SEGUNDO SIMPOSIO INTERNACIONAL EN EPIDERMOLISIS BULOSA 17 Y 18 DE NOVIEMBRE 2005, SANTIAGO DE CHILE

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SEGUNDO SIMPOSIO INTERNACIONAL EN EPIDERMOLISIS
BULOSA17 Y 18 DE NOVIEMBRE 2005, SANTIAGO DE
CHILE

• EPIDERMOLISIS BULOSA
• Y
• ANEMIA
• DR FRANCIS PALISSON
• DIRECTOR MÉDICO DEBRA CHILE

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CAT AND BIRD 1928 PAUL KLEE
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Qué es Anemia?

• Hb lt 13 gr/dl
• Palidez
• Fatiga
• Disnea de ejercicio
• Taquicardia de Reposo
• Inadecuado Transporte de Oxígeno
• Retardo en la cicatrización de heridas
• Retardo del crecimiento

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Anemia
7 nm
Deficit de He
Anemia por Enf Crónicas
Anemia Megaloblástica Por deficit de Vit b12
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Deficit de Folato???? Enfermedades Crónicas
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Deficiencies of Vitamins and Minerals in RDEB
cont.
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EPIDERMOLISIS BULOSA

• ALTERACIONES DE LABORATORIO
• ANEMIA MICROCÍTICA HIPOCRÓMICA
• FIERRO SÉRICO DISMINUIDO
• ERITROPOYETINA AUMENTADA
• TROMBOCITOSIS
• VHS AUMENTADA
• PCR AUMENTADA
• HIPOALBUMINEMIA

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Pobre ingesta de He???? Mala Absorción??? Pérdidas
Aumentadas???
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EPIDERMOLISIS BULOSA CHILE 1982-2003
DG CLÍNICO
124 CASOS
IHQME y BIOL MOL
49
2003
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COMPROMISO X ANEMIA
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EPIDERMOLISIS BULOSA 1982-2004
HB lt a 12 gr/dl EBS 0 de 142 EBJ 3 de 142 EBD 28
de 142
DG CLÍNICO
167 CASOS
IHQME y BIOL MOL
84
2005
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EPIDERMOLISIS BULOSA y ANEMIA

• No conocemos sus causas íntimas, asumimos que
  existe una anemia microcítica hipocrómica por
  pérdidas aumentadas
• Existe un estado inflamatorio crónico que
  mantiene la
• médula ósea frenada
• Los pacientes tienen estados nutricionales
  desmejorados. En parte dado por una pobre ingesta
  nutricional y probablemente por una absorción de
  nutrientes disminuída.

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Metabolismo del Hierro
Finch J, Anemia y Metabolismo del Hierro, En
Hematología Oncología, Ed. Panamericana, 2001
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Metabolismo del Hierro
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EVIDENCIAS DE LA LITERATURA

• Correction of the anemia of epidermolysis bullosa
  with intravenous iron and erythropoietin
• Fridge, Jacqueline L. Vichinsky, Elliott P. MD
• n 5 pacientes

J Pediatr 1998132871-3
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PROTOCOLO VENOFER

• Pacientes con criterios de entrada
• n10
• Pacientes que abandonaron el estudio
• n 5
• Pacientes que recibieron fierro EV durante 6
  semanas y se controlaron una vez x sem x 20 sem
• n 5

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Hemoglobina post Venofer x 6 sem
SE IDENTIFICAN 2 GRUPOS EN TIEMPO O COTA SUPERIOR
PROMEDIO DE HB 11 EL GRUPO 1 QUE PARTE EN 9 HB
LLEGA A 11 EN 5 SEM EL GRUPO 2 PARTE EN 8 Y SE
DEMORA 11 EN SEM
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PCR post Venofer x 6 sem
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Ferritina post Venofer x 6 sem
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Eritropoietina post Venofer x 6 sem
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Plaquetas post Venofer por 6 sem
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ANEMIA DE EB

• ANEMIA MICROCÍTICA HIPOCROMA POR DEFICIT DE HE
• ANEMIA POR ENFERMEDAD INFLAMATORIA CRÓNICA
• ANEMIA POR DEFICIT NUTRICIONAL
• OTROS

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Equipo de Trabajo

• PAULETTE CONGETT, PhD
• ALUMNOS DE MEDICINA UDD
• MATIAS DONOSO
• CAMILA LETELIER
• FERNANDO MANRÍQUEZ
• FRANCIS PALISSON

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www.debrachile.cl debrachile_at_mi.cl Muchas
gracias!
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• Figure 1  Distribution of iron within the body.
    The normal distribution of iron within the body
  is shown. Adults typically have 35 g in total.
  About 0.52 mg of dietary iron is absorbed each
  day through the proximal small intestine. This
  intake is balanced by loss of a similar amount of
  iron, through blood loss and the sloughing of
  skin and mucosal cells. Most iron is found in the
  erythroid bone marrow and in mature erythrocytes,
  contained within the haem moiety of haemoglobin.
  Iron for new red-blood-cell synthesis is
  primarily supplied by reticuloendothelial
  macrophages, which recycle iron from old red
  blood cells. Circulating iron is bound to
  transferrin. Around 0.1 of the total body iron
  is found in this transit compartment. Transferrin
  delivers iron to developing erythroid precursors,
  as well as to other tissues of the body. Stored
  iron is primarily found in the hepatocytes of the
  liver. The distribution of iron is altered in
  response to pregnancy, iron deficiency and iron
  overload. (TF, transferrin.)

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• Figure 2  The transferrin cycle.  
  HOLOTRANSFERRIN (HOLO-TF) binds to transferrin
  receptors (TFR) on the cell surface. The
  complexes localize to clathrin-coated pits, which
  invaginate to initiate endocytosis. Specialized
  endosomes form, and become acidified through the
  action of a proton pump. Acidification leads to
  protein conformational changes that release iron
  from transferrin. Acidification also enables
  proton-coupled iron transport out of the
  endosomes through the activity of the divalent
  metal transporter 1 protein (DMT1). Subsequently,
  APOTRANSFERRIN (APO-TF) and the transferrin
  receptor both return to the cell surface, where
  they dissociate at neutral pH. Both proteins
  participate in further rounds of iron delivery.
  In non-erythroid cells, iron is stored as
  ferritin and haemosiderin.

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• Figure 3  Cellular iron transport.   There are
  four cell types that have special functions in
  iron handling. a Duodenal enterocytes absorb
  iron from the diet. Non-haem iron is reduced by a
  ferric reductase in the brush border and is
  transported into the cell through the
  transmembrane iron transporter DMT1 (for divalent
  metal transporter 1). Some iron is stored within
  the cell in ferritin the remainder must pass
  through the basolateral membrane to reach the
  plasma. An iron exporter, ferroportin1, probably
  carries out basolateral iron transfer in
  cooperation with hephaestin, a possible
  ferroxidase. Hephaestin is homologous to the
  plasma multicopper oxidase ceruloplasmin (CP),
  and might have a function analogous to that of CP
  in iron export from other cells. Absorbed iron is
  loaded onto apotransferrin (APO-TF) to give
  holotransferrrin (HOLO-TF) through a mechanism
  that is not yet understood. b Erythroid
  precursors take up iron through the transferrin
  cycle, as described in Fig. 2. Erythroid cells
  probably have no iron-export mechanism
  essentially all iron in these cells is
  incorporated into haemoglobin. c Hepatocytes
  take up iron through at least two distinct
  pathways. They have a functional transferrin
  cycle and a transport system to take up
  non-transferrin-bound iron. The molecules
  important for non-transferrin-bound iron
  transport have not yet been identified.
  Hepatocytes store iron in ferritin. When iron is
  needed elsewhere in the body, they can release it
  to transferrin. The mechanism of hepatocyte
  export is not known, but it may involve
  ferroportin1. CP seems to aid in iron export from
  hepatocytes, but its precise function has not yet
  been defined. d Reticuloendothelial macrophages
  carry out iron recycling. They ingest senescent
  red blood cells (RBC) and lyse them in a
  phagolysosomal compartment. Haemoglobin is
  degraded and iron is liberated from haem. The
  enzyme haem oxygenase may participate in this
  process. Iron is then exported through the cell.
  The mechanism of macrophage iron export is not
  known, but may again involve ferroportin1 and CP,
  similar to iron export from hepatocytes. (TFR,
  transferrin receptor.)