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

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

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

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 o the r a lie n inva de rs

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

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 o 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 !)

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

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

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.

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

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)

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

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 )

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)

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

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

Huma n g lobin g e ne s α - like ge ne s on c hr 16 ζ α2 α1 HS-40 β α β - like ge ne s on c hr α β 11 ε G γ A γ δ β LCR

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

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

Diso rde rs o f he mo g lo b in  He mo g lo b in va ria nts ,O Ara b  He mo g lo b in C,D,E  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 e po re  He mo g lo b in L  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, S β 0 , S β + ,E β 0

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 xc e ss γ c ha ins to dime rize ( γ 4 ) in the infa nt,  E a nd e xtra β c ha ins ( β 4 ) 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

Alpha tha la sse mia Mate r nal ζ α2 α1 HS-40 ζ α2 α1 HS-40 Pate r nal

Alpha tha la sse mia Mate r nal ζ α2 α1 X HS-40 ζ α2 α1 HS-40 Pate r nal

Alpha tha la sse mia Mate r nal ζ α2 α1 X X HS-40 ζ α2 α1 HS-40 Pate r nal

Alpha tha la sse mia Mate r nal ζ α2 α1 X X HS-40 ζ α2 α1 X HS-40 Pate r nal

Alpha tha la sse mia Mate r nal ζ α2 α1 X X HS-40 ζ α2 α1 X X HS-40 Pate r nal

Alpha thalassemia αα / αα Norma l αα / α - Mild mic roc ytosis, NO a ne mia αα / - - Mild mic roc ytosis, mild a ne mia – no α -/ α - the ra py re quire d 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

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

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

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

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

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 o ve rlo a d

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

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

Bo ne Ma rro w T ra nspla nt  Only c ura tive o ptio n  Upfro nt mo rta lity a b o ut 5% with ma tc he d sib ling do no r  Upfro nt mo rta lity a b o ut 15% with unre la te d ma tc he d do no r  Mo rb idity fro m immuno suppre ssio n, to xic ity o f c he mo the ra py/ ra da tio n, g ra ft vs ho st dise a se