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NEUTROPENIA

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

21-day cycle with


fever and mouth
ulcers

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

IgG, IgA, IgM

?
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

May have immune


thrombocytopenia
and anemia

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

Ig=immunoglobulin, NK=natural killer, RBC=red blood cell, XR=X-linked recessive.

b. Faktor ekstrinsik (acquired)


Condition

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.