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BAB I

Pendahuluan
Pansitopenia adalah suatu keadaan dimana adanya penurunan jumlah komponen darah
yang terdiri dari 3 macam, yaitu yang terdiri dari Eritrosit (sel darah merah), Leukosit (sel darah
putih), dan trombosit. Ketiga tersebut jika mengalami penurunan akan mengakibatkan terjadinya
anemia, leukopenia dan trombositopenia.
Etiologi terjadinya pansitopenia dapat berupa primer, sekunder, dan infeksi virus. Primer
merupakan yang belum diketahui penyebabnya, bisa berupa idiopatik atau keturunan. Sekunder
yang berasal dari obat-obatan seperti NSAID, Sitotoksik, atau berdasarkan dari obat seperti
respon idiosinkrasi. Sedangkan berdasarkan dari infeksi virus yang sering menyebabkan
terjadinya pansitopenia adalah virus hepatitis B dan C.
Terjadinya penurunan jumlah komponen darah tersebut dapat diketahui melalui
pendekatan dari anamnesis, pemeriksaan fisik dan pemeriksaan penunjang. Pada anamnesis
biasanya didapatkan adanya kelainan seperti anemia aplastic, Sindrom gagal sumsum tulang
turunan, adanya riwayat keguguran, riwayat menderita keganasan, adanya gangguan metabolic,
riwayat penyakit hati dan adanya riwayat penggunaan obat sitotoksik dan radioterapi.


BAB II
PENDEKATAN DIAGNOSIS PANSITOPENIA

Pansitopenia adalah Penurunan jumlah 3 komponen darah Eritrosit, Leukosit dan Trombosit.
Yang akan mengakibatkan Anemia, leukopenia, dan trombositopenia. Penyebab penurunan
produksi darah di sumsum tulang, Bone marrow faillure syndrome, Immune mediated
destruction, Non immune mediated sequestration in perifer.
Etiologi


Table of etiologies for pancytopenia. Abbreviation: GVHD, graft-versus-host disease From the collection of Jeff K. Davies



Derajat pansitopenia
Ringan Hemoglobin <8 gr/dL, sel PMN > 2000/mm
3
, trombosit >20.000/mm
3

Sedang Hemoglobin <7 gr/dL, sel PMN < 500/mm
3
, trombosit <20.000/mm
3

Berat Leukosit <200 /mm
3
, trombosit <10.000/mm
3




Pendekatan Diagnosis
Anamnesis
• Anemia aplastik
• Sindrom gagal sumsum tulang turunan
• Riwayat keguguran
• Riwayat menderita keganasan
• Gangguan metabolik
• Riwayat penyakit hati
• Riwayat penggunaan obat sitotoksik dan radio terapi
Pemeriksaan fisik
Mata :
• Perdarahan retina (trombositopenia)
• Infiltrasi lekemik (leukimia akut)
• Sklera ikhterik (Paroxysmal nocturna hemoglobinuria, hepatitis, sirosis)
• Epiphora (dyskeratosis congenital)
Oral :
• Ptekie/ Perdarahan di rongga mulut (trombositopenia)
• Stomatitis/chelitis (neutropenia, def. Vit B12)
• Hiperplasia gusi (leukimia )
• Kandidiasis oral/ eksudat faring (neutropenia, infeksi herpes virus)
Kardiovaskular:
• Takikardi, edema, CHF
• Bekas pembedahan jantung (sindrom kongenital)
Respiratori :
• Clubbing (ca. paru)
• Takipnea



Abdomen :
• Nyeri perut kakan atas ( hepatitis )
• Limfadenopati (infeksi, penyakit limfoproliferatif, HIV)
• Tanda penyakit hati kronis
• Splenomegali (infeksi, penyakit myeloproliferatif, limfoproliferatif)
Kulit :
• Malar rash (SLE)
• Purpura (trombositopenia)
• Pigmentasi retikular, kuku displastik (dyskeratosis congenital)
• Area hipopigmentasi
• Hiperpigmentasi, café au lait (anemia fanconi
Muskuloskeletal :
• Short stature ( fanconi anemia, kelainan congenital lain)
• Artritis, sinovitis (SLE)
• Jari-jari abnormal (anemia fanconi)
Tanda yang berhubungan dengan infeksi HIV :
 Morbiliform rash
 Sarkoma kaposi, nodul ulseratif











LABORATORIUM
Pemeriksaan standar
 Hitung darah lengkap
 Apusan darah tepi
 Hitung retikulosit darah
 Fungsi hati dan serologi hepatitis
 Tes koagulasi, bleeding time, fibrinogen, D-dimer
 Tes direct antiglobulin
 Serum B12 dan folat
 Seru HIV
 TES anti nucleid acid
Biopsi Sumsum Tulang
Selularitas:
 ↓: gangguan produksi darah: pasca kemoterapi, sepsis/infeksi akut, HIV Stadium lanjut,
syndrom myelodisplasi hipoplastik, IBMFS,anemia aplastik idiopatik, SLE, PNH
 N/↑: produksi yang tidak efektif/↑destruksi/sekuestrasi sel-sel darah: myelodisplasia,
leukimia akut/kronik,myeloma dengan plasma selnya, infiltrasi keganasan, HIV stadium
dini/akut, anemia megaloblastik.

Histologi :
 Infiltrasi sel
 Blast
 Gambaran myelodispplasia

Aspirasi Sumsum Tulang
 Sitologi (perubahan megaloblastik, perubahan displastik, infiltrasi sel abnormal dan
infeksi)
 Imunofenotif (leukimia akut dan kronik, penyakit limfoproliferatif)
 Sitogenik (myelodisplasi, leukimia akut dan kronik, penyakit limpoproliferatif).
Temuan laboratorium
Common
Differential 1 st test Other test
Chemotherapy • peripheral blood: anisocytosis,
poikilocytosis, basophilic
stippling
• bone marrow aspirate: variable
hypoplasia
• bone marrow
biopsy: hypoplasia,
megaloblastosis

Radiotherapy • peripheral blood: anisocytosis,
poikilocytosis, basophilic
stippling
• bone marrow aspirate: variable
hypoplasia
• bone marrow
biopsy: hypoplasia,
megaloblastosis

Vitamin B12
deficiency
• peripheral blood film: oval
macrocytic RBCs, irregular size
and shape of RBCs (anisocytosis
and poikilocytosis),
hypersegmented granulocytes (>5
lobes)
• serum reticulocyte
count: usually low
• serum B12: low in B12
deficiency
• bone marrow
aspirate: hypercellular,

megaloblastic erythroblasts, giant
metamyelocytes
• serum LDH: moderately raised
• serum bilirubin: moderately
raised, mostly indirect
Folic acid
deficiency
• peripheral blood film: oval
macrocytic RBCs, irregular size
and shape of RBCs (anisocytosis
and poikilocytosis),
hypersegmented granulocytes (>5
lobes)
• serum reticulocyte
count: usually low
• serum RBC folate: low in folate
deficiency
• bone marrow
aspirate: hypercellular,
megaloblastic erythroblasts, giant
metamyelocytes
• serum LDH: moderately raised
• serum bilirubin: moderately
raised, mostly indirect

Bone marrow
infiltration by
nonhematologic
malignancy
• peripheral blood film: leuko-
erythroblastic cell forms
• bone marrow aspirate: clumps
of tumor cells
• CXR: mass (lung cancer)
CT of abdomen: may reveal
abdominal or renal mass
serum prostatic-specific
antigen: elevated in prostate
cancer
• serum LFTs: elevated ALT and
AST ( hepatic metastases)
• serum coagulation
profile: prolonged PT and PTT
• serum fibrinogen and D-
dimer: diminished fibrinogen and
elevated D-dimer (indicative of
chronic disseminated
intravascular coagulation)
thyroid ultrasound: irregular
mass or nodule
breast imaging: mass or
calcifications
Non-Hodgkin
lymphoma
• peripheral blood film: variable;
may show circulating lymphoma
cells
• bone marrow aspirate: increased
proportion of lymphoid cells
• immunophenotyping (of
peripheral blood or bone
marrow): clonal population of
lymphoid cells
• lymph node
biopsy: lymphoproliferative
disorder

Hepatitis C • peripheral blood
film: macrocytes, target cells,
stomatocytes, acanthocytes
• reticulocyte count: elevated or
normal
• serum LFTs: elevated
• serum antihepatitis C virus
(HCV): presence of HCV
antibodies
• bone marrow
aspirate: hypercellular,
erythroid hyperplasia
Autoimmune
hepatitis
• peripheral blood
film: macrocytes, target cells,
stomatocytes, acanthocytes
• reticulocyte count: elevated or
normal
• serum LFTs: elevated
• autoantibody screen: positive
• bone marrow
aspirate: hypercellular,
erythroid hyperplasia
HIV • peripheral blood film: atypical
lymphocytes (acute
seroconversion), rouleaux,
dysplastic neutrophils
• reticulocyte count: reduced
• HIV serology: positive
• bone marrow
aspirate: hypercellular (acute
seroconversion), hypocellular,
dyserythropoiesis
• protein
electrophoresis: polycl
onal
hypergammaglobulinem
ia
Hepatitis B • peripheral blood
film: macrocytes, target cells,
stomatocytes, acanthocytes
• reticulocyte count: elevated or
normal
• serum LFTs: elevated
• serum HBsAg: positive
• bone marrow
aspirate: hypercellular,
erythroid hyperplasia
Hairy cell
leukemia
• peripheral blood
film: circulating lymphoma cells
• bone marrow aspirate: increased
proportion of lymphoid cells
• immunophenotyping (of
peripheral blood or bone
marrow): clonal population of

lymphoid cells
Chronic
lymphocytic
leukemia
• peripheral blood
film: circulating leukemia cells
cells
• bone marrow aspirate: increased
proportion of lymphoid cells
• immunophenotyping (of
peripheral blood or bone
marrow): clonal population of
lymphoid cells
• lymph node
biopsy: lymphoprolifera
tive disorder
Myelodysplasia • peripheral blood film: may have
irregular or macrocytic RBCs,
dysplastic granulocytes, platelets
may be large and hypogranular
• serum reticulocyte
count: usually low, may be
normal or raised
• bone marrow aspirate: usually
hypercellular, rarely, hypocellular
(hypocellular myelodysplasia),
dysplastic changes
• cytogenetics: may be
abnormal
Cirrhosis • peripheral blood
film: macrocytes, target cells,
stomatocytes, acanthocytes
• reticulocyte count: elevated or
• bone marrow
aspirate: hypercellular,
erythroid hyperplasia
normal
• serum LFTs: elevated
Cytomegalovirus
infection
• peripheral blood film: atypical
lymphocytes, spherocytes if
coexisting hemolysis
• CMV-specific IgM and
IgG: positive
• bone marrow
aspirate: cellularity usually
increased, hemophagocytosis may
be prominent
• bone marrow trephine
biopsy: cellularity usually
increased

Mycobacterial
infection
• peripheral blood film: rouleaux
• reticulocyte count: reduced
• bone marrow aspirate: reduced
cellularity, hemophagocytosis
• bone marrow trephine
biopsy: reduced cellularity,
granulomas, fibrosis
• bone marrow culture: positive
for organism






Uncommon
Differential 1
st
test Other test
Acute myeloid
leukemia
• peripheral blood film: blasts on blood
film, presence of Auer rods
• serum PT, PTT, fibrinogen, D-
dimer: may be abnormal, suspect DIC
• bone marrow aspiration: usually
hypercellular with blasts, rarely
hypocellular
• bone marrow biopsy: presence of
blasts, infiltration, Auer rods
• immunophenotyping: detection of
clonal population of blasts
• cytogenetics: identification or
nonrandom chromosomal abnormalities
• serum PT, PTT, fibrinogen, D-
dimer:prolonged PT, PTT; diminished
fibrinogen, elevated D-dimer

Acute
lymphocytic
leukemia
• peripheral blood film: blasts may or
may not be present
• bone marrow aspirate: hypercellular
with blasts; occasionally hypocellular
(childhood ALL)
immunophenotyping (of
peripheral blood or bone
marrow): detection of
clonal population of blasts
cytogenetics: identificatio
n of nonrandom
chromosomal
abnormalities
Multiple
myeloma
• peripheral blood film: rouleaux,
circulating plasma cells may rarely be
present
• bone marrow aspirate: plasma cell
infiltrate, abnormal plasma cells,
plasmablasts
• immunophenotyping (of peripheral
blood or bone marrow): plasma cells
exhibit restriction of kappa or lambda
light chain expression
• serum and urine
electrophoresis:monoclonal serum
protein and urinary Bence-Jones
proteins (light chains) detected
• radiologic skeletal
survey: lytic lesions
and/or osteopenia
Myelofibrosis • peripheral blood film: leuko-
erythroblastic, tear drop RBCs
• bone marrow aspirate: hypercellular
and fibrotic, often dry tap and
nondiagnostic
• serum and RBC
folate: usually
diminished
• serum B12: usually
elevated
Lysosomal
storage
disorders
• leukocyte glucocerebroside
activity:reduced or absent
• peripheral blood film: pancytopenia
• reticulocyte count: may be high,
normal, or reduced
• bone marrow aspirate: may reveal
Gaucher cells
• bleeding
time: prolonged
Anorexia
nervosa
• peripheral blood film: red cell
acanthocytes, poikilocytosis and
basophilic stippling
• reticulocyte count: low
• bone marrow aspirate: hypocellular,
reduced hematopoietic cells, may show
gelatinous transformation
• bone marrow trephine
biopsy: hypocellular without
infiltration or fibrosis
• diepoxybutane test: normal

Graft-versus-
host disease
• peripheral blood film: no specific
features
• reticulocyte count: low
• bone marrow aspirate: hypocellular,
reduced hematopoietic cells, increased
macrophages, erythrophagocytosis
• bone marrow trephine
biopsy: hypocellular without
infiltration or fibrosis, increased
macrophages
• skin, liver, upper GI
biopsy: characteristic appearances of
acute GVHD
• HLA typing of peripheral blood
lymphocytes: chimerism

Heavy metal
(arsenic)
poisoning
• peripheral blood film: basophilic
stippling
• bone marrow aspirate: hypocellular
without infiltrate or fibrosis, decreased
hematopoietic cells, dyserythropoiesis
• bone marrow trephine
biopsy: hypocellular without
infiltration or fibrosis dyserythropoiesis
• diepoxybutane test: normal
• screening for PNH clone: negative
• arsenic level (serum, urine, hair,
nails):elevated

Parvovirus
infection in
sickle cell
anemia
• CBC: drop in hemoglobin
concentration of >30 percent secondary
to complete arrest of erythropoiesis
• reticulocyte count: decrease or
absence of measurable reticulocytes
• bone marrow biopsy: remarkable for
severe aplasia

Dyskeratosis
congenita
• peripheral blood film: red cells
usually macrocytic
• reticulocyte count: low or absent
• bone marrow aspirate: hypocellular,
reduced hematopoietic cells,
dyserythropoiesis common
• bone marrow trephine
biopsy: hypocellular without
infiltration or fibrosis
• diepoxybutane test: normal
(peripheral blood lymphocytes)
• screening for PNH clone: may be
present
• peripheral blood and/or bone
marrow
immunophenotyping: normal
• blood and/or bone marrow
cytogenetics:clonal abnormalities
present in some patients
• genetic studies: may
identify 1 of several
genetic mutations
• telomere
length: abnormally
short; length in
lymphocytes and
granulocytes <1
percentile for age
Paroxysmal
nocturnal
hemoglobinuri
a
• peripheral blood film: polychromasia
• reticulocyte count: relative
reticulocytosis
• bone marrow aspirate: hypocellular,
reduced hematopoietic cells, mast cells
may be increased
• diepoxybutane
test: normal
• screening for PNH
clone: positive
Idiopathic
aplastic
anemia
• peripheral blood film: normocytic or
mildly macrocytic RBCs, no immature
precursors present
• serum reticulocyte count: low or
absent
• bone marrow aspirate: hypocellular,
mild dyserythropoiesis common
• bone marrow trephine
biopsy: hypocellular without fibrosis
or infiltrate
• diepoxybutane test (peripheral blood
lymphocytes): normal
• screening for paroxysmal nocturnal
hemoglobinuria clone (peripheral
blood, bone marrow): detectable in up
to 30% of patients
• peripheral blood, bone marrow
immunophenotyping: normal
• peripheral blood, bone marrow
cytogenetics: abnormal clones present
in a minority of patients

Fanconi
anemia
• peripheral blood film: RBCs usually
macrocytic
• reticulocyte count: low or absent
• bone marrow aspirate: hypocellular
dyserythropoiesis
• diepoxybutane test (peripheral blood
lymphocytes): increased chromosomal
breakage

Idiopathic
portal
hypertension
• peripheral blood film: no specific
features
• reticulocyte count: elevated or normal
• serum LFTs: normal or mildly
elevated
• bone marrow
aspirate: hypercellular
, erythroid hyperplasia
• bone marrow
trephine
biopsy:hypercellular,
erythroid hyperplasia
Chronic
myeloid
leukemia
• peripheral blood film: myeloid
maturing cells, elevated basophils,
eosinophils
• cytogenetics: Philadelphia
chromosome positive
• bone marrow biopsy: granulocytic
hyperplasia

Brucellosis • peripheral blood film: no specific
features
• bone marrow aspirate: trilineage
hypercellularity, hematophagocytosis
• blood and bone marrow
cultures: positive for organism

Leishmaniasis • peripheral blood film: rouleaux;
organisms rarely seen in peripheral
blood film
• bone marrow aspirate: trilineage
hypercellularity; organisms may be
seen within macrophages (Leishman-
Donovan bodies)
• bone marrow trephine
biopsy: trilineage hypercellularity,
hematophagocytosis, small
granulomata

• immunochromatographic or PCR-
based tests on peripheral blood or
bone marrow aspirate: positive for
organism
Hemophagocy
tosis
syndromes
• peripheral blood film: no specific
features
• bone marrow aspirate: trilineage
hypercellularity, hematophagocytosis
• blood and bone marrow
cultures: positive for organism
autoimmune
screen: positive ANA and
anti-ds DNA
serum ferritin: >10,000
mcg/L
molecular genetic
testing: specific karyotype
present
Drug-induced
immune
pancytopenia
• platelet-specific antibodies: positive
• peripheral blood film: no specific
features
• reticulocyte count: elevated
• bone marrow aspirate: hypercellular
• bone marrow trephine
biopsy: hypercellular

Evans
syndrome
with
associated
neutropenia
• peripheral blood film: polychromasia,
spherocytes
• reticulocyte count: elevated
• direct antiglobulin test: positive
• platelet, neutrophil-specific

antibodies:positive
• bone marrow aspirate: normal or
trilineage hypercellularity
• bone marrow trephine
biopsy: normal or trilineage
hypercellularity
Systemic
lupus
erythematosus
• peripheral blood film: rouleaux
• autoimmune screen: positive ANA
and anti-DNA
• ultrasound of the
abdomen: splenomegaly
• bone marrow aspirate: hypocellular,
Adysplastic changes,
hematophagocytosis
• bone marrow trephine
biopsy: hypocellular, benign lymphoid
aggregates

Rheumatoid
arthritis
• peripheral blood film: rouleaux
• autoimmune screen: positive
rheumatoid factor
• bone marrow aspirate: hypocellular,
dysplastic changes,
hematophagocytosis
• bone marrow trephine
biopsy: hypocellular, benign lymphoid
aggregates
• ultrasound of the
abdomen: splenomegaly

Infectious
mononucleosi
s
• serum monospot: positive
• peripheral blood film: atypical
lymphocytes
• Epstein-Barr nuclear
antibody: present
• blood serology (specific IgM and IgG
titers) for viral capsid
antigen: positive

Felty
syndrome
• bone marrow biopsy: myeloid
hyperplasia with excess of immature
forms
• autoimmune screen: positive
rheumatoid factor
• ultrasound of the
abdomen: splenomegal

















BAB III
Kesimpulan
Pansitopenia bukanlah suatu gejala melainkan suatu triad yang di sebabkan suatu proses penyakit
yang melibatkan sumsum tulang baik primer maupun sekunder. Pansitopenia adalah masalah
sering di temui dalam praktek sehari-hari. Untuk menegakan diagnosis pati perlu di lakukan
pemeriksaan yang lebih spesifik.


























Tinjauan Pustaka
1. Evaluation of pancytopenia Diagnostic approach-Eppocrates online
hhtps://online.epocrates.com/u/29211024/evaluation+of+pancytopenia.
2. Makalah lengkap Bandung hematologi oncology meeting 2013, page 7-15