[PPT] - F e tal Ane mia 02/ 25/ 2015 Anjulika Chawla, M.D. Asso c ia te PowerPoint Presentation

SLIDE 1

F e tal Ane mia

02/ 25/ 2015

Anjulika Chawla, M.D.

Asso c ia te Pro fe sso r Divisio n o f Pe dia tric He ma to lo g y/ Onc o lo g y

SLIDE 2

Obje c tive s

 De finitio n o f a ne mia  Dia g no sis o f fe ta l a ne mia  No rma l de ve lo pme nta l he ma to po ie sis  E

tio lo g y o f fe ta l a ne mia

 De c re a se d pro duc tio n

Co ng e nita l, a c q uire d

 Ma lfunc tio n o f he mo g lo b in pro duc tio n

Alpha tha la sse mia

 I

nc re a se d de struc tio n

Blo o d lo ss, he mo lytic a ne mia

 T

re a tme nt o ptio ns

SLIDE 3

Wha t do e s b lo o d do ?

 T

ra nspo rts g a sse s, nutrie nts ,wa ste s, ho rmo ne s, he a t

 Re g ula te s wa te r b a la nc e , pH  Pro te c tio n fro m infe c tio n, a nd

the r a lie n inva de rs

SLIDE 4

T he b lo o dmo b ile

 https:/ / www.yo utub e .c o m/ wa tc h?

v=F utnu_6NmQo &list=RDF utnu_6N mQo

SLIDE 5

Wha t is b lo o d?

 Re d b lo o d c e lls (fle xib le sa c ks o f

the pro te in he mo g lo b in whic h c a rry O2 a nd CO2)

 White b lo o d c e lls (c e lls with

diffe re nt me c ha nisms to kill

rg a nisms)

 Pla te le ts (ma ke te mpo ra ry wa lls to

ke e p fro m b le e ding )

 Pla sma (sa lt wa te r tha t c a rrie s

e ve rything e lse !)

SLIDE 6

Ane mia

 De finitio n:  De c re a se d

le ve ls o f re d b lo o d c e lls o r

SLIDE 7

Ane mia

 De finitio n:  De c re a se d

le ve ls o f he mo g lo b in

Pic tur e fr

m

http:/ / me dstat.me d.utah.e du/ We bPath/ HE ME HT ML / HE ME 008.html

SLIDE 8

SLIDE 9

Ane mia

 T

he fe tus use s re d b lo o d c e lls to c a rry o xyg e n in its c irc ula tio n just a s c hildre n do .

 Whe n a ne mia is se ve re , the fe tus

c a n e xpe rie nc e he a rt fa ilure a nd de a th.

SLIDE 10

Dia g no sis o f fe ta l a ne mia

 Spe c tra l a na lysis o f

a mnio tic fluid

 Co rdo c e nte sis  Do pple r ultra so und – c he c k

fo r ve lo c ity o f b lo o d flo w in the b ra in

 Ultra so und o f the he a rt c a n

sho w sig ns o f stra in

SLIDE 11

Dia g no sis o f fe ta l a ne mia

 Spe c tra l a na lysis o f

a mnio tic fluid

 Co rdo c e nte sis  Do pple r ultra so und – c he c k

fo r ve lo c ity o f b lo o d flo w in the b ra in

 Ultra so und o f the he a rt c a n

sho w sig ns o f stra in

 Ultra so und c a n a lso sho w

sig ns o f tissue e de ma in se ve re a ne mia (hydro ps fe ta lis)

SLIDE 12

E tio lo g y o f fe ta l a ne mia

 Mo st c o mmo n is b lo o d lo ss (i.e .

b le e ding )

 Ob ste tric a l c a use s  F

e to -ma te rna l, fe to -pla c e nta l, fe to -fe ta l tra nsfusio n

 I

nte rna l he mo rra g e

 I

a tro g e nic

SLIDE 13

E tio lo g y

 I

nc re a se d re d b lo o d c e ll de struc tio n

 I

ntrinsic : E nzyme de fe c ts, me mb ra ne de fe c ts, he mo g lo b ino pa thie s

 E

xtrinsic : I mmune me dia te d (a nti Rh) Ac q uire d he mo lysis (infe c tio n suc h a s ma la ria o r pa rvo virus 19, drug e xpo sure )

SLIDE 14

E tio lo g y

 De c re a se d re d b lo o d c e ll

pro duc tio n

 Co ng e nita l hypo pla stic ma rro w  Bo ne ma rro w suppre ssio n

(pa rtic ula rly fro m pa rvo virus B19)

 Nutritio na l a ne mia (ma te rna l iro n

de fic ie nc y)

SLIDE 15

T ha la sse mia : no n-immune intrinsic he mo lytic a ne mia

 Ca se study:  27 yo Asia n wo ma n ha s misc a rrie d

twic e . Ultra so und sho ws sig ns o f a ne mia , a nd e a rly hydro ps.

 Be c a use o f pre vio us misc a rria g e s

a nd e thnic ity, a mnio c e nte sis is do ne a nd sho ws a fo ur g e ne de le le tio n a lpha tha la sse mia

SLIDE 16

No rma l He mo g lo b in

 2 α−like g lo b in

c ha ins

 2 b -like g lo b in

c ha ins

 4 he me ring s  4 o xyg e n

mo le c ule s Ga s tra nspo rt O2, CO2, NO

SLIDE 17

Huma n g lobin g e ne s

α- like ge ne s on c hr

16 β-like ge ne s on c hr

11

ζ α2 α1

ε

Gγ Aγ δ β

LCR HS-40

α α β β

SLIDE 18

Pro g re ssio n o f Glo b in Synthe sis

SLIDE 19

Diso rde rs o f he mo g lo b in

 Muta tio n in DNA  GE

NE T I C DI SE ASE S

 L

e a ds to

 de fe c t in pro duc tio n o f

he mo g lo b in (tha la sse mia s)

 de fe c t in he mo g lo b in func tio n

(he mo g lo b ino pa thy)

 de fe c t in he mo g lo b in sta b ility

SLIDE 20

Diso rde rs o f he mo g lo b in

 He mo g lo b in va ria nts  He mo g lo b in C,D,E

,O Ara b

 De fe c ts in pro duc tio n o f he mo g lo b in, o r its

sub units

 α-tha la sse mia  β−tha la sse mia  He mo g lo b in L

e po re

 Diso rde rs in the he mo g lo b in struc ture  He mo g lo b in E  He mo g lo b in S  He mo g lo b in C  Mixe d diso rde rs  SC, Sβ0, Sβ+,Eβ0

SLIDE 21

SLIDE 22

Alpha T ha la sse mia

 A g e ne tic de fe c t whic h c a use s a re duc tio n

in the g e ne pro duc t

 De c re a se d α c ha ins pro duc e d  E

xc e ss γ c ha ins to dime rize (γ4) in the infa nt, a nd e xtra β c ha ins (β4) in the a dult

 T

he se “pse udo he mo g lo b ins” pre c ipita te in the RBC, da ma g ing the me mb ra ne a nd c a using he mo lysis

 T

he e nsuing a ne mia stimula te s ma rro w to pro duc e re d c e lls tha t die e a rly: ine ffe c tua l e rythro po ie sis.

 He mo lysis a nd ma rro w e xpa nsio n le a d to

multisyste m dise a se

SLIDE 23

SLIDE 24

Alpha tha la sse mia

ζ α2 α1

HS-40

ζ α2 α1

HS-40

Mate r nal Pate r nal

α-/ - -

He mog lobin H dise a se – some time s re quire s tra nsfusion the ra py

-/ - -

He mog lobin Ba rts – Hydrops F e ta lis unle ss tra nsfuse d in ute ro

SLIDE 30

Na tura l Histo ry

 Gro wth re ta rda tio n  De la ye d pub e rty  Pa llo r  Va rying ic te rus  Skin Bro nzing : g ra y-

b ro wn pig me nta tio n



F e a ture s o f hype rme ta b o lic sta te



He pa to sple no me g a ly

 Skull c ha ng e s:  fro nta l b o ssing  ma xilla ry hype rpla sia  Ra dia ting stria tio ns

SLIDE 31

Na tura l Histo ry

 Re c urre nt infe c tio ns  Co mplic a tio n due to b o ne

de fo rma tio n

 Ble e ding te nde nc y  I

nc re a sing hype rsple nism

 Ga llsto ne s  L

e g ulc e rs

 E

xtra me dulla ry he ma to po ie sis

SLIDE 32

SLIDE 33

SLIDE 34

T re a tme nt

 Ge ne tic c o unse ling  T

ra nsfusio n the ra py

 I

ro n o ve rlo a d tre a tme nt

 Bo ne ma rro w tra nspla nt

SLIDE 35

T ra nsfusio n the ra py

 Co rre c ts a ne mia a nd ine ffe c tive

e rythro po ie sis

 Co nse q ue nc e s:  Risk o f fe ta l lo ss with e a c h inva sive

tra nsfusio n

 T

ime / e ffo rt/ mo ne y

 Re a c tio n,infe c tio n  I

ro n o ve rlo a d

L

ive r de po sitio n le a ds to c irrho sis

E

ndo c rine

Ca rdia c de po sitio n le a ds to fa ilure
I

ro n c he la tio n the ra py

SLIDE 36

Na tura l Histo ry with T xfn

 E

ndo c rine disturb a nc e s – pa nhypo pituita rism

 I

mpa ire d g o na do tro pins

 Hypo g o na dism  I

DDM

 Adre na l insuffic ie nc y  Hypo thyro idism  Hypo pa ra thyro idism  Cirrho tic live r fa ilure  Ca rdia c fa ilure due to myo c a rdia l iro n

ve rlo a d

SLIDE 37

I ro n c he la tio n



De sfe rro xa mine

 Ve ry hig h a ffinity a nd spe c ific ity fo r iro n  Re mo ve s it fro m b o th e xtra a nd intra c e llula r spa c e s.  Mo stly e xc re te d thro ug h urine (iro n mo stly fro m RE

S), tho ug h so me a lso fe c a lly(iro n mo stly fro m live r) e xc re te d.

 Go a l to ke e p fe rritin <2500  L

ive r iro n sto re s <15mg / g m

 Ma ny dra wb a c ks

Side e fffe c ts: He a ring lo ss, re tina l da ma g e , g ro wth fa ilure ,

lo c a l skin re a c tio n hype rse nstivity

Must b e g ive n c o ntinuo us sub c uta ne o usly
E

xpe nsive



De fe ra siro x



Ora l iro n c he la to r, simila r pro file o the rwise to de sfe rro xa mine

SLIDE 38

Ca use s o f de a th

 Co ng e stive he a rt fa ilure  Arrythmia  Se psis (po stsple ne c to my)  Multiple o rg a n fa ilure due to

he mo c hro mo c yto sis

 T

hro mb o sis

SLIDE 39