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CuplulCuplul FierFier--CupruCupru esteeste
necesarnecesar pentrupentru preventiapreventiasisi tratamentultratamentul anemieianemiei
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1 ANEMIA FERIPRIVA
CUPLUL Fe -Cu
FACTORI CARE INFLUENTEAZA ALEGEREA TRATAMENTULUI
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Cuprins:
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Istoric:
WHO 1968:
a condition in which the hemoglobin content of the blood is lower than normal as a
result of a deficiency of one or more essential nutrients, regardless of the cause
of such deficiency.
Iron deficiency was present in 4099% of the pregnant women studied and was
undoubtedly responsible for the major proportion of anemia
1989
Iron deficiency anaemia is the most prevalent nutritional disorder in the world
today. . . Iron deficiency is by far the commonest nutritional cause of anaemia; it
may be associated with a folate deficiency, especially during pregnancy. Other
nutrient deficiencies, such as vitamin B-12, pyridoxine (PN) and copper are of
little public health significance because of their infrequency.
2004
the prevalence of anaemia has often been used as a proxy for IDA. Although this
approach may be useful in settings where iron deficiency is known to be the
major cause of anaemia, it is not valid in settings where the etiology of anaemia
is more complex
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Cauze:
Dieta: la copii si la varstnici
Absorbtie deficitara
Utilizare crescuta ( de exemplu in caz de sarcina, alaptare
sau in perioada de crestere)
Utilizare deficitara (afectiuni cronice)
Sangerare
Deficienta altor micronutrienti: Cupru, B12, acid folic
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0
2
4
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8
10
12
0 10 20 30 40 50 60 70
Men
Women
Required iron intake
(mg Fe/1000 kcal)
Stoltzfus, 1997
Pregnancy
Necesarul de Fier
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Prevalenta anemiei feriprive
Normal (
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1 ANEMIA FERIPRIVA
CUPLUL Fe -Cu
FACTORI CARE INFLUENTEAZA ALEGEREA TRATAMENTULUI
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Cuprins:
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Homeostazia Fierului si a
Cuprului Puncte de interactiune
James F Collins. Metabolic crossroads of iron and
copper, Nutrition Reviews Vol. 68(3):133147
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Transportul celular al Fe si al Cu
Puncte de interactiune
James F Collins. Metabolic crossroads of iron andcopper, Nutrition Reviews Vol. 68(3):133147
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Transportul celular al Fe si al CuPuncte de interactiune
James F Collins. Metabolic crossroads of iron andcopper, Nutrition Reviews Vol. 68(3):133147
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Cuplul Fier-Cupru
Metabolismul Fe
Ceruloplasmina
Absorbia fierului prin mucoasa intestinal i, n special,transportul su prin membrana bazolateral a enterocitelor
Deplasarea fierului de la nivelul esuturilor n care este depozitat(ficat, mucoasa intestinal, etc), prin catalizarea reaciei
Fe2+ Fe3+
Fixarea fierului de transferin i transportarea sa ctre mduvaosoas, unde se produc hematiile
Deficienta de Fe si Cu determina anemie si afectarea transportului intestinal al
fierului este asociata cu patologii care includ anemia afectiunilor cronice si
hemocromatoza ereditara
James F Collins
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Cuplul Fier-Cupru
Sintezei hemoglobinei (citocrom oxidaz)
Catalizeaz reacia Fe2+ Fe3+n eritroblati (precursoriihematiilor)
Transferul fierului intracitoplasmatic
ctre mitocondrii,
urmat de ncorporarea sa n moleculele de hemoglobin
Hematopoieza
Cu2+joac un rol esenial n maturizarea celulelor hematopoieticestimulnd hematopoieza
Aportul deficitar de Cu2+ cauzeaz anemie i neutropenie, ambele
putnd fi corectate prin suplimentarea cu Cu2+
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Ceruloplasmina este necesara pentru efluxul de Fe din ficatul matern
Pacientii cu aceruloplasminemia au un nivel crescut de Fe in ficat
Transferul fierulul la fat este compromis
nivelul fierului seric si hepatic al fatului scade
Given the high incidence of maternal anaemia during pregnancy,
and that many of those who are prescribed iron supplements show
no significant improvement, it is tempting to conclude that at least
some of the cases are a consequence of low copper . when considering
supplementing iron, copper status must also be taken into accountH. J. McArdle,Rowett Research Institute, Aberdeen, UK.
Deficitul de Cupru - femei insarcinate
Transportul Fe si
Cu prin placenta
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Deficitul de Cupru -adulti
Procent important de anemii neexplicate dar asociate
cu deficit de Cupru
Un numar semnificativ de pacienti care au fostdiagnosticati cu anterior cu deficit de vitamina B12 au
deasemenea hipocrupemie nediagnosticata
Calin I. Prodan, Hypocupremia Associated With PriorVitamin B12 Deficiency, American Journal of Hematology 82:288290 (2007)
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Aport neadecvat
Prematuritate
Malabsorbtie Pierdere excesiva de Cupru
Doze mari de Fier
Deficitul de Cupru - copii
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Manganul
Rol : Activarea diverselor sisteme enzimatice i, n consecin, n
diverse tipuri de metabolism celular de la nivelul oaselor, lipidelor,
carbohidrailor i proteinelor.
In protejarea mpotriva radicalilor liberi
o Catalizeaz reacia de dismutaie a peroxidului de hidrogen
(H2O2) n ap i oxigen (superoxid dismutaz)
Manganul interfera cu metabolismul fierului si al cuprului
este importanta suplimentarea cu mangan cand se
administreaza Fe + Cu
Abraham J. & Giachetti I. (1992). Apports nutritionnels conseills pour la population franaise. Technique et documentation, Paris.Finley J. W. and Davis A. C. D. Manganese deficiency and toxicity: Are high or low dietary amounts of manganese cause for concern? BioFactors, 1999, vol. 10.no1, pp. 15-24.
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1 ANEMIA FERIPRIVA
CUPLUL Fe -Cu
FACTORI CARE INFLUENTEAZA ALEGEREA TRATAMENTULUI
2
3
Cuprins:
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Ce tratament alegem?
Fier sau Fier + Cu + ?
Saruri feroase vs saruri ferice?
Eficienta si complianta
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Solutie sau tablete?
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Fe sau Fe +Cu?
Time course of papers published on the copper/iron connection. The papers
represent the authors non-systematic, and certainly incomplete, collection of
references that primarily concern both iron and copper metabolism (534
articles through February, 2002)P. Fox- The copper-iron chronicles: The story of an intimate relationship,Biometals 2003
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Fe sau Fe +Cu?
Combinatia Fier- Cupru in tratamentulanemiei a fost studiata clinic inca din 1928
Combinatia Fier- Cupru a determinat un
raspuns maxim in regenerarea hemoglobinei,
fata de monoterapia cu Fier, care a determinat
un raspuns neadecvat, printr-o cresteremoderata a hemoglobinei.
(C. A. ELVEHJEM, IRON VERSUS IRON AND COPPER IN THE
TREATMENT OF ANEMIA IN INFANTS, American Journal of Disease ofChildren, 1937
Curves showing the ineffectiveness of therapy during the
first few weeks of life (cases 1 and 2) and curvesshowing the interference by infection with the effect of
treatment (cases 3, 4 and 5).
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Fe sau Fe +Cu?
(C. A. ELVEHJEM, IRON VERSUS IRON AND COPPER IN THE TREATMENT OF ANEMIA ININFANTS, American Journal of Disease of Children, 1937
Curves comparing the hemoglobin response to 25 mg. of iron plus
1 mg. of copper with that to 25 mg. of iron alone
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Saruri feroase vs saruri ferice?
Sarurile ferice sunt disociate Fe2+ sau Fe3+
Fierul se absoarbe sub forma de Fe2+
It has been shown that preparations containing ferrous salts (+2) aremore easily absorbed than those containing ferric salts (+3) since the
former can be immediately absorbed by the duodenal mucosa. The
study reported here reveals that oral ferrous gluconate in liquid form is
more effective and above all better tolerated than other solid or liquid
formulations containing elementary iron. ( Casparis, Minerva Ginecol
1996)
Gluconatul feros in forma lichida este mai eficient si mai bine tolerat
decat alte formulari solide sau lichide de fier (Ghidul Societatii
Britanice de Gastroenterologie 2005)
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Solutie sau tablete?
Indiferent de varsta, se recomanda
forma lichida
Iron deposition in the upper GI
tract is common in patients takingiron tablets. It is frequently
associated with mucosal disruption
in the oesophagus and stomach
(Kaye P, Abdulla K, Wood J, James P, Foley S,
Ragunath K & Atherton J (2008) Histopathology 53,
311317)
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Patterns of iron deposition. A, Oesophageal ulcer showing crystalline iron coating the surface (pattern A) and haemosiderin in granulation
tissue (pattern B) (H&E). B, Gastric biopsy specimen showing surface iron (pattern A) with underlying reactive gastritis (H&E). C,
Gastric biopsy specimen with haemosiderin in lamina propria (pattern B) (H&E). D, Gastric biopsy specimen showing more subtle
focal iron deposition engulfed by foreign body giant cell (H&E). E, Perls Prussian Blue stain showing iron (blue) in glandularepithelium (pattern C). F, Duodenal biopsy specimen showing haemosiderin in histiocytes at villous tips (pattern D) (H&E)
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EficientaIron Polymaltose Versus Ferrous Gluconate in the Prevention
of Iron Deficiency Anemia of Infancy
Lutfi Jaber, MD J Pediatr Hematol Oncol 2010;32:585588
Valoarea medie a Hb semnificativ mai mare in grupul tratat cu gluconat feros
(12.040.09 g/dL vs. 11.680.11, p>0.014)
Valoarea Hb
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Efficacy of Tothema in the treatment of iron
deficiency anemia in early childhood withconcomitant copper deficiency
Eficienta si Complianta
Mtvarelidze Z et al. Georgian Med News 2005; (121):68-71
Protocol:Tothma 5mg/kg/zi pn la normalizarea Hb i apoi
2 mg/kg/zi, pana la 3 luni
Criterii de includere:42 pacienti 0,4 i 3 ani
grupa I : prematuri (n = 16)
grupa II : copii nscui la termen, cu diaree
prelungit i natural (n = 11)
grupa III : copii nscui la termen, care nu prezint diaree
Grupa martor: copii de aceeai vrst, dar sntoi (n = 24).
Criterii de evaluare:- Bilanuri clinice i biologice (Hematologic: Hb, eritrocite, reticulocite, morfo-
eritrogram;
- Biochimice: fier seric, CTF, cupru, ceruloplasmin; Radio-imunologice : feritin
realizate nainte i dup tratament.
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Eficienta si Complianta
Concluzie: Tothma este un medicament eficace n
tratamentul anemiei prin caren de fier la
copiii de vrst mic, care prezint o caren de cupru asociat
Tothma permite corectarea nivelului rezervelor de fierdar i de cupru
Tothma previne apariia formelor rezistente de anemie prin caren
de fier
Tothma administrat copiilor de vrst mic este bine tolerat, cu efecte
nedorite rare i trectoare
Rezultate:Eficacitate clinic :
- ameliorarea strii generale
- diminuarea rapid a simptomelor de anemie
Eficacitate paraclinic:
- normalizarea complet a parametrilor
hematologici, biochimici i a feritineidup 3 luni de tratament
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Eficientasi Complianta
Anmouth S.Y. New developments in the treatment of iron deficiency anaemia in childrenMedical journal Of Diseases, Newborns and Children, 2001
93 Copii de la 6 luni -16 ani
Grup 1-Hb : 95
.5
+/- 0.12Grup 2 Hb : 78.9+/- 0.34 g/l
Evaluarea eficientei clinice (simptome) si de laborator (Hb) dupa
tratamentul cu Tothema
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Eficientasi CompliantaRezultate:
Tratament eficient in tratamentul atat la copii mici cat si la adolencentiCrestere rapida si semnificativa a Hb atat in cazurile moderate cat
si cele mai severe
Bine tolerat
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TOT`HEMA
1
IDA :Deficienta
multipla
Cuplu Fe-Cu
2Saruri
feroase
3
Solutie
Profilaxia si Tratamentul
Anemiei Feriprive
Eficienta,
Complianta
Gluconat Feros 50 mg
Gluconat de Cupru 0.7 mg
Gluconat de Mangan 1.33 mg
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