Anemia

Anemia

anemia: is reduction of RBC volume or Hb concentration below the range of values occurring in healthy persons.
Types:
Hemolytic
Inadequate production
Cellular causes:
membranopathy: hered. Spherocytosis, = elliptocytosis, = pyropoikilocytosis, = stomatocytosis, PNHU
Enzymopathy: G6PD def, Pyruvate kinase def
Hemoglobinopathy
Macrocytic:
folate def, vit. B12 def, B1 def (thiamine), Vit. C def (↓conversion of folic acid)
Marrow failure (aplastic an., Pearson synd)
Black-Diam.(cong. pure red cell aplasia)
Orotic acidurea
Lesch-Nyhan synd
Drugs: phenytoin, methotrexate
Extracellular causes:
autoimmune.
Fragmented hemolysis, DIC, HUS, TTP, extracorporeal memb.oxygenation, prosthetic heart valve, burns
Hypersplenism
Plasma factors: liver dis., Aβ-lipopr, infec, Wilson dis, vit. E def
Microcytic:
iron def an, B6 def
Sideroblastic an
Hemoglobinopathies (thalass., Hb E def)
Lead intoxication


Normochr. Normocytic:
B2 def
an.of chr.dis, Chr.renal failure, Juvenile R.A, Hypothyr.
Transient erythrolastopenia of childhood

- physiologic adjustments to anemia:

1. ↑cardiac out put
2. ↑O2 extraction
3. shunting of blood flow toward vital organs &tissues.
4. ↑concentration of 2,3-diphosphoglycerate w`in the RBCO2 dissociation curve shift to Rt ↓affinity of Hb for O2 more complete transfer of O2 to the tissue.

Folic acid deficiency anemia

- folate present in : green vegetables, fruits, liver, kid
- megaloplastic anemia occur after 2-3m on a folate-free diet
- routine folic acid supplementation is advised in very low birth weight.
- peak incidence in 4-7 m age
- irrit., chr diar., failure to gain weight
- in advance cases: hemorrhage from thrombocytop
Etiology:
1. inadequate folate intake
2. ↓folate abs. ex. celiac dis, anticonv.drugs ex.phenytoin.
3. cong. abnormality in folate metabolism dihydrofolate reductase def.
4. drug induced abnormality in folate metabolism:
methotrexate
pyrimethamine
methoprim
abnormality in folate metab.(cong.or drug induced) can be Rx w` folinic acid
Lab.: MCV > 100fl
S.folic acid < 3 ng/ml
Rx:
- folic acid oral or parenteral 1 mg/day for 3-4 wk. the hematologic response oc w`in 72.
After 4 wk, maintenance therapy w` multivit.(contain 0.2 mg) is adequate.


Vit. B12 deficiency
- normally the humans can not synthesize Vit. B12, vit. B12 released in the stomach by microorganisms, transcobalamin 2 carry vit. B12 to liver, BM, & o` storage sites
-in contrast to folate, the child have sufficient vit. B12 stores to last 3-5 yr
Etiology:
1. inadequate intake : in strict vegetarians.
2. impaired absorption
3. absence of transport protein: S&S in 1st wks of life. Dx: by severe megaloplastic anemia w` normal serum vit. B12 & folate & no o` inborn errors of metab. Rx : large parenteral doses of vit. B12 twice a week for life. Most children w` this disorder die if the Rx is not provided in infancy
4. lack of IF: a) pernicious an.: it is immunologic dis. atrophy of gastric mucosa, achlorhydria, Ab to IF. It is ass.w` o` im abn.ex. hypoparath b) gasric surgery
Rx:
- parenteral B12 1mg w`in 2-4 days the hematologic response oc.
- physiologic req.of B12 is 1-5 µg/days
- if neurologic involv. : Rx by 1mg I.M daily for at least 2 wk
- maint. Rx through out the life monthly I.M 1mg B12.
- oral Rx is not advisable because of uncertainly of abs.

Iron def anemia IDA

- iron requirement is 1 mg/day
& bec.of only 10% of dietary iron is absorbed, so, the diet should contain 10 mg daily for optimal nutrition.
- exclusive breast fed infant should receive iron supplementation from 4 months of age.
C.F:
- mild to moderate iron def. (Hb 6-10 g/dl) compensatory mechanisms which mentioned before
- Hb< 5g/dlirrit., tachycardia, cardiac dilation, systolic murmur, anorexia
- monoamine oxidase (MAO) is iron dependent enz. & has important role in neurochemical reactions in the CNS.
Rx:
- oral ferrous salts (sulfate, gluconate, fumarate)
- elemental iron is 20% in ferrous sulfate.
- daily 4-6 mg/kg/day of elemental iron ÷3
- parenteral iron (iron dextran):
Imferon (dextran) IV or IM
C.I: renal dis
Jectofer (sorbitol) IM only
C.I: previous allergy
- response to parenteral iron is no more rapid or complete than oral iron unless malabs is a factor.
-parentral iron therapy indicated in: (1) intolerance to oral iron
(2) GIT bleeding
S.E : allergy , t.staining , malig.change
- educate the family about the pt diet
- oral salts 4-6 mg/kg/day elemental ÷3 . each 100 mg tab:
Gluconate 10 mg
Sulfate 20 mg
Fumarate 30 mg
Lactate 19%
Ammonium citrate 20%
- causes of failure of iron Rx:
1. not receive the medication
2. iron given in a form that is poorly abs.
3. continuing unrecognized blood loss
4. menstrual periods
5. incorrect Dx. ex.thalass, lead pois, hypothyr
- response to iron therapy: 1 day neurological improvement
3 day reticulocytosis
1 month ↑Hb level
3 month repletion of bone marrow stores
- daily req. of iron :dietary 8-15 mg/kg elemental 0.8-1.5 mg/kg
- factors ↑abs.of iron: ascorpic acid cystine methionine ferrous form ↑erythropoiesis ↓iron store intake of fish & meat, cauliflower, bananas
- factors ↓abs.of iron: phytate (cereals,bread) phosphate (egg, milk, cheese) xanthine compound (tea) oxalate
- enzymes depend on iron: MAO cytochrom catalase
- pt w` IDA is more susceptible to infec bec.:
1.↓peroxidase enz in RBC
2. decrease MAO change in behavior
- progression of iron depletion at which the lab.test a` changed:
1st: depletion of BM, liver ,&spleen reserves represented by ferritin.
Then: ↓transport iron as represented by transferring saturation.
Finally: ↓Hb & MCV
So that, the absence of anemia does not exclude the possibility of iron def.


Thalassemia
Is a group of inherited diseases characterized by decrease or absent amounts of hemoglobin, the oxygen carrying protein inside the red blood cells. There are two basic groups of thalassemia disorders: alpha thalassemia and beta thalassemia. Theseconditions cause varying degrees of anemia, which can range from insignificant to lifethreatening.
- hematopoiesis oc.in 3 stages:
Yolk sac begin at 10 days gestation
Liver = = 6 wk =
B.M = = 2nd trim
- hemosiderosis: deposition of Fe in RES
- hemochromatosis: = = = = parenchymal cells
- thalassemic mutations disrupt the maturation of RBC in the B.M ineff. erythropoiesis. The marrow is hyperactive but there a` few retic & severe an.

Thalass. Major

- transfusions a` necessary du. the 1st 2 yr age
- severe thalassemic facies, pathologic #, HSM, cachaxia
- features of ineff. Erythropoiesis: expanded medullary spaces (spec.of face & skull), extramedullary hematopoiesis, huge caloric need.
- pallor, hemosiderosis, & jaundice a` combine to produce greenish brown complexion
- ↑iron abs. an.
- compl. of iron overload:
Liver: fibrosis, cirr.
β-cells of pancreas: DM
pit.gl:
testis: growth ret. & hypogonadotrophic hypogonadism
ovaries:
parathyr.: hypoCa, osteoporosis
heart: arr., myocarditis, intractable HF
most compl.can be avoided by iron chelator
Rx of thalassemia:
1. blood transf. (packed RBC) but hypertransf. S.b avoided bec.of iron overload & Post-transfusion Hb level of 9.5 g/dl is the goal.
2. prev. of transfusional hemosiderosis by deferoxamine 50 mg/kg/day S.C over 10-12 hr by pump, 5 days aweek. Max dose 2g/day.
- why give desferal SC & not IV or IM?
Bec. of rapid action w`in 1/2 hr so better to give S.C for chelating to avoid S.E. I.M is painful & poorly abs.
- Folic acid enhance the action of desferal. It s.b given in every case of hemolytic an.
- add zink to the Rx bec. Desferal also chelate Zn.
- uses of desferal: β-thalass , iron toxicity, aluminum tox., Diamond-Blackfan synd
3. Splenectomy:
4. B.M.T: curative


Sickle cell dis.
- is due to change thymine for adenine at 6th codon of β-gene change encodes valine instead of glutamine in 6th position on β-globin molecule Hb S
SS valine replace glutamic acid at position 6
C lysine = = = = =
E = = = = = 26
Rx of SCA:
1. directed toward prevention of compl
2. Rx the dehyd w` isotonic fluid (ex. Normal saline) & avoid hypertonic fl. Which may sickling
3. avoid tight clothings & tourniquet bec. vascular crisis
4. conjugate pn.coccal vaccine & all o` routine vaccines
5. at age 2 m all children should begin penicillin proph. 125 mg× 2, and at age 3 yr 250 mg ×2
6. folate supplementation bec.of thrombotic nature of the sickle Hb & ↑RBC turnover
7. Rx of pain:
8. bl.transf:
9. drug therapy:
Hydroxyurea ↑HbF↓morbidity.
Dose 15 mg/kg/day then gradually ↑to max. 30 mg/kg/day w` monitoring of CBC, liver function, HbF level monthly.
10. BMT: is the only cure for the disease.

ملاحظات:

- best contraceptive for SCA pt is progesterone or barrier method bec.: 1. combined type venooclusion
2. intraut.device pelvic sepsis & heg.


Pancytopenias (Aplastic anemia)
- severe aplastic an oc wn:
1. hypocellular BM biopsy
&2. ↓in at least 2 out of 3 peripheral bl.counts:
Neutrophil < 500 cell/mm3
Plat. < 20,000 =
Retic. < 1%
Constitutional (cong.) pancytop.:
- rare
- Fanconi an is the best example. It is autosomal recessive
-↓granulocyte-macrophage colony-stim.factor(GM-CSF), stem cell factor, & IL-6 in fanconi synd suggest abn cytokine network contributes to the pathogenesis of.
Rx:
-steroid & androgen (specially oxymetholone or nandrolone) alone or in comination.
-relapse is com.
-improvement in RBC precede the WBC
-the only curative therapy is BMT
Acquired pancytop.:
-incidence is low
-Parvo v. B19 is classically ass w` isolated RBC aplasia, but in pt w` sickle cell dis or im.def it transient pancytop.
- cases of acq.apl.an.:
1.idiop. 80%
2.radiation
3.d. & chemicals ex. Benzene, gold, chloramphenicol
4.viruses ex. Parvo, EBV, AIDS, CMV, hep. B,C,nonAorBorC
5.im.dis ex. Hypogammaglobulinemia, eosinophilic fasciitis, thymoma
6.preg.
7.paroxysmal nocturnal Hb uria & collagen vascukar dis.
8.marrow replacement: leuk, myelodysplasia, myelofibrosis, neuroblastoma
Rx of acq. Apl. An.:
- BMT.
- for those w`out sibling donor: im.sup.
- for those who fail to respond to im.sup or relapse after im.sup.: matched unrelated donor BMT & high dose cyclophosphamide.


G6PD deficiency
-G6PD def episodic hemolytic an.
Spontaneous chronic non spherocytic hem.an.
6-phosphoglyconic acid
-G6P G6PD
NADPH is produced maintain glutathione in reduced state

Glutathione neutralize the agents that potentially oxidize the Hb

-if G6PD def premature RBC destruction.

الأدويه والمواد الممنوع تناولها للمرضى المصابين بنقص انزيم الباقلاء:
الأدويه المسكنه للالام
الاسبرين, phenacetin
المضادات الحيويه
السلفا, المثبريم, ناليدكسيك اسيد, كلورامفنيكول, نايتروفيورانتوين, فيورازوليدون, الكوينيدين,Dapsone , ceprofloxacin
الأدويه المضاده للملاريا
الكلوروكوين, البريماكوين, البايريميثامين
الأدويه الحاويه للسلفا
الدابسون, سلفاديازين(فلامازين)
أدويه ومواد أخرى
البروبنسيد, مثيلين بلو(الدواء الازرق), فنيل هايدرازين, النفثالين, دايمركابرول(بال)
مأكولات ومواد منزليه
الباقلاء(النيئه واليابسه), البزاليا, النبق, الخوخ ذو الفروه, عصير البرتقال الطبيعي, فيتامين سي, الحناء, الكحل, السماق


الدكتور
صلاح مهدي فرحان
اختصاصي طب الاطفال والخدج