anemia of inadequate production

8/15/2019 Anemia of Inadequate Production

1/49

Anemia of Inadequate

production


2/49

Anaemia

Hemoglobin level below the normalrange for the age and sex

• Neonate < 14 gr/dl

• 11! months < 1" gr/dl

• 11! #ears < 11 gr/dl

• Hemoglobin at birth $ cord blood % 1&1' gr/dl• !44' hour of age $ Increase due to hemoconcentration• ( months of age )rop up to *+, $ 11 gr/dl


3/49

-auses of AnaemiaImpaired red cell production


4/49

Approach to -ommon -auses of Anemia in -hildren

)#smorphic


5/49


6/49

Iron )ecienc# Anemia

• Iron .etabolism

• 0tiolog#

•

-linical manifestations• aborator# investigations

• )i2erential )iagnosis

•

3reatment


7/49

Iron .etabolism

• 3otal bod# iron content – New born bab# $ !," mg nelson "+, gr 5

– Adult 4 , gr

• Iron requirement – 3o fulll the decit 4+, gr over 1, #ears

• 4+, gr/(&, % "+' mg/da#

– 3o replace Iron loss via epithelial shedding

– 3otal elemental iron requirement % 1 mg/6g/d

Iron requirement• 7ne #ear old infant % 'mg/da#• 8ather % * mg/da#

• .other %1, mg/da#


8/49

Iron inta6e

• 9reast mil6 $ 1+, mg/ $ ,": absorbed

• Infant formula $ ,* ;1!5 mg/ $ 1": absorbed

– reterm formula 1,mg/l for b+wt < 1'"" gr

•

-ow=s mil6 $ "+, mg/ $ 1": absorbed• .ixed diet $ 4* mg/da# 1"1,: absorbed

– Interfered b# food $ tea tanin5> -aws mil6 calcium5>High ber foods ph#tate5• Iron from cereals onl# 1: is absorbed

– 8acilitated b# $ 9reast mil6> vitamin -

– Iron supplementation• After 4 months for exclusivel# breast fed babies


9/49

Iron )ecienc# and Anemia

• ?@ – 1! #ears $ *: decient ( : anemic

nelson5

–

Adolescent *: iron decient

!:anemicnelson5

– revalence of iron decienc# 1': whites and ((:immigrants illustrated5

•

@ri an6a – ("4" : anemic

– Iron )ecienc#


10/49

0tiolog#

• Inadequate inta6e iron reclaimed b# drop in Hb in !(mo5 – 0arl# 9B or unusual blood loss at birth

– *!4 mo 3erm babies

• Absorption – Interfered b# cows mil6>

– 8acilitated b# Cit -

• 9lood loss – DI3 $ pol#p> hemangioma> inEammator# bowel disease>

Hoo6worm> -hronic diarrhea> cows mil6 protein allerg# – 9lood loss due to heat labile protein in cows mil6

– 9lunting of villi due to iron decienc# can lead to loss of iron

– Intense exercise conditioning in girls


11/49

-linical .anifestations

• allor

• Irritabilit# F behavioral problems

•

Impaired neurological andintellectual functions girls with @erum ferritin level lessthan 1! ng/l improved after ' wee6s of iron5

• agophagia

• -ardiac $ tach#cardia> cardiomegal#> s#stolicmurmur

• 9reath holding attac6s are reduced b# irontherap#Iron is found in .onoamine ox#dase> c#tochromes > catalase and peroxidase


12/49

aborator# 8indings in iron

decienc#

• @erum ferritin

• @erum iron

• Iron binding capacit#

• 3ransferin saturation

• 8ree 0r#throc#te protoporph#rine 085

• .-C F .-H .icroc#tic> H#po chromic5

• 9lood picture $ hoi6iloc#tosis> NucleatedG9-

• Geticuloc#te relative 5

•

3hromboc#tosis similarit# of er#thropoietin F 3hrombopoitin5


13/49

)eferential )iagnosisH#po -hromic .icroc#tic Anemia

• 3halasaemia trait beta> alpha> 05 – G9- count raised in thal trait> not in iron decienc#

– G)B is wide in iron decienc#

• Anemic of chronic disease usuall# Normoc#tic but can be .icroc#tic5

• ead poisoning• 7ther .icroc#tic anemia

– @ideroblastic anemia dimorphic and high G)B> serum iron increased>transferring saturation increased and ring sideroblasts in the marrow5

• -ongenital sideroblastic anemia lin6ed withlioniation5

– AtransferinemiaJ congenital absence of iron bindingprotein treated with apotransferrin5


14/49

3reatment

• Gegular response to ironK

• @imple iron salts can be used sulphate>gluconate>fumarate5

–

@odium iron editate and pol#sacharide ironcomplex does not stain teeth

• )ose 4& mg/6g of elemental iron in threedoses

– onl# !": of ferrous sulphate is elemental iron• )uration

– ( months

– ' wee6s after blood value come to normal


15/49

3reatment ct+

• Intolerance to iron is uncommon in #oungchildren than adolacents and adult

• -onsumption of mil6 should be reduced

• 0xpected rate of Hb rise 1 gr/dl/wee6 "+,mg/dl/da#5

• 9lood transfusion not necessar# and canbe dangerous due to h#pervolemia and

cardiac dilatation+ – Hb value less than 4 gr/dl should get onl#

4ml/6g of pac6ed cells at a time+


16/49

Gesponse to iron therap# in iron

decienc# anemia

Time afterironadministra

tion

Response

1!%!4hours

Geplacement of intracellulariron> subLective improvementJdecreased irritabilit#>

increased appetite

(&4' hours Initial bone marrow response Jer#throid h#perplasia

4';! hours Geticuloc#tosis> pea6ing at ,;


17/49

.egaloblastic Anemias

1+ Ine2ective er#thropoiesis $ Activeer#thropoiesis with premature death of cells

!+ High .-C and h#per segmented B9-(+ )ecienc# of 91! or folate and rare

metabolic disorders


18/49

8olate decienc#

• 8olate abundant in green vegetableand animal food M heatlabile pol#glutamate5

• ol#glutamate monoglutamate b#folate conLugase in entire intestinalbrush border

• 8olic acid 3etrah#drofolate biological# active form5 b# 3etraH#dro 8olate reductatse en#me

• 9od# stores are limited $ Anemia in


19/49

-linical features

• Neonate and infant – -ommon in Cer# low birth weight babies $

routine supplementation

–

ea6 incidence $ 4; mo earlier than irondecienc#5

– @igns and s#mptoms related to anemia

– Irritable> fail to gain weight> chronic diarrhea

–

3hromboc#topenia and Hemorrhage• 7lder children

– @igns and s#mptoms related to anemia


20/49

0tiolog#

• Inadequate inta6e

• )ecreased absorption

•

-ongenital abnormalities in folatemetabolism

• )rug induce abnormalities of folatemetabolism


21/49

0tiolog#

• Inadequate inta6e – Increased demand pregnanc#> infanc#> hemol#sis5 – Aggravate b# infections

• )ecreased absorption

– -hronic diarrhea and other bowel disease

– Antiepileptic drugs hen#toin> primidone>henobarbital5

• -ongenital abnormalities in folate metabolism

– 3reated with high doses of folate

• )rug induce abnormalities of folate metabolism – .3> 3rimethoprim> #rimethmine


22/49

aborator# ndings in 8olic acid

)ecienc#

• .acroc#tic $ .-C 1"" E

• Geticuloc#te count low

•

Neucleated G9-• Neutropenia and thromboc#topenia

• Geduced G9- folate level normal 1,"

&"" ng/ml5• 9one marrow h#percelluler


23/49

3reatment

• 8olic acid $ "+, 1 mg/da#

• High doses ma# correct 91!decienc# anemia also+ 3herefore Ifthe diagnosis is in doubt J trial of folicacid "+1 mg/da# for one wee6 andsee the response

• )uration of treatment $ (4 wee6


24/49

Citamin 9 1! )ecienc#


25/49

Citamin 91! -obalamin5 decienc#

• -obalamin produced b# microorganisms

• @tomach $ -ombine with G protein and I8

• )uodenum $ 9rea6 down G protein b# pancreatic en#mes

• Ileum distal5 $ absorption

• lasma $ 9ind to trans -obalamin II andtransported to liver> bone marrow>

•

-ells $ Geceptor mediated endoc#tosis and converted tometh#lcobalomin and adenos#l cobolamin J 3ransfer of meth#lgroups to )NA


26/49

0tiolog# of 91! )ecienc#

• Inadequate Inta6e

• ac6 of intrinsic factor

•

Impaired Citamin b1! absorption• Absence of Citamin 91! transport

protien


27/49

0tiolog# of 91! )ecienc#

• Inadequate Inta6e

– @tores suOcient for (4 #ears neonates 4, mo5

– @trict vegetarians and their babies

• ac6 of intrinsic factor

– -ongenital ernicious anemia – Puvenile pernicious anemia

– Dastric surger#

• Impaired Citamin b1! absorption

–

Intestinal pathologies or resections N0-> I9)5 – 9acterial overgrowth or tapeworm

• Absence of Citamin 91! transport protein

– 3- II decienc# normal 91! level due to 3-I and 3-III5


28/49

-linical features of 91!)ecienc#

• Deneral $ Bea6ness> fatigue> 8ailureto thrive> irritabilit#> pallor> glossitis>Comiting> diarrhea> icturus+

• Neurologic $ aresthesia> sensor#decit> H#potonia> seiures>development dela#> regression>

neurops#chiatric changes• H#poreEexia babins6i responses and

clonus


29/49

aborator# ndings in 91!

)ecienc#

• Identical with folate decienc#

• @erum 91! levels below 1"" pg/ml

• Increased levels of meth#lmelonic acid in urine

normal " (+, mg/!4 hr5• @chilling test

– -,; labeled 9 1! 7rall#

– High dose Eushing dose5 of 91! aretaral ! hrs later

–

Normal $ 1"(": -,;

labeled 9 1! excretion in urine – I8 decienc# $

– Intestinal patholog# $ Not corrected b# I8


30/49

3reatment of 91! decienc#

• arenteral 91! 1 mg5

• Gesponse in !4 da#s

•

Neurological deciencies I. dosesdail# for ! wee6s

• .aintenance $ .onthl# 1 mg I. forlife


31/49

7ther .egaloblastic Anemia

• 7roticaciduria

• 3hiamineGesponsive .egaloblasticAnemia

• )ecienc# of adenos#l -obalaminand meth#l -obalamin


32/49

h#siologic Anemia ofInfanc#


33/49

h#siologic Anemia ofInfancy

• At birth Hb $ 1'!" gr/dl

• At '1! w6 Hb *11gr/dl $ h#siologic anemia5

• Geasons for ph#siologic anemia

–

Increase of availabilit# of ox#gen saturation fromfetus to new born from ,": to *,:

– -hange the t#pe of Hb Hb8 HbA5

– )own regulation of erthropoitin production

–

0r#thropoiesis is suppressed• Iron is rec#cled and suOcient up to !" w6s

with no inta6e


34/49

h#siologic Anemia of Premature Infants

• .ore rapid and extreme drop of Hb ;*gr/dl b# (& wee6s ma# be lower in Cer# prematurebabies5

• -auses for anemia of premature infants

–

9lood loss due to @ampling – @uboptimal er#thropoietin response

hepatic Genal occur around 4"wee6s 5

– @hort survival of G9- 4"&" da#s Cs 1!"da#s

– Gapid growth

–

@low ongoing hemol#sis


35/49

h#siologic Anemia of Premature Infants

• 3reatment $ on the clinical condition can tolerate up to &+,gr/dl5

• 8olic acid and iron 4& mg/6g/d5

• 9lood transfusion $ 1"1, ml/6g

• 0r#thropoietin

• revention – .inimie blood loss b# sampling

, ml from a '"" gr bab# % ,"" ml from a '" 6g '"

""" gr5 man


36/49

-auses of AnaemiaImpaired red cell production


37/49

• )iamond9lac6fan Anemia

• 3ransient 0r#throblastopenia of

childhood 30-5

• arvovirus 91* infection

• Anemia of -hronic )isorder A-)5 F

AG8

• -ongenital )iser#thropoietic Anemia-)A5

her -auses Anemia of inadequate producti

d cell aplasia


38/49

)enition for @evere Aplastic

Anaemia

• 3wo or more of the following cell lineare compromised in a patient withmoderate or severel# h#po cellular

bone marrow

– Absolute neutrophil count less than

,""/mm(

– A latelet count less than !" """/mm(

– A reticuloc#te count less than 1: after

correction for the hematocrit


39/49

Aplastic Anaemia

• Geduction of all three cell lines $ anc#topenia – G9- $ Anaemia

– latelets $ 3hromboc#topenia

– Bhite cells $ leucopenia

• -auses of Aplastic anaemia – Inherited

• Infections $ hepatitis

• )rugs $ @ulphonamides> chemotheraph#

• 3oxins $ 9enene> glue

– Acquired $ 8anconi anaemia

– Idiopathic


40/49

8anconi Anemia

8 i A i -li i l


41/49

8anconi Anaemia $ -linicalfeatures

• .ost comment inherited anaemia

• Autosomal recessive inheritance

• Associated with congenital abnormalities – @hort stature

– Abnormal radii and thumb

– Genal malformations

–

.icropthalmia – igmented s6in lesions

• @igns of bone marrow failure usuall# appears at ,& #rs ofage

8 i i


42/49

8anconi anaemia $)iagnosis

• Neonates with 8anconi nearl# alwa#shas normal blood counts

• Increased chromosomal brea6age ofperipheral blood cells

• )eath due to aplastic anaemia orleu6emia

• 3reatment $ 9one marrow transplantfrom una2ected siblings

@ h )i d


43/49

@chwaman )iamonds#ndrome

• Gare

• Autosomal recessive

• -linical features – Aplastic anaemia

– ancreatic exocrine failure

– @6eletal abnormalities

• Gis6 of acute leu6emia


44/49

3ransient 0r#throblastopenia of -hild

hood 30-

• 3he most common acquired red cellaplasia

• -ommoner than congenital red cell

aplasia

• & months to ( #ears of age mostabove 1 #r5

• 3ransient immunologic suppressionof er#thropoiesis ma# follow viralinfections but not arvovirus 91*

• Neutropenia in !":


45/49

3ransient 0r#throblastopenia of -hild

hood 30-

• .-C $ normal

• Hb8 $ Not present

• Ged -ell A)A levels $ Normal highin other congenital aplastic Anemias5

• Gecover within 1! months

• 3ransfusions ma# be required usuall#onl# one5


46/49

Acquired anc#topenias


47/49


48/49

Acquired anc#topenias

• Gadiation

• Immune diseases

• regnanc#• arox#smal Nocturnal

Hemoglobinuria


49/49

anemia of inadequate production

Documents