Pediatric)Hematology)

Teaching)cases))

Dr#Amel#Haider##
Consultant##Academic#General#Pediatric###
HMC#

Objec7ves##

History#in#hematology#cases#
Important#physical#signs#
Labs#interpreta>on##
Acute#management#and#followAup#plan##

Bleeding#Disorders##
Platelet#disorders#
Coagula>on#factor#deciency##
Blood#vessels#defects#\#connec>ve#>ssue#
disease#

Bleeding#Disorders##
Platelet)disorders)
Coagula7on)factor)deciency))
Blood#vessels#defects#\#connec>ve#>ssue#disease#

Hemostasis##
Steps)in)hemostasis:)

1.Vasoconstric>on#due#to#local#neural#response,#and#release#
of#endothelin#from#the#endothelium#

2.Primary#hemosta>c#plug:#due#to#platelet#adhesion,#
ac>va>on,#degranula>on(ADP,#TXA2)#and#recruitment#of#
other#platelets#

3.Secondary#hemostasis#due#to#ac>va>on#of#coagula>on#
cascade#by#>ssue#factor#and#phospholipid#via#extrinsic#
pathwayA#the#end#result#being#brin#which#traps#the#cells#in#
the#blood#forming#a#clot#

all#components#are#found#in#the#
vasculature)##

Involves#both#intra#and#
extravascular#elements##

#factor#XII#ac>vators#:#
#In#vitro:#glass,#
dextran.##
In#vivo:#components#
of#basement#
membranes#(collage,#
glycosaminoglycans)#

Vitamin#K#dependent#
Coagula>on#factors:#Factors#2#
(prothrombin),7,9,10##

all#components#are#found#in#the#
vasculature)##
#factor#XII#ac>vators#:#
#In#vitro:#glass,#
dextran.##
In#vivo:#components#
of#basement#
membranes#(collage,#
glycosaminoglycans)#
Hemophilia#C#

Hemophilia#A#

Involves#both#intra#and#
extravascular#elements##

Christmas#factor#
Hemophilia#B#
Vitamin#K#dependent#
Coagula>on#factors:#Factors#2#
(prothrombin),7,9,10##

all#components#are#found#in#the#
vasculature)##

Ac>vated#
Par>al#
Thromboplas>n#
Time##
(

Involves#both#intra#and#
extravascular#elements##

Prothrombin#
>me#

aPTT)#

Vitamin#K#dependent#
Coagula>on#factors:#Factors#2#
(prothrombin),7,9,10##

1A#PT#
2AaPTT#
3A#Mixing#study#(Inhibitor#screen):##
when#a#pa>ent#has#a#long#PT#or#PTT,#the#next#step#is#to#note#whether#the#deciency#
is#due#to#a#deciency#in#the#cloXng#cascade#or#the#presence#of#a#coagula>on#
inhibitor##
Mechanism:#
#pa>ents#plasma#is#mixed#in#a#1:1#ra>o#with#the#plasma#of#a#normal#donor.##
The#PT#or#PTT#is#repeated.##
Since#only#30A40%#of#normal#ac>vity#is#required#to#maintain#PT#or#PTT#within#the#
normal#range,#if#results#are:##
#
(1)#Normal:#than#pa>ents#abnormal#PT#or#PTT#was#due#to#a#factor#deciency##
(2)#Prolonged:#than#the#pa>ents#abnormal#PT#or#PTT#was#due#to#a#coagula>on#
factor#inhibitor#because#the#inhibitor#will#con>nue#to#neutralze#the#specic#
coagula>on#factor#in#the#donor#plasma#

Case#1#

#
case#1##

1A)History):)

#Yasir#,#A#10AyearAold#male#is#to#undergo#an#elec>ve#
tonsillectomy.#

#The#preAopera>ve#history#describes#signicant#bleeding#a`er#a#
recent#tooth#extrac>on.##

The#mother#reports#that#the#bleeding#occurred#several#hours#
a`er#the#tooth#extrac>on,#a`er#they#had#returned#home#from#
the#den>sts#oce.#
#

Case#1#

Bleeding#Disorders#
1A#History#:#
A#10AyearAold#Caucasian#male#is#to#undergo#an#elec>ve#tonsillectomy.#
The#preAopera>ve#history#describes#signicant#bleeding#a`er#a#recent#
tooth#extrac>on.#The#mother#reports#that#the#bleeding#occurred#
several#hours#a`er#the#tooth#extrac>on,#a`er#they#had#returned#home#
from#the#den>st s#oce.#

What#addi>onal#ques>ons#regarding#the#pa>ent s#history#would#be#
important#to#determine#if#the#pa>ent#has#an#underlying#
coagulopathy?#
#
#
#

Case#1#

Bleeding#Disorders#
1A#History#:#
A#10AyearAold#Caucasian#male#is#to#undergo#an#elec>ve#tonsillectomy.#The#preAopera>ve#history#
describes#signicant#bleeding#a`er#a#recent#tooth#extrac>on.#The#mother#reports#that#the#
bleeding#occurred#several#hours#a`er#the#tooth#extrac>on,#a`er#they#had#returned#home#from#
the#den>st s#oce.#

What#addi>onal#ques>ons#regarding#the#pa>ent s#history#would#be#important#to#determine#if#
the#pa>ent#has#an#underlying#coagulopathy?#
#
! Is#there#a#history#of#bleeding#a`er#surgery#or#injuries?#Circumcision,#post#vaccine,#dental#
extrac>on,#upon#walking,#etc.#
! Was#he#taking#any#medica>on#at#the#>me#of#his#dental#extrac>on,#and#is#he#taking#any#
now?#What#medica>on?##
! ##Is#there#a#family#history#of#bleeding#disorders?# #esp:Maternal#history# #
! Other#history#:#severity,#complica>on,#other#cell#lines#.#
#

Case#1#

Yasir#:##
#
The#pa>ent#and#his#mother#report#that#he#has#not#had#any#
other#previous#surgery#or#trauma.##
They#report#only#what#they#perceived#to#be#excessive#
bleeding#a`er#a#recent#tooth#extrac>on#as#described#earlier.##
#
The#mother#also#recalls#that#her#son#may#have#had#increased#
bleeding#a`er#his#circumcision.#

Case#1#
Important#points#in#history#of#bleeding#disorder#:##
Evalua>on#of#prior#bleeding#has#been#shown#to#be#predic>ve#of#a#bleeding#disorder.##
Evalua>on#of#a#pa>ent s#history#should#focus#on#spontaneous#bleeding,#bleeding#a`er#trauma#and#
surgical#procedures,#and#in#women,#the#presence#of#menorrhagia.##
Someone#who#does#not#have#bleeding#complica>ons#a`er#trauma#or#surgical#challenges#is#less#likely#to#
have#a#signicant#coagula>on#disorder.##
Disorders#of#platelet#func>on#or#number#tend#to#produce#immediate#bleeding#a`er#surgical#
procedures#or#trauma,#in#contrast#to#disorders#of#the#coagula>on#system,#which#may#present#as#delayed#
bleeding#a`er#ini>al#hemostasis#was#obtained.#
Family#history,#when#posi>ve,#is#also#strongly#associated#with#inherited#bleeding#disorders,#although#
gene>c#coagula>on#disorders#may#also#arise#from#spontaneous#gene#muta>ons.#
medica>ons#that#increase#the#risk#of#bleeding,#take#a#history#of#all#prescribed#and#overAtheAcounter#
medica>ons.#

Case#1#

PHYSICAL#EXAM#
What#aspects#of#the#physical#exam#do#you#think#would#be#
most#relevant#in#this#case?#
#
#

Case#1#

PHYSICAL#EXAM#
What#aspects#of#the#physical#exam#do#you#think#would#be#
most#relevant#in#this#case?#
#
" ##Skin#
" #Joints#
" ##Eyes#
" #Liver#
" CNS#
#

Case#1#

Yasir#:##
#No#obvious#ecchymosis#or#petechial#were#appreciated#in#this#
pa>ent.#His#fundi#and#sclerae#were#normal#
#
Eyes#free#
The#abdominal#exam#in#this#pa>ent#did#not#reveal#any#signicant#
ndings#of#tenderness,#splenomegaly#or#abdominal#masses#
#
The#pa>ent#had#a#swelling#and#reduc>on#of#mobility#in#the#right#
knee#joint,#sugges>ng#that#he#may#have#had#previous#bleeds#into#
this#joint.#

Case#1#

LABORATORY#DATA#
Which#of#the#following#tests#should#be#ordered#to#help#in#the#
ini>al#evalua>on#of#this#pa>ent?#
#
!##Complete#blood#count#with#dieren>al#and#evalua>on#of#blood#
smear#
!##Prothrombin#>me#(PT)#and#par>al#thromboplas>n#>me#(PTT)#with#
mixing#studies#
!##Bleeding#>me#
!##Measurement#of#von#Willebrand#ac>vity#and#an>gen#level#

Case#1#

LABORATORY#DATA#
Which#of#the#following#tests#should#be#ordered#to#help#in#the#
ini>al#evalua>on#of#this#pa>ent?#
#
!##Complete#blood#count#with#dieren>al#and#evalua>on#of#blood#
smear#
!##Prothrombin#>me#(PT)#and#par>al#thromboplas>n#>me#(PTT)#with#
mixing#studies#
!##Bleeding#>me#
!##Measurement#of#von#Willebrand#ac>vity#and#an>gen#level#

Case#1#

In#this#pa>ent,#the#complete#blood#count#was#normal,#demonstra>ng#a#
normal#platelet#count#with#normal#platelet#morphology#
Because#the#PTT#was#signicantly#prolonged#in#this#pa>ent#(50#sec),#and#
the#PTT#corrected#with#a#1:1#mixing#study,#it#is#suggested#that#the#e>ology#
of#the#prolonged#PTT#was#a#factor#deciency#rather#than#a#factor#inhibitor.##

Case#1#

Given#these#laboratory#results,#which#of#the#following#are#possible#
diagnoses#in#this#pa>ent?#

##Von#Willebrand#disease##
##Hemophilia#A#
##Hemophilia#B#
##Glanzmann s#thrombasthenia##

all#components#are#found#in#the#
vasculature)##
#factor#XII#ac>vators#:#
#In#vitro:#glass,#
dextran.##
In#vivo:#components#
of#basement#
membranes#(collage,#
glycosaminoglycans)#
Hemophilia#C#

Hemophilia#A#

Involves#both#intra#and#
extravascular#elements##

Christmas#factor#
Hemophilia#B#
Vitamin#K#dependent#
Coagula>on#factors:#Factors#2#
(prothrombin),7,9,10##

 Laboratory#Test#Results#
What#factor(s)#would#you#test#to#diagnose#this#disorder?#
!
#
!
##
!
##
!
##

##Factor#VIII#
##Factor#IX#
##Factor#XI#
##Factor#XII#

 Laboratory#Test#Results#
What#factor(s)#would#you#test#to#diagnose#this#disorder?#
!
#
!
##
!
##
!
##

##Factor#VIII# hemophilia#A #
##Factor#IX# #hemophilia#B #
##Factor#XI# hemophilia#C #
##Factor#XII#

Yasir#:#
#

Factor#VIII####:#4%###########(normal:#50A100%)##

#PATHOPHYSIOLOGY#of#hemophilia#A:##
Hemophilia#A#is#an#inherited#bleeding#disorder#due#to#a#deciency#of#
func>onal#factor#VIII.##
The#gene#for#factor#VIII#is#located#on#the#long#arm#of#the#X#chromosome,#and#
thus#almost#all#aected#pa>ents#are#male.#
#Carrier#females,#however,#may#be#found#with#factor#VIII#levels#of#less#than#
50%,#and#may#have#an#increased#bleeding#risk#with#surgery#or#major#trauma.#
up#to#one#third#of#pa>ents#the#muta>on#may#be#spontaneous#and#not#
inherited.#No#single#muta>on#accounts#for#all#hemophilia#A#cases.##
The#clinical#severity#of#hemophilia#correlates#with#the#level#of#plasma#factor#
VIII#

Yasir#is#planned#t#o#have#an#elec>ve#tonsillectomy#,#how#
are#going#to#manage#him?##

Yasir#is#planned#t#o#have#an#elec>ve#tonsillectomy#,#how#are#going#to#manage#
him?##

With#the#elec>ve#tonsillectomy#planned#for#the#near#future,#prophylac>c#administra>on#of#a#factor#
VIII#product#prior#to#surgery#will#be#required#to#enable#the#pa>ent#to#achieve#normal#hemostasis#and#
healing#during#and#a`er#the#surgical#procedure.##

recombinant#factor#VIII#prepara>ons#are#more#commonly#used#
When#to#use#it#?#
" a`er#trauma#or#spontaneous#bleeds#into#muscles#or#joints.##
" #severe#hemophilia##:#many#of#these#pa>ents#bleed#spontaneously,#severely#aected#pa>ents#are#o`en#treated#
prophylac>cally#to#prevent#bleeding#episodes.##
" mild#to#moderate#hemophilia#A,#would#require#prophylac>c#factor#VIII#administra>on#prior#to#the#planned#
surgeries##
" Factor#VIII#should#be#administered#prior#to#the#procedure#to#achieve#factor#VIII#levels#of#100%,#with#addi>onal#
dosing#post#opera>vely#to#maintain#approximately#50%#of#normal#factor#VIII#levels,#to#allow#for#healing#from#
the#surgical#procedure.##

Case#2#

3#years#old,#presented#with#rash#over#face,#
extremi>es#and#trunk,#started#the#night#before#
the#presenta>on.###
H\O#URTI#2#weeks#earlier#
Other#wise#well#
What#further#history#you#want#to#ask?#
Cause##
" easily#bruising##
" Bleeding#gums#
" Swelling#of#joints#
" Bloody#stool#or#urine#,#CNS#

"PMH:#Surgical##trauma##
"Drug#??#
"Family#history#of#bleeding##
" Other#cell#line#involvement##
#

Case#2#

Further#history:##
"2#wks#earlier#:#runny#nose#,mild#cough,#no#fever#
"Easily#bruising#for#few#days#
"Bleeding#gums#on#brushing#
"No#h\o:#joint#swelling#or#pain,#normal#stool,#yellow#urine,#
no#headache,#vomi>ng,#fully#awake#but#somewhat##
irritable#
"was#circumcised#with#no#problem,#vaccinated#with#no#
complica>ons,#no#surgeries#
"No#pallor,#no#recurrent#febrile#illness#

Case#2#

What#are#looking#for#in#examina>on?#Why#?#
"Vitals#,#wellness##
"#skin#:#Describe#rash,#color,#size,#type# #palpable?#
tender?#blanching?#distribu>on? #
"Eyes##
"Mucus#membranes##
"Joints##
"Abdomen:#organomegaly##
"Lymphadenopathy##
"CNS##

Case#2#

In#his#examina>on#:##
"Stable#vitals,#afebrile,#not#pale##
"Non#blanching#rash#,Not#palpable#
,Not#tender,#All#over##
"Submucosal#bleed#on#lower#lips#
"Bleeding#gums#
"No#HSM#
"No#Lymphadenopathy##
"Free#joints##
"Eyes#:free#
"CNS#:normal#

Case#2#

Dieren>al#Diagnosis#?#
Platelet#disorder#Vs#coagulopathy##
#
low#platelets#count##:#
#Decreased#produc>on#
Acquired##
Inherited##

#Increase#consump>on#\#destruc>on##

Normal#platelet#count#:##
#Decreased#func>on##
Acquired##
Inherited##

Case#2#

What#inves>ga>ons#you#want#to#perform#?#

Case#2#

Inves>ga>on##
CBC#
PS##
PFA#:##
Bleeding#>me#
Platelet#func>on#analysis#
Platelet#aggrega>on##

PT,PTT,INR#
RFT##
#

Case#2#

Giant#platelet,#few##

CBC##

RBC######4.5X1012/L##(4.0A5.2)#
HGB#####13.4g/dL#####(11.5A15.5)#
MCV#####82.3#fL#############(77A95)#
MCH#####29.6##pg###########(25A32)#
MCHC###35.9#g/dL#######(31A36)#
WBC#:#8x#10#9/L#
N############44%##
L############39%#
M##########14%#
E############1%#
B#############2%#
Plt####<#5x109/L###(150A455#x109#/L#)#
Coagula>on:#INR#0.91#,#PTT#24.8##

Normal#PS##

PS#

Giant#platelets#are#o`en#seen#in#pa>ents#with#ITP#,#These#platelets#reect#the#increased#
megakaryocy>c#mass#in#the#marrow#

Case#2#

PS#

Spurious#thrombocytopenia#due#to#platelet#clumping#or#platelets#
adhering#to#neutrophils#(platelet#satelli>sm#

Giant#platelets#are#o`en#seen#in#pa>ents#with#ITP#,#These#
platelets#reect#the#increased#megakaryocy>c#mass#in#the#
marrow#

#BernardASoulier#syndrome,#can#be#diagnosed#based#on#the#
results#from#the#peripheral#smear##

In#HUS#,#a#striking#degree#of#red#blood#cell#fragmenta>on#is#seen#
in#addi>on#to#thrombocytopenia##

Case#2#

Bleeding#>me##

This#is#a#valuable#test#for#disorders#of#primary#hemostasis;##

this#test#is#highly#operatorAdependent#and#is#not#
recommended#as#a#rou>ne#screening#test.##

Under#these#condi>ons,#the#cessa>on#of#bleeding#results#
from#the#forma>on#of#a#primary#hemosta>c#plug.##

Bleeding#>me#is#prolonged#with#platelet#counts#below#
75,000/L#

should#not#be#performed#on#pa>ents#with#
thrombocytopenia.##

A#prolonged#bleeding#>me#with#a#normal#platelet#count#is#
very#signicant#and#indicates#a#qualita>ve#platelet#
disorder.##

In#disorders#of#secondary#hemostasis#(eg,#hemophilia#A#
and#B),#bleeding#>me#is#almost#invariably#normal.#

The)platelet)aggregate)forma7on)depends)on))
(1))vWf)binding)to)collagenAcoated)nitrocellulose)
membranes,)
)(2))platelet)adhesion)to)vWf)via)platelet)GP)Ib)
platelet)ac7va7on,)and)
)
)(3))platelet)aggrega7on)mediated)by)the)interac7on)
of)GP)IIb/IIIa)with)vWf)and)brinogen.))

Case#2#

InAvitro#PFT##

In)vitro)platelet)func7on)analyzer)100)
assesses)primary)hemostasis)under)shear)stress.))
2)types)of)membranes:))
collagen)plus)ADP)(Col/ADP)membrane))or)
)epinephrine)(Col/Epi)membrane).))
Normal)closure)7mes)range)from)77)to)133)seconds)for)the)Col/ADP)membrane)and)98A185)seconds)
for)the)Col/Epi)membrane.))
The)closure)7me)using)the)Col/Epi)cartridge)is)abnormal)in)pa7ents)with))
congenital)platelet)func7on)defects,)
)von)Willebrand)disease,)
)or)aspirin)inges7on,))

whereas)the)closure)7me)with)the)Col/ADP)cartridge)is)abnormal)mainly)in)pa7ents)with))
von)Willebrand)disease)or))
congenital)disorders.))

Glanzmann)thrombasthenia,)BernardASoulier)syndrome,)and)most)mild)von)Willebrand)
diseases)are)associated)with)a)prolonged)closure)7me)with)both)cartridges,).))

Case#2#
Platelet)disorder))

Normal)platelet)
count))decreased)
func7on))

Acquired))

Drug)induced))

CBC#

Inherited\)
congenital)))

Glanzman)
throbasthenia)))
)
VWD)

Low)platelet)count))

Inherited)
\congenital))

Acquired))

Decrease)
produc7on))
)
)

BM)suppression))
BM)inltra7on))
)

Increase)
destruc7on)
\consump7on))

Digeorge)syndrom)
TAR)

Immune)
ITP)

Nonimmune)
HUS)

SLE))

DIC))

Case#2#

Back#to#case#2#:##
3#years#old,#presented#with#rash#over#face,#extremi>es#and#
trunk,#started#the#night#before#the#presenta>on.###
H\O#URTI#2#weeks#earlier#
Petechial#rash##
Other#wise#well#and#free#examina>on##
CBC#:#only#thrombocypenia#
PS:#giant#platelets#
PT,#PTT#,#INR#:#Normal#

Case#2#

What#is#the#diagnosis#?##
ITP#=##
Immune#thrombocytopenia#
Idiopathic#Thrombocytopenia##

Case#2#

What#is#the#next#step#in#management#?#
ASH ##

The#goal#of#all#treatment#strategies#for#ITP#is#to#achieve#a#platelet#
count#that#is#associated#with#adequate#hemostasis,#rather#than#a#
normal#platelet#count#
)
Children):))
A#single#dose#of#IVIG#(0.8A1.0#g/kg)#or#a#short#course#of#cor>costeroids#
should#be#used#as#rstAline#treatment.#
#
#IVIG#should#be#used#instead#of#cor>costeroids#if#a#more#rapid#
increase#in#platelet#count#is#required.#
#
#
#An>AD#may#be#considered#for#rstAline#therapy#in#Rh+#
nonAsplenectomized#children#

Case#2#

Subsequent#Management#of#ITP#
#

#Assessment#of#Disease#Status:#

What#bleeding#is#the#pa>ent#experiencing?##Determine#the#>ming,#loca>on,#and#
severity#of#bleeding#symptoms.#
Does#this#pa>ent#have#a#change#in#history#or#physical#examina>on#that#requires#
evalua>on#for#another#diagnosis#that#could#be#causing#thrombocytopenia?#
#Does#this#pa>ent#have#any#contraindica>ons#to#splenectomy?#
#How#is#the#diagnosis#of#ITP#aec>ng#the#pa>ent s#ability#to#work,#go#to#school,#or#
par>cipate#in#ac>vi>es?#
Does#the#pa>ent#respond#intermixently#to#his#or#her#current#drug#therapy?#
#Is#the#pa>ent#experiencing#side#eects#from#chronic#medica>on#use?#
#How#is#the#pa>ent#coping#psychologically#with#having#a#low#platelet#count?#

2011#Clinical#Prac>ceGuideline#on#theEvalua>on#andManagement#of#ImmuneThrombocytopenia#(ITP)AASH#

Case#2#

2011#Clinical#Prac>ce#Guideline#on#the#Evalua>on#and#Management#of#
Immune#Thrombocytopenia#(ITP)AASH#

DiGeorge#syndrome#

22q11.2#dele>on#syndrome#
#mild#to#the#very#serious.#Symptoms#shown#to#be#common#include:#

VeloACardioAFacial#syndrome# Congenital#heart#disease#(40%#of#individuals),#(tetralogy#of#Fallot,#

interrupted#aor>c#arch,#ventricular#septal#defect,#and#persistent#
truncus#arteriosus)#
Palatal#abnormali>es#(50%),#cle`#palate,##
characteris>c#facial#features#including#hypertelorism#
Learning#dicul>es#(90%),#but#broad#range#
Hypocalcemia#(50%)(due#to#hypoparathyroidism)#
Signicant#feeding#problems#(30%)#
Renal#anomalies#(37%)#
Hearing#loss#(both#conduc>ve#and#sensorineural)#(hearing#loss#with#
craniofacial#syndromes)#
Laryngotracheoesophageal#anomalies#
Growth#hormone#deciency#
Autoimmune#disorders#
Immune#disorders#due#to#reduced#T#cell#numbers#
Seizures#(with#or#without#hypocalcemia)#
Skeletal#abnormali>es#
Psychiatric#disorders#

Thrombocytopenia) )late)occurring ))
#

 TAR#syndrome,#thrombocytopenia absent radius

#the#level#of#platelets#in#the#blood#goes#
up#and#down.#
##
Episodes#of#thrombocytopenia#are#most#
frequent#during#the#rst#two#years#of#life.##
Episodes#may#be#preceded#or#triggered#
by#certain#infec>ons,#such#as#viral#
illnesses#(par>cularly#diges>ve#
[gastrointes>nal]#illnesses),#surgery,#
stress.#

Case#3##
#Omar#is#a#4#years#old#boy#,#
visi>ng#his#grandfather#who#lives#
in#a#farm.##
He#presented#with#a#sudden#
onset#of#pallor,#jaundice#,#dark#
urine#.#
#He#has#a#maternal#unkle#who#has#
similar#episodes#and#received#
blood#transfusion#.##
#

Case#3##

What#further#history#you#need#to#obtain#?#

Case#3##

What#further#history#you#need#to#obtain#?#
#

Cause))
Color#of#urine##red#,#tea#
colored,#dark#orang###
Jaundice##
Pallor##
Acute#versus#chronic#or#
recurrent##
Abd#disten>on/pain##
Skeletal#pain#/abdominal#pain##
Chest#pain##
Joint#swelling,#pain##
Edema,#breathlessness,#
decreased#urine#produc>on#,#
easily#bruising##

Complica7on))
Hemodynamic#stability##

Autoimmune#disease##
Neonatal#jaundice,#neonatal#
screen##
Drug#exposure,#chemicals,#food.##
Recent#febrile#illness,#travel,#
contact#with#sick#pa>ents#
Insect#bites?#
Family#history#.?????##
Blood#transfusion#
Splenectomy#
Autoimmune#disease#
Cancer,#surgeries#

Other#cell#lines#involvement##

Case#3##

What#is#important#to#look#for#in#examina>on#?#

Case#3##

What#is#important#to#look#for#in#examina>on#?#
"Pallor##
"Jaundice##
"Vital#signs;#tachycardia,#gallop#rhythm#
"Unusual#features##
"Scars#
"HSM#
"Chest:#?#Pneumonia?##
"Skeletal#abnormali>es#:#joint#swellings#,#deformi>es,#bone#
pain#esp.:#sternum#,#vertebrae#,#limb#discrepancy#,##
"CNS:#hemiplegia#,#focal#neurological#manifesta>ons#
"CVS#:#anemic#heart#failure##
"Urine#examina>on#:#color,#SG.#

Case#3##

Omar#is#previously#healthy##
This#is#the#rst#>me#to#have#these#complain#
History#of#neonatal#jaundice#,#needed#phototherapy#
His#grand#father#is#a#farmer#and#its#the#season#of#fava#bean#harvest,#it#is#the#
rst#>me#he#visit#in#this#season##
#never#ingested#fava#bean#before#
No#h\o##recent#drug#intake#
No#h\o##joint#swellings#or#skeletal#pain#,#chest#pain##
Nega>ve#surgical#history#,#blood#transfusion,#recent#fever#
Examina>on#:#pallor,#jaundice#,#tachycardia,#tea#colored#urine#.#No#HSM.#

Case#3##

What#inves>ga>ons#you#want#to#do?##

Case#3##

Inves>ga>ons:##
CBC#
PS#
LDH#
Haptoglobin##
Urine#dips>ck##
Serum#bilirubin# #Indirect# ##
DCT#
G6PD#level???#

Case#3##

CBC#3#months#before#was#normal#
#Current#CBC#

#RBC######2.5X1012/L##(4.0A5.2)#
HGB#####5.4g/dL#####(11.5A15.5)#
MCV#####85.3#fL#############(77A95)#
MCH#####30.6##pg###########(25A32)#
Re>culocytes###10#%#
RDW#14#
WBC#12#x109/L#
N############60%##
L############20%#
M##########15%#
E############1%#
B#############4%#
Plt#230x109/L###(150A455#x109#/L#)#

Case#3##

PS#

Bite#cells#,#schistocytes##

Heinz#bodies=#denatured#
Hemoglobin##

Case#3##

LDH#high##
Haptoglobin#low##
DCT#nega>ve##
G6PD##level#is#Normal##

Case#3##

The#World#Health#Organiza>on#classies#G6PD#gene>c#variants#into#
ve#classes,#the#rst#three#of#which#are#deciency#states.[3]#
" Class#I:#Severe#deciency#(<10%#ac>vity)#with#chronic#(nonspherocy>c)#
hemoly>c#anemia#
" Class#II:#Severe#deciency#(<10%#ac>vity),#with#intermixent#hemolysis#
" Class#III:#Mild#deciency#(10A60%#ac>vity),#hemolysis#with#stressors#
only#
" Class#IV:#NonAdecient#variant,#no#clinical#sequelae#
" Class#V:#Increased#enzyme#ac>vity,#no#clinical#sequelae#

Case#3##

How#to#manage#this#pa>ent?#
Evaluate#the#need#for#
transfusion#
Monitor#the#hemolysis##
Educate#the#family##

Case#3##

Hemoly7c)Anemia))

DCT)ve))

DCT)+ve))

Intrensic))
RBCs)defects)

Extrensic))
Outside)the)RBCs)

Autoimmune)))

Alloimmune))

Red)cell)memrane)
defects))

Red)cells)ezyma7c)
defect))

Red)cell)
hemoglobinopathy))

DIC)
HUS))
Prosthe7c)valve))
Others))

AIHA))
Autoimmune)
disease))

Rh)incomatability))
ABO)
incompastability))

Elliptocytosis)

G6PD)

Sherocytosis))
)

Pyrovate)
Dehydrgenae)def).)

SCD)
Thalassemia))
Others))

Case#4##

Case#4#
#HISTORY#
A#fourAyearAold#African#American#boy#
diagnosed#with#sickle#cell#disease#in#the#
newborn#period#was#admixed#to#the#hospital#
with#abdominal#pain.#Two#days#prior#to#
admission,#he#was#seen#in#the#emergency#room#
for#abdominal#pain#and#sent#home#with#a#
prescrip>on#for#morphine.#
#

Case#4##

What#history,#including#symptoms,#would#be#
most#helpful#in#evalua>ng#this#pa>ent?#
#
"##Prior#episodes#of#abdominal#pain##
"History#of#other#types#of#pain##
"##Fever##
"##Cough#and#shortness#of#breath##
"##Medica>ons#,#vaccina>ons#and#follow#up#
"##Family#history##

Case#4##

Omar#had##Two##similar#episodes#in#the#last#year.#
Recurrent#episodes#of#back#and#upper#leg#pain#and#
swollen,#some>mes#painful,#ngers#(dactyli>s)#
He#had#a#temperature#of#101#degrees#Fahrenheit#
(38C)#yesterday.#
#He#has#been#coughing#2A3#>mes#a#day#and#
intermixently#through#the#night.#
The#child#has#been#prescribed#penicillin#prophylaxis#
and#folic#acid#why?#
#One#cousin#has#some#kind#of#sickle#cell#disease#and#
one#brother#has#Type#1#diabetes#

Case#4##

What#are#you#looking#for#in#
examina>on?#
" Vitals#
" Growth##
" Skin#
" Chest#
" Abdomen#
" Genitals##
" CVS#
" CNS#
" Musculoskeletal##

Case#4##

On#examina>on##

Case#4##

Problem#list#:#
#

Case#4##

Problem#list#:#
"Acute#painful#crises/#vasoAocclusive#crisis##
"Acute#chest#syndrome#Vs#pneumonia##

Case#4##

How#are#you#going#to#inves>gate#this#
child#?#

Case#4##

How#are#you#going#to#inves>gate#this#
child#?#
Assess#acute#problem#
Look#for#complica>on#of#the#disease##

Case#4##

The#dieren>al#showed#80%#neutrophils,#15%#lymphocytes,#and#5%#
monocytes.##

Case#4##

What#other#labs#would#you#request?#
#

Case#4##

What#other#labs#would#you#request?#

##Peripheral#blood#smear##
##Hemoglobin#electrophoresis##
##Amylase#and#lipase##
##Blood#cultures##
##Blood#type#and#screen#for#an>bodies##
##Haptoglobin##
##LDH##
##Renal#and#liver#func>on#laboratory#studies##
##Dips>ck#urinalysis##

Case#4##

Peripheral#blood#smear#

Hemoglobin#electrophoresis##
##
##

The#direc>on#of#electrophoresis#is#to#the#
le`.#There#are#two#lanes.#The#lower#lane#
consists#of#the#laboratory#standard#and#
contains#a#mixture#of#HbA,#HbF,#HbS,#and#
HbC.#The#pa>ent's#sample#is#in#the#upper#
lane#and#consists#mostly#of#HbS#and#a#faint#
trace#of#HbF.##

Case#4##

Which#of#the#following#tests#would#you#
request#at#this#>me?##
"##Chest#XAray##
"##Brain#MRI##
"##Echocardiogram##
"##Abdominal#ultrasound##
"##Transcranial#Doppler##

Case#4##

Which#of#the#following#tests#would#you#
request#at#this#>me?##
"##Chest#XAray##
"##Brain#MRI##
"##Echocardiogram##
"##Abdominal#ultrasound##
"##Transcranial#Doppler##

Case#4##

Chest#XAray##
" The#pa>ent#is#febrile#with#a#low#
oxygen#satura>on#level.##
" Pneumonia#and/or#acute#chest#
syndrome#(ACS)#could#be#
iden>ed.#
" RESULT:#This#pa>ent#has#
bibasilar#inltrates,#indica>ng#
pneumonia#or#ACS.#

Case#4##

What#is#the#dierence#between#pneumonia#
and#acute#chest#syndrome#?#
#ACS#=#chest#pain#+_dyspnea#+_#hypoxia+A############################
radiological#abnormali>es#+#SCD##

Case#4##

How#would#you#treat#this#pa>ent?##
#

Case#4##

How#would#you#treat#this#pa>ent?#
"#Oxygen#by#nasal#cannula##
"##Third#genera>on#cephalosporin#and#azithromycin##
"##Morphine##
"##IV#uids##
"##Blood#transfusion##
"##Folate##

Case#4##

Hospital#Course#:#
The#pa>ent#became#more#tachypneic;#his#
oxygen#satura>on#dropped#to#80%.#
#He#had#been#transfused#with#a#simple#
packed#red#blood#cell#transfusion,#but#his#
respiratory#distress#worsened.#???#
He#was#diagnosed#with#acute#chest#
syndrome.#
#He#was#transferred#to#the#pediatric#intensive#
care#unit#(PICU),#where#he#was#intubated#and#
underwent#exchange#transfusion.#

Case#4##

The#pa>ent#was#intubated#for#nine#days.##
He#received#maintenance#uids#of#1.5#L/m2#and#consistently#
had#a#posi>ve#uid#balance#and#an#elevated#blood#pressure#for#
his#age#(125/80).##
When#his#respiratory#status#was#improving#and#his#seda>on#was#
decreased,#he#had#a#complex#par>al#seizure.#He#received#
lorazepam#and#the#seizure#ceased.#A`erwards,#he#had#no#focal#
decits.#

)
What)do)you)want)to)do?)

MRI#brain##

#
An#MRI#showed#evidence#of#
infarcts#(see#red#arrow#on#image).##
Once#extubated,#the#pa>ent#did#
not#speak.##
He#was#weak#and#decondi>oned.#
He#was#transferred#from#the#PICU#
to#the#rehabilita>on#unit.##
Three#weeks#later,#he#was#
discharged#to#home#

What#is#next?#
(acute#chest#syndrome,#CVA)#
Ac>ve#management#:##

"speech,#physical,#and#occupa>onal#therapy##
"cogni>ve#tes>ng#
"lung#func>on#test##

Prophylaxis##

"chronic#transfusion#program#
"oral#iron#chelator##
"#hydroxyurea#
"Prophylaxis#from#infec>on:#an>bio>c##,#vaccina>on##

Saba#,#8#months#old#Nigerian#boy#
First#born#to#young#couple##
Painful#swelling#of#hands#and#feet,#
no#trauma,#low#grade#fever##
Mild#pallor#,#no#jaundice,#no#ac>ve#
bleeding##
Spleen:#3#cm#below#costal#margin##
##

"What#is#the#dieren>al#diagnosis#?#
"How#to#conrm#the#diagnosis#?#
"What#is#the#plan#of#management#?#
"What#is#the#complica>on?##

Case#5##
Yasmin#,#1#years#old#girl##
#her#Mother#complains#that#she#has#poor#appe>te#&#
poor#weight#gain##
Dietary#history#:#breast#feeding#up#to#6#month.#Early#
introduc>on#of#fresh#cows#milk#at#age#of#7#months.#
Her#main#diet#is#rice#and#cereals.#
She#is#pale.#Her#weight#is#below##the#`h#cen>le.#Her#
height#is#on#the#5th#cen>le##
The#I#year#CBC#check#up#showed#Hb#of#6.5#gm/dL#

 What#further#history#you#want#to#obtain?#
What#important#physical#ndings#you#will#look#
for#in#examina>on?#
How#are#you#going#to#inves>gate#this#pa>ent#?#
What#is#the#plan#of#management#?#

CBC):)

RBC######2.5X1012/L##(4.0A5.2)#
HGB#####6.7g/dL#####(11.5A15.5)#
MCV#####63.3#fL#############(77A95)#
MCH#####19.6##pg###########(25A32)#
Re>culocytes###1%#
RDW#25#
WBC#12#x109/L#
N############60%##
L############20%#
M##########15%#
E############1%#
B#############4%#
Plt#730x109/L###(150A455#x109#/L#)#

 PS:##

IDA#

Normal#smear#

 What#other#inves>ga>ons#you#will#obtain#?#

 Assess#iron#status#:#
Serum#iron####
Total#iron#binding#capacity#TIBC#
Iron#satura>on##
Serum#ferri>n##

Hb#electrophoresis#?#Too#early##

 Assess#iron#status#:#
Serum#iron####low###
Total#iron#binding#capacity#TIBC#high##
Iron#satura>on##low#
Serum#ferri>n##low##

Assess#other#element#decincies##

 How#are#you#going#to#manage#this#pa>ent#?#
"Elemental#iron#supplement#6mg\kg\day#x#3#
months#
"Diet#advice#
"FollowAup#clinically#and#by#blood#chemistry##

Microcy>c#
hypochro
mic#
anemia##

Low#
intake#
#
#

IDA##

Thalassem
ia##

Lead#
poisoning##

Sidroblas>
c#anemia#

Increase#
loss#
#

Evidence#
of#
hemolysi
s#
FH#
HSM#
#

Environm
ental#
exposue#
PICA#
PS#:basop
hilic#
s>ppling#
CNS##
#

Rare#
BM#faiure##

Decreased#
absorb>on##

FH#

Anemia#of#
chronic#
illness##
h\o#chronic#
disease#

 Ring#sidroblast##