APLASTIC ANEMIA

Dr dr H IRZA WAHID SpPD KHOM FINASIM

SUBDIVISION OF HEMATOLOGY & MEDICAL ONCOLOGY
DEPARTEMENT OF INTERNAL MEDICINE
FACULTY OF MEDICINE ANDALAS UNIVERSITY
09-02-2015

Hematologi Dan Onkologi Medik

Hematologi : Ilmu + Darah
Hemopoesis :
Sum-sum tulang --------------------------------> Darah tepi
* Eritropoesis eritrosit Anemia / Polisitemia
* Megakariopoesis trombosit Trombositosis / Trombositopenia
* Granulopoesis leukosit Leukopenia / Leukositosis
* Monositopoesis monosit Monositopenia / Monositosis
* Limfopoesis limfosit Limfositopenia / Limfositosis

Extramedular --------------------------------------- > Hati / Limpa

Onkologi Medik : Ilmu + Tumor + Non Surgery

ANEMIA
PARAMETER : Kadar hemoglobin Metode Sahli
Pria dewasa : Wanita dewasa : Hamil : Hb < 13 : < 12 : < 11 gr %
GEJALA & TANDA
Hb
hipoksia
kompensasi kardiovaskular
* Pucat
* angina pektoris
* kardiomegali
Mukosa
* claudicatio intermiten
* palpitasi
Kulit
* tinitus
* dispneu
* berkunang
* bising sistolik
* cepat lelah
* gagal jantung
DIAGNOSIS
Gradasi
anemia ringan : sedang : berat : > 8 : 6 8 : < 6 gr %
Morfologi
mikro / normo / makrositer -- hipo/normo/hiperkrom
Patofisiologi defisiensi aplastik hemolitik perdarahan
Etiologi
Cacing, low intake, ggn imun, trauma, chronic disease

Anemic Ranges of Hemoglobin and Hematocrit Values

WHO. Worldwide Prevalence of Anaemia 1993-2005.5
*These are only guidelines and some physicians feel the thresholds should be higher for adults.
Age/Sex (yrs)

Hemoglobin (g/dL)

Hematocrit (%)

Children (0.5-4)

< 11.0

< 33

Children (5-12)

< 11.5

< 35

Children (12-15)

< 12.0

< 36

Adult Men

< 13.0

< 39

Non-pregnant
Women

< 12.0

< 36

Pregnant Women

< 11.0

< 33

Definition

Peripheral Pancytopenia
Anemia
Leucopenia
Thrombocytopenia

Reticulocyto-penia

Aplastic bone marrow

Hypocellular with all
elements down; mostly fat
and stroma
Residual hematopoietic
cells are normal
No malignancy or fibrosis
No megaloblastic
hematopoiesis

Severity of Disease
Severe Aplastic Anemia (SAA)
Marrow of less than 25% normal cellularity
2 of 3 abnormal peripheral blood values
Absolute reticulocyte count < 40,000
ANC<500
Platelets <20,000

Very Severe Aplastic Anemia (VSAA)

Above with ANC <200

History of Aplastic anaemia

Paul Ehrlich (1854-1915) described
the first case of aplastic anaemia in a
pregnant woman who died of marrow
failure in1888.
The term aplastic anaemia first
used by Anatole Chauffard in 1904.

Aplastic Anemia epidemiology

annual incidence in Europe and US - 2 cases per
million population, but 4 cases in Bangkok 6 in
Thailand and 14 in Japan.
no racial predisposition exists in the United
States; however, prevalence is increased in the
Far East.
The male-to-female ratio is approximately 1:1.
Aplastic anemia occurs in all age groups.
a small peak in incidence in childhood.
a peak incidence in people aged 20-25 years, and a
peak in people older than 60 years.

Aplastic Anemia - Etiology

Congenital/inherited (20%)
Patients usually have dysmorphic features or
physical stigmata. Occasionally, marrow failure may
be the initial presenting feature.

Fanconi anemia
Dyskeratosis congenita
Shwachman-Diamond syndrome
Familial aplastic anemia

Acquired

Aplastic Anemia: (Cont.)

Acquired:
* Drugs
- Cytotoxic drugs
- Antibiotics
- Chloramphenicol
- Anti-inflammatory
- Anti-convulsant
- Sulphonamides
- 2-3 months usually between exposure and the development of aplastic anemia.

* Radiations
* Chemicals e.g., Benzene and pesticides
* Viruses:

Hepatitis B, C
Herpes simplex
E-B virus
HIV

* Immune: SLE, RA (rheumatoid arthritis)

* Pregnancy
* PNH
* Idiopathic ( Primer ): 75%

Pathogenesis
Immune mechanism responsible for
most of the cases of Idiopathic
acquired aplastic anemia
Activated Cytotoxic T cells in Blood
& Bone marrow Bone marrow
failure

Clinical Features
Anemia
Bleeding: Ecchymoses ,Bleeding
gums, Epistaxis
Infections: Fever,Mouth ulcers

Diagnosis
Blood peripheral smear :
Pancytopenia and reticulocytopenia
Bone marrow aspiration & biopsy :
Hypocellular / aplastic bone marrow
with increased fat spaces
Tests for underlying cause ( viral titers)

BM Aspiration

BM
Biopsy

BM biopsy
hypocellular ,increased fat spaces

 Other causes of Pancytopenia:

Sign of congenital disease
Drugs,
Viral
Megaloblastic anemia
Bone Marrow infiltration or Replacement:
SLE, RA
Disseminated TB
PNH
Sepsis
If (-)
idiophatic or primary acquired aplastic
anemia

Aplastic Anemia - Treatment

Withdrawal of etiological agents.

Management of underlying disesase
Supportive.
Restoration of marrow activity:
Bone marrow transplant
Immunosuppressive treatment
- Prednisolone - Antilymphocyte globulin.
- Cyclosporin
- Splenectomy

Androgens
Growth factors

APLASTIC ANEMIA treatment

Supportive care
Transfusion
Treatment of anemia
Treatment of bleeding
Prevention and treatment of
infection

Hematopoietic stem cell

transplatation in severe aplastic
anemia
1. Advantages
- correction of hematopoietic defect
- long-term survival: 80% - 90% (HLA-matched sibling
donor)
- majority of the patients appear to be cured

2. Restrictions
- age below 40
- suitable donor available in less than 30% (sibling)
- 25-40% risk of GVHD
- 5-15% risk of graft failure in multitransfused patients
- high mortality after MUD-HSCT
- solid tumors (12%)

Immunosuppression
Immunosuppression is NOT curative
Goal is sustained remission
20-36% have recurrent aplastic anemia
20-36% develop clonal disorder, PNH, MDS or acute
leukemia

Combination therapy is best

Antithymocyte globulin (ATG) first choice
Toxic side effect is serum sickness, tx with steroid
Can lower platelet counts, transfuse prn

Cyclosporine first choice

High dose corticosteroids tappering off
Alemtuzumab
Azathioprine
Mycophenolate mofetil