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Pendekatan Diagnostik

Pansitopenia
Dian Riani 2009730132
Pembimbing : Dr. Tuti Sri Hastuti Sp.PD
M-Kes
↓ jumlah 3 komponen darah:
Eritrosit, Leukosit dan Trombosit.
Anemia, leukopenia,
dan trombositopenia.
 ↓ produksi darah di
sumsum tulang
 Bone marrow faillure
syndrome
 Immune mediated
destruction
 Non immune mediated
sequestration in
peripher



Table of etiologies for pancytopenia. Abbreviation: GVHD, graft-versus-host disease
From the collection of Jeff K. Davies
Primer
Idiopatik
Kongenital
• Fanconi anemia
• Dyskeratosis congenital
• Diamond blacfan anemia
• Shwachman diamond syndrome
• Severe congenital neutropenia
• Kostman syndrome
• Amegakaryotic thrombocytopenia
Sekunder
Obat-obatan
 Sitotoksik
 Chloramphenicol
 Respon idiosinkrasi (immune mediated) :
• NSAIDS
• Colchicine
• Chlorampenicol
• Sulfonamid
• Phenothiazine
• Thiazid
• Anti thyroid
• Anti epileptik
• Anti diabetik
Infeksi virus
 Sering : hepatitis B dan C
 Jarang : cytomegalo virus, epstein Barr Virus,
HIV, Hepatitis A, rubella, influenza, measles,
mumps
Infeksi mycobacterium
Penyakit autoimmune
Kimiawi (benzene, arsenik)
Infiltrasi keganasan
 Hematologi: limfoma, leukimia, myeloma
 Tumor solid
 Paroxysmal nocturnal haemoglobinuria
 Spplenomegali
 Radiasi
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
Derajat pansitopenia
Anamnesis
Pemeriksaan fisik
Pemeriksaan Hitung darah lengkap
Analisis darah tepi
Aspirasi dan biopsi sumsung tulang
• 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
Oral :
• Ptekie/ Perdarahan di rongga mulut
(trombositopenia)
• Stomatitis/chelitis (neutropenia, def.
Vit B12)
• Hiperplasia gusi (leukimia )
• Kandidiasis oral/ eksudat faring
(neutropenia, infeksi herpes virus)
Mata :
• Perdarahan retina (trombositopenia)
• Infiltrasi lekemik (leukimia akut)
• Sklera ikhterik (Paroxysmal nocturna
hemoglobinuria, hepatitis, sirosis)
• Epiphora (dyskeratosis congenital)
Respiratori :
• Clubbing (ca. paru)
• Takipnea
Kardiovaskular:
• Takikardi, edema,
CHF
• Bekas pembedahan
jantung (sindrom
kongenital).
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)
Sign assosiated with 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 1st Tests Other Tests
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)
•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)
•CT of abdomen: may reveal
abdominal or renal mass
•serum prostatic-specific
antigen: elevated in prostate cancer
•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
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: lymphoproliferative
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 normal
•serum LFTs: elevated
•bone marrow
aspirate: hypercellular, erythroid
hyperplasia
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
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: polyclo
nal
hypergammaglobulinem
ia
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 1st Tests Other Tests
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: identification 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
hemoglobinuria
•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
Hemophagocytosis
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 mononucleosis •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
• Pansitopenia bukanlah suatu gejala melainkan
suatu triad yang di sebabkan suatu proses
penyakit yang melibatkan sumsum tulang baik
primer maupun sekunder
• Pansitopenia masalah sering di temui sehari-
hari
• Perlu pemeriksaan yang lebih spesifik untuk
mengetahui penyebabnya.
Tinjauan Pustaka
1. Evaluation of pancytopenia Diagnostic
approach-Eppocrates online
hhtps://online.epocrates.com/u/29211024/
evaluation+of+pancytopenia.
2. Makalah lenkap Bandung hematologi
oncology meeting 2013, page 7-15