Definisi: Penurunan jumlah neutrofil dan neutrofil bands dalam darah tepi <1500 sel/L pada
anak usia > 1 tahun dan <1000 sel/L pada anak usia 2 bulan 1 tahun
Absolute Neutrophyl Count (ANC) = Jumlah Leukosit (L) x % PMN (PMN + bands)
100
Klasifikasi
1. Derajat Neutropenia
a. Ringan (mild neutropenia)
: ANC 1000-1500/L atau 1-1.5 x 109/L
b. Sedang (moderate neutropenia) : ANC 500-999/L atau 0.5-0.99 x 109/L
c. Berat (severe neutropenia)
: ANC <500/L atau <0.5 x 109/L
2. Etiologi
a. Kelainan intrinsik pada prekursor myeloid (congenital/inherited)
Condition
Severe Congenital
(Kostmann)
Inheritan
ce
AR
Severe Congenital
AD
and
sporadic
Cyclic
AD
Pathogene
sis
HAX1
mutations
causing
disturbed
regulation
of myeloid
homeostasi
s
Marrow
arrest at the
promyelocy
te stage
ELA2
mutations
on the face
of
the
molecule
opposite
the
active
site causing
accelerated
apoptosis
GFI1
mutations
target ELA2
ELA2
mutations
clustering
Occurre
nce
Rare (1/1
to
200,000)
Associated
Findings
ANC
<500/mcL
(0.5109/L)
Leukemia
risk
of
15% to 20%
Rare (1/1
to
200,000)
Two
families
ANC
<500/mcL
9
(0.510 /L)
Leukemia risk of 5%
to10% T and B
cells Marrow has
immature
myeloid
cells
0.5
1/106
to
ShwachmanDiamond
Syndrome
AR
Familial Benign
AD
Marrow
Failure
Syndromes:
Fanconi
AR
Dyskeratosis
Congenita
Usually XR
(also
AR
and AD)
Blackfan Diamond
Syndrome
Sporadic
75%
AR
and AD
near
the
active site
of
the
molecule
SDS
gene
conversion
from
the
pseudogene
,
resulting
in failure of
neutrophil
production
Defect
in
RNA
processing
Decreased
CD34 cells
Decreased
marrow
release
Gene
(FANC)
defects
in
DNA repair
DKC1 (TERC
or TERT in
AD)
mutations
Telomerase
defect,
ribosomal
dysfunction
RPS19
mutations
that affect a
ribosomal
protein
in
25%
of
families
?
Mechanism
of
erythropoiet
ic failure
Many
patients
1/50,000
Pancreatic exocrine
insufficiency, short
stature,
metaphyseal
dysplasia,
marrow
failure, and leukemia
risk (15%)
Common
Africans
and
Yemenite
Jews
Periodontal disease
Dysplastic thumbs,
pancytopenia, other
anomalies
1/106
Abnormal
skin
pigmentation,
leukoplakia,
dystrophic nails
Erythroid
syndrome
failure
Neutropenia in 25%
to 40%
Thumb
and
craniofacial
anomalies
Increased
RBC
adenosine
deaminase
Leukemia risk of 2%
to 3%
Dysgammaglobuli
nemia or HyperIgM
XR
AR)
(also
respond to
glucocortico
ids
CD40 ligand
mutations
?
Immune
neutropenia
,
but
antineutrop
hil antibody
is negative
WHIM Syndrome
and
Myelokathexis
Chediak-Higashi
Syndrome
AD (also ?
AR)
AR
Reticular
Dysgenesis
AR
Cartilage Hair
AR
Imbalance
in pro- and
antiapoptosis
Defect
in
CXCR4
receptor
leading
to
failure
of
neutrophils
to leave the
marrow
CHS1
?
defect
in
lysosomal
fission
Abnormal
protein
trafficking
Decreased
neutrophil
chemotaxis,
degranulati
on,
and
killing
Stem
cell
failure
in
lymphoid
and myeloid
developmen
t
RMRP
mutations
Case
reports
Rare
Neutropenia
only
seen in XR
Warts,
hypogammaglobulin
emia, infections, and
myelokathexis
(WHIM)
NK
and
function
T-cell
Albinism
Neurologic damage
and giant lysosomes
Rare
Severe
combined
immunodeficiency
with neutropenia
Rare
Fine
hair,
shortlimbed,
dwarfism,
lymphopenia, CD4
and CD8 cells
Metabolic
Glycogen Storage
Disease 1b (also
aminoacidopathie
s)
AR
Griscelli
Syndrome Type 2
AR
Barth Syndrome
Cardiolipin
defect
Mutations in
the Cdc42
binding site
in the WASP
gene
Results in Xlinked
neutropenia
XR
IgA
AR=autosomal
Impaired
lytic granule
release
TAZ
mutation on
the
X
chromosom
e
XR
Wiscott-Aldrich
Syndrome
Selective
Deficiency
Defect in a
ribonuclear
protein
ribonucleas
e
G6PT1
mutations
(glucose-6phosphate
translocase)
in 1b
RAB27A
mutations
Unknown
or
multifactor
ial
recessive,
Unknown
AD=autosomal
Infections,
particularly varicella
zoster
1/105 live
births
Hypoglycemia,
dyslipidemia, uric
acid, lactic acid,
and neutropenia in
most patients
Rare
Partial
albinism,
neutropenia,
infections,
and
thrombocytopenia
with
hemophagocytosis
and T-cell defect
Rare
Dilated
cardiomyopathy
1
to
10/106
Common
(1/600)
dominant,
Skeletal myopathy
Mitochondrial
abnormalities
Impaired
lymphoid
development
and
maturation
of
monocytes
Associated
with
eczema,
thrombocytopenia,
and
immune
deficiency
Infections
of
the
upper
and
lower
respiratory tracts in
one third of patients
ANC=absolute
neutrophil
Pathogenesis
Occurrence
Associated Findings
count,
Infection
Viral
marrow
suppression or viralinduced
immune
neutropenia
Bacterial
sepsisendotoxin suppression
Direct
marrow
suppression
Immune destruction
Primary
(molecular
mimicry)
Secondary
(SLE,
Evans
syndrome)
Alloimmune
maternal sensitization
Due
to
maternal
autoimmune
neutropenia
Ineffective
or
decreased production
Common
EBV/parvovirus/HHV6
other viruses
Less common
Severe infection
Common
Underlying condition
Less common
Common
Monocytosis common
Sequestrati
on
Hypersplenism
Nutritional
Vitamin B12 or
acid deficiency
Impaired
processing
Common
spleen
enlarged
Rare
children
Druginduced
Autoimmun
e
Newborn
Immune
Chronic
Idiopathic
EBV=Epstein-Barr
erythematosus.
virus,
folic
and
Rare
Antigen
difference
newborn and mother
Maternal neutropenia
Common
if
is
Consider
also
familial
benign neutropenia Often
asymptomatic
Mild neutropenia Enlarged
spleenmany causes
in
Marrow megaloblastic
DNA
HHV=human
in
Hypersegmented
neutrophils
herpesvirus,
SLE=systemic
lupus
Daftar Pustaka
1. Assessment of Neutropenia. (n.d.). Retrieved from http://bestpractice.bmj.com/.
2. Garna, H., & Nataprawira, H. M. (2012). Pedoman Diagnosis dan Terapi Ilmu
Kesehatan Anak.
3. Hillyer, C., Strauss, R., & Luban, N. (2004). Handbook of Pediatric Transfusion
Medicine. Elsevier Academic Press.
4. Segel, G. B., & Halterman, J. S. (2008). Neutropenia in Pediatric Practice. Pediatrics in
Review.