aplastic anemia pediatrics It compromises a group of disorders of the hematopoietic stem cells resulting in the suppression of one or more of erythroid, myeloid and megakaryotic cell lines. thrombocytopenia

1. Dipak Yadav
MBBS 7th Batch
Roll 139

2. Aplastic Anemia
• It compromises a group of disorders of the hematopoietic stem cells
resulting in the suppression of one or more of erythroid, myeloid and
megakaryotic cell lines.
• It may be inherited or acquired.

3. History
• 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.

4. 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.

5. Haematopoiesis

6. Etiopathogenesis
Hematopoietic stem cell may be deficient due to :
1. Acquired injury from viruses, toxins, chemicals
2. Abnormal marrow microenvironment
3. Immunological suppression( mediated by Ab or cytotoxic T cells)
4. Mutation in genes controlling hematopoiesis

9. Clinical features
• Anemia: pallor and/or signs of congestive heart failure, such as
shortness of breath.
• Thrombocytopenia: bruising (eg, ecchymoses, petechiae) on the skin,
gum bleeding, or nosebleeds.
• Neutropenia :fever, cellulitis, pneumonia, or sepsis
• jaundice and evidence of clinical hepatitis in subset of patients

10. • adenopathy or organomegaly should suggest an alternative diagnosis.
• In any case of aplastic anemia, look for physical stigmata of inherited
marrow failure syndromes such as:
• skin pigmentation
• short stature
• microcephaly
• hypogonadism
• mental retardation
• skeletal anomalies

11. Investigations
• CBC
• PBS
• Reticulocyte count
• B12/folate.
• Liver function tests
• Virology
• Bone marrow aspirate & biopsy

12. • Anemia is common, and red cells appear morphologically normal. The
reticulocyte count usually is less than 1%.
• Thrombocytopenia, with a paucity of platelets in the blood smear.
• Agranulocytosis (ie. decrease in all granular white blood cells, including
neutrophils, eosinophils, and basophils) and a decrease in monocytes are
observed. A relative lymphocytosis occurs.
• The degree of cytopenia is useful in assessing the severity of aplastic
anemia.

13. Bone marrow exam
• A bone marrow biopsy is performed in addition to the aspiration. In aplastic
anemia, these specimens are hypocellular.
• Only fat cells, fibrous stroma, scattered lymphocytes and plasma cells presents
• Bone marrow revels little materials (“Dry Tap”)
• Hence biopsy is appreciated.

14. BM Aspiration BM Biopsy

15. Normal Bone marrow

16. BM biopsy
hypocellular ,increased fat spaces

17. Other investigations
• Hemoglobin electrophoresis - may show elevated fetal hemoglobin.
• Biochemical profile, including evaluation of transaminases,
bilirubin, lactic dehydrogenase, Coombs test, and kidney function,
is useful in evaluating etiology and differential diagnosis.
• Serologic testing for hepatitis EBV, CMV, and HIV
• Autoimmune disease evaluation for evidence of collagen-vascular
disease
• The Ham test or sucrose hemolysis test frequently is performed for
excluding PNH.
• Histocompatibility testing should be conducted early to establish
potential related donors, especially in younger patients.

19. Diagnosis
• Pancytopenia
• Bone marrow histology and cytology
• - decreased marrow cellularity (< 25%)
• - increased fat cells component
• - no extensive fibrosis
• - no malignancy or storage disease

20. • No preceding treatment with X-ray or antiproliferative
drugs
• No lymphadenopathy or hepatosplenomegaly
• No deficiencies or metabolic diseases
• No evidence of extramedullary hematopoiesis

21. Differential Diagnosis
• FANCONI ANEMIA
• DYSKERATOSIS CONGENITA
• Acute Myelogenous Leukemia
• Anemia
• Aplastic Anemia
• Hairy Cell Leukemia
• Paroxysmal Nocturnal Hemoglobinuria
• Immune pancytopenias in connective tissue disorders (eg, systemic
lupus erythematosus, refractory anemia)

22. Fanconi anemia
• hyperpigmentation of the trunk, neck, and intertriginous areas, as
well as café-au-lait spots and vitiligo, alone or in combination.
• Most patients have short stature. Growth failure may be associated
with abnormal growth hormone secretion, or with hypothyroidism.
Absent radii and hypoplastic, supernumerary, bifid, or absent
thumbs are common. Anomalies of the feet, congenital hip
dislocation, and leg abnormalities are seen.
• Males may have an underdeveloped penis; undescended, atrophic,
or absent testes; and hypospadias or phimosis

23. • . Females can have malformations of the vagina, uterus, and
ovary.
• Many patients have a Fanconi “facies,” including
microcephaly, small eyes, epicanthal folds, and abnormal
shape, size, or positioning of the ears
• Approximately 10% of patients are mentally retarded.
• Ectopic, pelvic, or horseshoe kidneys are detected by imaging,
as well as duplicated, hypoplastic, dysplastic, or absent organs.

24. café-au-lait spots
(coffee in milk)
Thumb attached by a thread
Short stature
Epicanthal fold
Broad nasal bridge
Microcephaly

26. DYSKERATOSIS CONGENITA
an inherited disorder of the
mucocutaneous and hematopoietic
systems in association with somatic
abnormalities.
• The diagnostic ectodermal triad is
reticulate skin pigmentation of the
upper body, mucosal leukoplakia,
and nail dystrophy
• Skin and nail findings usually
become apparent in the 1st 10 yr of
life, whereas oral leukoplakia is
seen later.

27. • These manifestations tend to progress as patients get older.
• DC is a constitutional pancytopenia; aplastic anemia occurs in
approximately 50% of cases, usually in the 2nd decade of life
Patients also have a predisposition to cancer.
Approximately 85% of patients are male, compatible with X-linked
recessive inheritance.
Approximately 15% of patients appear to have either autosomal
dominant or autosomal recessive modes of inheritance

28. Treatment- AA
• Supportive care
Severe Anemia- packed red cells
Sever Thrombocytopenia- Platelets transfusion
Infection- Antibiotics
Definitive therapy
Hematopoietic stem cell transplant (HSCT)

29. Criteria for HSCT
1. Young age
2. Severe aplastic anemia
3. Availability of matched siblings
SAA who cannot go for HSCT
• Infusion of antithymocyte globulin(ATG)
• Or, antilymphocyte Globulin(ALG) with
Oral cyclosporine

30. • Pt. with neutropenia with infections
• A trial of granulocyte colony stimulating factor (G-CSF)
• It should not be continued for >7 days even if neutrophil
count does not increase
• As prolonged use increase the risk of malignant
transformation

31. Harvesting
HSCT

32. Harvesting

33. Prognosis
• SAA is at risk of cardiac failure,infections,severe bleeding
• The major prognostic determinant is the blood
count; severe disease is defined by the presence of two of
three parameters: absolute neutrophil count <500/µL,
platelet count <20,000/µL, and corrected reticulocyte
count <1% (or absolute reticulocyte count <60,000/µL).
• with current transplantation regime the survival rate is 60-70%

34. • Survival of patients who fulfill these criteria is ∼20% at
1 year after diagnosis with only supportive care
• patients with very severe disease, defined by an absolute
neutrophil count <200/µL, fare even more poorly
• Treatment
has markedly improved survival in this disease.

35. References
• Nelson Textbook Of Pediatrics 19th edition
• Ghai Essential Pediatrics 8th edition
• Harrison's Principles of Internal Medicine, 18edition
• Robbins Basic Pathology, 9th Edition