We are still without

a trust worthy
medicine wich can
always be relied
upon to control
purpura.
 Manifestaciones
Hematolgicas asociadas
a Enfermedad de
Gaucher
Diagnstico diferencial y manejo
Anemia

Trombocitopenia

Esplenomegalia

Enfermedad sea
Hb < 13 H
Hb <12 M
 ETIOLOGY

produccin destruccin
HIPER PROLIFERATIVA
25%

HIPO PROLIFERATIVA
75%
 ANEMIAS CON
RETICULOCITOS BAJOS

CARENCIALES
ENFERMEDAD CRONICA / IRC
DE CAUSA DESCONOCIDA
 Nutricional

Hemlisis

Enfermedad
Hematolgica
Crnica
Regenerativa

Arregenerati
va
 JAMES HOMER WRIGHT ()

Original Articles. jagged or fimbriate outline. There is thus to be

distinguished in the blood plate two portions,
THE ORIGIN AND NATURE OF THE BLOOD
namely, a central, granular, red to violet staining
portion and a marginal, homogeneous, hyaline,
PLATES. blue staining portion. The diameter of the
BY JAMES HOMER WRIGHT, M.D., S.D., central portion and the width of the marginal
portion
vary, the latter being usually narrower
Director of the Pathological Laboratory of the Massachusetts General
School.
Original Articles.
Hospital; Instructor in Pathology, Harvard University Medical
than the diameter of the former.
The giant cells present the following peculiari- jagged
A prolonged study of the comparative mor-
ties which are of importance for the subject of
phology of the blood corpuscles of a wide range this paper:
disting
of animals has shown me that all of the many
THE ORIGIN AND NATURE
The cytoplasm
OF THE
making up the central and
BLOOD
namely
theories hitherto proposed concerning the origin
usually
and nature of the blood plates are untenable andPLATES.
the greater portion of the giant cell is portion
erroneous.
crowded more or less densely with closelyblue
set, s
minute, red to violet granules, for the most part
In this paper I shall not set forth my reasons
BY JAMES HOMER
for coming to this conclusion, but I shall confine
like those of M.D.,
WRIGHT, the central
S.D., portions of centra
the blood
myself to a briefDirector
statementof
Hospital;
the
of myPathological
own
Instructoropinions
in
plates,
Laboratory
blue
Pathology,
while
of
stained.
Harvard
Figure 4.2
at the
the
This
James Homer
periphery
Massachusetts
hyaline
University
Wright, during
it
peripheral
his
is
General
Medical
later
hyaline
years
portion
and
Figure
portion
4.3 Tit
Pathological Techni
concerning the origin and nature of these bodies forms a definite narrow zone of somewhat variable
School. than th
by both
and a summary of the facts and observations upon
which my opinions are based. width, but
He
is
also veiy
wrote a
narrow as compared with the
chapter on other infections for The
Dr. Wright had a
A prolonged study of
diameter
By means of a staining fluid,1 devised by me for finely ragged the
that of comparative
the
work. whole
During his
Dr. Wrightoralsofimbriate
cell
early and
years
edge.
authored a twice-yearly
inhas mor-
Boston,a smooth
ration
In appearance
review
and
ties
by his
orexamina
book withwh D
phology
use in the staining of blood films the of blood
according to
it corpuscles
of
suggests the
progress in of a
pathology
ectosarc wide
in the anrange
ofBoston ameba.
Medical his 1901The
this contributio
the method of Leishman, which gives the so-
of polychrome has shown
animalsstaining, majority andofSurgical
that the Journal.
all
giant of
Th is was
cells a
themultipage
are of sum-
spherical nique, in which
form, pa h
called Romanofsky I have me mary
but minority
a of published
are research
of with
varied a detailed
and manylitera-
irregular shape The
briefly boiling it in
theories
been enabled to stain hitherto
characteristically
in sections of fixed tissues and
the blood
so by proposed concerning
ture review. Th e
reason of the distortion
Councilman in
series
1893,
had
but Dr.
the
been initiated
Wrightof took
by
their origin
Dr. staining.
it over cytoplasm
No additi
section technique c
BLOOD PLATES-WRIGHT.

Origin of the blood plates from the giant cells of the bone marrow.
12
Etiologa de las Anemias
HIPER PROLIFERATIVA
10%

HIPO PROLIFERATIVA
90%
Etiologa de la Trombocitopenia

BAJA PRODUCCIN
10%

EXCESO DESTRUCCIN
90%
 ETIOLOGY

Medicina Interna (paciente hospitalizado)

Consulta Externa (trombocitopenia aislada)

Unidad de Cuidados Intensivos y Urgencias.

Unidad Coronaria

Zonas endmicas

Embarazadas
 ETIOLOGY

produccin destruccin
secuestro
Combo 1:
Hemograma
Reticulocitos
ferritina
LDH
Haptoglobina
Bilirrubinas
Creatinina
Combo 1:

FROTIS DE SANGRE
PERIFRICA
Grover S, Barkun A, Sackett D. Does this patient have
splenomegaly? En The rational clincal examination. JAMA 2009,
Cap 46.
Philipe Gaucher
Epidemiologa
Patognesis
Diagnstico

Beta Glucosidasa Acida

Glucocerebrosidasa
OTROS PAISES
31%

USA
50%

ISRAEL
19%
100
94

80

60

40

20

5
1
0
TIPO 1 TIPO 2 TIPO 3
The distribution of ages at diagnosis

Arch Intern Med. 2000;160(18):2835-2843

 Curso Clinico
Progressive
Pulmonary
neurologic
involvement symptoms*

Hepatosplenomegaly Thrombocytopenia
and anemia

Skeletal
involvement
* In neuronopathic subtypes only.
HALLAZGOS AL DIAGNOSTICO
%
100.0
86.7 85.8
80.0
76.3
80.0

60.0
45.2
40.0
22.6
20.0

0.0

Esplenomegalia Anemia Hepatomegalia Plaquetopenia Leucopenia Dolor seo

ADENOMEGALIAS
Linfomas
Esplenomegalia
Hepatomegalia
Trombocitopenia
ENFERMEDAD SEA
 RNM
T1-weighted MRI: marrow infiltration
T2-weighted MRI: bone infarcts.
GAMAGRAFIA
Hot spots: Osteomielitis
Coold spots: Necrosis
RX
DENSITOMETRIA
PEORAMIENTODELACALIDADSEAYAQUEELBAZOESUNRESERVORIO DEFORMIDADENLO
NATURALDECLULASDE'AUCHER"EIGTHON &IGURA)  ELGENUVARO,AOST
COMOELCORTICALYP

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%L MECANISMO POR EL CUAL LA INlLTRACIN DE LA MDULA
SEALLEVAALAAFECTACINSEATODAVAESDESCONOCIDO5N ,AINlLTRACIND
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SEAAMARILLADURANTEELDESARROLLONORMALDELOSMIEMBROS
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Osteoporosis
Anemia
 ETIOLOGY

produccin destruccin
Combo 1:
Hemograma
Reticulocitos
ferritina
LDH
Haptoglobina
Bilirrubinas
Combo 2:

* Glucocerebrosidasa
*Quitotriosidasa
Valoracin Inicial
BIOMARCADORES
ESTUDIO MOLECULAR
Arch Intern Med.
2000;160(18):
2835-2843
 Genotipo

N370S
L444P
84GG
 TRATAMIENTO

Splenectomy
Enzyme replacement
Bone marrow transplantation
Sustrate Inhibition Treatment
Terapia de Reemplazo Enzimatico
Barton NW et al. N Engl J Med
1991;324:1464-1470.
Barton NW et al. N Engl J Med
1991;324:1464-1470.
Barton NW et al. N Engl J Med
1991;324:1464-1470.
Barton NW et al. N Engl J Med
1991;324:1464-1470.
 Effect of Macrophage-Targeted Glucocerebrosidase on the
Hemoglobin Concentration in Patient 12.

Barton NW et al. N Engl J Med

1991;324:1464-1470.
Barton NW et al. N Engl J Med
1991;324:1464-1470.
Effect of Glucocerebrosidase on Serum Acid Phosphatase
Activity in Patient 11:

Barton NW et al. N Engl J

Clin Genet. 2008 May; 73(5): 430440.
Clin Genet. 2008 May; 73(5): 430440.
 Inhibicin de Suatrato
Miglustat
Eliglustat
 ELIGLUSTAT

Eliglustat, an investigational oral therapy for Gaucher

disease type 1: Phase 2 trial results after 4 years of
treatment
Blood Cells, Molecules, and Diseases
Volume 53, Issue 4, December 2014, Pages 274276
 Fig. 1 Improvements in hematologic and organ volume parameters through 4 years of eliglustat treatment. Data are reported as percent
change from baseline for platelets, liver and spleen, and change from baseline for hemoglobin in g/dL. All values are mean...

Elena Lukina , Nora Watman , Marta Dragosky , Gregory M. Pastores , Elsa Avila Arreguin , Hanna Rosenbaum , Ari Z...

Eliglustat, an investigational oral therapy for Gaucher disease type 1: Phase 2 trial results after 4<ce:hsp sp="0.25"/>years of
treatment
Blood Cells, Molecules, and Diseases, Volume 53, Issue 4, 2014, 274 - 276

http://dx.doi.org/10.1016/j.bcmd.2014.04.002
 Fig. 3 Mean lumbar spine bone mineral density improvement from osteopenia to normal range after 4 years of eliglustat treatment. Values for
the lumbar spine represent the mean changes in T-score from baseline and the significance of the changes at each ti...

Elena Lukina , Nora Watman , Marta Dragosky , Gregory M. Pastores , Elsa Avila Arreguin , Hanna Rosenbaum , Ari Z...

Eliglustat, an investigational oral therapy for Gaucher disease type 1: Phase 2 trial results after 4<ce:hsp sp="0.25"/>years of
treatment
Blood Cells, Molecules, and Diseases, Volume 53, Issue 4, 2014, 274 - 276

http://dx.doi.org/10.1016/j.bcmd.2014.04.002
Monitoreo / Metas
4ABLA$ATOSCLNICOSSOBRELARESPUESTASEAALATERAPIADE TIASPUESFRECUEN
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 Sospechar en ...
Gaucher is a progressive, debilitating and
sometimes life-threatening disease.
Symptoms can include:
easy bleeding and bruising, fatigue, anemia,
weak bones, bone and joint pain, and
enlargement of the spleen
or liver.
Symptoms can appear at any age.
*National Gaucher Foundation (NGF)
www.gaucherdisease.org
*National Organization for Rare Disorders
(NORD)
www.rarediseases.org
*National Institutes of Health
www.rarediseases.info.nih.gov/
Genzymes Gaucher disease website
www.gauchercare.com
 *National Gaucher Foundation (NGF)
www.gaucherdisease.org
*National Organization for Rare Disorders (NORD)
www.rarediseases.org
*National Institutes of Health
www.rarediseases.info.nih.gov/
Genzymes Gaucher disease website
www.gauchercare.com
 #LULASDE'AUCHER

/STEOCLASTOS

&IGURA-ODELODEINTERACCINENTRECLULASDE'AUCHERYOSTEOCLASTOS
RESULTANDOENREABSORCINSEA7ENSTRUP2* #LULASDE'AUCHERSE
CRETANFACTORESQUEINmUENCIANLADIFERENCIACINOSTEOCLSTICAYPROMUEVEN
LAREABSORCINSEA
Bone Marrow Biopsy and Aspirate Specimens.

Larsen EC et al. N Engl J

MRI Scans of the Pelvis and Femurs.

Larsen EC et al. N Engl J Med

Abdomen of Patient 7 before (A) and after (B) Six Months
of Enzyme Replacement.

Barton NW et al. N Engl J Med

 Gaucher Disease
Gaucher disease is
inherited (passed from
parent to child).
Both parents must be
either carriers or have
the disease for the
disease to present in
a child.
Abdomen of Patient 7 before (A) and after (B) Six Months of Enzyme Replacement.