anemija zaradi pomanjkanja železa - združenje hematologov … · 2013-11-15 · anemija zaradi...
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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
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
Absolute iron deficiency
Iron sequestration
Functional iron deficiency
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 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
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
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
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)
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
%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 •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 –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
• 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
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 : Incorrect diagnosis Complicating illness (cancer, inflammatory
disorders, CKD) Non-compliance -Inadequate prescription (dose and form) Iron losses in excess of intake (Rendu-Osler) Iron malabsorption 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
Figure to be redrawn with no tradenames
Iron dextran
Iron sucrose
High
Low
Imm
unogenicity2
Correlates w
ith risk of anaphylaxis*
High
Toxic effects of labile iron1 Correlates with molecular weight of iron complex
Ferric carboxymaltose
Ferric gluconate
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
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 Kombinacija z EPO
• v okviru indikacij • Uvajanje pri Hb < 100g/L • Tarčni Hb je 120 g/L • Pred uvedbo EPO in med zdravljenjem preveri:
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
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
HVALA za POZORNOST
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