REFERAT Pendekatan Klinis Pansitopenia

8/11/2019 REFERAT Pendekatan Klinis Pansitopenia

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Pendekatan DiagnostikPansitopenia

Dian Riani 2009730132

Pembimbing : Dr. Tuti Sri Hastuti Sp.PDM-Kes


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Definisi

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


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Etiologi

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


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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 autoimmuneKimiawi (benzene, arsenik)

Infiltrasi keganasan

Hematologi: limfoma, leukimia, myeloma

Tumor solid

Paroxysmal nocturnal haemoglobinuria

Spplenomegali

Radiasi


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Pendekatan diagnosis

Ringan Hemoglobin 2000/mm3, trombosit

>20.000/mm3

Sedang Hemoglobin


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namnesis

Anemia aplastik

Sindrom gagal sumsum tulangturunan

Riwayat keguguran Riwayat menderita keganasan

Gangguan metabolik

Riwayat penyakit hati

Riwayat penggunaan obatsitotoksik dan radio terapi


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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)


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Respiratori :

Clubbing (ca. paru)

Takipnea

Kardiovaskular:

Takikardi, edema,

CHF

Bekas pembedahanjantung (sindrom

kongenital).

Abdomen :

Nyeri perut kakan atas (hepatitis )

Limfadenopati (infeksi,penyakit limfoproliferatif,HIV)

Tanda penyakit hatikronis

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 ( fanconianemia, kelainancongenital lain)

Artritis, sinovitis (SLE) Jari-jari abnormal

(anemia fanconi)

Sign assosiated with 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


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Biopsi sumsum tulangSelularitas:

: gangguan produksi darah: pasca kemoterapi, sepsis/infeksiakut, 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 denganplasma selnya, infiltrasi keganasan, HIV stadium dini/akut,

anemia megaloblastik.

Histologi : Infiltrasi sel

Blast

Gambaran myelodispplasia


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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 1st Tests Other Tests

Chemotherapy peripheral blood: anisocytosis, poikilocytosis,

basophilic stippling

bone marrow aspirate: variable hypoplasiabone marrow biopsy: hypoplasia, megaloblastosis

Radiotherapy peripheral blood: anisocytosis, poikilocytosis,

basophilic stippling

bone marrow aspirate: variable hypoplasiabone marrow biopsy: hypoplasia, megaloblastosis

Vitamin B12 deficiency peripheral blood film: oval macrocytic RBCs, irregular

size and shape of RBCs (anisocytosis and

poikilocytosis), hypersegmented granulocytes (>5lobes)

serum reticulocyte count: usually lowserum B12: low in B12 deficiencybone marrow aspirate: hypercellular, megaloblastic

erythroblasts, giant metamyelocytes

serum LDH: moderately raisedserum bilirubin: moderately raised, mostly indirect


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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 lowserum RBC folate: low in folate deficiency

bone marrow aspirate: hypercellular,megaloblastic erythroblasts, giant metamyelocytesserum LDH: moderately raisedserum 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 PTTserum 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 cancerthyroid ultrasound: irregular mass or

nodule

breast imaging: mass or calcifications

Non-Hodgkin lymphoma peripheral blood film: variable; may showcirculating 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


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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


or bone marrow): clonal population oflymphoid 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 raisedbone 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 normalserum LFTs: elevated

bone marrow

aspirate: hypercellular, erythroid

hyperplasia


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Hepatitis B peripheral blood film: macrocytes, target cells,

stomatocytes, acanthocytes

reticulocyte count: elevated or normalserum LFTs: elevatedserum HBsAg: positive

bone marrow

aspirate: hypercellular,

erythroid hyperplasia

Hepatitis C peripheral blood film: macrocytes, target cells,stomatocytes, acanthocytes

reticulocyte count: elevated or normalserum LFTs: elevatedserum antihepatitis C virus (HCV): presence of

HCV antibodies

bone marrowaspirate: hypercellular,


Autoimmune hepatitis peripheral blood film: macrocytes, target cells,

stomatocytes, acanthocytes

reticulocyte count: elevated or normalserum LFTs: elevatedautoantibody screen: positive

bone marrow

aspirate: hypercellular,


HIV peripheral blood film: atypical lymphocytes(acute seroconversion), rouleaux, dysplastic

neutrophils

reticulocyte count: reducedHIV serology: positivebone marrow aspirate: hypercellular (acute

seroconversion), hypocellular,dyserythropoiesis

proteinelectrophoresis: polyclo

nal

hypergammaglobulinem

ia


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Cytomegalovirus infection peripheral blood film: atypical lymphocytes, spherocytes if coexisting

hemolysis

CMV-specific IgM and IgG: positivebone marrow aspirate: cellularity usually increased, hemophagocytosis

may be prominent

bone marrow trephine biopsy: cellularity usually increased

Mycobacterial infection peripheral blood film: rouleauxreticulocyte count: reducedbone marrow aspirate: reduced cellularity, hemophagocytosisbone marrow trephine biopsy: reduced cellularity, granulomas, fibrosisbone marrow culture: positive for organism

Uncommon


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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 hypocellularbone 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)


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


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Myelofibrosis peripheral blood film: leuko-erythroblastic, tear drop RBCsbone 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: pancytopeniareticulocyte count: may be high, normal, or reducedbone marrow aspirate: may reveal Gaucher cells

bleeding time: prolonged

Anorexia nervosa peripheral blood film: red cell acanthocytes, poikilocytosis

and basophilic stippling

reticulocyte count: lowbone 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 featuresreticulocyte count: low

bone marrow aspirate: hypocellular, reduced hematopoieticcells, increased macrophages, erythrophagocytosis


infiltration 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 stipplingbone marrow aspirate: hypocellular without infiltrate

or fibrosis, decreased hematopoietic cells,

dyserythropoiesis


infiltration or fibrosis dyserythropoiesis

diepoxybutane test: normalscreening for PNH clone: negativearsenic 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 reticulocytesbone marrow biopsy: remarkable for severe aplasia

Dyskeratosis

congenita

peripheral blood film: red cells usually macrocyticreticulocyte count: low or absentbone marrow aspirate: hypocellular, reduced

hematopoietic cells, dyserythropoiesis common


infiltration or fibrosisdiepoxybutane test: normal (peripheral blood

lymphocytes)

screening for PNH clone: may be presentperipheral blood and/or bone marrow

immunophenotyping: normal

blood and/or bone marrow cytogenetics:clonalabnormalities 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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Paroxysmal nocturnal

hemoglobinuria

peripheral blood film: polychromasiareticulocyte count: relative reticulocytosisbone marrow aspirate: hypocellular, reduced hematopoietic

cells, mast cells may be increased

diepoxybutane test: normalscreening 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% ofpatients

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 macrocyticreticulocyte count: low or absentbone marrow aspirate: hypocellular dyserythropoiesisdiepoxybutane test (peripheral blood

lymphocytes): increased chromosomal breakage

Idiopathic portal

hypertension

peripheral blood film: no specific featuresreticulocyte count: elevated or normalserum LFTs: normal or mildly elevated

bone marrow

aspirate: hypercellular, erythroid

hyperplasia

bone marrow trephine

biopsy:hypercellular, erythroidhyperplasia

Chronic myeloid peripheral blood film: myeloid maturing cells


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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: trilineagehypercellularity, hematophagocytosis

blood and bone marrow cultures: positive for

organism

Leishmaniasis peripheral blood film: rouleaux; organisms

rarely seen in peripheral blood film

bone marrow aspirate: trilineagehypercellularity; 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 marrowaspirate: positive for organism

Hemophagocytosis

syndromes

peripheral blood film: no specific featuresbone 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/Lmolecular genetic testing: specific

karyotype present


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Drug-induced immune

pancytopenia

platelet-specific antibodies: positiveperipheral blood film: no specific featuresreticulocyte count: elevatedbone marrow aspirate: hypercellularbone marrow trephine biopsy: hypercellular

Evans syndrome with

associated neutropenia

peripheral blood film: polychromasia, spherocytes

reticulocyte count: elevateddirect antiglobulin test: positiveplatelet, neutrophil-specific antibodies:positivebone marrow aspirate: normal or trilineage hypercellularitybone marrow trephine biopsy: normal or trilineage hypercellularity

Systemic lupus

erythematosus

peripheral blood film: rouleauxautoimmune screen: positive ANA and anti-DNAultrasound of the abdomen:

splenomegaly

bone marrow aspirate: hypocellular, Adysplastic changes, hematophagocytosisbone marrow trephine biopsy: hypocellular, benign lymphoid aggregates

Rheumatoid arthritis peripheral blood film: rouleauxautoimmune screen: positive rheumatoid factorbone marrow aspirate: hypocellular, dysplastic changes, hematophagocytosisbone marrow trephine biopsy: hypocellular, benign lymphoid aggregates

ultrasound of the abdomen: splenomegaly

Infectious mononucleosis serum monospot: positiveperipheral blood film: atypical lymphocytesEpstein-Barr nuclear antibody: presentblood 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 factorultrasound of the abdomen: splenomegal


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Simpulan

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.


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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 lenkap Bandung hematologi

oncology meeting 2013, page 7-15

Documents

REFERAT Pendekatan Klinis Pansitopenia