocrit, ESR &
MCV (Red cell Parameters Part 1)
17 PM Mon 21 Mar
29% 0

C. Snake bites & Toxins

G6PD Deficiency Causes Intravascular and

Extravascular Hemolysis as bree radicals will cause cell
also it not then will done
lyin
spleen
by
.

Sickle Cell Anemia also Causes Both Hemolysis But

Extravascular More than Intravaseular Hemolysis
.Clinical features of Extravascular Hemolysis
i. Splenomegaly
i. Increase is indirect Bilirubin
ii. Increase is urinary urobilinogen

iv. Increase is fecal urobilinogen

v. Pigmented gall stones

Clinical Features of Intravascular Hemolysis

i. Hemoglobinemia
ii. Hemoglobinuria
iti. Hemosiderin uria

iv. lower Back Pain

in hemolytic Anemia
Reticulocytotic is
common

O0:18:54
Hypo proliferative Anemias

No cells are produced

Anemia-hematopoietic
i. Aplastic
Anemia C Pure Red
cell Aplasia) -

only RBC
i. Pure Red cell Aplastic
Anemia
Reticulocyte attaint
want increased - Hemolytic
proliferative
.Reticulocyte Ghent
want decreased Hypo

Anemia
Amount
Reticulocyte want
Normal or decreased
Nutritional Anemia

to Anemia &
Approach
Understanding Hematocrit, ESR&

Unaer alRarameters Part

-1*8 from
4:48 PM Mon 21 Mar

-fgf
29%
there 3
Reasons Blood loss can also
cause anemia .

Blood loss Anemia (hemorrhagic Anemia)

i. Acute blood loss
il.Chronic blood loss
count will help in identification apart
*
Reliculougte
brom this Parameters Useful to ldentify Anemic

Chronic blood loss Parameters Useful to ldentify

Anemia
1 to
MCV [Mean corpuscular volume]
It's approximate volume ofa line Red cell

Normal value 92 + 9fL -

C 80 -
loot c)

<80fL Microcytic
100 fL Macrocytic

2. PCV(packed cell volume/ Hematocrit]

Total volume of all Red Blood cells.

MCV X RBC = PCV

Macrocytic cells Packed cell Volumie is measured by
wintrobe method Microcytic cells packed cell volume

This is better
is measured by capillary tubes, a

method

pcv

MIC
CRO
MACRO

Capillary
Wintrobe
tube
ube
3mm

Quick results & used

generally .

110mm/11cm Fig:3

Approach to Anemia &

Hematocrit, ESR &&
Understanding
MCV (Red cell Parame ters Part - 1)
 e 29%U
4:48 PM Mon 21 Mar

* Wintrobe Method
n
plasma
110 mm of a the tube is filled with blood, it is
→

b coat
Bobby
→

centrifuged for 30 mins at speed of 3000 rpm → RBC

Ey
,
=
45 I
-

Normal PCV-457 (males) 37-427 (Females)

calli berated
It is
doubly
• .

ESR- Erythrocyte sedimentation Rate :

1Cm

10cm

20cm
30 Fig: 4

I t as measured in wintrobe Tube or Westergren's

Tube
✓Westergren's Tube is the ideal tube clanger)
Normal values Males 3 to 7 mm in one hour
Females 5 to 9 mm in one hour ( As lets RB C)

.Wintrobe's bone diameter -> 3mm

.Westergren's bone diameter 2.5 mm

→ open from
both side

Fig: 5
4.48 PM Mon Zi Ma 28%0

ESR measurement occur in 3 stages.

i. Rolueux formation occurs in 10mm

i.Sedimentation Formation takes 4Omin

Packing stage-occurs for 10 min

Wintrobe uses Anticoagulant - Dipotassium EDTA
Westergren's uses Anticoagulant-Trisodium citrate
(1:4)

Factors lncreasing ESR

factors ESR
i. Inflammatory condition
decreasing
increase fibrinogen

i .IN#gggYmRBe
-

i. Increase
viscosity
in
increase rolodex formation
.

cause ( ↑ ) in
ii. Acute Phase Reactants increase ESR except albumin

viscosity
.

ii. Decreased viscosity of blood increased ESR

iii.
change
in
shape of RBC .

v. Increased specific gravity increases ESR

v.tt#fmsizeARB
ESR mostly has Prognostic significance.
es
Rhone prognostic significance mainly
.
•

Diagnostic significance of ESR:

i. Temporal arteritis
ii. Polymyalgia Rheumatica

ii. Human Immunodeficiency

iv. Rheumatoid Arthritis
v. Tuberculosis
vi. Multiple myeloma.

Approach to Anemia &

Understanding Hematocrit, ESR &
MCV (Red cell Parameters Part )
4:49 PM Mon 21 Mar 22%D

APPROACH TO ANEMIA AND UNDERSTANDING

MCH, MCHC, RDW (RED CELL PARAMETERS
PART-D

Immersed
Approach to Anemia &t understanding MCH, MCHC
RDW
off
3 Mean corpuscular Hemoglobin (MCH)

MCH-Hemoglobin p☆oT
Potential in one RBC •
N value 29-51=2.5 CWHO )

at
went
/
Normal value 28-32 pg
cpicogram)
q MCHC-Hemoglobin present in all RBCs MCH cone

Mpaa
→ for
Formal Hh Hbx 1
PCV MCV x RBC
-
=

Normal Value 33-1-5%

¥500T =

32-367 ≈ 22%

Mean corpuscular Hemoglobin Concentration

Megaloblastic Anemia MCHC can be Normal or

decreased cmam is not

be 2- telling M-egaloblast.ee
to document if blast Mairoeytieaid as

4 Folie
megalo deb most ]
as B12

Spherocytosis-increased MCHC .

is .

CAS membrane were lost but Hb conc is as it is ]

.
.

RDW O0:03:30

Red cell Distribution width

I t correlates with anisocytosis
Anisocytosis is a vacation in size of RBC's
RDW very important in differentiating Iron deficiency
Anemia &

.Thalassemia Trait

Approach to Anemia & Understanding

MCH, MCHC, RDW
(Red Cell Parameters Par -19
4:50 PM Mon 21 Mar e 28%0

Microcytosic Hypochromic Anemia canbeseenin

sideroblaetie

Iron deb .
IDA Thal Trait

Thalesemic oo0000
péncie ④
A
RDW -

Anemia of .
cells
Chronic disease
( 1ˢᵗ Ncnc but later
Leptocytes > RDW
MCHC ) > 14
(
large ceeebut more
)
hypochromia
.Normal value of RDW-> 12-14%
RDW increased in spherocytosis heptocytes
.

O
o o
o

Polychromatophills
800 Target c.
HE

>

1g

nomoegt.ec#omfeRBc
tells
o
* Pencil

'
≤ 3rd central pallor

Fig:
MCHC increased in spherocytosis
.Mentzer Index 13- Thalassemia g) Inheredetary
SPHETROCYTOSIS
.Mentzer index> 13 Iron Deficiency Anemia
Gio
.RDW increase in iron Deficiency Anemia Ihr
ORIAL Polychromatophitlis
.RDW Normal in Thalassemia Trait. sp&adRBc having
C) Mctyc .

of cells teen
types
•
Two are

so RDWC↑ )
-

Approach
I to Anemia & Understanding
MCH, MCHC, RDW
(Red Cell Parame ters Part - 1)
 ☒a*
-

g. q
.

microglia
remember
hypochromia
if this is
but

a case of
thakhemia then Red cell count be
⑥ → As may
Mavrocytie Cp That trait)
BM is
producing enough
cells

-6kg
-

→ It is a index counted to
confirm
hypochromia =
thalesemia
'

-
BTT

q .

Hb ✗ 3 =
PCVC Hematocrit )

¥Fg bra of RBC

'

*
>
Maerovalocytes seen with
onegalo
blast in
meojalobeaetie
anemia chronic
Chipper cells
having
less pallor ]
-

•
Eliptical cells
having
more central pallor are pencil cells

seen in IDA
 Approaches to
Hemolytic Anemia :

Approach to Anemia
chronic

Acute

IntravascularHemolysis ?

tb bound with
[ Serum ) k
heptoglob.in to taken up
⇐ )
form
>

( Lett )
Lett hb bound →
with hemopenin

helot heme +
→
Albumin
( Lett hb )

CHB PCT)
Herren up
by
Extravascular
hemolysis % -

BB Dog

ᵗᵈ°ʳʰᵗʰᵈʰ#ѧy
SO i

→ Left hb come in
} blood bound to

heptvglobin
-

→ As hemopesein ie

Haemoglobin →
→
not needed .

→ It indicate increases

in
endogenous ¥ .

→ will
in
study
platelet .

t .

of AIHA
It is a
type
-

Note → A patient to op ☐ with jaundice

splenomegaly
come ,

. Gall stone with anemia think of Ertl .

& with C) Hb , heniosiderin in urine think IVH .

YTIC AN
ci)
spherocytosis:
Hereditary
-> autosomal dominant.
Generally
itis
Normal RBC membrane.
->

vertical
by
stability
BAND3, 4.2

Anyrin
protien
↳>It
provides horizontal

stability.
-> Let
Gene for
Anchyrin dysfunctioned.
is Membrane
will be compromised.
Stability ↓
defective membrane
the
spleen will pull
out

>W RBC -
34 central
pallor

RBCW- >Denser structure.

all. As them
let
this spken
go.
isk

↓
when

them.
Again they go spleen, splenic
to
macrophage will al

I
Exte CSO pt. Starts with jaundice, Gall
I stone

spigmented) a
splenomegaly.
 of presentation →
age
In content their RBC
guilds
newborn Hb be 21 so

may
• .

ed without central
bully haemoglobin having any
are 's

pallor .

↳
by seeing
so
peripheral smear of a newsor
you

spheroeylosis
can't it
diagnose
as .

off
•
→
TIS / 9
•
CBC of the pt ! _
•
↓ MCV

◦
↑ MCH C

↑ RDW will
high as BM starts

producing
•

cells .

Note → If C) MCHC Y -

35 & RDW > I 4

thing of Hs .

•
pxc (↑)

peripheral smear

Polychromatop
÷} →
hill

spherocytes

confirming
→ It means are
you
it
hereditary
as

sphere
s
cytosis I
.

P No , this can also be

in Autoimmune
occur

anemia & 96 PD .
hemolytic
→ In
AIHA when
produced can't do
IgG they
are

lysis they Just opsonin .

so
opsonised RBC 's are

damaged condition
in spleen .
so same as 00

Hs .

→ so . Go bor coomb 's test then rule out

the of
chance AIHA .

pathologist
→ Let you are a new & You
are unable to
spheroeytosis
.
see .

I
test
fragility
90 bor osmotic _

osmotic test test

fragility It is a
confirmatory
confirmed it is a
ton
sptreroeytes If are
you
.

for coomb 's test

spherocytosis
then
.

of
go
case

Normal
→
RBC

↑ n
n

cells
starts
swelling starts
cells complete
eyeing cell
lysis
.
spheroeytie
RBC
;D ÷qy: a
↓ 0*352 ☆BB
Does nothaue
i. e. central
enoughto space →
×

pallor expand
.

analysis complete
starts cell
lysis
.

spheroytie
>
cells .

~⑨ Tail of
fragile
celllj ,

that
many
It means

starts
spherocytee
at cone
lying ⑧
But in
same
-

RBC cell tail does not appear

.

→ This take lot of time so

nowadays we
.

have
EMA BINDING TEST -
 EM 9- BINDING TEST !
↓
Eosin Melanite
Assay
5

It is fluorescent
•

dye
a .

Go & bond to

→ Give fluorescence .

Ankyrin
→
is ⊖ then fluorescence will not there •
It is
tested in flow
cytometry
.

cytometry Test
malleability
Ekta : the of RIC .

Mother : the vertical bond which

always
It is

is
broken down in sphere
hereditary
cytosis .

It BAND 3 detective → PINCERED CELLS

are seen

ANKYRIN → Most common

9^2 → Autosomal Recessive Hs .

Spectrin → or
type
severe is .

prognosis
→
Bad .
 spectrin not cause
debiciency generally
→ does

spherocytosis
.

It came te
I
.

Elliptoeytosis -

also Ha south East Asian

oralocytosis
-

commonly
seen in Indonesia .

Noten : -

*
test bor Thalesem :c
→
confirmatory
trait
^ .

→ In India

shows NESTROF
many pregnant
+ve but HPLC
women

re as

they
are
subteringbrom
IDA .

→ Here also RBC 's are

, hypochromia
at the
so
they are not
eyced
conc .

Of 0<36 % saline .
Cii ) Sickle cell Anemia :

( Hbs)
BE

¥
& they
polymerise

-4
In liver so

hepatomegaly
.
4:51 PM Mon 21 Mar
27% 0

>
>
->
UNDERSTANDING SICKLE CELL ANEM1A
-
-
-

Genetic !
Point mutation
Glutamic Acid replaced by Valine on 6th nutrition in sti
Bchain
Adenine replaced by Thiamine which changes the

olubility
codon and a different amino acid attach ·
thus the s

of Hb to
changes & Biconcave shape of RBC changes
Pathophysiology of Sickle cell Anemia O0:00:0s sickle
shape.
.Hypoxia leads of
to RBC's to turn into sickle cells which
on oxygenation turn into normal RBC's, this at first
reversible but with repeated cycles leads to membrane

damage and sickling becomes irreversible

O Hypoxia crepeated)
Ca Memb
damage
clotrimazole
irrevere sickle
ISC
all

Some drugs like clotrimazole damage

Calcium pumps of RBC's which causes
doesn't · allow
Calcium to accumulate in the RBC's and ~D
I
⑧
Sickling becomes Alg
irreversible 4

↓
There will be
venoocclusions.

Irreversibly damaged sickle cells cause

Phosphatidylserine of the membrane flips outside, cell

Understanding Sickle
Cell Anemia
4:51 PM Mon 21 Mar 7%

becomes more negative at which activates coagulation

pathway and thrombosis occurs

Sickle cells killed in spleen by extravascular hemolysis

Iff
which causes jaundice which causes jaundice due to

increase in indirect bilirubin cos → As it is

hemolytic jaundice )
.The sickle cells block the venous circulation of spleen
which leads to congestion and splenomegaly ( chronic venous
congestion .

.Calciunm, Iron, Macrophages accumulate in spleen in

" "
the form ofBooboo purple Ir)
"
"Gonne gandy bodies Cca is amorphous → Blue -

>
Sickle Cell also occlude arterial circulation of spleen
leading to splenic infract which ultimately leads to

auto splenectomy [ Repeated •

episodes of intranets & fibrosis )

.Sickle cells also undergo intravascular Hemolysis which

leads to thrombosis •
so , a
pot . with
early Hoo anemia

splenomegaly but later

show
can
tutosplenee
tony
.

Clinical Features of sickle cell Anemia O0:18:00

↓
i. Vaso occlusive crisis or
tyre
gGfge£Ég£"ʰᵈᵈʰ
s" this a

where
a. Hand & Feet Syndrone coagulationof
to
& also
Hemolytic Anemia
bind

splenorasiqz.EE
not
His
damage no leading you may
b. Acute Chest syndrome megaey
BREE
.

.Child: cause is infarction

d-

Adult: cause is infarction

c-

C. a
vertebralb- arteries occlusion
osteomyelitis is
commonly
seen
pot of stage cell
.

vertebrae Anemia -

.Fish Mouth Vertebrae

occurs
Mainly
d. Salmonella
due to
^

osteomyelitis
✓
e. Kidney

.Hyposthenuria -

Unable to concentrate urine

Nephrotic syndrome: FSGS Urine

Understanding Sickle
Cell Anemia
4:51 PM Mon 21 Mar
27% 0

medullary
Papillary Necrosis
carcinoma or
kidney
Papillary Necrosis in Renal system
Causes

D diabetes mellitus (Most common)

O - Obstruction

S Sicklecell Anemia
A- Analgesics (Most specific)

N¥☒f☆§femolyn°s
f. Medullary carcinoma of kidney more Fe is absor -

&0§g§gFe medullary
g. Liver so memosiderosis can be

i. Hemosiderosis

ii. Anemia
* Due to Anemia Extra hematopoiesis
s#--fnfg→wwgear
-a. Extramedullary Hematopoiesis
once of shale & .

i. Crew Cut skull

Retiueloeytoiu .

* Complications of sickle cell Anemia OO:19:57

r-ohfDBEEArisis.qkffris.es
i. Vascularize Crisis
ii. Myeloblastic crisis
ii. Aplastic crisis

gffˢ&&-oiuis
iv. Hemolytic crisis

Hemolytic
v. Sequestrationcrisis
crisis

Megaloblastic crisis
Due to increased turnover of RBCs, there could be
folate deficiency
Treatment is to supplement folic acid

Understanding Sickle
Cell Anemia
4:52 PM Mon 21 Mar 27%

Aplastic Crisis

I t occurs due to parvo virus

.Parvo virus damages colony forming unit of

erythroid

Sequestration Crisis
.It occurs in less than 3yrs of age
There is sequestration of large number of RBC' S in
spleen Leads to splenomegaly
So much sequestration of RBC's Leads to
hypovolemic shock
I t is one of the most which leads to death.
Not common
very
·

crisis
Hemolytic can be increased.
M

Hemolysis
·

of sicle
Pathology all Anemia:
·

>
=>
conde which
-
affect
sickling
-
- does
-> It not
polymerise
with thos

the
sickling.
-> (f) in tbf decrease

If it bind then also itis the

->
effect
of
(4) in
->
Has core. (4)
sickling.
sickling.
the

② MCMC(4) as it
going
is outside so cell
dehydrated.
is

In MCACH.) I iis
G-thalesemia good
->

pt. of

for
sickling.
(Notbs No
polymerisation)
-

Understanding Sickle
Cell Anemia
 ③ Ht
quantity
2.3 -

BPG : r in there the

.
worsen

sicking
.

It leads to more
unloading
so
02

polymerisation
more of Hbs .

⑨ Transit time : whenever the transit time ( ↑)

it increases the
seeling
.

In time of
infection more e- selections are

expressed on endothelium so
infectionC) .

Diagnosis
• :

✓ ✓

Conan Conlon
homozygous
SS
heterozygous
As
I
↓
This
pt .

will present
get
here will
with

smear singeing
.
on
peripheral NormallyRBC
Normal on PS .
you
→ But pt .
will present with

vomiting
a
yr
old child joint pain
C ischemia with colon blood
) Baek 4 Abdominal pain
supply ,

peripheral
repeated intentions But on

will ⑨ RBC
get smear we
.
 ↓
should do test
always ya
we a

SIC KUNG TEST .

Reaving agent
→

corer slips →
Blotto
↓
with wax sickle cell
along
.

Now ,
as

trait is
present so

polymeric
will
RBC
*

→ It is a butter
used in

solubility test .

→ false + ve can

in
high
-
Beaner be seen
in
kept
are

pain
to see
viscous fluid or pt
through Adeeb
.

with leukemia -

Inference : Blood willbe

hazy
as cells are

false
polymereiing → ve can
. -

also be seen in
pt
.

with Anemia .

test on Electrophoresis .
 -

to
Hydro reurea
given
pt .

of sin to produce
Hbf smh that Hbs
con c- * ) .

> As
ctleterozygous )
( Hbs + Mbc )

its is AA
lysine
a tire
Hbc →
.

→ HBD & Hba are bound in people of Punjab ,

they also have

mobility like Hess .
 *
test
confirmatory
More is HPLC .

Pti on
HYDROXY UREA '

& also
→
Heterozygous A#
.

→ ESR also be done sickbed RBC &

spheroey
can as -

tie RBC will not stalk .

Es Rcti ) -

elution
microscopy
→
.

punt
drug approved
→ >

'
by FDA
¥
there will be anemia &
'

-
.

no

Vaso -
occlusion .
Summary
of
diagnosis-(1) Peripheral smear
-Y
test
·

spcangive
due. Sickling
↓
test
solubility
A

Ebetrophoresis
-
H PLC

Spotters:

Sickle cell
cond
Heterozygous
-

as more RBC
↓

function
Aspenia
as
nuclear doesn't
maturation
central
Hb
case
in of
seen

B-thalesemia
takes place
perfectly.
q

13
~

W
Nucleated RBC
Aultimate
poesis.
extramedullary
compound heterozygote
ES
order of
polymerisation

raft
ax

I
 Deficiency
Liii ) GGPD :

manner so
→ Inherited in ✗ -
linked rewire
male are more affected .

is
> It GGPD
not there
.

3
& if needs
NADPH
2

free radical

attached
sulphahydriigrp
-
are

will bind up &

to tho they
Hb will den at urate & reside
on surf all

→ Can be seen with

live main
wing
suprauttal dye
.

Due to #F↳
in
P .
 As Heinz bodies so
spleen
try
→ to remove >

spherocytosis
I
s.tt/vCt- → .

haemoglobin cuddle all the

will

towards
→ spleen

opposite
the end .

Halt of the cell is vacant .

/
/ Blister
hemi
ghost cue
cell .

→ thence remember GGPD is also

important cause of

spherougtoeis
.

varianlsNG6PI-
→ Natural

F-

who classification ≠

No
hemolysis as there
{
⑥
activity
is Gopi .
Note →
GGPD Odisha Kerala
Kalyan
-

, GGPD -
are

-1 also known .

point mutation at posh

99 C Alanine → )
Glycine
Clinical correlates
__
•• patient will ⊕ of
typical history
INTERMITTANT
very

Bleeding hemolysis episode

/

+
Sir I colour but it
got brown urine
stops know
.

↓
when bleed ? doriot
hemolysed
→

young Rbc bot

no tree radical is ont in RBC

young
.

FR accumulates and destruction

Gradually *
starts
↓
hemolysis
Now
cytls
Bone Marrow
→ New
Reticule
4

stops
Bleeding
+

continue
cycle
.

• whenever
you
see a
patient of GGPD never

Cmeans
take the sample rent
day
of
symptom
bleeding
take sample
immediately
never after
episodes ) because will
nothing
you bind as new

formed
by
cells are Bone Marrow .
 be a)
Bleeding like hemolysis by
•
/ can some

traitor → Infections cmosf common )

as
infection
body produces tree radical
during
Drugs
→
Prim
aguirre it induce
-

as can

oxidative stress →
hemolysis
-

→ food Fava beans ( Dis

Ha
-

-
also

FARISM )
Diagnosis : 1 .

peripheral smear -

BITE CELLS

SPHEROCYTES
%
Suporavital stains -

Heinz bodies

test
screening
3.

Indirectly
-

measures NADPH

activity
.

2
>

Methylene blue will activate

by activating pentose
NADPH NADPH produces them sconce
on ur
phosphate
pathway
.

>
Meth hb ⑨ teb

4. Dx of choice
Enzyme by EUSA
-
-
 body
.

2-
Hein

→ GGPD & sickle cell are most common

adaptation in
malarial
plasmodium .
there plasmodium can't
survive &
killed free radical
by
.

→ In
neonates jaundice is than
anemia
more common

b.cz
.

majorly
see Heinz bodies are not

damaging so not intravascular

hemolysis
.

But spleen kill them so EVH .

t
so
pt -

is
not anemic but can show jaundice .
take
awayof
→ never
diagnosis of
spheroeyto
make a -

sees in Ps neonate

haemoglobin
as cell are more

send so you can mile .

& above written

point about jaundice .

Enzyme deficiency
* in art • a • PD

Pyruvate kinase
•

Pyrimidine
nucleotidase
• -

5-

most ie common in

poisoning
lead .

Pyruvate
→ but
debicieney
kinase are rare ⊕

with
Ectliwocytes projection
regular
-
small .

due to
prolonged kept sample in
•
EDTA
-

Me cause .

•
Renal abnormalities .

pyruvate deficiency
•
kinase .
Civ )
paroxysmal Nocturnal tlaemoglobinuria
:

Acquired debut
genetic
→ -

→
Appears people
elderly
in .

stenosis ?
prettier are

Cheuxroegtelweutrophillic
Alkaline phosphatase
*

just molecule
s+É☆E@
a

⊕ in LAP
stabilise

[5

→ In
PNH PIGA lost
gene
,
is .

↳ & as convertase
regulate
No one to
t

they will activate the compliment in ALTERNATE

pathway
.

t ↓

iuiwy
IVH Endothelial
to
pt ⊕ with teburia tvnwstderinuriai but
Release of No
.

> Hb released will neutralise the

NO There will
. be vasoconstriction .

Cds
dilation
)
& constriction equally
managed
 ↓
Activation do platelets &
coagulation
system
.

↓
Thrombosis .

→ PNH & sickle cell Anemia are thrombosis

producing hemolytic
Maior
anemia .
Pmt is
purely
by
but SCA is Ertl
'

IVH

so if will ( ↑ ) till
→ It is
acquired mutation
ablated
got
all the stem cells
'

the lost BM starts

→ so once all pig A gene
destroying stem cells .

1- .

Aplasia
'

t.

Initially pt prevent with

erythroid hyperplasia
.

it
paneytopeuia
will with
but later ⊕ -

triad
typical
paneytopenia Cpt will not come

at the
generally
Elderly stage of
hyperplasia
IVH Thrombosis

* since attested are

lost
the stem cells are ,
genes
leukemia
Acute
myeloid
later this
pt
undergo
on .

can
Dan:
that
patient with
typical history get
when I
→ ⊕ up

morning got
in the I teburia
.

&
It is a misnomer that IVH
only occurs at
night
what
happens is

→
÷: → Acidosis
-6

Activate
↓
the
complements
IVH → tlburia .

→
ps : n → of Ds
Initially
-

RICA
.

but later
pye → Aplasia .

→ Bone
Marrow Aspirate : Hyper cellular →
hypo
f-
Aplastic
Special stains
→
: AS NAPA ) / LAPA ) ( alto in
call , NAP
is Cf ) )

test / test
screening
→ : Ham Acid
tyres
.

the blood
Take
±

Add of pt other 's matched serum

any
serum
.

or

it
aeieaioy at 6.5 .

±
complements out → CELL LYSIS .
.
This is a cumbersome procedure .
so we come

with
up
test
Gee card
compatibility testing
→ Blood bank .

have Anti
gels Af & Anti MRL
These ☐

antibody
so Rise forms
agglutination
& do
not come down so test is ⊕ .

not the of choice

diagnosis
→ It is as can
you
of stem
showing
miss the care where 1% cells are

later
surely spread
PNH .
but on it will .

* D.✗ of choice → FLOW CYTOMETRY .

d) eheex the populations of cell positive /

Neg
.

for ↳ 55 & CD b- 9 C Moy . which bind to DAF

& MIRL
Respectively ) .

only
^ '
A → +ve for contr
c D
; C → bor 55
only
+ve
i
-
- - -
-

G)55
- n - . .
_

I
D → tire for both
B A
.

1
, B→ -
ve for both
>
CD59
p¥ with PNH .
 DAF
→ MIRI is
imp prettier to
diagnose than .

(1) Dx of choice →

↳ Detect
GPI
directly
protien &
↓
Muros once
give
Pt
.

is
-1¥ .

*
*

Pif

Rim : what understood is that

Basically
we

PNH is a
type of complementapathy .

controls
directly C5
so Eculizvmab
drug
→ → →
.

It has ebteits will preterit like deb

body
→ side
-

as

of complement so pt .

are
prone to meningococcal
ienbeitioy .

→
Costly
.

have to under close swwilllance as

→ Pmt pt
.

common cause of death in these pt .

is

thrombosis .
Pt may
-

die due to stroke .

Note → cause of Aplastic anemia in Childrens & adult
are different .

Adult pt .

with Aplastic anemia should be Dx

with PNH .

Autoimmune
Hemolytic Anemia
c)

of Ab
Types
-

Activate at temp [ 377

body
.

Pent→#→B
usually
•
→

can activate

complements controlled
by DAF & MRL
→ can be
↓

MIRI controls the cos convertase cimp.is MIRI

& about DAF
Till MIRL is ⊕ MAC is not formed I don't
. know
↓
molecule
by
cells well coated Bb as

MIRI is ⊕ +

cells will remain coated & Czb → God .

t
Liver have receptor for Csd .
 ↓
Kup wer cell will
digest Gsd complement coated
cells .

↓
activate
EM
Cdlthough Igm complement ] can

DS .
is
known as COLD AGGLUTININ DISEASE
what happens is
peripheral part of body
have

colder
temp .

by
which
dissociates
cells coated will
Red IgM central
Ab

RBC when
part more to
-

( warm
temp ] .

destroyed complement costs bound to cell & will

only in liver .

↓
EVH .

pt
of cold
agglutinin disease
-

presented with if
are Tim
IgM
are activated more or MIRL is less

than normal
.

* this Ab ?
why Igm
 Antigen :

are produced
against
±
antigen
in 99%
transformed which is ⊕

of adult people .

eruption :

there active Ab But

IgG usually
→
is
.

warm

which ie all-in
-

is a
special present Ab
cited at colder temp Kya DONATH
LANDSTEINER
.

Antibodyactivate
.

→ This
IgG & can
complements cause

Ivy .
so
IgG are Ha Biphaeie Ab .

COLD Active ANTIBODY

'
-1
. ↓ ,

IgM
↓
IgG
CDLA)
cryo globulin
I ,

cold
Agglutinin Ds . ↓

paroxysmal
vasculitis

urea
cold
haemoglobin
& CAD
→
pct is creamed in syphilis
tnbeitiors cancer
occurs due due to
drugs
.

,
,
 P'
'

Grate Ag
.

C Both)

↓
+ Does not
Mycoplasma & about RBC

TM can convert
i into
Ag
"
IA
form .
There can occur in both

they
occur
3 diseases as

periphery
in .

Clinical manifestation :

CAI PCI
→ caused
by IgM → caused
by Tga
.

→ when the ↓
you take

very good
Pt sample you
.

can
Hit is a

opsonin
phagocytes
so
see
agglutinates
_

coated Rbc
are at eat
up Iga
 ↓
sides of test tube
erythrophagocytoeis
.

0000 →

IgG
coat the cells at low
÷
088 temp but activate
they
.

at
→
RBC count are complement core
temp .

Iv ¥
done in Coulter 's
.
Pain in ball
Machine
Dancurine tlburia
.

binding → RBC + .

the
spleen
→
Cas it will count removes
H) .

Membrane so salvos .

4- 1 Rsc)
clump as

but bfel cells

MCVC ↑ ) ,
MCH ) keep
doriot have the benefits
the

they
warm
of sinusoids so
✗
sample
the
totally
◦ o o removes
RBC ⑨ MCV ⑨ MUT ⑨
, , cells .

also
↓
blood
grouping
→ In

will encounter SPHEROCYTOSIS

you
the earlier
problems as

formed
agglutinates
are

but will find AB

you
+re But it is
your
.

cold
agglutinin Disease .
 Diagmeeism :

oof

FIT

↓
will shed off
at core temp
Czb → Czd
.

: OBE
should be

µ ditoerentiated from
HS .

I
=

Cheredetary
spheroeytosii )
Noten :
test

Cindireet )
( Direct)

$05
coated
Rbc
by IgG
•
are

test
Coombs
performed
•
is

by adding antis era

Iga
*
Agglutination is formed .

plasma is taken to detect

Ab
the
presence of
.

Ef
compatibility
→ Ict is done in

testing ↓
in blood bank
donor is taken to
sample
Cheng the anti cab - .

*
pt sample
.

is taken and

mix with donor

sample then .

anti Sera is added .

Eg → In
Rh
incompatibility
if foetal RBC is taken
9 coomb 's test a- done it is Dct & it mothers
plasma is taken & cheered for Ab it is Ict
* caused warm AIHA → Infections

drugs
malignancies
C chronic

disorders like
lymphoproliferative
CLL
)

predominantlyAEHA
→ CLL causes warm but can

also came cold .

→ EVAN SYNDROME : ITP + AIHA . ( Immune

thrombocytopenia
)

Drug
induced
hemolytic Ananias
→

V -1
V

Drug Absorption Needy Autoimmune

type type
some
type
binds to RBC does not
Drug drug
• •
Now

drugs get & becomes new

my
bind with RBC
adsorbed to RBC or RBC but the
triggers
.

11 ◦ Ab boomed binds with Ab

formation _

caused
Commonly oomf
both RBC A bots
drug
•

Ab are formed by methyl

against drug
.

Agglutination reaction
↓
halbhazard
of RBC 's clumping
* This is Router formation
t

stalks of RBC 's .

*
⑨ =
= tis

S .

Reti
=
ailocgtes
formed in
spheroeytes •
are

tis
◦
PCH
Abi
acting
• warm

•
GGPD Def .
2
IMERETI Anemlttsn : Rk
Citlways
↓)
-

1*1
"

Pure Red cell Aplasia

Anemia
C. PRCA )

→ CMC )

rest are →

?
how does Aplaeia
they
cause

→
✗

Intrinsic stem cell debut T cell immune

Eg → PNH -
Piaa
gene dysregulation
↳ current ]
they
eventuallyinto theory
progressed
Aplastic Anemia
probably
'

TH , cell
activated
get
.

IFNY ,
TNF → stem cell .

to in Aplasia ?
going
see
what are
you
→
fat
BM contain
particles → cells +
1 : 1

[ too
Age
=

cellularity ]
-

[ 20%
cellularity is ok ) .
 of
myeloid Erythroid
→ cells made :
up
3 : 1 .

Sinusoids
+
Br are

normally
collapsed .

A BM
B.
Try trabecula

cells are lost .

fat ⊕
only
.

Biopsy
This is Bonemarrow
.

* when B M is
hypo cellular P →
Paneytopeneea
.
-

Hb < to
gnldl
Pt < 1 lakh
WBC ( yooo

in next you
paneytopenia Aspirate
→ when see Ps
you
should do is Bone
Marrow
.

As BM not have cell → DRY TAP .

 ↓

Next
investigation
↓
you should do is

Biopsy
.

cellular Marrow [ two )

typo case
.

if CD34 * )

↓ L
×

then tell MDs

you can
Leukemia
it is
Aplastic anemia I
there should not CD 34C )
&
be presence of
splenomegaly
.
Myelodysplastic syndrome is a group of disorders when
the blood cells produced in the bone marrow do not
mature into healthy cells. This leaves you with fewer
↓ healthy blood cells in your body. The blood cells that
have matured may not function properly.
if
enlarged then Myelodysplastic syndrome (MDS) is a form of cancer.
spleen is

spleen eat those cells .

may ↓
then cause Of Aplastic Anemia .

"
×

if case of Adult case of child

+
f-
aplastic
testing
Pm Inherited
anomie
syndrome
.

- thumb
abnormality
* How do we
work for aplastic Anemia →

Mi toney sin
adding
on

c. own
got break
down .

Tt there is no

Fanconi Anemia
then
repair would
have occurred .

But radial formation is

abnormally
seen .

ch are joined .

Tod
N → 6 ooo -

tooo
N → I 5 •

lakh

↓
N→ 2% Of 500 0000

Cii ) PRCA : cause is idiopathic

generally
→
urn

infection
attack

→ There will be
maturation arrest .

also do maturation arrest .

They
+

Large Granulocyte lymphoma

* disappears
thymus
on s✗
PRCA
.
 infection retain for 7 transient
* parvovirus to
days
10 so

Red cell Aplasia

.

↳ But pt with .

tmmunosupresrim like transplant or

Hiv it be persistent
may
.

* Inherited form of PRCA Diamond Blackfan Anemia

⑨ → PRCA is due to parvovirus .

Dog ear protrusion

is
cytoplasm
•

bluish
&
very
nice → soy of

Erythroblast
cell so ,

◦
protrusions can

easily
seen .

•
Inclusion in Nu .

:
3
IREY TOILE HYP0cnRoM1CANEMltm
→ once the Hb enters the cell → cell division stops in

Erythroid precursors
.

Hi in size
division stops Nu

Normally
→ when cell
.

→ But now cell site also HS

significantly -4 cells are less

haehioglobinised Og
.
 Normal
concept : _

www run

first about absorption & transportation

study
→ we will
of iron .

can't absorbs felt it converted

Body
• so is

feat Duodenal cytochrome

to
by B.

Fest Divalent metal transporter 1

by
absorbed
.

C also absorbs west MNF ,

ferritin & transported

remaining
stored as

by Ferroportin .

d.

transport fest so HEPHAE

only
TRANSFERRIN
-

STI N convert feat felt to .

bound with
* Yzrd of Transferrin
Normally
is

fest C Transferrin saturation

.

is 16 -50% )

Normally as 33%
 -

CTIBC )

( SI ) ( U IBC )

Transferrin
saturation CTS )
◦

dl total
Tst UIBC = Tl BC
300mg / It is the
c. o →

/ to
×

33% in ÷ ° ' Bc =

200mg
Idf .

Receptivity
bind arm
a normal people ↓
/ de )
Clooney when there is deb .

of iron
receptivity
for
few )
binding
of .

↓
Now this transferrin bound Eron reaches
to BM .

fest
endocytosis
mediated
Receptor →
goes
inside the endosome .

Acidification of Endosome .

In

transferrin released boom

receptor 4
receptor to cell membrane
go
.

I
fest is converted to feat inside the Endosome
 ↓

fest come out of endosome

through DMTI 80% -
.

got .

go
to mitochondria for beam
synthesis &
remain in ferritin
10-1
cytoplasm
.
as .

→ PEM

↓
It has max -

Transferrin Ree -

ti
when it converts to hate
erythroblast it shed

down Ms TFR
↓

Erythropoiesis
Serum
•

•
.
TFR ✗ .

"
to do with iron
Nothing
.

NII→ ferroportin is present

in (1) Duodenum

Macrophage Bry
a) of

C) foetal placenta .
Serum iron which is bound to
transferrin
Iron

TS -715-507 ( 33% )
→ TSM ) → It means teeouostderosts .

TSH ) → IDA & ACD .

→ TIBC : / dl
300µg
.

Some terms & Parameters :

→ As ferritin is a

Acute phase Reactant

-

C unbound
iron → toxic GoingRBC
" dead
to
Fenton mm .
] ,

macrophage

↳
to make

☆ Hq *In → in case
of Aa>

as * iron & trot

F-
My
TIBC

Afoot
① Anemia :
deficiency
Iron

→ There is Aron dueto hookworm

dietaryother
deficiency
no
.

infection or due to reason

any
.

I
serum iron a) , TSH )
↓

Receptivity ↓ iron
for ) → Tl BCH )

Ferritin * I → Most sensitive for

detecting
in
IDA
I.
* stage

Blown

features of cells in

stage

C Red cell Deviation width )

•
cells

} 4£

→ Serum transferrin division is

receptor (↑ ) at cell

not
stopped dueto ⊖ of tels .
④ Anemia of chronic disease : -

A to Doc tutorial
wording
on amount of chronic inflammation
" infection

starts
or some

malignancy
. our
body
releasing
It 6 .

↓
It -6 →

-1

teepci din
*

Goes portent
& block Ferro
,

All the iron trapped as ferritin in Duodenum

 ↓

Hep chain out as controller of Iron release .

by controlling the port .

↓
Serum felt ) ,
TS Cti )

Anemia a ACD .

*
this occurs in case of chronic disease which

lasts for period of 1- month -

It excludes Anemia of Renal ,

liver & endocrine
diseases .

✓ If

* so , whenever serum Iron c) → ttepciedin (↑ ) & control

iron metabolism .

E- :
i. e, Rheumatoid A. ,
TB ,
Crohn's
Ds .
cag-e-spt.to ≥

two case

transferrin
s.tf.pro/H)reuptor(
serum

) ↑
 ⑧

& #

Genes regulates

* HFE
9 Memo javelin mutations seen in

hemochromatosis .

couainly tire -

28247
C .

Hereditary hemochromatosis (he-moe-kroe-muh-TOE-sis) causes your body to absorb too

much iron from the food you eat.
↳ leads to iron overload
•
DMTI Mutations :

→ DMTI helps in fest transport .

out of
Endosome mutated feat will not
→ come
It it ie

obstructed heme will

syn
so
.
.

↓
card ?
microegtie hypochromia
their iron but iron
Macrophages releasing
→ are

absorption is not
place properly
taking
.

feat &
As endosome not
releasing Macrophage
releases felt so ,
serum Fe ↑

TS ↑

but TIBC ⑨ .

As Freon overload → hepctdin ( ti )

.

no

>Transferrin
*
is absent .

Off

ge☆
*
→ As in both case Fe is not
transported to lives

*
FIESTAymphaeytes
heptoeytes
> pencil
cells .

Note → Platelet 1 in
IDA as Eaythroeytosis E)
megaiaryoeytosis
so also .

*
Gold standard for A of Marrow Aspirate
IDA → Bone .

Cheek for iron stores with

IDA )
prussian blue C
Early
. .

* serum transferrin receptor is used to dew IDA &

ACD -
Ciiisideroblastie Anemia :

containing erythroblast
Iron
.

↓
blast accumulate in

containing
iron cells

why Marrow ?
*
goes to
feat Ff-

→ sideroblastie Anemia
coebeet with its formation)
C Iron donof incorporated )
* vif.BG in Heme
iup
synthesis
role
play
a
.

as a CO -

FACTOR

-1
is

Inherited

• Detect in ALA synthetase

C.Amino hevolwenie Acid )

✗ linked
• -

→ consume BG

Myelodysplastic
e isoniazide)

Syndrome
Anemia
◦
Retractive
with sieaeoob last
Ring
.

@
what in staeroblastie Anemia ?
happens
•
Miho % *
Normally
10 -20% of
iron stored in
cytoplasm
as ferritin
Contento ↓
} be
↓
Erylh
a Rs And of
approx 90%
.
.

RBC precursors void have

precursors
having accumulating
iron
in mitochondria .
this iron store
↓
.

Normally
Hence cells are

51DEMOB Rs
LAS TK NOT .

in IDA Tron
normally
→ ferritin is a soluble boron so

stores are lost fast i. e , ferritin .

RS can be documented in peels Prussian Blue .

Rs come in blood & Nucleus is lost as a

pro
-

do
Erythropoiesis
we
.

Blood
→ can be seen
by PPB .

be due to a insta
remy * in
en
BHB
may
. -

erobeastie Anemia or
post
splenectomy .

*
In BM
killing
of
Erythroid cells Ha
.

Ineffective
to erythropaenes
Anemia .
 ↓

EPO
Erythroid hyperplasia
.

→
f.

Body starts Eron absorption (↑ )

doing
-

+
in Ineffective
erythropoiesis
.

Results Rs →

€
have
person will
Slowly vion overload .

I
Sfe (↑ ) , TSC ) ,
TBC (t ) / N ,
iron stores @ ) ferritin,
[↑)
↓
whenever these conlon order
peripheral
you
see a

smear .

fending → ① Anemia
② Dimorphic RBC
MCHC cells ,
Nornioeytie
ntormoehronuee
*

As it is not a
global
is
Conlon normal
still there .
erythropoiesis
Dimorphic
① Stderoblaetie
② Blood transfusion → If Recipient have

anemia

Megaloblastie
.

③ IDA +

in tmaerocytie
 ③ Pappenlri ewer bodies
↳ tune put PPB . .

Next you should do

BM smear
↓

RE
wo-te-sstaeroblast.ie
normal in a

person
.

classifying
•
for Std -

eroblastic anemia
under MDS there should be 715% Rs but .
if SFSBI
mutation 415 also be under
is
present RS can
%
MDS .

↓
with patient dr is ④
of Miss
having
Rs soot .

karyotype
but 10 -15% of
people shows deletion of ch 5 -

Protoporphyrus levels
high
* In

poisoning pt
lead .

are .

* stderoblastie Anemic patient should kept in follow

up
as 10%
may
lead to Leukemia C
Mainly MDs pt )
. .
.

g.
 Thalassemia % -

mmmm

• This anemia earlier found in →

↳ Discovered this anemia

.

→ Let ch 16 be
girl 4 ch il be Gene from this 2 oh
boy
-

- -

combine & make hb .

hb

hb

hb

of lhalasemia
Pathology
:

→
quantitative debut
→ If there is no
p.ie , BY p° B Thalassemia Maior
" "
P but aint -

is less B thatanemia Minor / trait

p° / Pt B thalassemia intermedia
.

11 11

BY & →
of Entrant
switching of tlb
by
class occurs 1
year
•

life .

month
rapidly
•
After a Hbf will forms .

It there is p then ✗ will forced to combine

•

no
 with Y and booms fetal CHBF )
haemoglobin
.

→ some amount of formed

✗ 282( )
Hb Az also .

→ Hbf is selfish
high albinthf
a
hb .
It have for

02 not want
stay
✗ does to with
9
.

→ It there is
formed
forcefully
no p tebf is .

Hypoxia →
Epo release .

↓
9 are less & also ✗ does not want to bind with it
so
✗ born ✗ 2142 ✗ tetramers
.

↓
507 hbf are formed as ✗ tetramers

containing RBC
undergo apoptosis .

Ineffective
erythropoiesis
.

Na

°
0

BM

↓
some of RBC which out of BM
having 9
come

4 lots of
detective
✗ are so that spleen
kill them with %)
may stay
.

K does not want to

↓

have lot of in elutions in them

They .
 ok

8 • •

0
•

nuclear heat mitotic

In
Rbc spindle
remanent are there
CCABOT RINGS ) polyriebosomes
debt
[HOWELL JOLLY BODIES)
( BASOPHIL LI C

STIPPLING )
↓

not formed
properly
Hes .

formed RBC division

only
when teb is
proper
stops but now
you
can see

Microeytie hypochromia
• cell .

SM
significantly
•
↑ Cts
voi . rotas
↓

You have to accumulate that ↑

SA En small
anti
of rot so membrane in centre
excess
appears
.

Target
••
cells .

*
As
hypoxia erythropoiesis
I also drove for ↑] .

↓
at > • month
complication
usually
these
pt
got
.

of active
At that
.

age
.

time all BM are

Erythroid hyperplasia
So , leads to →
 CREW CUT APPEARANCE
THA LASS EM 1C FACE
*

starts Na
Extra
erythropoiesis
also
Splenic
Erythropoiesis
Medullary
.

Due to
rapid division nucleated RBC comes

to blood .

8 month old . thaleseniee

main Pt
Microeytie hypochromia
•
'

• ◦
Pls -7 cell

Target cells .

Nucleated RBC 's .

RBC with Howell bodies

Jolly
.

Cabot
ring
H 11 .

Basophillie
stippling
.

Summary
of
pathogenesis
↑ tlbf
*

hypoxia

( T)

Deaths due to
* A new
update
✗ chains
+ accumulating → It results in
Band 3 Of RBC change
in

Apoptosis
thiury
tonic to RBC →

considered
Now altered Band 3

foreign neg
as

them
Ab are

.
formed

t .
or
spleen destroy
So , Ertl → Jaundice Cso thalami -

anemia
Hemolytic
is
type of
a a

↓
Now should do oyc count
you
.

&

Although RICH )
but is not )
proportional
ienbbeetire
to
degree
of Anemia due to
erythropoiesis .

BB

f-
↓
but not )
Pls of thalassemia minor
Anisopoiriloeytosrs
.

1-

significantly
-

As there is
hypoxia
no
•
RD WH ) no ,

extramedullarey erythropoiesis
.

→
predominant A- hb ie teh

→ RDW → normal .
 confirmation of thalassemia done
electrophoresis
by
ie
*
.

& HPLC .

D , of choice HPLC performance liquid Ch)

Cieigh
in Normal HPLC →
HBA 795% that -

Major → Hbf > 90%

Hbf
41% Hb of = 0
Hb
Az 44%
HbA2→ variable

÷
↓

he/she
Generally
→ what
happened is
pt come to is late so
you
.

have blood transfusions test

may got so
you may got
but
elevated
always go with Hbf
percentage
-
GIVE ofthalasemian :
-

§
-

SETTff2-EDF☆
DEA

Ha
'

Cintron)

→ It should ⊕ for

to
splicing
occur

eooeitirely
.

*
prettier .

It there is mutation that can occur at 3 place -7

T
translation
mem in

} → not ⊕

detective

intervening
C At
sequence C Addition or

1 at 5ᵗʰ
position G → c. Ft deletion)
Carmen codon

come earlier)
is the problem
splicing
me
y ,

in India) common frame shift

mutation in India is
at +8 ,
-19 , +41 ,
+ 42 posh
new
nucleotide is added .

* All these are non -

deletion al mutation seen in p -

thalassemia Ivs Cl 5) Irs [ 1) -18/9 1-41/92

.

1-
-

.
, , ,

In contrast to this Deletion al mutation are common

in ✗ - thalassemia .
Ncte → Deletion al mutation
thalassemia
1 can also occur in B-

bp.CA MENthat is at 619 HMS / TIP

NIe_→ thalassemia trait parents give

Generally
rise to

thalassemia major patients .

→ so if does not confirm thalassemia from Ps

,
you .

you
have to for
go genotyping
.

* In
peripheral area where difficult
diagnosis
are

to do & HPLC is
expensive
t .

We do ALKALI DENATURATION TEST

Principle : Hbf does not denatwates application

of
alkali by

"
4
→ Supernatant is

>
engineered tlbf

> quantitate it .
 BY pt : Thalassemia minor > B- chain is produced but

quantity
in less .

switching ✗ will bind to p ✗ there

→ when class occurs is

that
enough p so HBA Caz Ba ) can formed .

little less bind 8-

→
As B is so ✗ have option to to 7 4
↓

✗ binds with 3 but

→
2282 7 4% in never ↑ more

than 8% .

Pt is
asymptomatic as there is no
hypoxia
.
.

↓
But a chains more than
are
p .

↓
✗ chains accumulate in marrow ,
can act as

&
by spleen
new

Af
EM .

In this pt .
→ tlb = 7-9
gmt .

but RBC ↑T .

MCV ↓

MCHC cells

RIC ⑨/ or
slightly
.

↓
Antin atal female
Suppose a 25
yr
+
come to OPD C
pregnant OH
Drive for epoc ↑ )
Little bit of
hypoxia
so

thees
p
accumulates so , ✗ → Erm .

t .

findings → teb
Mcv
=

=
9 gm #
Go →
you can think IDA .
 but RBC = b-million ( from somewhere
is

erythropoiesis'
drive

coming
-

going
on
some
degree
of
hemolysis
↓
count
ihumidiately
MENTZER INDEX .

MC V 60
= = 12
5-
.

RBC
↓

thinking p thalassemia
Hence it comes to {B → start of
trait .

t .

Send for HPLC .

it will be
IDA then
bindings
→ It was a

tlb =
9 gm
MCV 60
Pg
=

RBC = 3 million

M I-
=
60-3 = 20

differentiate
very good parameter
* Mentzer Index is a to
between BTT & IDA .

It MI is 413 then send for HPLC .

↓
-

of Hb Az > 9%

finding
HPLC →

↓
also if found
screening
Husband 's done .

positive for PTT then

lady
is told to abort .
✗ Thalassemia :
-

is the most common mutation in ✗ that

-

but mutation B- thalassemia

splicing
.

are me in -

( H)) →
Asymptomatic
B will form tetramers ( Bn ) Na Hbte disease .

Golf ball inclusions are formed in

mature
RBC C B is it does- ¥
good boy)
so

albeit
erythroid precursors .

◦
98 →
Can be seen in
avital stain
super
.

- -

I - -

→ y will form tetramers 94 in

embryonic
stage
.

betalis → foetus will die

Hydrops
.

>

Golf - ball inclusions

→ Dx of choice → Gap PCR -

del 3- 7 4 42 commonlyseen .
 •
MEEEEE Troy :
MCV > 1006L

Megaloblastie Anemia

d) Vif
Deficiency
B12

saliva
+

IS
In duodenum
R- binder detached
>
Proffered ) & Intrinsic factor
binds .

binds with
in stomach
•M

> secreted
by
stomach
[Absorbed )
✓

* B12 will transport

blood
through
in

Transcobalamin -
I
bound
✗ I
transporter cstoongabbinity )
quickly
•
Give B12
,

to tissues

Most
physiologically
•

active form .

vi7;* goto Boneoyaorow

TC + B12

↑Thomo
cysteine
-

↓ Changed to
④ in
Methylmalonyl
contmethionine
Ht)
↓
no s
proper
f- myelination *
sewing counter
•
A for
subacute
of cord .
degeneration eotaitr
for

•
+
homocysteine can ing
cause → thrombosis of
 Note : folic acid is present in diet as
annates
polyglot
✗

circulatory
of folic acid
forms
is
Absorption < Mono
glutamate
methy
b- THF .

CµfDBBggggA4
B12 are

_☒uired for the

au cells of
•

FA
It Cbl is ⊖ then
will stored
g@tffzdseries.J
as b- Me THF
Ha
f- ORATE TRAP .

utility of B12 in folic acid

pathway
•
• ◦
are

cobalamin helps conversion

in

of
cis
Methyl into
Methyl THF THE -

cobalamin FA
Adenosyl helps
Retaining
Cii ) in

by RBC ( FA )
degraded
as

easily
in RBC .

riot RBC folate leveled

deficiency
Hence in .

B12 .

* not formed
deficiency
In B12 DTMP is so dump
is
incorporated into DNA -

t.

detective DNA
.

I
sieve like chromatin
t
Apoptosis of
.

cells .

↓
Those show Howell
will bodies
remains
Jolly .

Cabot Boso Phillie

stippling in Ps
.

,
 of Ineffective
There are
signs Erythropoiesis
.

An
myeloid
will
precursors
show sieve like
feature .

As
megaloblast
→ means
name
precursors
sugges
cells size is more .

precursors in BMG bigger cell

so in
Bigger Ps .

BM Pool PS

RBC precursor binding to appear

megakaoyoiykj µ N⑧DF#goeEBnent binding .

Giant < B

Boggy
slab
cell C. 2ⁿᵈ
↓ to binding
appear &
( ) last
binding
Blast cells are to

1ˢᵗ to +
disappear after
binding alter Rx
cnoferiea for
↳ '

disappear hypersegmented
'

so can't
you
see
Neutrophil
sieve like chromatin
after
Ry .
29 -

48hr alter Also

✗
occur in
myelodysplastic syndrome
post ↓chemotherapy .
.

Last to Foiled after Rx

disappear
.

12
→ Because there are so
large cell so

they
can't
sinusoid so
pt start ⊕ with
through
come out
.

t
.

P Away top EMA

Cspeiialcf
Nutritional anemia)
of
megaloblastie
But when
you see
Buy aspirate you
not
surprise
proliferative
by cbut.by seeing panytopeuia
cells
seeing hyper
.

of
you are
thinking hyproli
-

terative ) anemia

Jaundice can occur but mild due to Ineffective

erythropoiesis .

RICH)
Clinical features :

50
Yr 9-
paneytopenia
.

Knuckles Chipper pigmented)

spleen ⑨

-
Pls EE
Mauro
cytes .
Macro -

oraloeytes tlb

hypersegmented neutrophils Mcv C ↑ )

'

Marc ↑ )
BM Aspirates ( As RBC count
As Anemia
Erythroid hyperplasia
•
so than
Wilmore
lots of last
Megalob
• .
teb conc .

]
MCHC ⑨ /* )
Giant slabs &
metamyeloiytes
•

NC ↓/ ⑥
of
& a site
megaecaryaeyts .
→ Marc can never increased as v4 .
of RBC (↑ ) so

conc .

⑨ / C) .

After Ry Rlc ) at hence Nutritional

day
→ 5- 7- ,

therapy
anemia shows to
response
.

Dx of choice : _

hmm

Trans cobalamin I
Assay Early deficiency
• - .

→ B12 .

Cause of B12
deficiency ≠
•

3 phases (1) Protein B12 →

Dietary deficiency
-

(H ) R -
Binder -
B12

411 ) If -

B12 > PERNICIOUS ANEMIA

d) Cubulin
These
Receptor ←
#
Receptor
also ⊕ in Edney ×

↓ Rec absent in •
Aligarh parietal cell
.

albumin
binding Intensions GRAS BEK
Ab
against IF
• -

receptor syndrome
.

*,

usually
occurs in

50
Years .

this female
already
have

predisposes to autoimmune ds .

~
> Atrophic gastritis
Ileum
> It there is pancreatic
•
Resenting N Ileum
disease → proteases are not
•

Diphylobolhoeium Melun
tatum
released → R binder does -
not
sitting
in
leave B-12 / Due to
Bacterial
overgrowth alternation in pH
•
.

then can't bind

B12 to
Receptor .
PI-naeg.mu :

newest
Maerooraloeytes
N
wogs →
.

BM iron levels
hypersegmented
•
/

always
1 in
Neutrophils .

megaloblastie
anemia as there

cycle degradation by phage

is of

then E)
hypoxia [↑ ) Fe absorption
→ .

Cholo
trans
cobalamin is affected in
I)
deficiency
B12
-

Gastric
↓ tongue
atrophic
↓
¥eeby tongue
lead to
May Gastric cancer

Not → It you Adie acid alone then it will add to folate

give the
trap & worsen
symptom
-
 itntinatal female bor
generally
FA to
→ is

prevention given
of tube debut Ot should document
Neural . so

that she doesn't have

Vif
deficiency
.
B12 .

test
Schilling
mm ~
: to cheer Ihe cause of B12
deficiency .

first Radiolab elkd B12

opere It will
→
absorbed then
in urine
passed .

Then
give TM root B12 after 2hr of oral radio _

Abetted B12 store

It will I
→
deplete all TC -
-

so that radiolabcelled B12 will absored then

enereted not stored -

In urine
,

× →

{ 10 %
> 10% → ⑧
¥
radiolab eked B12 + If It excretion A)
give
then →

then Dx → pernicious
anemia .

↓
If not then Antibiotic if enuution
give
u + →

C) then there
be bae
growth
.

may
-

Ft not there is some other causes .

donof do test
days this
→ Now a we .
 f- 1GW Test In case of folate deb you .

can see foramino Glutamic

aetd.in urine .

Gare Histidine ¥> Glutamine in urine .

> for amino Glutamic aeeod (t ) .

differentiate
* we donot do this test abcz
been v17 &
if can't

deficiency
.

B12 FA .

then how ?

RBC & THEIR INCLUSIONS :

maturation
f. Nuclear size
during
have RNA]
c.
Reticuloeyte some

→
Activity done
by spleen
to remove the extra
=
like inclusion bodies
things .

* In
hematology we use
Romanosky
stain .

Methyl Blue + Eosin C mixed in Acetone tree

methanol .

disturbing erythrocyte
maturation
But to
* see the RNA without the
we should
the supravital stains use .
 stains
*
methylene Blue
Sv -
New

bowing things
Brilliant
cresyl blue
*
stains the

Globin
seen in 34 mutation

C At least
2 dot should ( )
been to confirm

it as RNA )

Baerrground is in blue
colour cells -

are also in
blue colour
↓

stain is sustain
> RETI COLO CYTES
.

*
this is blue colour stain
→
Again 1-
.

Sr stairs

than 2- BODIES C denatured Hb seen

deficiency )
in GGPD

→ seen in ✗ - thalassemia where 34 Chains

are deleted .

↓
B tetramers are formed .
Some other Inclusions :( seen in stain )
Ronianosky
→ Nucleus have to be rumored .
so if there is Wu .
remanent
due to
splenic hypobunction te
, Asp tenia .

Excess remanent Ineffective

Nu → In
Erythropoiesis
.

Anemia )
C
Megaloblastie
( thalassemia )
*

Ha Howell
Jolly
bodies well seen in
very Romaniany slain

i.e
→
If spindle is not removed ,
cause is same ,
⊖

of spleen .

Cabot
Ha rings 8 →
spindle
→
It have cluttered
polynibosones
we
÷:
seen
Ineffective
in
← fine
<
×
two
types
coarse
erythropoiesis ↓

they appear
as

poisoning
In lead

bassop billet
stifling
↓
: read ⊖ pyrimidine
.

nucleotidase .

CIT eats the ribosome

 baeophillie
sapling
coarse

* Some other inclusions

→ tlb
crystals → At 6th posh of
chain
B
globin
.

Glutamic avid
is
replaced by
hyping .

having starts
forming
seen in pti
both sickle &
crystal crystal
.

RBC t
shaped
-

of
At some
posh
GA valine
→ =

tubs .

*
pappenhiener bodies

In BM → The cells which have normal iron content are Ha

siederob last -

t,

when
by
somehow Fe it not incorporated into prolopor -

if starts mitochondria
plugin accumulating in .
 ↓
Iron avunculate in perinuelear fashion .

it Rs at least
to call as
should covered
up by granules
.

Rs can be seen in stderoblastie anemia & this

type
of
anemia
usually ↓
associated with
myelodysplastic syndrome .

Conan are
ya MDs with Rs _

CAT least should have 715% RS )

you
↓

But whenever Sf 3 B1 mutation are present .

if
you
least condos
ringed
at
get ☐% or siederob last the
should be classified as
MDS ≤ Rs .

CSFZP I meet .
are Hallmark in RS ) JIPMER .

C New WHO )

To pearls blue
see Rs we use
prussian
→ this iron surrounds the
nucleus
to
in BM but when the come

the
periphery ,
Rbi
containing
iron are
ya pappenhieuier bodies .

-6

stain
summary eeial

a
1

→
fatal
•
.

( )

*
*

±
at
Dohle
ay
bodies
tiegglin
Anomaly
DB MY 179
mutation

stain
→
→
Romanosxy
pH [ It shored of Rs to

see schooner dots )

+

plasmodium vtrak

s p viran ⊕ in
.

MBC
 Extra SA should
be kept in some
Where 4 i.e, in
centre

⇐ SA)
Dueto it
appears
that =
'

{ add pitcher .
to RBC .

}
* Increase in sq →

layer * only
only inner
layer C)
→

estero

+ ↳ Mouth
spike like cell &

in → keep RBC in
disease
EDTA for more +
Kidney
than 24hr .
* *
spheroeytosis
target
duet
Ankyrin
cells detect
to

Detect in
vertical
attachment
+

hereditary spheroeytosis
Seen in

warm

Paro
autoimmune
Hemolytic A-
no
signal cold
hemoglobin
ceria

96 PD def .

* Ctieredetary Elliptouftosis )

→
Elliptoeytes due to detect in spectrin
&
Debut in Horizontal
allignment
*
Ds →
.

south East
Asian
oralocytons
:

summary