Aplastic Anemia for Pediatrics students

1. Aplastic Anemia
By
Dr. Imran Mahmood
Associate Professor
Department of Pediatrics
Fazaia Medical College, Islamabad

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.

4. Epidemiology
• Annual incidence in Europe and US – 2-6 cases per million
population
• Higher in Asia- Japan 14 cases per million population
• The male-to-female ratio is approximately 1:1
• Aplastic anemia occurs in all age groups.

5. Pathophysiology

6. Haematopoiesis

10. 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.
• Lymphadenopathy or hepatosplenomegaly should suggest an
alternative diagnosis

11. Investigations
 Blood CP
 Anemia--- Normocytic
 Reticulocyte count--- less than 1%
 WBC---Low
 ANC---- Less than 1500/mm3
 Platelets---Low
 Bone marrow aspiration and Biopsy

12. Bone Marrow Aspiration and Biopsy
 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 are seen
 The presence of more than 70 % lymphocytes has poor prognosis.

13. BM Aspiration BM Biopsy

14. Normal Bone marrow

15. BM biopsy
hypocellular ,increased fat spaces

16. Management
 Hematopoietic stem cell transplantation (HSCT)
 Only approximately 20% of patients have an HLA-matched family member
donor.
 The risks associated include graft failure and graft-versus-host disease.
 Late adverse effects include secondary cancers, cataracts, short stature,
hypothyroidism and gonadal dysfunction.
 For patients without a sibling donor, the major form of therapy is
immunosuppression with horse Antithymocyte globulin (ATG) and
cyclosporine, with a response rate of 70–80%. The median time to response is
6 month.

17.  For patients who show no response to immunosuppression or who experience
relapse after immunosuppression, matched-unrelated HSCT and T-cell–
depleted haploidentical family member–donor HSCT are treatment options,
with a response rate approaching 90%.
 Androgens, corticosteroids, and Plasmapheresis have inconsistent results.
 Ongoing studies using eltrombopag (an oral thrombopoietin mimetic agent)
or alemtuzumab have shown promise in patients with refractory disease.

18. Complications
 Life-threatening bleeding from prolonged thrombocytopenia
 Infection (bacterial and invasive mycoses) secondary to protracted
neutropenia.
 Alloantibodies to RBC antigens.
 Require iron chelation therapy for transfusional iron overload.

19. Prognosis
 Spontaneous recovery from pancytopenia rarely occurs.
 If left untreated, severe pancytopenia has an overall mortality rate of
approximately 50% within 6 month of diagnosis and of >75% overall, with
infection and hemorrhage being the major causes of morbidity and mortality.

20. Fanconi Anemia
 Fanconi anemia (FA) is a rare multisystem hereditary disorder resulting in the
development of bone marrow failure.
 They have congenital malformations.
 Incidence: 1 in 200,000, higher in Ashkenazi Jews (1 :30,000)
 Inheritance: Mostly Autosomal recessive, One uncommon form is X-linked
recessive.
 In 1927, Guido Fanconi first reported 3 brothers with macrocytosis,
pancytopenia, and physical abnormalities.

21. Pathology
 Faulty DNA repair and increased chromosomal fragility caused by DNA
interstrand cross-linking agents such as diepoxybutane and mitomycin C

22. Clinical Manifestations

24. Complications
 High risk of developing cancer.
 Squamous cell carcinomas of the head and neck and carcinoma of the upper
esophagus, vulva, anus, cervix.
 Benign and malignant liver tumors can occur (adenomas, hepatomas) and
are usually associated with androgen therapy for aplastic anemia.

25. Investigations
 Blood CP
 Anemia--- Normocytic
 Reticulocyte count--- less than 1%
 WBC---Low
 ANC---- Less than 1500/mm3
 Platelets---Low
 Bone marrow aspiration and
Biopsy
 Chromosomal breakage study
done
 Ultrasound abdomen and
echocardiography for congenital
anomalies.
 Growth hormone levels
 Thyroid hormone levels

26. Chromosomal Breakage Study

27. Management
 If hematologic abnormalities are mild to moderate and stable and there is no
transfusion requirement, patients can be observed closely with peripheral
blood counts every 3 months.
 Annual screening for carcinomas by physical examination.
 Hematopoietic stem cell transplantation (HSCT).
 Survival rates are higher for patients who undergo transplant at <10 year of
age and before receiving multiple transfusions.
 Androgens (oral oxymetholone and danazol) (bridge therapy) produce a
response in approximately 70% of patients, heralded by reticulocytosis and a
rise in hemoglobin within 1-2 months . White blood cell counts may increase
next, followed by platelet counts.

28.  Side effects of androgens include masculinization, increaseds linear growth,
increased mood swings or aggressiveness, elevated hepatic enzymes,
cholestasis, and liver tumors. Screening for these should be performed
regularly.
 Granulocyte colony-stimulating factor (G-CSF) can usually induce an
increase in the absolute neutrophil count; however, there may be a
heightened risk of expansion of bone marrow cells with clonal cytogenetic
abnormalities such as monosomy 7.

29. Prognosis
 FA surviving into their 30s.
 Unfortunately, there is an increased risk of solid tumors after HSCT. For
example, head and neck cancer risk is increased 4.4-fold and is accelerated
by approximately 15 year compared to nontransplanted patients.

30. References
 Nelson Textbook of Pediatrics, 20th Edition.
 Basis of Pediatrics by Dr. Pervez Akbar, 10th Edition.

32. Questions and comments?