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Enzymatic Defects

G 6 PD Defeciency
Is X -linked disease , is most important dis. Of hexose
mono phosphate pathway , is responsible for 2 clinical
syndromes : --
a - an episodic H. A ( hemolytic anemia ) induced by
infection , drugs , fava bean .
b - spontaneous chronic non spherocytic hemolytic
anemia .
A --- episodic H. A ; --- Oxidized glutathione
NADP ----- by G 6 PD --- NADPH --- Glutathione
reductase
reduced glutathione
( as anti oxidents )
Glutathione act to neutralized agent that potentially oxidized either Hb or
components of Red cell membrane .
If reduced glutathione can not sustained to remove O 2 radicalls generated by
oxidants drugs leading to Hb precipitate forming heinz body and
Red cell membrane is critically damaged leading to premature destruction
or hemolysis .

• .

Clinical feature

recurrent or episodic attack of H. A where clinically appear as pallor &
red urine , developed after 24 -48 hr after ingestion of oxidant properties
• Agent precipitate hemolysis in patients with G 6 PD def. :---
• A - medication : --- 1 - antibiotic like nalidexic acid , chloromphenicol, sulfa.,
nitrofuradantin 2 - anti malaria 3 - others like phenacetin , asperin,
vit. K analogue , phenazopyridine .
• B -chemical as benzene , naphthalene , phenylhydrazine .
• C - illness ; - D. K. A , hepatitis , sepsis .
• the degree of hemolysis varies with :---
• 1 - inciting agent . 2 - amount of ingestion
3 - the severity of enzyme def. in the patients .
• If hemolysis is sever – Hb uria , jaundice
& Hb is reduced to be life threatening .
Favism mean as acute H. A induced by fava bean & thought to more freguent
associated with G 6PD B minus variant .
• Lab finding : ----
• 1 - decreased PCV ,
• 2 - IF episode is sever resulting Hb emia & Hb -uria
• note : most individual with G 6PD are asymptomatic & no clinical manifestation
unless triggered by infection , drugs and fava bean
• If haemolysis is sever leading to Hb binding protein called haptoglopin are saturated
and free Hb may appeared in the plasma and subsequently in urine . .
--- 2 --

3 -unstained or supra -vital preparation of RBC reveal Heinz body( Hb ppt)

.
4 - blood film ; - reveals a few fragmented cell & polychromatophilic (
bluish large RBC ) & the retic count often 5 -15 %
• Diagnosis : --
• 1 - direct measurements of G 6 PD level within RBC ( enzyme activity in
affected person is 10 % of normal or less ) .
• 2 - satisfactory screening test are based on -- :--
• a - decoloration of methylene blue .
• - on reduction of met Hb ( measured the reduction of met Hb production
after NADP reduction . .
• - on fluoroscent of NADPH( is direct test to measure the generation of
reduction NADPH from NADP and the test is positive if blood spot is failed to show fluoresent
under U/ V light .. .
• N . T immediately after hemolysis --- increase retic count & young RBC have
significantly higher enzyme activitly than older cell in A - variaty & testing
may deferred for a few wks before diagnostically low level of enzyme can be
shown .
• G 6 PD variants also can be detected by electrophoretic & molecular analysis
.

• Fava bean ( green and dry are induced hemolysis)

G 6 PDdef. Developed jaundice in neoborn baby
• Heinz body

Prevention : -- 1 - assay for G 6 PD for those pts are liable for G 6 PD

deficiency as in ethnic group , those with + ve family history of G 6 PD .
2 - avoid triggered factors that induced hemolysis
• Treatment : ---
• 1 - Admission to hospital .
• 2 - chart for observation ( PR , RR ) .
• 3 - frequent checking of PCV , retic count .
• 4 - given I. V. fluid in form G/ W or saline to induce more diuresis +
added NAHCO 3 to prevent ppt of Hburia within renal tubules &
prevent its damage .
• 5 - if PCV continue to be decreased associated with increased
PR, RR , --- more anemia with cardiac compromised needs blood
transfusion .
• -- 4 --

Auto Immune Hemolytic Anemia

• A number of extrinsic agents & disorders may lead to premature destruction
of RBC due to presence of antibodies .
• The hallmark of this disease is a positive coombs tests which detect coated
of antibody ( IG ) or component of complements on the RBC surface .
• erythroblastic fetalis is most important example in pediatric practice.
• Auto Immune either : ---- a - warm type
• b - cold type
• Warm type : --- 2 type either : -
• 1 - transiant form ( account 70 -80 % of cases , occur between
2 -12 years & last 3 -6 month .
• 2 - prolong or chronic coarse which more frequent in infant &
children older 12 year , hemolysis continue for months or years .

Auto immune ( warm type ) due to : ---

a - idiopathic type ( primary ) .
B - secondary – 1 - lympho proliferative dis.
• 2 -CTD as in SLE
• 3 - Chronic infl. Dis as ulcerative
colitis 4 -non lymphoid tumor as in ovarian
tumor .
» Auto immune ( cold type ) :-- with
cold reactive auto Abs( cryptogenic H. A )
• a - idiopathic type .
• b - secondary type --- :-
• 1 -lympho proliferative dis.
• 2 -infection as in mycoplasma , IMN
• 3 - paroxysmal cold Hburia .
• c - drug induced as in : -- by Hapten mechanism as
pencillin , cephlosporine or Ternary immune complex as ( quinidine
or quinine , anti T. B, tetracyclin , insulin ) or True antibody as in
methyl dopa , Brufen ,voltarene ,interferone alfa ..

Diffrenitiation between warm from cold type

• warm cold
• 1-c |f pallor pallor
• 2-tempera. 35 -40 c less than 37
• 3-diag. Direct coomb test indirect coomb
• 4-type of A. B . IgG IgM
• 5-site of destruction spleen liver & spleen
• 6-complement no need complement need complement
• 7-treatment prednisolone plasma pheresis
• blood transfusion immune suppression
• if no response IVIG OR NOT response to C. S or
• chemotherapy like splenectomy

• Rituxamab, mpnoclonal Ab
• plasma pheresis in refractory cases which generally is not helpful
-- 7---

Guide lines for pediatric RBC transfusion

• A -- :-children & adolescent : -
• 1 - acute blood loss of more than 25 % circulatory blood loss .
• 2 -Hb less than 8 gm/ dl perioperative period .
• 3 -Hb of less than 8 gm/ dl & sympt. Chronic anemia.
• 4 - Hb of less than 8 gm/ dl & marrow failure.
• 5 - Hb of less than 13 gm/ dl & sever cardiopul. Dis.
• B - Infant within 4 month .: --
• 1 - Hb of less than 13 gm& sever cardiopul. Dis.
• 2 - Hb of less than 10 gm & moderate pul. Dis.
• 3 -Hb of less than 10 gm& major surgery .
• 4 -Hb of less than 8 gm& sympto. Anemia .
• - 8 -

Guide line for pediatric platelets transfusion: --

A - children & adolesent : ---
• 1 -plat. Of less than 50 000 & bleeding .
• 2 -plat. Of less than 50 000 & invasive surgery .
• 3 - plat. Of less than 20 000 & marrow failure with Hrr. risk factors .
• 4 -plat. Of less than 10 000 & marrow failure without Hrr. risk factors .
• 5 - plat. Dysfunction at any count with bleeding or invasive procedure.
• B -infant of less than 4 months : --
• 1 -plat . Of less than 100 000 & bleeding or clinically unstable.
• 2 -plat . Of less than 50 000 & invasive procedure .
• 3 - plat. Of less than 20 000 & clinically stable .
• 4 - plat. At any count with plat. Dysfunction plus bleeding or invasive
procedure .
• --- 9 ---

Guide lines for pediatric FFP Transfusion : --

In infant , children & adolescent
• 1 -sever cloting factor & bleeding or invasive procedure .
• 2 - emergency reversal of warfarine effects .
• 3 - DIC & bleeding .
• 4 - anticoagulant protein replacement ( anti thrombin 3 , protein
C & S )
• 5 - Plasma exchange replacement for thrombotic –
thrombocytopenia purpura .
--- 10 --

Approach patient with pallor

pallar
Send for Hb 1F decreased
Send
Retic count ( normal 1% ), more than 3% H. A
Low (< 1% ) for 2 occasion N or High( n= normal )
Send for
Hypoplastic anemia
Do
B.M. aspiration ( Bone marrow) comb test
-ve +ve MCV (n : 75-90 ) 1) Immune H.A (investigate for the causes)
2) ABo or Rh incompatability ( in neonate )
Low (< 75 ) normal or high
1) Blood loss,IDA do
2) Thalassemea
Send for peripheral blood smear
1) S.Iron , IBC,
2) HB -Electrophoresis
normal abnormal
1) blood loss 1) Hereditary spherocytosis –do osmotic fragility test
2) infection or Elliptrcytosis
3) rare cause )hexo kinase deficlency ( 2) G 6PD : biting cell in Blood film& assay after 6 wk
3) P.K. deficiency : -assay its level
4) D.I.C. send for PT,PTT,bleeding time+,platlat count&D -diamer


رفعت المحاضرة من قبل: Ahmed monther Aljial
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