Paroxysmal Nocturnal Hemoglobin uria (PNH)

DX :

acquired genetic defect of hematopoietic stem cell CBC :

anemia or panoytopenia
-
-

→ PIGA gene on X chr -

.
→
glycosyl phosphatidylinositol (GPI ) anchor loses protective effect on RBCs .

Flow cytometry :
absence of CD 55 & CD59 on RBC
RBC destruction by complement & RES → intra & extra vascular hemolysis Coombs Test Negative
.
→ -
-
:

( absence of complement inhibitors) →

also platelet activation & thrombosis
involved proteins CD 55 / DAF ; CD -59 / MIRL}absent impaired neutrophil function Serum : I haptoglobin
-
: .
→

can also occur in pts w/ aplastic anemia

→

-
TRIAD :
Hemolytic anemia pancytopenia & thrombosis ,
-

Tx :

→
Pallor excessive fatigue & weakness
,
.

Prednisone → initial
→ Intermittent Jaundice .

Eculizumab →
anti -

CS antibody (complement -1 )
→
Episodes of Hemoglobin uric → Pink / red / dark urine -

Bone marrow transplantation it Bm hypoplasia

→
Venous Thrombosis in unusual locations eg .

hepatic ,
cerebral abdominal
,
'

Allo genic stem cell transplantation

→ Vasoconstriction .

Iron & folate supplementation

Headache pulmonary HTN
-

Abdo pain dysphagia , ,

erectile dysfunction
-

complications :

→ T Risk of Infections •
Vasoconstriction & thrombotic emboli
-
t risk of acute leukemias

↳ 0
absent

Enzyme Defects
Glucose 6- -

Phosphate dehydrogenase 166 PD ) Deficiency DX :

Blood smear : irreg contracted

.
cells
due to macrophages removing denatured
-

most common human enzyme deficiency 6400 million worldwide) •

Bite cells I fragmented RBCs) hemoglobin inclusions of RBCs ltieinz bodies)

bk 0×1 stress causes Hemoglobin denaturation Hb precipitates
linked recessive affects males us%A4.fi?anklmm99oitsme&sEAsialsevere1-smedit lmost severe) Heinz bodies as small inclusions wli
"
X
,

→
erythrocytes
-
- -

a- 6PD rate-limiting enzyme of pentose phosphate pathway that reduces NADP NADPH → ( which can neutralize Ros ) & free radicals
ghost red cells (Hb retracted to
→

w/o glutathione RBCs susceptible to oxidative stress that can damage RBC membranes
→ → Intra -
& Extra vascular Hemolysis
-
.
Hemi -
one side)

causes of T Oxidative stress are triggers of hemolytic crisis : -

Polychromatic macrocytes
→ most common cause :
bacterial I viral infections
blot NADPH + destruction of Phagocytesed
pathogens .
-

signs of Intravascular Hemolysis

→
FAVA beans drugs 1 anti malarial quine sulfa limp smh Nitrofur NOVMOCY tic anemia T LDH
-

drugs
'
"
NSAIDs ciprofloxacin )
-
"
-

. . , ,
,

→ Inflammation produces free radicals → diffuse into RBCs metabolic acidosis

-
T Reticulocyte count .

I Hapto globin
,

T Unconj Bilirubin
Hemoglobin uria
-
-

( normal btw crises ) screening Test : fluorescent spot test

CF most asymptomatic
-
- :

add GGP & NADH → measure NADPH fluorescence

recurring hemolytic crises may occur w/ triggers
'
-

arise w/ i 2- 3d after Tox stress

-
.
-

Confirmatory Test Quant -66 PD enzyme analysis :

.

sudden onset back or abdo pain

-

Jaundice 1 neonatal usu w/o hemolysis)

-
Tx : avoid triggers
,

dark urine
-
blood transfusions only in rare ,
severe cases

transient * selective advantage in areas endemic malaria for carriers

splenomegaly
-

recurrent severe infections → sx of chronic granulomatous disease ( hetero . females ) → less severely affected esp .
A falciparum

Pyruvate kinase Deficiency

-

autosomal recessive defect in PK

→
PK catalyzes last step of glycolysis (converts phosphoenolpyruvate →
pyruvate)
→
glucose only energy source for RBCs .
:
w/o PK ,
ATP deficiency in RBC
hemolysis
↳ →

*
disrupts gradient along RBC membrane Rigid RBCs
cation
accumulation of 2,3 bisphosphoglycerate T release of Oz from - →
→ →

Hb
T extra vase
→ masks
.

syrup of anemia
.

CF usu symptomatic DX t.PK enzyme gene mutation activity PKLR

-
: :
;
-

Newborn jaundice due to hemolysis .

Gallstones .
Blood film poikilocytosis & distorted prickle cells
:
" "

splenomegaly
•

Frontal bossing , leg ulcers

-

Pallor fatigue
, ,
weakness .

Rare :
hydrops fetal is -

Tx Phototherapy and / or exchange transfusions

:

splenectomy if severe anemia or exces enlarged spleen .

 Hemoglobin opathies
Hemoglobin C disease

B- globin mutation ( glutamate replaced by Lysine) DX :

- -

→
Hemoglobin C formed Hess soluble than HBA → forms crystals → RBC dehydration Amato)) -

Peripheral smear in HOMOZY

:
Anisopoikllocytosis ,

TRBC rigidity & + deform ability → extra vase

& shorter
.
hemolysis
lifespan
Target Spherocytes
cells & shaped ,
Rod -
RBCs

containing precipitated hemoglobin C Crystals

.
RBCs + oxygen binding capacity
-

CF :
mild hemolytic anemia → Jaundice , Splenomegaly
* Hbsc
gene mutation lone Hbo .
one Hbs ) → milder -
TX : folic acid supp to counter RBC .
depletion
-

sickle cell disease [see other note]

-

Thalassemia [see other note]

Extrinsic
Autoimmune Hemolytic Anemia

1 Warm Agglutinin Disease 2 . Cold Agglutinin Disease

-

autoimmune disease w/ heat sensitive I 37°C) antibodies

-
>

binding to RBCs → taken up by RE macrophages → -

autoimmune disorder w/ cold sensitive co -

4°C) antibodies
parts of membrane lost I becomes more spherical binding to RBCs agglutination I lysis of RBCs
→

agglutination IT Extravascular hemolysis by RES spleen

→ & liver -

mainly IgM antibodies → Intra & Extra vascular hemolysis

- -

mainly IgG but could have complement action as well → intra mediated through complement system
→
but little to no intravasc .
hemolysis 1 unlike cold aqg.nl lgml
-

usually idiopathic some 2° ,

causes :

mostly idiopathic but some 2° causes :

Mycoplasma pneumoniae or EBV infection
-
-

malignancy lymphoma CLL :

Malignancy eg Cell
-

. .

.
Autoimmune diseases : SLE .

Walden Strom macroglobulin emia

-

Drugs rifampin phenytoin penicillins

:
, , ,
d- methyl dopa
-

CF : more acute & severe than warm

-

CF :
onset gradual .
Often remit & relapse .
Anemia → pallor fatigue weakness , ,

hemolytic anemia w/ varying severity fatigue pallor Painful cyanosis of extremities Cairo cyanosis)
→
weakness
•
-

, ,

.
mild splenomegaly .

Lived 0 reticular is (reddish blue discolouration of skin in net-like pattern

-

DX :
Extravascular hemolysis →
spherocytes agglut .
. RBCs ,
-

DX :

polychromasia -

Peripheral blood spherocytes polychromasia :

, ,

Coombs ⑦ agglutination of RBCs

-

coomb 's ④
Agglutinin titre ( through warmer circulation )
no IgM b/c eluted off as passing
-

Tx : -
T cold .

1. remove / Tx underlying cause •

ti Gd CH
2.
3.
Corticosteroids
Monoclonal Ab
→

→
initial
Anti -

CDZO
tx of choice
( Rituximab) } ""
" "et"" " "
-

Tx :
mild → avoid cold exposure
4. Splenectomy -

if above tails mod -

severe →
immunosuppression w/ Rituximab
5. Immunosuppression
6. Folic acid supp if severe or chronic .
-

Comp : VTE
7. Blood Transfusion it severe anemia lymphoproliferative disorders
8. High dose 1g
9. VTE prophylaxis Prognosis :
Spon remission w/ i few weeks common
-

.
lsolmmune

Hemolytic Disease Of Fetus & Newborn IHDFN )

blood group incompatibility btw mother & fetus → leads to destruction of fetal RBCs by maternal Antibodies
-

ABO incompatibility maternal antibodies :

(anti A and/or anti B) against nonself
- -

antigens of ABO system even if sensitization has

not occurred → fetal hemolysis may occur during 1st prey .

→
present in ~ 201 .
of all pregnancies ; however only 5- 101 newborns .

symptomatic
-

Rhesus incompatibility :

in Rh neg mother & 12h pos newborn : maternal exposure to fetal blood lfetomaternal hemorrhages → production of maternal
- -

IgM antibodies
against 12h antigen ( 1st borns not affected ) → sero conversion overtime to Rh IgG cable to cross placental -

in subsequent pre g. w/ Rh pos newborn rapid production of maternal IgG anti D antibodies to fetal RHD antigens
- : -

→ Rh -

IgG agglutination of fetal RBCs w/ hemolytic anemia → risk of HDFN w/ possible hydrops fetal is
•

Rare following routine anti D -

prophylaxis
-

Kell blood group 2nd most :

common cause of severe HDFN after 12h disease

Rts for HDFN : maternal exposure to fetal blood during pregnancy 10.01 -0.03mL of fetomaternal hemorrhage sutiicientl

antenatal procedures
→
amniocentesis C section termination of preg :
,
-

,
.

prey related complications ectopic pre g. placental abruption

→ - :
,

→
Trauma
DX req evidence of hemolysis in presence of letomat blood incompatibility
:
-

CF : -

Prenatal DX :
-

Prenatal Hydrops fetal is corny expected in rn inwmp )

: -
.

uts determine hydrops fetal is

-
:

Postnatal :
Doppler of fetal BV T flow rate indicates fetal anemia
- :

neonatal anemia
-

Hypoxia -

Postnatal DX :

Hepato splenomegaly
-

Prematurity -

coomb 's Test if newborn has signs of hemolysis

-

Neonatal jaundice
-

scattered petechia -
→
Rhin comp : positive
→ ABO incomp : weak positive or negative
-

Tx :

prenatal :
'

Postnatal
-
Intrauterine blood transfusion via umbilical vein ,
-

Anemia iron supp & RBC transfusion

: lit necessary)

artery peritoneal cavity

,
or heart -

Hyper bilirubin emia phototherapy & :

exchange transfusion iii. necessary )

Possible NIG in severe cases

-

severe : NIG

Prevention
1.
screening :

A. ABO & Rh
typing of mother → Rh ④ no further
screening needed .

→
12h -0 =
screening for Anti D antibodies -

if NO (not sensitized )
↳ =
repeat at 28 Wks gestation & delivery
↳ if YES (sensitized ) =
( anti D antibody titre i. 8)
-

> → amniocentesis & imaging

B. Feto maternal Hemorrhage in Rh -

neg mother
I. -

conduct rosette test (initial test of choice) →

qualitative test to see if feto maternal hemorrhage has occurred
-

maternal Rh neg blood incubated w/ RhoA 1g which binds to Rh pos RBCs

-

,
-

addition of enzyme treated DCE indicator cells → Rh pos fetal RBCs form rosette
- -

pattern
II. If Rosette test positive → conduct Neibauer Betke test -

( quantitative test I
maternal blood smear exposed to acid then stained
-

adult Hb removed by acid whereas Hbflfetai) not →

appear pink on (t ) test
-

amount of Hbf determines amount of Anti -

D 1g necessary

C. Fetal Rh genotyping →
not routine

2. Anti D Immunoglobulin ( Rho a- AM ) 300mg 1150014) w/ IM

-
-

only indicated in un sensitized mothers (no benefit in sensitized )

-

administer during 28th wk gestation & w/i 72 hrs following birth of 12h pos -
.
baby
→ not necessary if father confirmed 12h neg -

efficacy relies on antibody mediated immunosuppression

-

also indicated in : after miscarriage ectopic preg , .

or termination , bleeding during preg .

.
after invasive procedures eg Cvs
.
Microangiopathic Hemolytic Anemia Macroangiopathic Hemolytic Anemia

Eti :
-

Eti :

HUS -

HELL P syndrome -

congenital cardiovascular anomalies

-
TTP '

HTM emergency
.

moderate & severe aortic stenosis

-

malignant HTM -

DIC
-

prosthetic heart valves

-

SLE -

Drug induced
-

eg quinine Tmp
.
.
-

smx , cyclosporine
-

Extracorporeal circulation
"
,
dialysis RBC destruction in feet
Exertionat March Hemoglobin uric
"
→

during strenuous exercise

-

systemic micro thrombi plug small vessels physical

-

RBC destruction in systemic circulation (large vessels )

intravascular shearing of RBCs passing through small -

vessels → Intravascular hemolysis schist ocytosis

, ,
t free Hb due to mechanical forces applied to RBC membrane
* also thrombocytopeniaconsumed) →
intravascular hemolysis schistocytes T free Hb
ymicrospherooytes hepatocytes ,
, ,

(platelets
-
CF : -

CF :

anemia →
pallor fatigue anemia →
pallor fatigue
-
-

, ,

Jaundice -

Jaundice
organ dysfunction renal dyst mental
→ status o
-

Petechia e due to thrombocytopenia

Tx :
depends on cause
 Sickle Cell Anemia
Hereditary Hemoglobin opathies

Increased incidence among Sub-Saharan African Indian . , I -

Prenatal :
CVS & DNA analysis @ 8-12 wks gestation
Middle Eastern or Mediterranean heritage screened
☒ ¥-0 Neonatal screening all newborns
→
-

Africa has highest prevalence of disease 130% heterozygote ) (t ) Repeat electrophoresis (a- OLD STANDARD)
-

→ : Hb
Hbs gene carried by 8-1. of African American pop in
É distinguish type
-

→ will
-

most common form of intrinsic hemolytic anemia worldwide -

older children & adults

Liquid chromatography & isoelectric focusing to
'

Point mutation in B- globin gene chr.lt @

quantify Hb subtypes
↳ Glutamic acid → valine (single aa substitution) .

sickle cell Test detects sickle cells in blood smear :

2 d- globin + 2 mutated B- globin Hemoglobin S ( Hbs) under anaerobic conditions

-

Peripheral Blood smear sickle cells lore scent shaped) : -

variant Glutamic acid Hemoglobin C ( Hbc )

.

* : →
Lysine Target cells Reticulocytosis.tt Howell Jolly Bodies -

Heterozygosity w/ Hbs & Hbc Hemoglobin SC disease Imaging hair on end

↳ "

ray skull crew cut

"
-

:X -
→ - -

intermediate severity btw trait & disease

due to periostealrxntoerythropoietic
↳
BM hyperplasia
Autosomal Recessive Hb Normal Trait Disease
-

Disease monitoring Palm function tests

" "
HBA 95 -98% 0%
lab
Heterozygotes ( Hbs A) trait 60%
sickle cell
-
:
-
.

.
,

Hbs 0% 40% 75-951

Homozygotes ( Hbss) sickle cell anemia Transcranial Doppler UK 1 stroke risk)
.

-
•

Hbf < a . <z, ,

, , ,, ,

when deoxygenated .
Hbs
polymerizes →
rigid crystal ,
-

like rods
distort membranes →
"
Sickles
"
0 LONG TERM -

Prevent infections pneumococcal & :

can be triggered by
-

→
+
:

at which poz level sicking

-

Hypoxia eg .
high altitudes (depends on % of Hbs (trait
occurs
vs .
diseased I meningococcal vaccines
-
Infections -
sudden 8in temp .
-
stress 0
-

Daily penicillin prophylaxis ( until syrs)

Dehydration Acidosis J If ? sepsis IV 3rd gen cephalosporin ceftriaxone)
Pregnancy leg
-
-
→
- -
.

I -

? meningitis → add vancomycin

1.
→
sickle cells lack
disrupts
elasticity
micro circulation
& adhere to vascular endothelium
→
vascular occlusion & infarction
¥ -

Prevent Vaso -

occlusive crises & manage Anemia

0 AVOID
2. Extravascular & Intravascular hemolysis common triggers
-

lñitiic oxide depletion)

r
.
stimulates erythropoiesis IT Hbfso Hbs

anemia folate deficiency CT demand due to T RBC turnover)

-

Hydroxy urea 1St =

Line proportionately t.it/vaso-occ episodes
0
.

→
, for freq acute painful episodes
-

.
or other vaso ou -

events OR severe symptomatic anemia .

3. Body produces
.

myelosuppression
THBF to compensate for t HBA se
-

p.
:

added if 9 not sufficient

,

c-
.

Erythropoietin
OR Blood Transfusions
CLINICAL FEATURES L Glutamine in recurrent acute complications of sci
-
-

Tanti oxidant capacities → t sicking of RBCs

-
T free
glutamine → -

-
SE : Constipation ,
Nausea headache cough pain cabdo back chest )
, , , , ,

SICKLE CELL TRAIT -

Folic acid supp .

-
often asymptomatic -

Cholecystectomy if cholelithiasis
gross hematuria due to renal Partial / Full splenectomy prevent recurrent splenic sequestration
painless papillary necrosis to
-
- -

↳ often
only symptom
-

Hyposthenuria nocturia enuresis :

,
ACUTE SC CRISIS
-

Recurrent UTIS
"
-

Prompt supportive Tx
RARE disease symptoms if deficiency Hydration Nasal 02
"
:
severe Oz
-
- -

Pain Mgmt w/ NSAIDs 1- opioids .

Bed rest
SICKLE CELL DISEASE •

TE prophylaxis
onset-

30% develop symptoms 1st year of life

: ~
; 901 by 6yrs > .
-

Blood Transfusions :

surgery ( pre op )
-

acute seven ysymp anemia

-

manifests after Gmo age as production HBF I & Hbs T

- .

→ ,

2. prophylaxis of acute Vaso occ events (stroke multi

organ fail ) pregnancy
-
-
-
. .

splenomegaly in childhood splenic atrophy in adulthood Exchange Transfusions Cerythrocytapheresis)

-
-
-

Acute Hemolytic crisis (severe anemia) •

automated removal of erythrocytes containing Hbs &

t
→
splenic sequestration crisis acute LUQ pain reticulocytosis.lv BP :
.

J
simultaneous replacement w/ Hbs free RBCs -

G splenic Vaso -

occlusion →
entrapment & pooling large amounts of blood in spleen intravasc . v01 .
depletion
-

if acute Vaso -

Occ . crisis
→
Aplastic crisis : acute ,
severe t in Hb , , reticulocytopenia E
-

Adv :
rapid effect precise control of Hbs &
,
iron accum .

↳ Dysmorphic RBCs susceptible to

parvovirus 1319 infh →
temp .

suppress bone marrow erythropoiesis

→ RBC aplasia
1-
'

Disadv :
expensive ,
not avail .
, experienced practitioner
→
Hyper hemolysis :
Intravascular & extravascular hemolysis (RARE) I
Infection : pneumonia meningitis osteomyelitis CURATIVE
¥f
-

, ,
1salmonella spp , stop . aureus)
,
in homozygous children 16 yrs w/
Allogenic BM
<

sepsis 1 strep pneum ) Transplantation

-

severe disease
-
. .
.

raso.name events :

→
crises : recurrent episodes of severe deep bone pain & dactyl it is
↳
most common symptom in children & adolescents Screening for complications :

.CdÉ¥¥e¥ )
"

acute chest syndrome → new chest infiltrate & resp syrup regular blood work 413C reticulates iron BUN ) LETS Cr
→
'
, , , , ,
.

→
priapism → sustained erection > 4 hrs not from sexual excitement ,
-

UIA annually ( proteinuria & glomerulopathy)

→ stroke (common in children ) •

Transcranial doppler Uls annually until lbyr

→
Acute sickle hepatic crisis RUQ pain jaundice →
, ,
nausea , fever ,
•

Retinal exams annually from 8 yrs

ECHO in late child /early adult for palm HTN
hepatomegaly T transaminase
•
.

→
Infarction of any organ Ise"pieen) & avascular necrosis

§É{
chronic hemolytic anemia → fatigue weakness pallor SCD & MALARIA
-

, ,

chronic pain -

individuals w/ sickle cell trait less likely to develop

-

Chok lithiasis (pigmented stones) severe forms of malaria & have t parasite prevalence ,
 Thalassemia
Group of hereditary hemoglobin disorders due to mutation of a or B- globin chains

EPI
-

a thalassemia : most common in Asian & African descent B thalassemia most common in Mediterranean descent
-
:

provides partial resistance against malaria found in regions where malaria is endemic & those emigrated from these regions
-
-
. .

ETI
-

autosomal recessive
-

a -

that : whole gene deletion of at least one of four d alleles on chr 16 .

→
severity of disease depends on # of defective d- globin alleles
1. Silent carrier (minima form ) one defective allele C- a / da) → Normal Hb slightly microcytic Hb Barts in 1- 3%
:
,
. .

2. Alpha That trait (minor form) two defective alleles c- a/ a or

. laa) → asymp anemia w/ low MCV MCHC Hb Bart in 5- 10%
: - - -

.
,
.
.

3. Hemoglobin H disease 1 intermedia form) three defective alleles f- 1- a) → excessive production of pathologically altered HBH Hours chains)
:

4. Hemoglobin Bart disease Imajor form) four defective alleles → excessive production of pathologically altered Hb Bart ( four Y chains / tetramers)
: -

B- That :
mutations (single base) in promoter sequences or
point splicing sites on chr 11. ( coded by 2 alleles)

1. B- That minor / Trait one defective allele

:

2. B- That major Hooley anemia) two defective alleles :

3. B- That combo of one defective B- globin allele & one defective Hbs allele
sickle cell :

4. Hemoglobin E /B- That combo of one allele w/ HBE variant done defective B- globin allele
: →
highly heterogeneous clinical spectrum
5. Hemoglobin E disease :
homozygous for HBE Variant →
can resemble B- That minor

PATHOPHYSIOLOGY
Anemia due to inefficient erythropoiesis & increased hemolysis
-

✓ \ ↳hen either dorp chains reduced > TT EPO

"""÷"""
a- that B- That I d
( intermedia
d
& major ) ( minor &
t,
major )
compensatory overproduction marrow expansion

[
"" "" " " "" "" " " ^ "" " "" "" " " "" " " " "" "" " " " "" " " " "
ti ti t bone deformity
It d- chains
, It B- chains
, excess globin chains precipitate hyper metabolism
t ti & form inclusions w/ i RBCs
wasting
impaired pairing of a with Ty ,
8 chains t gout
Bandy chains -
t folate deficiency
I THBF & Hb Az hemolysis
adyy
T iron absorption
class
TTHBH or Hb Bart Ketan

( higher affinity to 0, ) I Transfusions

splenomegaly ←
t, Protective in infants until overload
+ 02 delivery to peripheral tissue 6 months ,
then .
.
d
endocrine deficiency

÷ .
diabetes
cirrhosis
cardiac failure
Yersinia infection

CLINICAL FEATURES
-

d- That :

1. Silent carrier →
asymptomatic -

B- That
2. Trait mild hemolytic anemia w/ normal RBC & RDW 1. Minor unremarkable symptoms How risk of hemolysis
:
→
.

than B- that *
3. HBH * less severe
rarely splenomegaly)
:

jaundice & anemia at birth 2. Major

-

-
chronic hemolytic anemia that may require transfusions -

severe hemolytic anemia that often req transfusions .

↳ 2° iron overload hemochromatosis

hepato splenomegaly
→ 2°
-

hepato splenomegaly -

growth retardation
skeletal deformities Hess common )
-
-

skeletal deformities thigh forehead prominent zygomatic bones & maxilla)

,

4. Hb Bart 's hydrops fetal is syndrome

-

transient aplastic crisis 12 to Parvovirus 1319 in-1h )

-
'

intrauterine ascites & hydrops fetal is severe hepatosplenomegaly 3. Sickle cell B- That → features of sickle cell disease
-

& often cardiac & skeletal abhor .

severity depends on amount of B- globin synthesis

-

incompatible w/ life ( death in utero / soon after birth)

DIAGNOSTICS
-

Initial :

CBC : microoytic hypochromia anemia (Mcv 80 MCH 27) variable Hb levels normal RDW higher RBC than in iron def anemia <
-

<
, , , , ,

Hemolysis eval coomb 's negative I Haptoglobin TLDH.treticulocytes.unconj.BR T normal iron studies
:
, , ,

Peripheral Blood smear HBH inclusion bodies Target cells Teardrop cells Anisopoikilocytosis Erythroblasts Basophil ic stifling
:
. . . , ,

2 ↳

Am boss 2021 ,
AM boss 2021 ,

"
Hair on end
"
Am boss 2021
,

a- That minor a- That Intermedia / B That minor /

HBH disease intermedia / major

MCV / MCH Normal / LOW LOW LOW

HBAZ Normal 110W Normal / Low High

Hbf Normal Normal / High High I thin may

HBH maybe present Present Absent

* suspect B- That minor if HBAZ > 3.5% ( normal 1. 5- 3.5% ) *

Prenatal Diagnosis
-

Confirmatory :

d- That
Detection of variants
-

hemoglobin amniocentesis if risk of HBH and hydrops fetal is

electrophoresis
'

Hb -
→ Qualitative
Automated HPLC (high performance liquid chromatography ) → Qualitative
-

& Quantitative
-

Uts detects hydrops ,

can confirm w/ DNA studies
-

Genetic studies (PCR based ) → specific mutations -

-

B- That
-

Bone Marrow Aspiration (not routine) → rule out other

-

Uls
-

Amniocentesis 45152 (not ideal )

-
IMAGING (not routine )
-

chorionic Villus sampling -11152 →

preferred
-

Skull X-ray ( AP & lateral ) → assess craniofacial abn .

high forehead prominent zygomatic bones & maxilla Chipmunk facies

" "
↳
,

hair on end crew cut sign

"
↳ "

Thalassemia intermedia could mean

- - " "
:

CXR : for suspected extra medullary hematopoiesis in thorax -

2 combo mutations but some B- globin made

↳ mediastinal or pulmonary masses -

homozygous B- That but more HBF prod than usual

subperiosteal
.

↳ extension in ribs "

rib within rib
"

p That trait t unusual severity or other globin abn

a
- -

evaluate effect symptoms

.

MRI spine mass due

-

to extra med
-

A- That homozygous + d- that trait

.

hematopoiesis pseudotumours →
t, a :B chain imbalance :
did chain precipitation
t, ineffective
→
erythropoiesis
MANAGEMENT
Iron Chela tors
patient education genetic counseling screening tests for relatives
-

.
,

Thalassemia minor :
usually treatment req 'd
no .
Desferroxamine ( DEO )
Folic acid supplementation may be used episodically eg pregnancy int .
'

n
-

subcut portable syringe driver pump

,

12 -18ms of
,

Thalassemia intermedia / major

-

when serum ferritin 1500-2000 after transfusion

1. Transfusion therapy ( erythrocyte concentrates)

-0 before age 4
→ variable but
4-5 nights / week
Units every 3-4 wks (frequency depends severity)
-

usu 2-3 on
Toxicity Ototoxicity Ophthalmic changes bone changes
-
:
↳ indicated for Hb -70g / L OR marked clinical symptoms
. ,

Hb
& short stature hypersensitivity local lumps/ abscesses
↳
Target > 90-100 GIL
: , ,

* remove WBC to ti reactions *

Deferasirox Coral ) -
1st Line
2. Surveillance & Treatment of complications of DFO Deferi prone
2- 5 ✗
potency 10x
-

;
-
Iron overload chelating agents leg deferasirox)
:
.
-

once daily
Gallstones asthenia extra medullary hematopoiesis pseudotumours skin rash renal impairment
-

, , -

se : a- 1. , ,
Abn LF -1s
.

Endocrine disorders : diabetes , osteoporosis

-

Splenectomy : in
pts w/ severe splenomegaly *
pre op vaccination & penicillin prophylaxis
-
*
Deferiprone (oral )
stem cell transplantation (alto genic HSCT) potentially curative PBS if unable to take DFO
-
-
→

↳ use HLA matching sibling usu SE

agranulocytosis neutropenia joint effusions
:
- -

, , ,

Gene Therapy (experimental ) zinc deficiency abnormal LFTS

-

Hb Barts : no tx , majority terminated as fetal / maternal mortality risk