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