Usman Ghani, a 7-year-old boy, presented with pallor, easy fatigability, and bruising. Investigations revealed very low blood counts and a bone marrow biopsy showed hypoplastic/aplastic bone marrow. He was diagnosed with aplastic anemia. Aplastic anemia is a condition where the bone marrow fails to produce sufficient new blood cells, leading to pancytopenia. Treatment involves blood transfusions, antibiotics, growth factors, immunosuppressive drugs, and stem cell transplantation depending on the severity of the condition.

1. APLASTIC ANEMIA
DR ASIF AHMAD
POST GRADUATE RESIDENT
PEDIATRIC ‘B’ WARD
MTI-LRH

2. Case
Usman ghani of age 7 years presented to
our ward with pallor, easy fatigability and
multiple bruises on whole body. Patient
have history of multiple blood transfusions in
past.
On examination patient was pale looking
having pale conjunctivae,increased heart
rate and multiple bruises mainly on
abdomen and lower extremities.

3. Investigations
Special smear
Hb 2.9 gm/dl TLC 2410 /uL
RBC 0.81 millions /uL Neut 17.8 %
HCT 8.3 % Lymph 76.8 %
MCV 102 fL Mono 5.0 %
MCH 35.8 pg Esino 0.4 %
MCHC 34.9 g/dL Platelets
4000/uL

4. Trephine Biopsy
Gross appearance
Single linear grey white trephine piece of tissue
measuring 1 cm in length.
Microscopic Appearance
Sections of trephine biopsy reveal hypocellular
marrow overall cellularity 15% of the normal.
Megakaryocytes are not seen. Erythropoiesis and
myelopoiesis are depressed.Lymphocytes and plasma
cell are normal.

5. Bone Marrow Report
Cellularity Hypocellular fragments and trails
Erythropoiesis Depressed
Granulopoiesis Depressed
Lymphopoiesis Present
Megakaryocytes Markedly Reduced
Plasma cells Present
Abnormal cells Blast cells nill, Histiocytes seen
Iron Increased
Opinion Bone Marrow Hypoplasia / Aplasia

8. Contents
• Definition
• Pathophysiology
• Types
• Clinical Features
• Investigations
• Classification
• Differential Diagnosis
• Management

9. Definition
Pancytopenia with hypocellularity
(Aplasia) of Bone Marrow
Aplastic anemia can present initially
with a single cell line failure before the
onset of pancytopenia.

10. Pathophysiology

11. • Most cases have no clue but some are
less clear, a few cases clearly associated with
a non-A, non-B, non-C, non-G hepatitis.
• Severe pancytopenia 1-2 months after an
apparent viral hepatitis patients tend to
have a marked activation of cytotoxic
lymphocytes and tend to respond favorably
to immunosuppressive therapy

12. T cells of AA patients overproduce both IFN-
gamma and TNF-alpha both of these cytokines
inhibit colony formation in vitro. IFN-gamma
induces nitric oxide synthase (NOS) and
production of nitric oxide (NO) both induce
expression of Fas receptor on CD34+ cells and
activation of this receptor by its ligand induces
apoptosis and both appear to inhibit mitosis.
IFN-gamma increases IFN regulatory factor
1 which inhibits transcription of cellular genes and
entry into the cell cycle.

13. Types
2 Types of Aplastic Anemia
Aplastic anemia may be acquired or hereditary:
1. Acquired aplastic anemia
Acquired aplastic anemia can begin
anytime in life. About 3 out of 4 cases of acquired
aplastic anemia are idiopathic. This means they have
no known cause.

14. About 1 in 4 cases of acquired aplastic anemia
can be linked to one of several causes.
These include:
• Toxins, such as pesticides, arsenic, and benzene.
•Radiation and chemotherapy used to treat cancer.
•Treatments for other autoimmune diseases, such
as lupus and rheumatoid arthritis.
• Pregnancy. Sometimes, this aplastic anemia
improves on its own after the woman gives birth.

15. 2. Hereditary aplastic anemia
Hereditary aplastic anemia is passed down
through the genes from parent to child. It is usually
diagnosed in childhood and is less common than acquired
aplastic anemia.
Related Health Problems
People who develop hereditary aplastic anemia
usually have other genetic or developmental
abnormalities. Some of these include Fanconi’s anemia,
Shwachman-Diamond syndrome, and dyskeratosis
congenita

16. Clinical Features
If patient have a low red blood cell count
•Feel a little tired or very tired.
•Feel less alert or have trouble concentrating.
•Have a loss of appetite or lose weight.
•Have paler-than-normal skin.
•Have trouble breathing.
•Have a rapid heartbeat.
•Have reduced ability to exercise or climb stairs

17. If patient have a low white blood cell count
•Have repeated fevers and infections.
•Get bladder infections that may make it painful to pass
urine, or make you urinate more often.
•Get lung infections that cause coughing and difficulty
breathing.
•Get mouth sores.
•Get sinus infections and a stuffy nose.
•Get skin infections.

18. If patient have a low platelet count,
• Bruise or bleed more easily – even from minor scrapes
and bumps.
•Get heavy menstrual periods.
•Get nose bleeds.
•Get tiny, flat red spots under your skin, which are caused
by bleeding. These spots are called petechiae.
•Have bleeding gums, especially after dental work
or from brushing teeth. Check with doctor before
getting any dental work.

19. Investigations
• Blood Peripheral Smear with retic count
• Liver Functions Tests
• Vit-B12 and Folate level
• Hep A,B,C, CMV, EBV, HIV, ParvoB19
• ANA and ds-DNA
• Hgb F
• Blood lymphocyte diepoxybutane test (DEB test) for
chromosome breakage
• Flow cytometery for PNH
• Bone marrow aspirate and Biopsy
• Iron and Erythropietin level

21. Classification
Aplastic anemia Divided into 3 groups:
•Moderate
•Severe
•Very severe
Moderate aplastic anemia:
Low blood cells counts, but not
as low as with severe aplastic anemia. patient may
have few or no symptoms and may not recommend
treatment. Instead may need just keep an eye on blood
counts. condition may stay the same for many years.

22. Severe Aplastic anemia:
The growing cells in bone marrow (cellularity) occupy less than 25
percent of bone marrow. Normal bone marrow has a cellularity of
around 100 Minus age in years.
At least 2 of the following are true:
• Neutrophil count is less than 500 cells per
microliter (<500/mm3).
• Platelet count is less than 20,000 per
microliter (<20,000/mm3).
• Reticulocyte count is less than 20,000 per microliter (<20,000/mm3)

23. Very severe aplastic anemia:
• Neutrophil count is less than 200 per
microliter (<200/mm3).
•Blood counts are otherwise like those of
someone with severe aplastic anemia.
These categories were defined in 1975 by Dr. Bruce
Camitta and his team.

24. S.NO classification Criteria
1. severe Bone marrow Cellularity < 25 %
AND ≥ 2 of the following:
1. Peripheral blood neutrophil count <
500/mm3
2. Peripheral blood platelet count
< 20,000/mm3
3. Peripheral blood reticulocyte count
< 20000 /mm3
2. Very severe As above, but peripheral blood
neutrophil count
must be < 200 /mm3
3. Nonsevere Hypocellullar BM with peripheral blood
values not meeting criteria for severe
aplastic anemia

25. Differential Diagnosis
Pancytopenia with hypocellular bone
marrow
•Acquired aplastic anemia
•Inherited aplastic anemia
•Hypoplastic MDS
•Hypoplastic AML

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

27. Hypocellular bone marrow with or without
cytopenia
•Q fever
•Legionaires disease
•Mycobacteria
•Tuberculosis
•Hypothyroidism
•Anorexia nervosa

29. Management
The main goal of aplastic anemia treatment is to increase
the number of healthy cells in blood.
Supportive Care
Supportive care manage the symptoms of aplastic anemia.
This approach includes the use of:
•Blood transfusion
•Iron chelation to treat iron overload
•Growth factors
•Antibiotics

30. Blood Transfusion
The 2 types of transfusion typically used for aplastic
anemia patients are:
•Red blood cell transfusion
•Platelet transfusion
White blood cells live for a very short time.
So patients with a low white count rarely get
transfusions of white blood cells.

31. Iron Chelation Therapy for Iron Overload
Blood iron level checked regularly if patient get red blood cell
transfusions.
The transfusions can cause you to have too much iron in blood. This
can lead to a condition called iron overload, which can hurt heart and
other organs.
Iron overload can start to become a problem after as few as 20
units of red blood cells. A blood iron level, or ferritin of over 1,000 is
considered high enough to consider treatment
Three iron chelators are used to treat iron overload.
Deferasirox
Deferoxamine
Diferiprone

32. Growth Factors
Growth factors are proteins made by body. They
cause bone marrow to make blood cells. Most people
with aplastic anemia have higher natural levels of
growth factors than healthy people do because their
bodies are trying to stimulate the failing bone marrow
to make more blood cells.
Antibiotics
If low neutrophil level, Antibiotics are advised to
prevent and fight infection.

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

34. Haematopoietic stem cell transplantation
(HSCT)
HSCT continues to be the recommended first-
line therapy for individuals with severe or very severe
aplastic anemia who have a matched sibling donor.
The upper limit of age for this recommendation has
been 40 years, although there is increasing variation in
this regard, especially with use of less-aggressive
conditioning regimens. Results of matched sibling
HSCT have improved over time.

35. Immunosuppressive Drugs
The most common immunosuppressive drugs
used to treat aplastic anemia are:
•ATG (antithymocyte globulin) or
ALG (antilymphocyte globulin)
•Cyclosporine

36. Benefits of Immunosuppressive Drug Therapy
This therapy is usually the first treatment used
with older patients and with all patients who don’t have
a matched related bone marrow donor. It has several
benefits:
•It usually causes at least partial bone marrow
recovery.
•It usually causes few side effects.
•It usually requires only brief hospital stays.

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