( BETA EDITION)

With
Prof. Dr Mohammed Abo El-Asrar

Edited By
El-Azhar Medical students 2012

Hematology
MCQ X-Ray hematology


RBCs
Anemia
Platelets
bleeding disorders

WBCs

Anemia

-1

-3 Clinical presentation in general

-2

-4 Investigations

Definition
Pallor ) Pallor Pallor (
Hb < 11 CBC
18

4 1- Neonatal period
2- Infant
12 10
3- Childhood period
Adolescent 4- 18

: Fetus


1-Fetus in Intrauterine life

2 fetus Hb is Hb M
which has No good O2 dissociation
 fetus Partial hypoxia
 O2 sensors PO2  hypoxia
 fetus ) Erythropoietin (

 RBCs synthesis liver &spleen bone marrow more RBCs
normal Hb 18-22 gm.%
lung hypoxia Erythropoietin Hb 9 15 14  12
 10 6 ) (  gm.%9
physiological anemia of the newborn
 hypoxia  BM RBCs

! Iron !!
MCQ: - cause of anemia in newborn
1-haemolisis of RBCs 2-nutritional cause 3-bleeding tendency 4-decreas Erythropoietin level

(Causes Aetiology)

: Decrease RBCs Count
1- Decrease Synthesis as in:
1-BM problems
BM failure (hypoplastic Anemia)

2-Decrease requirements may decrease synthesis

1-RBCs
RBCs
Cell membrane + Cytoplasm (Hb)
( ) Vit A cell membrane
:
1-Heam
Iron(carry O2) + Protprophyrine (need "Copper + Vit B12")
2-Globin
Protein
cell membrane & cytoplasm

2-Stem cells
Stem cells
that form RBCs & other cells
- Need to Proliferate & Differentiate
Vit B1 , B12 + Folic Acid
RBCs
3-Vit E
Vit E (as anti-oxidants)
not for synthesis
RBCs RBCs  Free O2 radicals  
Vit E

2- Excess loss
1-Bleeding (hemorrhagic anemia)
2- Hemolysis of RBCs (hemolytic anemia)
Q:- Enumerate causes of nutritional anemia ? & discuss one of them.
deficiency -:
Iron def. Anemia Most common cause
nutritional anemia
B1, B12 & folic acid
Pancytopenia

Bone marrow failure

Causes

 Undifferentiated stem cells  BM

1- Receptors for Erythropoietin H

RBCs Erythropoietin H

2-Thrombopiotin Receptors
for platlets

3- inflammatory cytokines Receptors :
WBCs Interleukin

1- Hereditary cause
Gene defect
defect in Erythropoiesis (all are autosomal recessive genes)

1-Problem in Erythropoietin H receptors only:
.Pure red cells anemia  . stimulus
2- or All receptors :
Pancytopenia
called Fanconi anemia which is:
autosomal recessive gene
cause:
1- Pancytopenia
2- affection of brain cells (microcephaly & mental retardation)
3- decrease in GH secretion or it's receptors
short stature
4- Thumb & radius anomaly
5- Renal anomalies , abnormal distribution of melanin
ttt of hereditary
( prednisolone Receptors stem cells ) stem cells
BM Transplantation
2- Idiopathic Mostly
autoimmune
ttt:1-Immunosuppressive
2- Cortisone + BM transplantation
3- 2ry causes
1-sever infection by toxins & also septicemia
..  toxins

2-Drugs :as Chloramphenicol + cytotoxic drugs & some time Sulfa

3-Viruses:As EBV , Parvo V &HBV

4-Infeltration of BM

stem cells
5-may be Liver & kidney diseases

decrease Erythropoietin H or other hormones.
6-Irradiation.

Clinical presentation of Anemia {In general}

Symptoms:introduction
Function of RBCs
O2 Carrier
so, if RBCs
Manifestation of tissue hypoxia

Brain cells
1- Headache
- Mild decrease in O2 in Brain cells
compensation by VD
headache
2-then lack of concentration
HB ....... ( )3-Dizzness
( )
pallor vertigo
4-Syncopal attack :
cerebral circulation
. %20
5-Palpitation
- At beginning
compensation occur by HR
palpitation
-also may ischemia
angina pain
6-Easy fatiguability :
due to O2
intermittent claudication & muscle cramps
Signs
Tachycardia + Pallor ( )

Investigations
CBC .......

: CBC

-1

 11gm % ......... HB

-2
CBC
:
1- Mean corpuscular volume (MCV)
RBCs :
80 +/- 20 femto liter = RBCs

So -If HB is 9 gm% and MCV = 70
Normocytic anemia

-if HB is 9 gm% and MCV = 58
Microcytic anemia
-if HB is 9 gm% and MCV =110

Macrocytic anemia

2-Mean corpuscular HB (MCH)

MCH normally =26-32 picogram/liter
So,-if HB is 9 gm% and MCH =28
Normochromic anemia
-if HB is 9gm% and MCH =20
Hypochromic anemia

3-whats the etiology???

--- synthesis or +++ loss???

If +loss
so , +Bone marrow activity
CBC
Reticulocytic count
...... RBCs
total RBCs % 2-1 bone marrow
% 2.5 pediatrics
So , -if loss
reticulocytic count
-if synthesis
reticulocytic count
2 1

IRON DEFECIENCY ANEMIA IDA

Written not clinical
Def,etiology, clinical pic.,investing,ttt,
DD

Definition :
- defective synthesis due to iron
iron metabolism
-Daily requirement
2-3mg/kg/day
-animal sources

simple form so complex IDA 
HCL FERROUS STOMACH FERRIC IRON . IRON ABSORPTION ACIDITY

 BREAST MILK IRON

- ARTIFICIAL MILK

- But BREAST MILK NUTRIANT in reaction so, NO CHANGE IN PH so , ALL IRON of it is absorbed
& ARTIFICIAL MILKALKALINE IN REACTION DECREASE ACIDITY so, ABSORPTION OF its IRON
NSAID   may ulcer ANTACID IDA
ALKALINE may IDA

- 

- ABSORPTION occur IN THE UPPER PART OF THE DUDENUM <ACIDIC part> DEPENDANT ON a
CARRIER PROT. <APOFERRITIN>then CONVERTED TO FERRITIN TO CARRIIER PROT IN BLOOD
NB. apoferritin + iron = Ferritin


Transferritin ( ferittin in blood)
to stores in liver
.NB ) (

HEMOSEDIROSIS DEPOSITION in tissues FREE
-

free duodenal cells

stores 6 ..
.. .. IDA 6
1- if PT:
PT:

stores 3 ) (7,8,9   called PT

2- or if intrauterine growth retardation IGR:
9 FT 2.5 storesCalled intrauterine growth retardation
3- IDA of the mother during pregnancy:
- IDA ) ( stores 3

.. common
6  breast iron stores
breast stores 6.
 6 iron
. 9  called DELAYed WEANING

CAUSES OF IDA
either
1.INTAKE:

1- as cow milk
not a good source of iron.

:  iron Called fortified milk  Vit.
unfortified2.DELAYED WEANING
or
2 - absorption of iron
) a. alkalinity of the stomach (antacids +
b. the contents of the food:


1-Tea
Tannic acid chemically react with iron preventing its absorption

2- phytate & oxalate
: iron :  Phytate   iron
 .NB. Contents of food that iron absorption

)1. vit c as it acidity of stomach (ascorpic acid
2. protein
 digestion  pepsin pepsinogen HCL  HCL3- STORE as in
- pt or intrauterine growth retardation or IDA of mother
4- excess requirement
?how
15 -10) adolescence 17-12 (  ) RAPID RATE OF GROWTH (  O2
SO iron requirements
10-15 MG\KG

5- Excess loss of iron
iron RBCs)So, 1- chronic blood loss as excess menistruation ( not acute which lead to Hge shock
2- attacks of epistaxis
50-100 cm of blood
3- anclystoma
100
4- hematuria

?? What is the Cow milk protein allergy

sensitivity   inflm. Of wall of gut

Clinical manifestation of IDA:

- symptoms of anemia:

1- general symptoms
2- specific symptoms:

1-anorexia:
brain fedding center 
 cytochrome system  iron .
2- Pica:
:   
cycle in cytochrome system
 cycle  block
cytochrome system  abnormal signals  PICA
 true PICA pseudo PICA
   pseudo pica -  mainly due to severe IDA  true pica

Signs:
1-general signs. As before
2-specific signs.

1-red glaze tongue
2-spooning of the nails
atrophy
3-10-15%
spleenomegaly

Investigations
1-CBC
1-anemia or not
Hb < 11 gm %
2-type
microcytic ( MCV
< 60) hypochromic ( MCH
< 26) anemia.
even reched zero.

retigulocytic count

3-Cause:

synthesis

2-bloodfilm : no abnormal cells

3-serum iron or serum ferritin
( )
4-iron binding capacity

iron transferrin free sites

Fully saturated  3 transferrin iron binding capacity ( transferrine ) serum iron (. transferrine ... )
iron binding capacity 3 iron  saturated

transferrin iron zero

2 iron binding capacity .. iron IDA IBC serum iron

5- protoporphyin inside RBCs

protoporphyin BM iron  iron + protoprophyrin

heam

RBCs free protoporphyin

6- investigation of the cause as: stool analysis

( megaloplastic anemia )4 2

Q enmurate cause of microcytic hypochromic anemia , discuss diagnosis of one of them ?

manfistation of anemia

Or discuss D.D ??
1- iron deficiency anemia *
2- thalassemias *
3- lead poisoning
4- sidroplastic anemia
D.D
...
1- I.D.A
- retics
- blood film
no abnormal cells
- serum iron & iron binding capacity

2- thalassemia:
- retics
loss
- blood film

bizar shaped RBCs and anisocytosis

-Hb.electrophoresis
Hb.F
3- lead poisoning:

-Blood film :lead deposites inside RBCs

4- sidroplastic anemia
sidroplastic cells In blood film

TTT of IDA
1- prevention:
1- antenatal iron therapy
iron therapy stores2- proper breast feeding:

 breast feeding3- proper weaning:

4- iron supplementation if PT:
PT  IGR ) iron supplementation (2- curative
1-ttt of underlaying cause:
- As ttt of ancylstoma , bilharzia ,oephgeal varices
- fortified milk if cow milk

2- iron therapy oral or parental
1- parenetearal :
parenteral :
-1 anaphylaxis
-2 -3 hyper pigmentaion

severe gastritis oral partenteral gastritis
oral iron

2-oral:

- dose 6mg/kg/day actually absorbed

iron elemental

....
4 3 !!!
inbetween meals

72 reticulocytic count 

0.1 3 0.5
Hb .
9.5 9 11 3 13 12 14 4 6 stores
- common side effect

stool dark stool iron iron
? when

3- packed RBCs

:
6mg% or less

1-Hb

level heart HF anemic 6 10 iron 6
2- if anemic HF

3- surgical emergency
acute abdomen acute apendcitis pallor CBC
.. Hb 8 mg% ........ ttt

Haemolytic anemia
Def :
anemia due to short of life span of RBCs normaly 120 days
119
????????? diagnostic investigation of haemolytic anemia
.. life span
reticulocytes radio isotopes .. 15
haemolytic anemia
- 60 ) life span ( hypoxia

erythpiotin

stem cell activity 2 time
reticulocyte

30 life span hypoxia action 4 BM  normal

- 15

8 normal

BM 8 ... 15 So, clinical present only if life span decrease blow 15 dayes

)Causes (etiology
1- intrinsic cause = Corpuscular cause
- Problem in RBCs

1- Acquired :.
- As malaria merosoite enter RBCs RBCS 8
2- Hereditary :.
- Cell membrane Spherocytosis
- Hb abnormal :. Either Quantity Thalassemias or Qualitaty Sickle cell anemia
- Enzymes G6PD deficiency or pyruvatite kinase deficiency.
2- Exra-corpuscular = extrinsic cause
1- Toxins = non - immune cause
- Snak poisons
- Endogenous toxine ( sever infection or DIC )
2 - Antibodies immune cause
- Transplacental
Rh incompatibility or ABO incompatibility
- By blood transfusion
B

O in which serum contain Anti-B
O .... 
- Autoimmune Antibodies against RBCs
either Isolated ( aginst RBCs only ) Or aginst all systems as :. SLE

Enumerate 3 different types of anemia caused by 3 diff. parasites ?

1- Ancylstoma

2- malaria hemolytic anemia

3-

4- megaloblastic anemia

Classification of H. anemia
1- Acute:
- Intravascular haemolysis
blood vs.
as toxins & antibodies ( G6PD intravascular)
- Intacorpuscular malaria
2- Chronic : ( inside the spleen
Extravascular )
thalassemia, sickle cell anemia & spherocytosis

G6PD
:
. glucose 6 phosphate dehydrogenase
Free O2 radicles ( H2O2 or O3) lipoprotein RBCs cell membrane lipolysis of fat (O3) O2 H2O O H2 RBCs RBCs

reduced glutathion H2 -

Hexose monophosphate pathway NADPH H2 -

 glucose glucose-6-phosphate G6PD 6-

phsphoglucose
H2 NADP glutathion cell membrane
free radicles )acute hemolysis (intravascular free radicles -1 .: ) - (.................. -
) - ( free radicle heat b b b b
.: Drugs-2 ) . G6PDD (

Also, Sulphonamides , Cloramphnecole & Antimalarial drugs
-3 .:
 attack of haemolysis + ) (
4 5

- G6PDD destruction to cell membrane of RBCs

Causes of G6PDD :.
)(X-linked receissive gene defect
chromosom X receissive gen - general of population Called type B+  Enzyme synthesis

black races . type A+ genetics A  delated gene B- MCQ x common male Xy  male Xx  female
 X male X  X
X ) X (
 female .

clincal picture
1-history of exposure to oxidizing agent that relase free radicles.
...... infection free o2 radicles
RBCs Hb  free intra-cellular extacelluar pyrogenic effect
2- so, fever & rigors:
fever & rigors 3- manifestations of anemia :
RBCs manifistation of anemia sever pallor acute
4- jaundice

 Hb ) molecular weghite (M.W free gloumeruli acute renal failure plasma proteins high M.W liver Hb
kidney ) acute tubular necrosis plasma protein urine High
(M.W
plasma protein:1- hapatoglobine

2- hemopectin
both macroprotein take Hb - kedney

- spleen Hb ) (2&1

Hb is very

toxic
Hb globine & haeme indirect bilirubine fat soluble liver direct bile
indirect liver )( indirect5- lion pain:
free O2 Hb ) (2&1 free  kidney chemical tubular necrosis
so early loin pain bilateral unilateral .. 6- red color urine :
Hb  Hburia  urine Hb .7- More in male than female :
:
high grade fever ,pallor ,jaundice , ) irritable (pain
activity
:
1- G6PD
2- urinary tract infection
pyelonephritis
hematuria
.
Abdominal Examination
NB: pain
   tender kidney G6PDD  bilateral
-

unilateral acute pyelonephritis

-

G6PD one kidney

   Hb uria ) (
  opaque

Investigation :

1- CBC

- Hb < 11 gm%
- MCB ,MCV = normal
So, normocytic normochromic
as other RBCs are normal.
- RBCs
more erytropoitine
reticulocyte
So, retics ++

- Blood film
2- Urine analysis: Hb uria

3- Haptoglopine & Hemopectine
4- indirect bilirubine
intra vascular Hemolysis diagnostic  Enzyme
)6- G6PD Enz. Level : (DIAGNOSTIC
 attack 6 ) (

Complications :
 Hb14 gm %  Hb 7 gm % acute 
1- anemic HF
2- acute renal failure
3- complications of Bl. Transfusion :
- 

HB  5gm%  infection 
Hepatits & HIV

ttt :
 : + ttt of infection
1- Avoid precipitating factors


2- Packed RBCs
anaemic HF

acute tubular necrosis

3- Washing of the kidney
hypervolemia
, lasix  washing of the kidney  uine output
:

If patient with malaria & G6PD

/ .. merzoite  RBCs

 pentose pathway

... RBCs  immunomodulators antimalarial

collagen disease
  G6PD  Favism  Theories: certain Enzymes metabolism  free O2 radicles
) ( Hemolysis

 : ) Hemolysis (Favism G6PD. D G6PD. D

Favism
 7   .... . favism
: G6PD. D : ..
Diagnostic .. Enzyme assay : normal
6  normal  normal NADP  normal - glutathione ..

Chronic hemolytic anemia

) 1- c/p in general 2- investigation ( both
diagnosis
: life cycle of RBCs
BM 120  cell membrane  spleen
 channels ) ( phagocytic
cells  ) Heme (protoporphyrin + iron
- Protoporphyrin
indirect billirubin
fat solube
liver
change to direct
then excreted with bile
stool
oxidation in
)
to GIT
bact. Floora
change it to sterchobillinogen (colorless
GIT
sterchobillin
give the stool its brown color
-

(water soluble ) sterchobillinogen portal urobillinogen  kidney

)(colorless also
chronic hemolytic anemia

RBCs 12 -10   RBCs BM 8 

Clinical manifestations:
1- anemia not responds to hematinics
) ( ) ( hematinics   B12 & folic acid  anemia not responds to hematinics
2- history of frequent blood transfusion
3- spleen enlargement:
- spleen 100.000

RBCs 120 .

500.000 spleen  spleen enalrgment

) 4- indirect billrubin
with no compensation by liver ( which compensate only 4 times as normal
)
.. 400.00 100.000   

(   mild jaundice liver

 severe jaundice
biliary system liver 5- hepatomegaly  normal 6 liver
spleen liver spleen
6- also, dark stool
due to more sterchobillin ( mother complaint )

7- but urine is normal
8- mongoloid features or thalassemic features:
: marrow cavity normal 8 BM - In skull , prominent upper jaw ( so, widely separated teeth ) but lower jaw
contain white marrow (
)
Also , prominent zygoma
 mongoloid features
thalassemia  tahalssemic features
. 9- family history:
genetic -

Investigations
1-CBC :
normocytic normochromic Except Thalassemeia
mictocytic hypochromic + Reticeulocytes
2- Bl. Film
spherical shaped RBCs
spherocytosis
- or sickle shaped RBCs.
sickle cell anemeia
- or anisocytosis & target cells.
thalassemia
3- serum iron + IBG
4- indirect billrubin


not > 5 mg/dl ( due to liver
liver compensation )
5- stool analysis
sterchobillin.
6- urine analysis
urobillinogen.
7- X Rays

6 5

Complications of chronic hemolytic anemeia :

 complications of Bl. Transfusion :

1-

 Hepatits & HIVspleenomegaly & Hyperspleenism:

Hyperspleenism

2-

spleen channels normal cells1- RBCs:

RBCs   trabecule phagocytic cells ) (  spleen 
channels normal cells  spleen normal
RBCs abnormal RBCs
frequency blood transfusion  .
RBCs . channels  cells RBCs :2- platlet
thrombocytopenia
3- WBCs
infections
Hyperspleenism

Hyperspleenism
NB. Pancytopenia
3-traumatic rupture spleen :
liver spleen diaphragm thoracic cage liver ....... spleen ) 3  ( normal just felt.  costal margin 10-7 ) umbilicus  ( costal margin abdominal wall
 4-Hemosidrosis :
- serum iron
full saturation of transferrin
free iron which is very toxic
destroy endoplasmic
reticulum of cells.
- manifestations :

1- pituitary:
)Pan-hypopituitarism ( GH,TSH,LH,ACTH

2- Heart
deposition in cardiac muscle
 fibers 900    cardiomyopathy & H.F.

3- phagocytic cells of spleen

- cells of liver

4- pancreas
deposition in islet cells of it


DM

DM ( as type 2 DM )  insulin resistance  insulin receptors

5- gonadal cells
also, 1ry infertility  delayed puberty  testis due to LH & ACTH  2ry infertility  6- skin
( )
Exposed areas  sun L.L  hemosidrosis
stagnant blood
L.L ulcers  necrosis  itching sensation ulcers
5- gall stones:
normal 6 liver

 biliary stasis (gall stones) viscosity of blood 

may cause cholecystitis (acute or chronic)
6- heart failure due to
1-iron (haemosidrosos)
iron deposits in heart ms.
2-anemia
anemic HF
3-Repeated infection
toxic myocarditis.
7- crisis:

Another type of anemia with it and include :
1- megaloplastic crisis
requirements  8  B.M.
B12 iron
megaloplastic crisis stores folic acid
Here pancytopnea
pancytopnea
2- aplastic anemia
infection B.M.
pancytopnea
3- hyper - hemolytic crisis
favism   G6PDD  thalassemia
acute on top of chronic  RBCs
4- hemolytic crisis
 infection as tonsillitis thalassemia
phagocytic function  spleen

transient hyper-function of spleen
anemia  normal cells
8- Repeated infection

1- WBCs ( with pancytopenia)

due to (1) hypersplenism, (2) aplstic anemia, (3) megaloplastic crisis.
2- LSHF
pulmonary congestion
repeated infections of the lung.
3- incidence with capsulated organisms:
splenectomy   hypersplenism

with  infection

capsulated organisms
pneumococci, H.influnza, meningococci, salmonella, etc
incidence with capsulated organisms

cell migration chemotaxis phagocytosis
digestive enzymes cause intracellular killing
resist phagocytosis  capsulated organisms
phagocytic cells   capsulated organisms
  capsule is very smooth

capsulated organisms  glue like materials  -opsonins spleen 
( ) phagocytes < --organism
. spleen
9- Pathological fracture.
expected truma < ---physiological fracture non expected trauma  pathological fracture ( )
. truma medulla cortex 10- stunted growth. (
)
)

1- Endocrinal:
1- G.H.
2- somatomedins due to G.H.
as G.H.

somatomedins.
3- (T3 & T4) hypothyroidism
4- also insulin
D.M.
NB. G.H. need somatomedins
receptors
2- Anemia
No good oxygenation.
3- Chronic toxaemia .
4- Pathological fracture.

Treatment of hemolytic anemia

B.M. RBCs spleen bone marrow
transplantation failure .
:
1- Packed RBCs:

Rules:
) ( 1- Ordinary transfusion
6 Hb  6 H.F.

 ) (

    iron hemosidrosis it's incidence

:
  Hb 8-6 :
-   ... .
- anemia B.M. medulla bone
  dysmorphic features  .
hemosidrosis
) (

2- Hypertransfusion.

anemia <-- 11 <--- anemia

hemosedrosis mentality .
)(

3- Supertransfusion.

12mg ) (
2- Folic acid :
B.M. 8  5mg/day  folic acid
3- Treatment of complications:
1- Hemosidrosis.
)(iron chelating therapy
Parenteral
) (75
)

Desferroxamine
25-40 mg/kg/day

) (growth 5.
)Oral (under trials

benefit  desferroxamine parenteral oral.

2- Other complications as hypersplenism.
:
*
* ) (bleeding tendencies
* investigations pancytopenia
)??( how

12 : = 12 40

So, 12000/40= 300 ml/kg

sure sign of hypersplenism  250 ml liter/kg/Y

   capsulated organisms
splenectomy


vaccination  ..

spleen antigen presenting cells markers
spleen
emergency traumatic rupture of spleen long acting .penicillin 6 7

Spherocytosis
introduction
) (
:
biconcave  RBCs
  small capillaries and small trabiculae
1
*  120 spleen 2
: 1 )(biconcave
cytoplasm .
 mainly extracellular


main gate Na channels ... :

1- spectrin protein :
RBCs ) called ( spectrin ionized Na .
Na
.. small gates AA glucose main gaits
2- Na-pump
Na Na-pump ATP Na
. 21
:
?How spleen identifies RBCs after 120 days
?days
RBCS BM ATP Na pump 120 )
( 120 Na- pump Na small gates RBCs

phagocytosis spleen trabeculae Na spherical shape

. O
spherocytosis

Etiology
autosomal X +ve family history autosomal dominant gene defect
1:1 male or female
main gates Na ( abnormal)

non ionizable spectrin

Na ATP Na-pump
spleen spherical shape
(...... 10 5 )
( ) main gate :

Clinical picture:
1- +ve family history
2- No sex difference
3- Age of onset : since birth
RBCs
hemolysis
increase of bilirubin & the liver still immature leading to neonatal jaundice with indirect bilirubin
that may cross BBB leading to kernictrus= bilirubin encephalopathy
4- General c\p of chronic hemolytic anemia

- not responding to hematinics ttt , Increase frequency of blood transfusion & hepatosplenomegaly & dark
stool & normal urine , Dysmorphic features ( thalasemic features)
spherocytosis general c\p

Complications :
As all hemolytic anemia + complications of neonatal jaundice ( kernictrus)
+gall stones
.. hemolytic

investigations :
1- General investigations:
1- CBC :
normocytic normochromic anemia & retics increased & blood film is sphericalRBCs
+ polychromesia
2- Serum iorn increase + decrease TIBC
3- Indirect bilirubin

4- stool analysis

5- urine analysis 6- X ray

2- Diagnostic investigstions :
1- Osmotic fragility test
: test tubes variable concentrations of Na normal saline 0.9%
Na RBCs 0.2 0.3- 0.4 0.5 0.6 0.7 - % 0.8

RBCS

RBCS
0.9 0.8 Na .. RBCs 0.6
0.5
so start hemolysis normally at 0.5
.. 0.3
So complete hemolysis normally at 0.3
spherocytosis 0.7 so start hemolysis at 0.7
0.5 cells
So complete hemolysis at 0.5
2- Autohemolysis:
) ( ) (
0.9 RBCs 24
RBCS
RBCS
spherocytosis more dark
-

glucose 24 very clear

RBCS biconcave
DM DM

TTT
1- packed RBCs
3- iron chelating therapy 4- ttt of gall stones

2- folic acid

5- spleenectomy
Spleen complete clinical cure
laboratory RBCS RES trabeculae
spleen 5

major mature part of RES fulminant

infections LN
consent .

 :
spherocytosis hemolysis
.. ATP
.. 10 15
spleen RBCS spherical ..

chronic hemolytic anemia

spherocytosis Thalassemia sickle cell anemia splenectomy
BM transplantation
normochromic polychromesia
RBCS .. MCH normal range
RBCS Normal range
polychromesia

THALASSEMIA
Introduction
normal Hb abnormal Hb normal Hb soluble in cytoplasm
part Hb Hb alpha chains 2 16
-thalassemia
-thalassemia means quantitative
quantitative defect in chain synthesis of protein part of Hb
Hb
alpha alpha thalassemia 1- deletion of one gene :
deletion of one gene 3  silent carrier ) ( gene study2- deletion of 2 genes:
2 3- deletion of 3 genes
3 .4- deletion of 4 genes :
4 Hb abnormal RBCs anaemic HFs ) (hydrops fetalis
chains Hb chains Fetal Hb = Hbf

1- if chains
2 + 2

?? - Which has very bad O2 dissociation WHY

 iron chain O2 ) (chemical reaction oxidation

Gamma chain - 11

so, no thalassemia
) HbA (adult

2-if B chain
2+2B

- 2gene on 11chromome
after 6months will be the dominant Hb

: 1- B thallasemia minor
2- B thalassemia major
3-delta chain with make Hb A2

- gene on 11 chromosome
8 7

normal : 1- intrauterine:
itrauterine 6 cord blood - Hb F 70 % of total Hb & 30% of RBCs Hb A
RBCs spleen and liver
2- after delivery

no changes

3- after 6 months

- Decrease in Hb F + increase in Hb A
- To 1 year Hb F reach

1% , HBA

96% & the rest is Hb A2

: curve
- chain (gene)
constant
work since intrauterine life until death
- chain (gene)
intrauterine show maximaum activity till 6 months then decrease till
one year
- B chain gene

increase activity at 6 months

till 1year maximum activity

B thalassemia
B chains genes 2 11 B gene B thalassemia gene minor one gene of 2 genes pathological gene single gene defect
- Pathological gene is a ressive gene & the other normal Gene is a dominant gene
- so, geno type of thalassemia minor is Rr {heterozygos}
(R
normal dominant gene

r
pathological recessive gene)

gene)

- If another pathological gene present
rr {homozygos}
called B thalassemia major (intermedia)

severity intermedia major
B thalassemia major
- No B chain Genes so no B chain
1 - 1st 6 months of life:
70% of Hbf  6 Hb %100 7gm Hb F 10 gm hb

2- > 6 months:
% ................ % - % -% - %  activity gene 6
.  HB - So the onset of B thalassemia major 6months
But spherocytosis since birth & G6pD .D any time exposed
B thalassemia
Due to ineffective erythropoiesis Not hemolysis
Hb RBCs normal Hb

BM

hemolysis
maximal activity RBCs 2chain B  10 RBCs  20chain defective erythropiosis  only 1 RBCs
hemolysis

pure Hb  18 - Which is insoluble Hb that deposit on cell membrane of RBCs
cause intramedullary hemolysis
- Some of them get out from BM
bizar shape RBCs (abnormal shape)
: ................. 3 4 

target cells & anisocytosis (( ) diagnostic Bl.film)

spleen

hemolysis

only target cells ( which is non functioning cells)
extramedullary hemolysis
pathophysiology 3 .. 1- onset
> 6 months

gamma activity
2-
ineffective erythropiosis

- Also , microcytic hypochromic anemia
3-hemolysis:
Hemolytic 1- intramedullary hemolysis
in BM 2- extramedullary hemolysis
in spleen

Clinical manifestations
1- age of onset
> 6 moths
2- female = male
as its gene is autosomal
3- anemia not responding to hematinics
6
4- history of frequent Bl. Transfusion , jaundice , stool (darker) , no urine change , thalassemic features
due to hyperactive BM Or presented with complications etc
general -

Investigations:
- CBC
microcytic hypochromic Anemia + retics , Bl film
target cells + anisocytosis
- serum iron + IBG .etc as before.
+ X-ray on bone
hyperactive bone marrow
+ Diagnostic
Hb electropheresis

- in normal
if >= 1 year

- HbF
0.8%

HbA
96%

- HbA2
3.2%

- Here :
RBCs %100
Hb A
0% - only Hb A2 & Hb F ( mainly Hb F
) electropheresis test (  alkaline denaturation test  o2 dissociation HB F test
+ Antenatal diagnosis

Treatment

1- packed RBCs
2- iron chelation
not before 5 years .etc as before

Recent line of treatments

1- BM transplantation
stem cells BM   then BM transplantation early2- gene therapy: only under trial
 B-Gene  Hb A  B chain Hb + ineffective erythropiosis hemolysis
3- activity of gamma gene
butyric acid gamma gene ) (
4- incidence of hepatits & HIV
.
.. .
:   erythropoietin BONE MARROW .
RBCS ) (RETICULOCYTES 120  donor
4-3 .
)(NEOCYTE TRANSFUSION FROM SINGLE DONER
NB <-- butyric acid hypoxia on Excercise
:
SYNTHESIS reticculocyte
reticulocyte

B THALSSEMIA MINOR

SINGLE GENE defect (Rr) heterozygous


:
.. :

10 RBCs
RBCs
5 RBCs
HbA 60% Hb = 9-9.5


so, no severe anemia
as it is compensated

So , No hepatosplenomegaly only pallor called carrier
carrier
iron deficiency anemia :

1- CBC
Hb = 9-9.5 , microcytic hypochromic + reticulocytes

2- Iron level
) IDA ( iron + iron binding capacity
3- Hb Electrophoresis :
- in normal
HbA:HbA2 = 30:1
A
A2

- Here
20:1

Treatment
HEMISIDROSIS
.. MAJOR

:
1-follow up of iron level in blood.


tannic acid
2-After meal

Alpha thalassemia
4 alpha 16

alpha thalassemia

1-single gene defect

silent carrier
single gene defect carrier

. silent

2- 2 genes defect
mild hemolysis

3- 3 genes defect

normal RBCs
- etc ............. HEPATOSPLENOMEGALY

Hb electrophoreses

target cells
4 chain Hb which is insoluble called Hb- Barts (4 gamma chain)
6
6
Hb H ( 4B chain)
B-Major 4- 4 genes defect
hydrobs fetalis
. 6 Hb-H Hb-Barts 9 8

Sickle cell anemia

HbA TO BE SOLUBLE IN RBCS NEED ONE OF TWO FACTOR:
1. OXYGEN

or

2. GLUTAMIC ACID IN B chain

Insoluble hypoxia
B chain
sickle anemia

pathological gene presnt on autosomal chromosome
so, no sex difference

valine glutamic acid
So, qualitative defect
.. Hb S Hb A
- need oxygen to keep it solable
if o2 (hypoxia)
change to polymers or crystals

sickle shaped RBCs .
oxygen irreversible
6 B 
Risk factor (decrease oxygen to RBCs)

RBCs o2
:
1- o2

as high attitude , crowded areas
2- o2

any respiratory disease
3- water
Dehydration

4- Hyper osmolarity state
osmotic pressure

urea - Na - glucose 3
hyperglycemia ,renal failure & hypernatremia
hyper occlusive crisis occur in the follwing: MCQ
1- renal failure 2- hyper natrtemeia 3- uncontrolled DM
4- ALL OF ABOVE 5- non of above
5
5- consumption of o2 as in infection

o2 organism

autosomal recessive gene (Hbs)

soluble
sickle shap which is irreversible polymers
o2
sickle shap
emboli biconcave
emboli
artery or vein vascular occlusion
: arteries
1- end artery
infarction 

1-cerebral artety.
2-Renal artery
renal infarction.
3-coronary
4-pulmonary art.
pulm. Infarction
5- spleenic art.
spleenic infarction
autoauto-spleenectomy

2-non end artery
:
1-extremites
ischemia

Pain in the hands & foots
2-gut ischemia
as superior mesenteric artery occlusion
diffuse abdominal pain
called abdominal angina
3-other sites:

- if artery:
either infarction or ischemia
pain
So, this attacks called painfull crises or vasovaso-occlusive crises
- if vein :
spleenic vein  .. tributaries

filter spleen %20

Marked congestion in spleen

its capsule has sensory fibers
if stretched
severe pain


then syncopal attack..
WHY SYNCOPAL ATTACK ???
Due to :
1-vaso-vagal attack due to severe pain.
2- COP
as 20% of blood in spleen
severe hypotension
hypovolemic shock.
: 1-sever pallor

2- sever hypotention 3- weak pulse

4- marked distention in lt.hypochondricum
abdominal Examination is absoluttly contraindicated

palpation of spleen

called Sequestration crisis
if vein

crises 2 - May with G6pD-D
hyper haemolytic crises 
- May bone marrow failure
aplastic crisis
Investigation:
attacks attacks - during attack:
1- CBC
anemia
Normocytic normochromic  - Retics

+ blood film

sickle shape RBCs

2- iron & IBG .etc

- Inbetween attacks :
attacks
( ) arthritis
...........................
rheumatoid
- arthritis
sweeling, deformity
But here
just pain

(localization) arthritis

 O2 sickle cells

Diagnostic :

1-sickling test

na-metabisulphide O2 RBCs

sickle shape slide sickle shape

2-Hb electrophoresis
HB S

Treatment
attack
1-vaso occlusive crisis :
)- stop ppts factor (stop sickling
- -
- analgesic
- exchange transfusion canula canula

- If Cerebral infarction , chet pain ., sudden blindness

resistance . - cerebral stroke or chest pain sickle aneamia

transfusion

: .. CBC sickle shape

2- Sequestration crises:


vaccine

- Exchange transfusion or urgent spleenectomy
3- hyperhemolytic attack
as G6PDD
4- Aplastic crises
Bl transfusion
. in-between the attacks :
1- folic acid

2- vaccination
spleen  capsulated organisms spleen ..
   long acting penicillin for life sickle
3- S Hb & F Hb
1- butyric compound

2- if chronic myeloid leukemia give hydroxy urea
 immunosuppression  Erythropoietin to activity of BM

) 4- BM transplantation ( under trial

Bleeding Tendency
. 3 :
: Bleeding tendenacy
:
:
Q1:

1- massive uncontrolled bleeding

bl. Tendency

2-bleeding from one orifice
 systemic cause local cause3-from two non-repeated orifices
epistaxis )
Called 2 repeated orifices (false hematemesis
bleeding gums hematuria 2 non repeatant orifices4-uncotrolled bleeding after minor trauma
.. hemtoma bleeding tendency
5-or after minor surgery
circumcision 40 liver coag. factors
.. 40 ) (hematology
- menstruation

Q2 cause :
bl v trauma ... bleeding :
bleeding

blood flow

1-local v.c
2-platlets:

edge bl.v platelet adhesion 33-coagulation system : only if major injury

 close the opening  support platelet  fibrin
sub .cut. bleeding :
1- petichae:

petichae 2-1 2-purpura:

5-2
purpura , petichae insect bite

purpura ) ( -

insect bite -

3- ecchymosis:
ecchymosis echymosis multiple ecchymosis hematuria epistaxis

platlet & VC minor injury

co-agulation -

ecchymotic +  patches 3-1  multiple small minor bleeding under skin 3

Enmurate cause . discuss diagnosis of one of them
co agulation platlet or V.c
purpura
Cause of patches with purpura
Vascular causes:
causes
1-allergic inflammation of bl.v

2-autoimmune SLE

3-vit c difciency

4-sreroid

vessels support collagen 5- meningococcal septicemia
Platelet causes:
causes:
1- platelet count (thrombocytopenia): normal count: 150.000-400.000/mm2
or
2- defect in platelet function

Causes of thrombocytopenia:

 production
1.

Autosomal recessive gene

 all receptors of stem cells
pancytopenia
Fanconi Anemia.

2.

Defect in thrombopiotein receptors: (TAR syndrome)

absent radius receptor

3.

Suppression of bone marrow by:

Toxins Drugs Irradiation - Viral infection ( HPV, HBV, EBV) - Abnormal metabolites - Infiltration

with malignant cells. - Autoimmune
idiopathic type

TAR syndrome causes of bone marrow failure

Excessive destruction:

1- immune mechanism (ABs) either:

- only
ITP
- thrombocytopenia +anemia
Evan syndrome
- non-specific Abs
SLE
- post transfusion:
  %15 P. Antigen  %85 platelet
memory cells ABs immune system
( Abs ( ) p  )
not embryological Abs  Abs
- transplacental:
SLE Evan syndrome ITP
2- non immune mechanism:
1- hyper spleenism
....

consumption of platlet non immune

plasmine (fibrinolytic sys) thrombus inatravascular thrombus

platlet platlet + fibrin thrombus

as in:
2- in DIC

defect in coagulation
intravascular thrombus
which is destroyed by fibirinolytic system
formed again
destroyed

consumption  platelet< --

3-thrombotic - thrombocytopenic purpura

auto activation of platelets
thrombus formation--------------------------------------------

platlaet

4-Kaselbach-merritt syndrome
hemangioma
platelets 
10 9

5-hemolytic uremic syndrome:

 

causes gastroenteritis  certain strain of E-Coli on GIT

(only from this strain of E-coli) <-- verotoxin enterotoxins

which is rapidly absorped
reach blood
cause activation of coagulation cascade
form thrombus
consumption of platlets   fibrinolytic system

platelet toxins acute hemolytic anemia <-- hemolysis of RBCs toxins

RF <-- acute glomerulonephritis immune complex
gall stone spherocytosis :
 ) ( in attacks sickle cell
thalassemia spherocytosis

Spherocytosis: onset
since birth, so
more bilirubin but

& Thalassemia: > 6 months
Hb, but in thalassemia
normal Also, RBCs in spherocytosis

RBCs (due to ineffective erythropoiesis)
target cells
bilirubin
so, spherocytosis give more Hb so gall stone more in spherocytosis than thalassemia

Thrombothenia:
platelet
platelet adhesion
receptors platelets injured BVs wall Von willibrand factor (type of plasma protein) *
glycoprotein Ib receptors ) ( glycoprotein ... VWf
cell membrane
1-VWF

2-receptors

adhesion *

<--intracellular signals VWF  wall  platelets *

which activate intracellular enzyme (cyclooxygenase) which change arachidonic acid into thromboxane A2,
prostacyclin & prostaglandin
limit the coagulation
as cyclooxygenase needs phosphate from ATP
so , ATP gives ADP.
causes platelet aggregation  ADP *
glycoprotein 3a receptor glycoprotein 2b  
.........( ..ADP )ADP .. fibrin *

: thrombothenia
1.

Acquired: 
cyclooxygenase

Aspirin
 cyclooxygenase enzyme
ADP

Uremia:: why??
as urea
cyclooxygenase enzyme

Heparin in large dose
Also,  cyclooxygenase enzyme

2.

Hereditary:

Von willibrand disease

Glycoprotein 1b
Bernerd soulier syndrome

Glanzmans disease
no glycoprotein IIb or IIIa or both.

Coagulation disorders:
purpera or rash .. circumcision < --
Only echymotic
so, defect in coagulation factors.
extrinsic pathway , intrinsic pathway & common pathway
1-Extrinsic pathway
only factor vii
then activation of common pathway
2-intrinsic pathway
factor xii
xi
ix
viiic
then activation of common pathway
3-common pathway
x
ii
i(fibrinogen to fibrin)

defects

1-hereditary defects:
- no factor vii
-  intrinsic pathway
viii, ix or xi
hemophilia
which has 3 types:
b. ix

a. viiic

c. xi

- Common pathway

factor i
called fibrinogen ( ) or not activated called

dysfibrinogen ()
2- Acquired or 2ry:
- Vit. K
ii,vii,ix,x (1972)
3 pathways
- Liver dysfunction:
factors

 - Consumption of fibrin:

as in DIC, giant hemangioma.etc.

Investigations:
bleeding tendency
hematuria with no urinary affection
:
Vascular- thrombocytopenia-thrombothenia-coagulation system defect

minor injury 

bleeding time ... bleeding
prolonged MR bleeding time purpura
* Normally bleeding time
60 sec.- 5 min. (range )
prolonged > 5 min.
15 CBC ..vascular or platelet minor injury
 thrombocytopenia 100.000 platelets counts **
400-200 BM aspirate

* mother cells of platelets
megakaryocytes
if 
so , production

& if  megakaryocytes
excessive destruction.
platelet functions < -- vascular or thrombothenia

platelet normal CBC **

.

- if impaired
thrombothenia
- If normal
sure vascular
(prolonged bleeding time, ITP :
 platelet, BM:  megakaryocyte)
N.B: vascular causes known by exclusion
:If bleeding time is normal
coagulation system defect

Vii, xii, xi, viiicfactors

or

X, ii, I factors


 2cm

partial  Reagent (activate factor Xii) + stop watch
till formation of thrombus

thromboplastin time PTT, normally: 25-40 sec.
Reagent(activate vii) and calculate time till thrombus formation
prothrombin time PT, normally: 12-14
sec.
(so,normal intrinsic) normal

30 PTT -

(so,defect extrinsic)  vii 

hemophilia a or b or c c. xi

b. ix

a. viiic

prolonged 30 PT 

so ,prolonged bleeding time + normal PT + prolonged PTT(intrinsic pathway)

prolonged both PT & PTT + normal bleeding time -

Common pathway or vit. K (not DIC
prolonged bleeding time)& not liver cirrhosis

Henoch-schonleinpurpura
drug viral allergic vasculitis 2:1 - At any age but more common
2-8 years
2 2 :
1- Extremities
purpura
extensor surface of the forearm buttocks L.L special distribution.
palpable odema allergic ) ( purpura :
( L.L ) -

+ itching
2- Joint affection : Arthritis and arthralgia
Red,
Red, hot,
hot, swollen,
swollen, not

: non essential
1- Acute glomerulonephritis or any for
form of renal affection (nephritis
nephritis)
ritis)
2- GIT vascularitis Abdominal colic and diarrhea
intusussciption  loops -

: investigations
- normal CBC

- platelets : normal

: Complications
1- intusussciption 2- Renal failure

TTT:
- As any allergic : self limted
- may give steroids ( low dose ) with or without anti histaminic
if Joint affection Never give Aspirin
Give another analgesic Bleeding
11 10

Immune thrombocytopenic purpura: ITP

Which is the most common cause of thrombocytopenia
plaltelets auto antibodies immune system
immune system
viral infection unknown
replication replication DNA or RNA virus .target cell
new virus DNA or RNA immune system change antigenic pattern antibodies
. platelets C/P
viral infection etc.......... hematoma on mild trauma
stretch to the skin :
-important negative features :
- No pallor
- No organomegaly after abdominal examination
- No lymphadenopathy
LNs
-only petichea and echymosis
intra cranial hge -

Investigations:
prolonged bleeding time purpura -1
100,000 platelet CBC -2
. mega karyocytes B.M -3
*B.M aspiration is mandatory to exclude serious conditions & malignancy

TTT:
self limited platelets immune CBC

- if no clinical ( no active bleeding ) & if Platelet count > 40.000
just follow up
- CBCevery week or 2 weeks
(IC hge ( ) serious hge) 40.000 1- So, give immune suppressive as predinsolone .
2mg/kg/day_ max: 6mg/kg/day : ( )

 cortisone once indicated should be given

.. .. .
:2- IV immunoglobulin which is blocking Abs .
1- blocking effect :
immune system ABS platelets receptors platelets Abs  immune globulin destructive Abs .
2- suppression to antibody dependent cytotoxic cell :
Ig platelet ABS spleen b phagocytic cell b ) (antibody dependent cytotoxic cellb b ABb b b targetb b b b b
 .

IG suppression to antibody dependent cytotoxic cell.

IV IG

% 50 % 30 % 20 IV IG3- Anti-D Abs

anti-D abs IV IG Iv IG4- plasmapheresis
Iv IG Anti-D plasmapharises . ) (splenectomy or not ABs antibody dependent cytotoxic cell .
ITP platelet

immune system serious hge IC hge surgery GIT hge

chronic ITA :
6 Female SLE EVAN syndrome HIV
platelet sever bleeding

Hemophilia
3 types :
- Hemophilia A: deficient factor VIII - Hemophilia B: deficient IX - Hemophilia B: deficient factor XI
- Inheritance:
- A&BX-linked
resessive. - C Autosomal resessive. - so A&B more in males and C : Both.
A&B

Clinically
since birth

after delivery:
bleeding from the umbilical cord , after circumcisin or after IM injection of vit.k ( which is a routein)
then: Bleeding
- multiple echymosis without petiche or purpra
-minor trauma : hematoma
-severe bleeding on minor injury
sever bleeding - hemoarthrosis
( ) hemoarthrosis stiffness of joint . fibrosis (  bleeding inside joint) 
- sub periosteal He:
healing by fibrosis the sub periosteal Hge trauma muscles Bone calcification
Hemophilic pseudo tumor tumor long life diseases -

complications :
1- ICH (serious Hge )
2- complication of blood transfusion
3-hemoarthrosis lead to stiffness of joints .
4-hemophilic pseudo tumor.
5-factor replacement for life:

( ) factors ABS (inhibitors )

investigations :
1- bleeding time:
normal Bleeding time petichea or purpura 2- PT
for extrinsic factors
here, normal
3- PTT
for intrinsic factors
intrinsic
4- then Factor assay

:severity Factor - mild
if 6-30% of normal
- moderate
1-5%
- severe
< 1%

TTT
1- avoid precipitating factors:
trauma .. bleeding 2- factor replacement
replacement therapy

.. RBCs 1- fresh frozen plasma
contain all factors

. :
Hemophilia A,B,C and DIC and liver cirrhosis
2-cryoprecipetate:
VWF factor I Factor VIII cryoprecipitate:
DIC Hemophilia B,C VW diseases Hemophilia A
3- F VIII concentrate ( anti hemophilic globulin )
F VIII + VW Factor
3- Anti fibrinolytic system : as -amiono caproic acid & Tranexamic acid to prevent clot 4- TTT of complications .
5- analgesics as acetaminophen ( never aspirin )
. Factors Hemophilia NB

Thrombathenia
. 3
:
platelet functions : ADP reagent : 2 - .restocetin reagent : 1 glycoprotein 1B receptors VW F wall of blood vessel Restocetin .platelet
. platelet IIb + IIIa ADP :
. VWF 1b restocetin : Glanzmann`s

.IIIA IIb ADP platelet : disease

:
normal IIb & IIIa aggregation around ADP -

But not around restocetin No VWF or Ib add VWF if aggregate is VWF disease.
Bernerd soulier syndrome 
1- VW Disease
b b  kidney b b b b urine b  LMW protein  in intrinsic pathway  Viiic liver
b Viiic  VWF  kidney  carrier macroprotein    VWF
hemophilia A 
PT
normal PTT
- Viii
lost
prolonged Bl. Time  function  platlet adhesion VWF
+ petichea & purpura + normal ADP
+ with restocetin
No

VWF

- ttt : as hemophilia A
2- Bernerd soulier sundrome
sundrome
- No glycoprotein ib receptors
no platlet adhesion .
- bleeding time
increased , normal with ADP and impaired with restocetin (not corrected)
- CBC
thrombothenia .also , giant platlet ( platlet


glycoprotein 1b contraction in wall of platlet
decrease its size



spleen

thrombocytopenia
3- Glanzmann`s disease

deficiency of vit. K
- causes:
1- decrease intake .
2-vit. K is fat soluble
need bile
3-decrease in bact. Floora.
due to prolonged use of Abs for more than 1.5 months
- bleeding time normal , increased PT and PTT
NB. if active bleeding vit.K 72
give FFP ()

liver Dis. ( )
Multi System disorders  Bl. Transfusion leckocytosis pancytopenia DIC NB. VIII inhibitors
plasmapheresis .
. 11 1:27