pendekatan klinis pansitopenia

8/11/2019 Pendekatan Klinis Pansitopenia

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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.


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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 diseaseFrom the collection of Jeff K. Davies


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Derajat pansitopenia

Ringan Hemoglobin 2000/mm , trombosit >20.000/mm

Sedang Hemoglobin


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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


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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, caf 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


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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).


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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,

megaloblastosisVitamin 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,


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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


megaloblastic erythroblasts, giant

metamyelocytes

serum LDH:moderately raised

serum bilirubin:moderately

raised, mostly indirect

Bone marrowinfiltration 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 revealabdominal or renal mass

serum prostatic-specific

antigen:elevated in prostate

cancer


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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 nodebiopsy: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


erythroid hyperplasia


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Autoimmune

hepatitis

peripheral blood




normal

serum LFTs:elevated

autoantibody screen:positive

bone marrow



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


normal

serum LFTs:elevated

serum HBsAg:positive

bone marrow

aspirate:hypercellular,erythroid hyperplasia

Hairy cell

leukemia

peripheral blood

film:circulating lymphoma cells







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lymphoid cells

Chronic

lymphocytic

leukemia

peripheral blood

film:circulating leukemia cells

cells






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




bone marrow




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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 maybe prominent

bone marrow trephine

biopsy:cellularity usually

increased

Mycobacterial

infection

peripheral blood film:rouleaux

reticulocyte count:reduced

bone marrow aspirate:reduced

cellularity, hemophagocytosis


biopsy:reduced cellularity,

granulomas, fibrosis

bone marrow culture:positive

for organism

Uncommon


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Differential 1sttest 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

lymphocyticleukemia

peripheral blood film:blasts may or

may not be present bone marrow aspirate:hypercellular

with blasts; occasionally hypocellular

(childhood ALL)


peripheral blood or bonemarrow):detection of

clonal population of blasts

cytogenetics:identificatio

n of nonrandom

chromosomal

abnormalities


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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

elevatedLysosomal

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


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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


biopsy:hypocellular without

infiltration or fibrosis

diepoxybutane test:normal

Graft-versus-

host disease

peripheral blood film:no specific

features

reticulocyte count:low


reduced hematopoietic cells, increased

macrophages, erythrophagocytosis


biopsy:hypocellular withoutinfiltration or fibrosis, increased

macrophages

skin, liver, upper GI

biopsy:characteristic appearances of

acute GVHD

HLA typing of peripheral blood

lymphocytes:chimerism


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Heavy metal

(arsenic)

poisoning

peripheral blood film:basophilic

stippling

bone marrow aspirate:hypocellular

without infiltrate or fibrosis, decreased

hematopoietic cells, dyserythropoiesis



infiltration or fibrosis dyserythropoiesis


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


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Dyskeratosis

congenita

peripheral blood film:red cells

usually macrocytic

reticulocyte count:low or absent


reduced hematopoietic cells,

dyserythropoiesis common



infiltration or fibrosis


(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


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Idiopathic

aplastic

anemia

peripheral blood film:normocytic or

mildly macrocytic RBCs, no immature

precursors present

serum reticulocyte count:low or

absent


mild dyserythropoiesis common


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 marrowcytogenetics: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


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Idiopathic

portal

hypertension


features

reticulocyte count:elevated or normal

serum LFTs:normal or mildly

elevated

bone marrow

aspirate:hypercellular

, erythroid hyperplasia

bone marrow

trephine

biopsy:hypercellular,


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 marrowcultures:positive for organism

Leishmaniasis peripheral blood film:rouleaux;

organisms rarely seen in peripheral

blood film


hypercellularity; organisms may be

seen within macrophages (Leishman-

Donovan bodies)


biopsy:trilineage hypercellularity,

hematophagocytosis, small

granulomata


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immunochromatographic or PCR-

based tests on peripheral blood or

bone marrow aspirate:positive for

organism

Hemophagocy

tosis

syndromes


features


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


features

reticulocyte count:elevated

bone marrow aspirate:hypercellular


biopsy:hypercellular

Evanssyndrome

with

associated

neutropenia

peripheral blood film:polychromasia,spherocytes

reticulocyte count:elevated

direct antiglobulin test:positive

platelet, neutrophil-specific


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antibodies:positive

bone marrow aspirate:normal or

trilineage hypercellularity


biopsy:normal or trilineage

hypercellularity

Systemic

lupus

erythematosus


autoimmune screen:positive ANA

and anti-DNA

ultrasound of the

abdomen:splenomegaly


Adysplastic changes,

hematophagocytosis


biopsy:hypocellular, benign lymphoid

aggregates

Rheumatoid

arthritis


autoimmune screen:positiverheumatoid factor


dysplastic changes,

hematophagocytosis


biopsy:hypocellular, benign lymphoid

aggregates

ultrasound of the

abdomen:splenomegaly


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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


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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.


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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

pendekatan klinis pansitopenia

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