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

: Fetus
Fetus in Intrauterine life -1
which has No good O2 dissociation 2 fetus Hb is Hb M
fetus Partial hypoxia
O2 sensors PO2 hypoxia
fetus ) Erythropoietin (

RBCs synthesis liver &spleen bone marrow m
ore RBCs normal Hb %.gm 22-18
lung hypoxia Erythropoietin Hb 9 15 14
12 10 6 ) ( %. 9gm
physiological anemia of the newborn
hypoxia BM RBCs
!! Iron !
MCQ: - cause of anemia in newborn
haemolisis of RBCs 2-nutritional cause 3-bleeding tendency 4-decreas Erythropoietin level -1

)(Causes Aetiology

Decrease RBCs Count :
1- Decrease Synthesis as in:
(BM problems BM failure (hypoplastic Anemia-1
Decrease requirements may decrease synthesis -2

RBCs-1
( Cell membrane + Cytoplasm (Hb RBCs

( ) 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
(Bleeding (hemorrhagic anemia-1
(Hemolysis of RBCs (hemolytic anemia -2
.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

BM Undifferentiated stem cells

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)
:Problem in Erythropoietin H receptors only -1
Pure red cells anemia . . stimulus
or All receptors -2 : Pancytopenia
called Fanconi anemia which is:
autosomal recessive gene
cause:

1- Pancytopenia
(affection of brain cells (microcephaly & mental retardation -2
3- decrease in GH secretion or it's receptors short stature
4- Thumb & radius anomaly
Renal anomalies , abnormal distribution of melanin -5
ttt of hereditary
( prednisolone Receptors stem cells ) stem cells
BM Transplantation
Idiopathic -2 Mostly autoimmune
-:ttt
1-Immunosuppressive
2- Cortisone + BM transplantation
2ry causes -3
sever infection by toxins & also septicemia -1
.. toxins
2-Drugs :as Chloramphenicol + cytotoxic drugs & some time Sulfa
3-Viruses:As EBV , Parvo V &HBV
4-Infeltration of BM
stem cells
may be Liver & kidney diseases -5
.decrease Erythropoietin H or other hormones
.Irradiation-6

Clinical presentation of Anemia {In general}

-:Symptoms
introduction
Function of RBCsO2 Carrier so, if RBCs Manifestation of tissue hypoxia

Brain cells
1- Headache
- Mild decrease in O2 in Brain cells compensation by VD headache
then lack of concentration -2
HB ....... ( )3-Dizzness ) )
pallor vertigo
: Syncopal attack-4
cerebral
. %20 circulation
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
HB ......... % 11gm
-2
CBC
:
1- Mean corpuscular volume (MCV) RBCs :
RBCs = 80 +/- 20 femto liter

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

if HB is 9 gm% and MCV = 58 Microcytic anemiaif HB is 9 gm% and MCV =110 Macrocytic anemia(Mean corpuscular HB (MCH-2
MCH normally =26-32 picogram/liter
So,-if HB is 9 gm% and MCH =28 Normochromic anemia
if HB is 9gm% and MCH =20Hypochromic anemia???whats the etiology -3
???synthesis or +++ loss --
If +loss so , +Bone marrow activity
CBC
Reticulocytic count
RBCs ......
bone marrow % 2-1 total RBCs
pediatrics % 2.5
So , -if loss reticulocytic count
if synthesis reticulocytic count 1 2

IRON DEFECIENCY ANEMIA IDA

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

: Definition
defective synthesis due to iron metabolism iron
Daily requirement 2-3mg/kg/day -animal sources
so complex simple form IDA
FERRIC IRON STOMACH FERROUSHCL
ACIDITY IRON ABSORPTION .
ARTIFICIAL MILK BREAST MILK IRON 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 aCARRIER PROT. <APOFERRITIN>then CONVERTED TO FERRITIN TO CARRIIER PROT IN BLOOD
NB. apoferritin + iron = Ferritin
Transferritin ( ferittin in blood) to stores in liver
NB. ) (

FREE DEPOSITION in tissues HEMOSEDIROSIS
free duodenal cells stores 6 ..
.. .. IDA 6
1- if 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
:INTAKE.1
.as cow milk not a good source of iron -1
: iron Vit. Called fortified milk
unfortifiedDELAYED WEANING.2
or
absorption of iron - 2
) 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
- .

HCL

NB. Contents of food that iron absorption

(vit c as it acidity of stomach (ascorpic acid .1
protein .2
digestion pepsin pepsinogen - HCL

STORE as in -3
- pt or intrauterine growth retardation or IDA of mother
excess requirement -4
?how
adolescence (10- 15 17-12 ( )RAPID RATE OF GROWTH ( O2
SO iron requirements
MG\KG 10-15
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
cm of blood 100-50 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 - true pica mainly due to severe IDA

:Signs
7

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.
3-Cause:
retigulocytic count even reched zero.
synthesis
2-bloodfilm : no abnormal cells

3-serum iron or serum ferritin
( )
4-iron binding capacity
iron transferrin free sites

3 transferrin Fully saturated
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 3 )4 2

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

manfistation of anemia 3
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

of IDA

TTT
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 -hyper pigmentaion 3

severe gastritis oral partenteral gastritis
oral iron

2-oral:

- dose 6mg/kg/day actually absorbed

iron elemental
3 ....
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

 iron dark stool stool iron

3- packed RBCs when ?
:
1-Hb
6mg% or less
HF anemic heart level 6 iron 10 6 2- if anemic HF
3- surgical emergency
CBC pallor acute apendcitis acute abdomen
ttt ........ .. %Hb 8 mg

Haemolytic anemia
Def :

anemia due to short of life span of RBCs normaly 120 days

119
????????? diagnostic investigation of haemolytic anemia
life span ..
.. radio isotopes reticulocytes
haemolytic anemia 15
erythpiotin
hypoxia ( life span ) 60 stem cell activity 2 time reticulocyte

BM 4 action
hypoxia life span 30 normal
normal 8
15 15 ... 8 BM 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 ?

10

4- megaloblastic anemia

3-

2- malaria hemolytic anemia

1- Ancylstoma

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

G6PD
:
glucose 6 phosphate dehydrogenase .
(Free O2 radicles ( H2O2 or O3 lipolysis of fat cell membrane RBCs lipoprotein RBCs H2 O H2O O2 )(O3 H2 reduced glutathion RBCs H2 NADPH Hexose monophosphate pathway glucose glucose-6-phosphate G6PD -6
phsphoglucose
H2 NADP glutathion cell membrane
free radicles (acute hemolysis (intravascular free radicles -1 .: ) - (.................. -
) - ( free radicle heat
.: 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 + Enzyme synthesis Called type B
black races +type A . genetics delated gene A -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

11

 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 Hbis 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 urine Hburia 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 bilateral G6PDD
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

12

 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 uine output washing of the kidney
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

13

 ) ( channels
(iron + protoporphyrin ) Heme phagocytic cells
- Protoporphyrin indirect billirubin fat solube liver change to direct then excreted with bile
to GIT bact. Floora change it to sterchobillinogen (colorless) stool oxidation
in GIT sterchobillin give the stool its brown color
kidney portal ( sterchobillinogen (water soluble (urobillinogen (colorless also
chronic hemolytic anemia
8 BM RBCs 12 -10 RBCs

Clinical manifestations:
1- anemia not responds to hematinics
( hematinics) ( ) anemia not responds to B12 & folic acid
hematinics
2- history of frequent blood transfusion
3- spleen enlargement:
. 120 RBCs 100.000 spleen spleen enalrgment spleen 500.000
4- indirect billrubin with no compensation by liver ( which compensate only 4 times as normal )
)
100.000 400.00 ..
liver mild jaundice (
severe jaundice
biliary system liver - hepatomegaly 5 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

14

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

Complications of chronic hemolytic anemeia :

1-

complications of Bl. Transfusion :

Hepatits & HIV2spleenomegaly & Hyperspleenism:
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 ) .costal margin just felt umbilicus ( 7-10 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
900
fibers . cardiomyopathy & H.F
3- phagocytic cells of spleen
- cells of liver
4- pancreas deposition in islet cells of it

DM
( insulin receptors insulin resistance DM ( as type 2 DM

15

5- gonadal cells
delayed puberty also, 1ry infertility testis 2ry infertility due to LH & ACTH 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
RBCs acute on top of chronic
4- hemolytic crisis
phagocytic spleen
infection as tonsillitis thalassemia
function
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:
infection with splenectomy hypersplenism
capsulated organisms
pneumococci, H.influnza, meningococci, salmonella, etc
incidence with capsulated organisms

cell migration chemotaxis phagocytosis
digestive enzymes cause intracellular killing
capsulated organisms resist phagocytosis
phagocytic cells capsulated organisms

16

 capsule is very smooth

spleen opsonins- glue like materials capsulated
organisms >--organism phagocytes ) (
spleen .
9- Pathological fracture.
>--- physiological fracture expected truma non expected trauma pathological fracture ) (
cortex medulla truma .) ( 10- stunted growth.
1- Endocrinal:
1- G.H.
2- somatomedins due to G.H.
as
somatomedins. G.H.
3- (T3 & T4) hypothyroidism
4- also
insulin D.M.
receptors NB. G.H. need somatomedins
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
Hb 6 6 H.F. )
(
iron hemosidrosis it's
incidence
:
Hb 8-6 :
-1 ... .
-2 anemia .B.M medulla
bone dysmorphic features .
hemosidrosis
2- Hypertransfusion.
) (
anemia >-- 11 >---
anemia
hemosedrosis mentality .
3- Supertransfusion.
)(
12mg ) (
.B.M 8 folic acid 5mg/day

17

2- Folic acid :
3- Treatment of complications:

1- Hemosidrosis.
)(iron chelating therapy

Parenteral

Desferroxamine 25-40 mg/kg/day
) (75
) (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
ml liter/kg/Y sure sign of hypersplenism 250

capsulated organisms
splenectomy

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

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


main gate Na channels ... :
: spectrin protein -1
RBCs ( called ( spectrin ionized Na .
Na
.. small gates AA glucose main gaits
Na-pump -2
Na Na-pump ATP Na
. 12

18

:
?How spleen identifies RBCs after 120 days
120 Na pump ATP BM RBCS
small gates Na Na- pump 120 ( )
spleen Na spherical shape RBCs
. phagocytosis trabeculae
spherocytosis

Etiology
X ve family history+ autosomal dominant gene defect
1:1 male or female autosomal
main gates Na ( non ionizable (abnormal 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
:General investigations -1
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
: Diagnostic investigstions -2
1- Osmotic fragility test
%0.9 normal saline variable concentrations of Na test tubes :
RBCS 0.2 0.3- 0.4 0.5 0.6 0.7 - % 0.8 RBCs Na
RBCS
Na 0.8 0.9 0.6 RBCs ..

19

 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
2- folic acid 3- iron chelating therapy 4- ttt of gall stones
5- spleenectomy
Spleen complete clinical cure
laboratory RBCS RES trabeculae

spleen 5 major mature part of RES

fulminant infections 5 LN
consent .
:
1 spherocytosis hemolysis
.. ATP
.. 10 15
2 spleen RBCS spherical ..

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

THALASSEMIA
Introduction
normal Hb abnormal Hb normal Hb soluble in cytoplasm
part Hb Hb chains alpha 2 16
-thalassemia means quantitative defect in chain synthesis of protein part of Hb
alpha alpha thalassemia 1- deletion of one gene :

20

) silent carrier 3 deletion of one gene ( gene study

2- deletion of 2 genes:
2 3- deletion of 3 genes
. 3 4- deletion of 4 genes :
anaemic HFs abnormal RBCs Hb 4 ( hydrops fetalis)
chains Hb chains Fetal Hb = Hbf
2 + 2 1- if chains
- Which has very bad O2 dissociation WHY ??
( chemical reaction ) O2 chain iron
oxidation

11 - Gamma chain
so, no thalassemia
( if B chain 2+2B HbA (adult-2
2gene on 11chromome after 6months will be the dominant Hb : minor 1- B thallasemia
B thalassemia major -2
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 after delivery no changes -2
after 6 months -3
- 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 2genes 11 B gene B thalassemia gene one gene of 2 genes pathological gene minor
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 )
- If another pathological gene present rr {homozygos} called B thalassemia major
(intermedia)
21

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 Hb F 7gm gm hb 10

2- > 6 months:
%1 ................ 60% - 50%- 40% - 30% 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 RBCs 10 20chain defective erythropiosis 10 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
HbA 96% - HbA2 3.2% - HbF 0.8%
- Here :
Hb A 0% - only Hb A2 & Hb F ( mainly Hb F %100 RBCs
) test )electropheresis HB F o2 dissociation alkaline denaturation test -

22

 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 B chain Hb A 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

:
.. :

RBCs RBCs 10
5 RBCs HbA 60% Hb = 9-9.5
so, no severe anemia as it is compensated

So , No hepatosplenomegaly only pallor called carrier
iron deficiency anemia :
CBC -1
Hb = 9-9.5 , microcytic hypochromic + reticulocytes
2- Iron level
) IDA ( iron + iron binding capacity
3- Hb Electrophoresis :
- in normal HbA:HbA2 = 30:1

23

 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

. silent carrier
2- 2 genes defect mild hemolysis

3- 3 genes defect normal RBCs

HEPATOSPLENOMEGALY .............etc 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

Hb-Barts Hb-H 6 . 8 9

Sickle cell anemia

:HbA TO BE SOLUBLE IN RBCS NEED ONE OF TWO FACTOR
1. OXYGEN
or
2. GLUTAMIC ACID IN B chain
hypoxia
B chain

Insoluble

sickle anemia

pathological gene presnt on autosomal chromosome so, no sex difference

glutamic acid valine
So, qualitative defect
Hb A .. Hb S

24

- 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
glucose - Na - urea 3
hyperglycemia ,renal failure & hypernatremia
:MCQ hyper occlusive crisis occur in the follwing
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 auto-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:

25

- if artery:
either infarction or ischemia pain
So, this attacks called painfull crises or vaso-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.
: sever pallor
2- sever hypotention 3- weak pulse
4- marked distention in lt.hypochondricum-1
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

sickle cells O2

Diagnostic :
1-sickling test
O2 na-metabisulphide
sickle shape slide sickle shape RBCs
2-Hb electrophoresis
HB S

Treatment
attack
26

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 non repeatant orifices 24-uncotrolled bleeding after minor trauma
.. hemtoma bleeding tendency
5-or after minor surgery

27

 circumcision 40 liver
coag. factors
.. 40 ) ( hematology
- menstruation

Q2 cause :

bl v trauma ... bleeding :

blood flow
bleeding

1-local v.c

2-platlets:
edge bl.v platelet adhesion
33-coagulation system : only if major injury
fibrin support platelet close the opening

sub .cut. bleeding :

1- petichae:
2-1 petichae2-purpura:
) ( purpura 2-5 insect bite insect bite purpura ,petichae
3- ecchymosis:
ecchymosis epistaxis hematuria multiple ecchymosis
echymosis

minor injury platlet & VC co-agulation 3 multiple small minor bleeding under skin 1-3 ecchymotic +
patches
Enmurate cause . discuss diagnosis of one of them
platlet or V.c co agulation
purpura
Cause of patches with purpura
Vascular causes:
1-allergic inflammation of bl.v 2-autoimmune SLE 3-vit c difciency
4-sreroid
collagen support vesselsmeningococcal septicemia -5
:Platelet causes
platelet count (thrombocytopenia): normal count: 150.000-400.000/mm2 -1
or
defect in platelet function -2

:Causes of thrombocytopenia

production
Autosomal recessive gene

28

1.

 . 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 +anemiaEvan syndrome
- non-specific Abs SLE
- post transfusion:
%15 P. Antigen platelet 85%
ABs immune system
memory cells
( Abs ( ) p )
not embryological Abs 0 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
in DIC -2
defect in coagulationintravascular thrombuswhich is destroyed by fibirinolytic systemformed
againdestroyed
consumption platelet > --

3-thrombotic - thrombocytopenic purpura

auto activation of plateletsthrombus formation--------------------------------------------

platlaet

4-Kaselbach-merritt syndromehemangioma
platelets
10 9

5-hemolytic uremic syndrome:

certain strain of E-Coli on GIT causes gastroenteritis
(verotoxin --< (only from this strain of E-coli enterotoxins
which is rapidly absorped reach bloodcause activation of coagulation cascade form thrombus
consumption of platlets fibrinolytic system

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

acute glomerulonephritis --< RF immune complex
gall stone spherocytosis :
) ( in attacks sickle cell
29

thalassemia spherocytosis
but Spherocytosis: onsetsince birth, somore bilirubin
Thalassemia: > 6 months &
Hb, but in thalassemianormal 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
platelets injured BVs wall ( * Von willibrand factor (type of plasma protein
glycoprotein Ib ) ( glycoprotein ... VWf receptors
cell membrane receptors
VWF
2-receptors-1
adhesion *
>--intracellular signals VWF wall platelets *
which activate intracellular enzyme (cyclooxygenase) which change arachidonic acid into thromboxane
A2, prostacyclin & prostaglandinlimit the coagulation
.as cyclooxygenase needs phosphate from ATPso , ATP gives ADP
causes platelet aggregation ADP *
glycoprotein 3a receptor glycoprotein 2b
.........( ADP.. )ADP .. fibrin *

: thrombothenia
1.

2.

Acquired: cyclooxygenase
Aspirin cyclooxygenase enzyme ADP
Uremia: why?? as ureacyclooxygenase enzyme
Heparin in large dose Also, cyclooxygenase enzyme
Hereditary:
Von willibrand disease
Glycoprotein 1b Bernerd soulier syndrome
Glanzmans diseaseno 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
Extrinsic pathwayonly factor vii then activation of common pathway-1
intrinsic pathwayfactor xiixiixviiicthen activation of common pathway -2
(common pathwayxiii(fibrinogen to fibrin-3

defects
1-hereditary defects:
no factor vii - intrinsic pathwayviii, ix or xi hemophilia which has 3 types:
a. viiic
b. ix
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
30

 :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 counts platelets **
BM aspirate 200-400
* mother cells of plateletsmegakaryocytesif so , production
& if megakaryocytes excessive destruction.
platelet > -- vascular or thrombothenia platelet normal CBC **
. functions
if impairedthrombothenia If normalsure 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
normal (so,normal intrinsic) PTT30 (vii (so,defect extrinsic prolonged PT 30
hemophilia a or b or c a. viiic
b. ix
c. xi
(so ,prolonged bleeding time + normal PT + prolonged PTT(intrinsic pathway
normal bleeding time+ prolonged both PT & PTT . 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 special distribution. L.L

odema allergic ) ( purpura : palpable

31

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

( L.L ) -

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

: investigations

- normal CBC

- platelets : normal

: Complications

intusussciption 2- Renal failure -1

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

32

 CBC
if no clinical ( no active bleeding ) & if Platelet count > 40.000 just follow up CBCevery week or 2 weeks 40.000 ) (serious hge ) (IC hge1- 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 .
: blocking effect -1
immune system ABS platelets receptors platelets Abs immune globulin destructive Abs
.
2- suppression to antibody dependent cytotoxic cell :
Ig platelet ABS spleen phagocytic cell ) ( antibody dependent cytotoxic cell AB target
. 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
: types 3
- 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.

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

33

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 sub periosteal Hge trauma muscles Bone the calcification
Hemophilic pseudo tumor tumor long life diseases -

: complications
( ICH (serious Hge -1
complication of blood transfusion -2
. hemoarthrosis lead to stiffness of joints -3
.hemophilic pseudo tumor-4
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 . TTT of complications -4
5- analgesics as acetaminophen ( never aspirin )
. Factors Hemophilia NB

Thrombathenia
34

. 3
:
platelet functions : ADP reagent : 2 - .restocetin reagent : 1 glycoprotein 1B receptors VW F wall of blood vessel - Restocetin
. platelet
. platelet IIIa + IIb ADP :
. VWF 1b restocetin : .IIIA IIb ADP platelet : Glanzmann`s 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
kidney urine Viiic in intrinsic pathway LMW protein liver
kidney carrier macroprotein VWF
hemophilia A VWF Viiic
PT normal PTT - Viii lost
function prolonged Bl. Time platlet adhesion VWF
+ petichea & purpura + normal ADP
+ with restocetin No VWF
- ttt : as hemophilia A
2- Bernerd soulier 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
Glanzmann`s disease -3

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 Bl. Transfusion leckocytosis pancytopenia DIC disorders
NB. VIII inhibitors plasmapheresis .
11 1:27 .

35

36