RiadiWirawan

Departemen Patologi Klinik FKUI-RSCM

Decreased bone marrow production

.:. Aplasia

* Myelodysplastic syndrome (MDS)

* Myeloma

* Megaloblasticanaemia.i Paroxysmal nocturnal haemoglobinuria.1. Myelofibrosis.t Acute leukaemia

I ncreased peripheral destruction

Cause of pancytopenla

Pancytopenia

.i. Reduction in the blood count: RBC, WBC & platelets

.i. lt has several causes, which divided into :

! decrease BM production

.1. Splen

) increased peripheral destruction.

APLASTIC ANEMIA

APLASTIC ANEMIA

Pathogenesis

.i. Reduction in the number of hemopoieticpluri potential stem cell

.i. lmmune reaction against pluripotent stem cell )mixed them unable to divide and differentiatesufficiently to populate the bone marrow

.i. Primary fault in the marrow microenvironment

Fanconi type

.i. Autosomal recessive pattern of inheritance

..'. Associated with :

F congenital defects of

/ skeleton (microcephaly, absent radii or thumbs)

/ renal tract (pelvic or horseshoe kidney)

APLASTIC ANEMIA CONGENITAL

Congenital (Fanconi and

non-Fanconi types)

ldiopathic acquired

Causes of aplastic anaemia

/ skin (area hyper- and hypo pigmentation)

F growth retardation

lonizing radiation : accidental exposure (radiotherapy'

radioactive isotypes, nuclear power stations)

Chemicals : benzene, organophosphates and other

organic solvents, DDT and other pesticides,

organochlorines, recreational drugs (ecstasy)

Drugs

Those that regularly cause marrow depression (e g

busulfan, cyclophosphamide, anthracyclines,

nitrosoureas)

Those that occasionally or rarely cause : marrow

depression (e g chloramphenicol, sulphonamides'

gold, anti-inflammatory, antithyroid, psychotrophic,

anticonvutsant / antidepressant drugs)

Mruses : viral hepatitis (non-A, non-B, non-C, non-G in

EBV Epstein-Barr virus

most cases), EBV

(a) (b)

(a) X-rays showing absent thumbs in a patient with Fanconi's anaemia(FA) (b) lntravenous pyelogram in a patient with FA showing a normal

right kidney but a left kidney abnormally placed in the pelvis.

2

CLINICAL FEATURES APLASTIC ANEMIA

Onset at any age with a peak incidence around 30yearsi

Slight male predominant

lnsidious or acute symptom and signs resulting from :

) anemia

) neutropenia : infection in the mouth

& throat

) thrombocytopenia : bruising, bleeding gums,

epistaxes, menorrhagia

nt

{. leen are enla

Anemia normochromic normocytic or macrocytic (MCV> 92 fL)

Reticulocyte count extremely low

Leucopenia, selective fall in granulocyte

Thrombocytopenia in severe cases < 20.000/uL

No abnormal cells in the peripheral blood

Bone marrow show hypoplasia, with loss ofhaemopoietic tissue and replacement by fat

Severe cases aplastic anemia :

Severe Very severe

Neutrophil <500/uL <200/uL

Platelet <20.000/uL <20.000/uL

Reticulocyte <20.000/uL <20.000/uL

.:.

*

Aplastic anaemia : low power views of bone marrow show severereduction of haemopoietic cell with an increase in fat spaces. (a)Aspirated fragment. (b) Trephine biopsy.

t

MYELODYSPLASTIC SYNDROME

MYELODYSPLASTTC SYNDROME (MDS)

.1. A group of clonal disorders of multipotent

haemopojetlqtem rells which are characterized by

ing bone marrow fa

bocytopenia) and

orphology abnormalities)

quantitative

*t,

lncidence 4/100.000, slight male predominant

Over half of patient > 70 years

The evolution is often slow and the disease may be

found by chance when a patient has a blood countfor some unrelated reason

The symptom :

z in€fill0

/ neutropenia : recurring infection

- thrombocytopenia : bruising & bleeding

CLINICAL FEATURES MDS

PATHOoENESIS OF ITYELODY5PLASIA.

Secondory geneticor epigenelicobnormolities

Hoffbmnd lV. calGky D, Tuddenhq ECD. P6t9mdur" hoemldory. 56 cd. oxfort I Bl@ktcll

tlAyelodysplosticsyndrome

.1. Peripheral blood

) Macrocytic or dimorphic RBC, occasionallyhypochromic

D Reticulocytopenia

D Neutropenia (reduced number of neutrophil)

/ morphology neutrophil abnormal :

hypogranulation, Pelger-Huet anomaly

/ myeloblast are present in the blood

LABORATORY FINDINGS MDS

4

Myelodysplasia: appearances ofthe peripheral blood and bone marrow.(a) Multinucleate polychromatic erythroblasts. (b) Ring sideroblasts. (c)White cells showing pseudo-Pelger cells, agranular myelocytes andneutrophils.

(a)

(b) (c)

The World Health Organization (WHO) classification of myelodysplasia

Refraclory anaemia with ringedsideroblasts (RARS)

MULTIPLE MYELOMA

Refractory cytopenia wilhmultilineage dysplasia (RCMD)

Refractory anaemia with excessblasrs-1 (RAEB-1 )

Refractory anaemia with exessblasrs-2 (RAEB-2)

Bi-or pancytopenia or more

l\4DS associated wilh isolateddel (sq)

Patients with dysplasticfeatures and over 20016 blast cells in the bone marrow are considered tohave acute myeloid leukaemia with multilineage dysplasia (p 366)

Bi-or pancytopenia or morecell lineages and

Cytopenias or 5-'19% blastsor Auer rods

Erythroid dysplasia only and >

Dysplasia in > 10% of cell in z 2

Dysplasia in > 10% of cells in z 2myeloid lineages > 1 5% ringedsideroblasts

Uni or multilineage dysplasia5-9% blasts

Uni- or multilineage dysplasia10-19% blasts or Auer rods

Myeloid or megakaryocyticdysplasia < 5% blasts

t Neoplastic proliferation characterized by plasma

cell accumulation in bone marrow , the presence ofmonoclonal protein in the serum andror urine and

related tissue damage

Occur over the age of 40 years with a peak

incidence in the 7th decade

MYELOMA

*

5

DIAGNOSIS MYELOMA

oco0on

Alb ot q2 0 y Origiil+ Distance from origln

Patient with multiple myeloma ! ttorrullgGK mon(lonal protein 18 gr'd pattern

Serum protein electrophoresis in myeloma.

3. Related organ or tissue impairment such as

D C : hypercalcemia

D R:renal impairment

) A: anemia

F B : bone abnormality (osteoporosis, osteolytic

and fractures)

Plasma cell myeloma, cytologic features in marow aspirations showing variation frommature (A, B) to immature (C) plasma cells. The more mature cells have clumped nuclealchromatin, abundant cytoplasm, low nuclear-cytoplasmic ratio and only rare nucleolicompared to the less mature cells, which have more prominent nucleoli, loose reticular

McK€nn. ru, Xyl. M, Ku.hl M, Grqan lM, H.ili. NL, CoupEd RW Pl..ma

and a higher nuclear-cytoplasmic ratio

PAROXYSMAL NOCTURALHEMOGLOBTNURTA (PNH)

6

MembraneHereditary spherocytosis, heredrtary elliptocytosis

MetabolismG$PD deficiency, pyruvate kinase deficiency

HaemoglobinGenetic abnormalities (HbS, HbC, unstable)

Classification of haemolytic anaem

Cold antibody type

AlloimmuneHaemolytic transfusion reactionsHaemolytic disease of the newbornAllografts, especially marrow transplantation

Drug associated

Red cell fragmentation syndromes

March haemoglobinuria

lnfectionslvlalaria, clostridia

Chemical and physical agentsEspecrally drugs, indust, ial/domestrcsubstances, burn

SecondaryLiver and renal drsease

G-6PD, glucose€-phosphatedehydrogenase Hb haemoglobin

PNH

ls a rare, acquired, clonaldisorder of marrow stemcells cause by dificientsynthesis of theglycosytphosphatidyli nositol(GPl) anchorsGPI anchor a structure thatattaches several surfaceprotein to the membrane(CD59 dan CD5s)It results from mutation inthe X chromosome gene

MEGALOBLASTIC ANEMIA

Gly(an

frotein.e q C059. CD55

I

I

Glyen.ore

I

* ls a group of anemias in which the

erytroblast and the BM show a

- lnoitol

MEGALOBLASTIC ANEMIA

delayed relative to that of the

The causes is defective DNA

synthesis, usually caused by

deficiency vit B, or folate )anemia, leucopenia / neutropenia

& thrombocytopenia

I

7

Prorubricytes

Rubricyte

Metarubricyte

Difiusely basophilicerythroctrtes

Erythrocytes

sa. a

Laboratory tests for vitamin B,, & folate def

Serum vitamin B,,

Serum folate

Red cell folate

DIAGNOSTS OF VtT. B12 OR FOLATE DEF.

Periphera! blood

.3. Macrocytic anemia (MCV > 92 fL)

.!. Macroovalocyte RBC

{. Reticulocytopenia

* Leucopenia, hypersegmentation

1.. Neutropenia

Assay serum Brr, serum and red cellfolate

'l6G-925 ng/L

3.0-15.0 ug/L

160-640 ug/L

J

N/1N/J

N / borderline

J

J

HYPERSPLENISM

8

* Decreased life span of red cells, granulocyteS & platelets

that may be found in patients which splenomegaly due

to any cause

.i. The cytopenia with enlarged spleen are also partly

caused by increased pooling of blood cells within

HIPERSPLENISM

spleen & increased Plasma volume

.t Sequestration of blood cells in the spleen which

causes cvtopenias of peripheral blood

PATHOGENESIS HYPERSPLENISM

1. The spleen enlarge with increased pooling of bloodcells in the pulp of the sPleen

2. lncreased destruction of blood cells in the spleen

3. Total plasma volume increased in splenomegaly

CLASSIFICATION HYPERSPLENISM

Primary : ldioPhatic

Secondary : SymPtomatic

Portal hYPertension

Malignant lYmPhoma

LiPid storage diseases

Kala azar

Malaria

Thalassaemia mayor

Chronic lYmPhocYtic leukaemia

Myelofibrosis

.i. Hipersplenism criteria :

. Anaemia, leukopenia and thrombositopenia (2

out of 3 combinations)

. Normocellular / hipercellular marrow

. Splenomegaly

. Restoration after sPlenectomY

A Find the cause

DIAGNOSIS HYPERSPLENISM

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