This document defines aplastic anemia and discusses its etiology, pathology, clinical features, diagnosis, differential diagnosis, and management. Aplastic anemia is a failure of two or more blood cell lines caused by hypoplasia or aplasia of the bone marrow. It can be hereditary or acquired through radiation, drugs, viruses, or immune diseases. Clinically, it presents with pancytopenia and increased risk for infections and bleeding. Treatment involves blood transfusions, antibiotics, growth factors, immunosuppressive drugs, and stem cell transplantation.

1. Aplastic Anemia
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Dr. Kalpana Malla
MD Pediatrics
Manipal Teaching Hospital

2. 1. DEFINTION
2. ETIOLOGY
3. PATHOLOGY
4. CLASSIFICATON
5. CLINICAL FEATURES
6. DIAGNOSIS
7. DIFFERENTIAL DIAGNOSIS
8. MANAGEMENT

3. PANCYTOPENIA:
• Simultaneous presence of
anaemia, leukopenia, thrombocytopenia
• Causes: aplastic anemia
Subleukemic leukemia
cytotoxic drugs
radiotherapy
bone marrow infiltration
hypersplenism
megaloblastosis
SLE

4. APLASTIC ANEMIA:
• Failure of two or more cell lines
+ Hypoplasia or aplasia of the
marrow

5. ETIOLOGY
• Hereditary
• Acquired

6. HEREDITARY
• Diamond-Blackfan syndrome
• Shwachmann-Diamond syndrome
• Fanconi anemia
• Dyskeratosis Congenita
• TAR (thrombocytopenia with absent radii)
• Amegakaryocytic thrombocytopenia

7. ACQUIRED
• Radiation
• Drugs and chemicals
- chemotherapy
- benzene
- chloramphenicol
- antiepileptics
• Viruses:
- CMV
- EBV
- Hep B, C,D
- HIV
• Immune diseases:
- eosinophilic fascitis
- thymoma
• Pregnancy
• PNH
• Marrow replacement:
- leukemia
- myelofibrosis
- myelodysplasia

8. Pathology:
1. Absent or defective stem cells (marrow
failure)
2. Abnormal marrow microenvironment
3. Inhibition by abnormal clone of
hematopoietic cells
4. Immune mediated suppression of
hematopoietic cells –
Cytotoxic T cells in blood and marrow release
gamma IFN and TNF -> inhibit early and late
progenitor cells

9. Pathology:
• Hallmark: peripheral pancytopenia with
hypoplastic/ aplastic bone marrow

10. Camitta criteria - classification

11. CLINICAL FEATURES
RBC (anemia)
• Progressive and persistent pallor
• Anemia related symptoms
WBC (Leucopenia/neutropenia)
• Prone to infections -
Pyodermas, OM, pneumonia, UTI, GI
infections, sepsis
Platelets (Thrombocytopenia)
• Petechiae, purpura, ecchymoses
• Hematemesis, hematuria, epistaxis, gingival bleed
• IC bleed- headache, irritability, drowsiness, coma

12. NO HEPATOMEGALY
NO SPLENOMEGALY
NO LYMPHADENOPATHY
Failure of entire RES. No extramedullary
hematopoesis

13. Blood picture:
• Anemia-normocytic, normochromic
• Leukopenia (neutropenia)
• Relative lymphocytosis
• Thrombocytopenia
• Absolute reticulocyte count low
• Mild to moderate anisopoikilocytosis

14. Other investigations
1. BM : dry aspirate, hypocellular with fat (>70%
yellow marrow)

15. 1. Liver function tests
2. Viral studies
• Hepatitis
• CMV
• HIV
3. RA factor
4. ANA, anti-dsDNA
5. Chromosomal breakage analysis- Fanconi
anemia

16. DIFFERENTIAL DIAGNOSIS
• ITP
• LEUKEMIA
• MYELOID METAPLASIA

17. Differential Diagnosis
Pancytopenia with hypocellular bone
marrow
1. Acquired aplastic anemia
2. Inherited aplastic anemia
3. Hypoplastic MDS
4. Hypoplastic AML

18. Pancytopenia with cellular bone
marrow
1. Primary bone marrow
diseases PNH
2. Bone marrow
lymphoma SLE,
Sjogren’s disease
3. Vitamin B12 and folate
deficiency Overwhelming
infection Brucellosis
1. MDS
2. Myelofibrosis
3. Hairy cell leukemia
4. Hypersplenism
5. Alcoholism
6. Sarcoidosis

19. Hypocellular bone marrow with or without
cytopenia
1. Q fever
2. Legionaires
disease
3. Mycobacteria
4. Tuberculosis
5. Hypothyroidism
6. Anorexia
nervosa

21. Management:
• Identification and elimination of underlying
cause
• Supportive therapy:
1. Blood transfusion
2. Iron chelation to treat iron overload
3. Antibiotics
4. Growth factors

22. Blood Transfusion
• The 2 types of transfusion typically used for
aplastic anemia patients are:
• Red blood cell transfusion
• Hb < 6
• Platelet transfusion
• <10,000 / bleeding
• Maintain > 30,000 prior to ATG infusion
• White blood cells live for a very short time. So
patients with a low white count rarely get
transfusions of white blood cells.

23. Iron Chelation Therapy for Iron Overload
• Blood iron level checked regularly if patient get red
blood cell transfusions.
• Iron overload can start to become a problem after as few
as 20 units of red blood cells.
• ferritin of over 1,000 - treatment
• Deferasirox
• Deferoxamine
• Diferiprone

24. Antibiotics
• Prophylactic antibiotics
• If infection: cephalosporins + aminoglycosides
• + metronidazole
• Antifungals: amphotericin B, fluconazole (if fever
>10 days despite antibiotics)

25. HAEMATOPOIETIC GROWTH FACTORS
• GM-CSF
• G-CSF
• IL-3
• IL-1
• IL-6

26. Definitive Therapy
Acquired aplastic anaemia can be treated with
either
•Hematopoietic stem cell transplantation (HSCT)
•Immunosuppressive therapy.

27. BONE MARROW TRANSPLANTATION
• Treatment of choice
• HLA matched donor. Usually siblings
• Long term survival rates: 60-70%
• Donor stem cells > 4 X 108 cells/kg

28. IMMUNOSUPPRESSION
• Antithymocyte globulin (ATG)
• Antilymphocyte glubulin (ALG)
• Cyclosporin
• Intensive immunosupression :
cyclophosphamide
• Corticosteroids

29. ATG administration:
• IV administration of Ig preparations containing
antibody to human thymocytes
• Improvement in haematological indices in one-half
of subjects
• Anaphylaxis

30. ATG AND ALG
• Dose : 40 mg/kg/day X 4 days
• Hematologic response rate 45%
• Survival rate 60%
• Side effects: serum sickness

31. ANDROGENS
• No longer have primary role
• Increase erythopoietin producion
• Stimulate erythroid stem cells
• Increase Hb levels in normal males
• methyl testosterone, testesterone enanthate,
oxymetholone, danazol
• Oral dose : 2-5mg/kg/day, IM dose: 1-2mg/kg/wk
• Side effects: cholestatic jaundice, masculinization

32. Corticosteroids:
• High dose steroids combined with anabolic
agents
• Uncertain benefits
• Side-effects

33. Treatment summary
These are the most common treatments for
aplastic anemia:
•Blood transfusions
•Growth factors
•Antibiotics
•Iron chelation
•Immunosuppressive drug therapy
•Stem cell transplantation

35. Thank you
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