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Anemija zaradi pomanjkanja železa
Biljana Todorova
Master class iron metabolism and i.v. Iron
13.June 2013 Stockholm, Sweden
Prof. Yves Beguin
University of Liege, Belgium
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Anemija zaradi pomanjkanja železa
kot globalni zdravstveni problem
Vzroki in posledice anemije zaradi
pomanjkanja železa pri različnih
boleznih, z anemijo ali brez
Načini zdravljenja
IRON DEFICIENCY
Etiology
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Absolute iron deficiency
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Iron sequestration
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Functional iron deficiency
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Molecular defects in iron transport,
recycling and distribution
IRON DEFICIENCY - etiology
Absolute iron
deficiency
• no iron stores
IRON DEFICIENCY - etiology
IRON sequestration
iron stores present but blocked in macrophages
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Inflammation (Anemia of chronic disorder :ACD)
Infections
Malignancies
Auto-immune diseases
Chronic kidney disease
–Hepcidin-producing adenoma
–Iron-refractory iron deficiency anemia (IRIDA)
(TMPRSS6/matriptase mutation)
Hepcidin
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Peptidni hormon, ki se sintetizira v jetrih
Glavni regulator homeostaze železa !!!
Deficit hepcidina - ↑absorbcijo Fe iz prebavil in
deponiranje v vitalnih organih (beta talasemija)
Zvečane vrednosti hepcidina:
• (okužbe, maligne bolezni-IL6, sekretorni adenom, iron
overload, juvenilna hemohromatoza)
• zmanjšajo absorbcijo Fe iz prebavil in blokira Fe
v makrofagih
PRI ZVEČANI VREDNOSTI HEPCIDINA JE
PERORALNO ŽELEZO NEUČINKOVITO !!!
Iron refraktory iron deficiency
anemia-IRIDA
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Dedna avtosomno recesivna anemija
Defekt v genu TMPRSS6 za Matriptazo-2,
protein, ki je glavni regulator delovanja
hepcidina na feroportin na membrani
makrofagov in enterocitov
Hipohromna mikrocitna anemija, nizke
vrednosti Hb, nizka sat.transferina, normalen
feritin, normalen hepcidin
Diagnostika: družinska anamneza, anemija
ob rojstvu,izključititi druge ID anemije in
talasemije, genetsko testiranje
Zdravljenje: iv Fe, EPO, kelacija
IRON DEFICIENCY - etiology
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Functional iron deficiency
iron stores present but not able to match increased needs of
erythropoiesis
-High
feritin,
-low Tsat<20%
-high feritin >30, >100 (malignomi)
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iron cannot be mobilised for erythropoiesis, mediated by elevated
hepcidin
commonly seen in patients with end-stage kidney disease, whose
response to EPO may be optimised when ferritin levels exceed
200 g/mL
FID may also contribute to anaemia in patients with inflammatory
diseases such as rheumatoid arthritis
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%HYPO and CHr - useful indicators of FID.
Metabolizam železa
IRON DIAGNOSIS & PARAMETERS
Iron parameters are central to diagnosing ID,
with or without anemia :
–Serum ferritin
–TSAT
–Soluble transferrin receptor
–RBC indices
Parameters aid in distinguishing between
different iron deficiency states
IRON STORAGE
FERRITIN Serum ferritin
Represents iron stores
(macrophages and
hepatocytes) 1 μg/L = 120
μg/kg storage iron
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•Low serum ferritin < 20
μg/L (12–30 according to
assay) 100% specific for
iron deficiency
•Normal range varies with
age and sex
Conditions with falsely elevated
serum ferritin
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–Inflammation (including cancer)
–Some forms of cancer (e.g. neuroblastoma)
–Renal failure (lower limit 40–100 μg/L)
–Liver damage
–Hyperthyroidism
–Poorly controlled diabetes mellitus (ferritin
glycosylation)
–Hyperferritin-cataract syndrome
–Benign hyperferritinemia
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• Conditions with falsely
elevated serum ferritin
– Inflammation
(including cancer)
FERRITIN Serum ferritin
(μg/L)
• Lower limit = 100
(40–120) μg/L
• Lower levels define
absolute ID in cancer
patients
IRON DEFICIENCY- Oral iron
therapy
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200 mg iron per day
Ferrous salts Ferric carbohydrate complexes
less absorbed (better tolerated)
Better absorbed when given between meals
Better tolerated when given with meals
Duration : 3-6 months (1) 1–3 months for
correction of anemia (2) 2–3 additional
months for restoration of iron stores
Side effects : gastric intolerance, diarrhea,
constipation, black stools
Absorption decreased with inflammation, re
IRON DEFICIENCY - failure of
oral iron therapy
•Explanations :
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Incorrect diagnosis
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Complicating illness (cancer, inflammatory
disorders, CKD)
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Non-compliance
-Inadequate prescription (dose and form)
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Iron losses in excess of intake (Rendu-Osler)
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Iron malabsorption
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IRIDA
•Alternatives : - Optimize oral iron treatment Parenteral iron : IV, never IM
Oblike I.V. železa v Europi
Balance of risks for potential to induce oxidative stress vs.
hypersensitivity reactions for parenteral iron preparations
Toxic effects of labile iron1
Correlates with molecular weight of iron complex
High
Low
Ferric
gluconate
Iron
dextran
Correlates with risk of
anaphylaxis*
Ferric
carboxymaltose
Immunogenicity2
Iron sucrose
Figure to be redrawn with no tradenames
High
Bailie GR. Eur Haematol 2009;2:58–60
1. Van Wyck DB et al. J Am Soc Nephrol 2004;15:107–11
2. Hörl W et al. Nephrol Dial Transplant 2007;22(Suppl 3):iii2–6
IRON DEFICIENCY - IV iron
therapy
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Efficacy of IV iron in combination with
ESA
Efficacy of IV iron in iron deficiency
anemia
Efficacy of IV iron in iron deficiency
without anemia
Risk/benefit assessment of IV iron
therapy
IRON DEFICIENCY THERAPY
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Kombinacija z EPO
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v okviru indikacij
Uvajanje pri Hb < 100g/L
Tarčni Hb je 120 g/L
Pred uvedbo EPO in med zdravljenjem preveri:
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Zaloge železa, ev krvavitev
B12, folna kislina
ev hemolizo
CRP
EPO v serumu
• EPO ukini 4 tedne po zaključeni KT
Talasemije v RS-gensko testiranje
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Vzorci krvi od 24 pacientov, poslani v
Skopju v laboratorij za gensko testiranje.
Pri vsem je bil prisoten zvišan HbA2 in
HbF
Rezultati:
-17-heterozigoti Sicilian delta beta
talasemija
-5 heterozigoti Lepore BW
hemoglobinopatija
-1 heterozigot beta minor talasemija
- 1 zdrav
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HVALA za
POZORNOST