aplastic anemia, causes, diagnosis, management

1. Bone Marrow Failure
(Aplastic Anemia)
Classification, Epidemiology, Etiology
Clinical Features, Diagnosis, Complications,
Management, Prognosis
Prof. Imran Iqbal
Fellowship in Pediatric Neurology (Australia)
Prof of Paediatrics (2003-2018)
Prof of Pediatrics Emeritus, CHICH
Prof of Pediatrics, CIMS
Multan, Pakistan

2. What is Bone Marrow Failure ?
• Bone Marrow Failure is characterized by inadequate
production of formed elements of blood
• Bone Marrow Failure may affect production of RBCs, WBCs,
Platelets separately or all three elements together
• Bone Marrow Failure results from failure to produce Blood
cells at different levels of maturation
• Bone Marrow Failure may or may not be associated with
hypoplasia of Bone Marrow

3. Bone Marrow Failure – Cytopenias
Types
• RBC production failure – Anemia
-- Anemia of Chronic Disease
-- Pure Red Cell Aplasia
-- Congenital Dys-erythropietic Anemia (CDA)
• WBC production – Agranulocytosis (adverse drug reactions)
• Platelet production – Thrombocytopenia (congenital)
• Pancytopenia – anemia, neutropenia, thrombocytopenia
-- Congenital Fanconi Anemia (chromosomal breaks)
-- Acquired Aplastic Anemia

4. Anemia of Chronic Disease
Etiology
• Anemia of Chronic Disease is associated with –
-- Chronic inflammation
-- Autoimmune disorders
-- CKD (chronic renal disease)
-- Malignancies
• Etiology – cytokines responsible for ongoing
inflammation impair erythropoiesis and decrease RBC
life span

5. Anemia of Chronic Disease
Clinical Presentation and Management
• Clinical Presentation –
-- Anemia
-- Symptoms and signs of underlying disease
• Lab Diagnosis –
-- moderate anemia
-- normocytic, normochromic OR microcytic, hypochromic
• Management –
-- Treatment of underlying disease
-- Erythropoietin injections
-- Blood (packed RBCs) transfusion

6. Aplastic Anemia

7. Aplastic Anemia – Definition
• Aplastic anemia is a syndrome of bone-marrow failure
characterized by peripheral pancytopenia and marrow
hypoplasia
• Decreased RBC production ----- Anemia
• Decreased Neutrophils ----- Frequent infections
• Decreased Platelets ----- Purpura and mucosal bleeds

8. Aplastic Anemia – Epidemiology
• Aplastic Anemia is a less common cause of anemia in
children
• Incidence – 1 - 5 children per million population per year
• Male : Female ratio = 1 : 1

9. Aplastic Anemia – Types
• Congenital – 20 %
-- Fanconi Anemia
• Acquired Aplastic Anemia – 80 %

10. Fanconi Anemia
• Fanconi Anemia is a genetic, autosomal recessive disorder
• Etiology – abnormal chromosomal fragility and chromosomal
breaks
• Clinical Presentation – Phenotypic abnormalities or
Dysmorphic Features are present
-- absent, hypoplastic or bifid thumb
-- short stature
-- delayed development
-- dark skin color
-- Bone Marrow Failure usually develops by 5-10 years age
-- Anemia and purpura on skin are presenting symptoms

11. Fanconi Anemia
• Lab Diagnosis –
-- Pancytopenia (anemia, neutropenia, thrombocytopenia)
-- Low Reticulocyte count
-- Hypo-plastic Bone Marrow on BM biopsy
-- Chromosomal breaks on chromosomal breakage study
• Management –
-- Supportive – RBC, Platelet transfusions
-- Androgens - Oxymethalone
-- Bone Marrow Transplant

12. Aplastic Anemia
Acquired

13. Aplastic Anemia – Etiology
• Idiopathic
• Immune mediated, auto-immune cytotoxicity
• T – lymphocyte Cytokines suppress hematopiesis
• Viral infections
• Hepatitis B, Hepatitis C, Parvovirus B19, EB virus
• Human immunodeficiency virus (HIV)
• Medications
• Chloramphenicol, sulphonamides (idiosyncratic reaction)
• Cytotoxic drugs, Insecticides, Chemicals

14. Aplastic Anemia
Clinical Features

15. Case scenario – History and Examination
• A 7 years old girl is brought in Emergency Room with –
-- fever off and on for the last 2 months,
-- body pains for the last one month
-- bruises on the body for the last 7 days
-- bleeding from gums for the last 3 days
• On examination
-- temperature 102 F
-- markedly pale
-- purpuric spots on face and legs
-- lymph nodes, liver and spleen are not palpable
• What initial investigations are needed ?

16. Case scenario - Investigations
• HB = 6.3 gm / dl
• MCV = 75
• MCH = 33
• MCHC = 35
• Reticulocytes = 0.1 %
• WBC = 2500 / ul
• Polys = 20 %, Lymphos = 70 %
• PLT = 30,000
• Bone Marrow = Hypocellular
 What is the most likely diagnosis ?

17. Aplastic Anemia – Clinical Features
• RBC deficiency
• Pallor and Anemia
• Restless behavior / irritability
• Fatigue
• Poor appetite
• Dyspnea
• Nausea

18. Aplastic Anemia – Clinical Features
• WBC deficiency
• Sepsis
• Pneumonia
• Fever frequently
• Platelets deficiency
• Purpura
• Epistaxis
• Gum bleeding
• Melena

19. Aplastic Anemia – Investigations
• Pancytopenia
• Hemoglobin low
• TRBC count low
• MCV, MCH, MCHC in normal range
• Blood film – Normocytic, Normochromic Anemia
• Reticulocyte count low - < 0.5 %
• Leukopenia – WBC count low - TLC < 4000
• Neutrophils count very low – ANC < 1500
• Platelets decreased – PLT count < 100,000
• Bone Marrow = Hypocellular marrow with excess fat

20. Aplastic Anemia
Diagnosis

21. Aplastic Anemia – Diagnosis
• Clinical Diagnosis
• Anemia, purpura, fever
• No Lymphadenopathy
• No hepatosplenomegaly
• Lab Diagnosis
• Pancytopenia
• Bone Marrow aspirate / biopsy
• Hypoplasia / Hypocellular marrow

22. Aplastic Anemia
Differential Diagnosis

23. Differential Diagnosis – Pancytopenia
Anemia, Leukopenia, Thrombocytopenia
• Aplastic Anemia – Normocytic Anemia, Leukopenia,
Thrombocytopenia
• Acute Leukemia – Purpura, Lymphadenopathy,
Hepatosplenomegaly
• Megaloblastic Anemia – Macrocytes, Megaloblasts
(Folic acid, B 12 deficiency)
• Hypersplenism – large spleen due to various causes
• SLE (systemic lupus erythematosus) – auto-immune disorder
• Myelodysplastic syndrome – Bone marrow dysplasia

24. Aplastic Anemia - Differential Diagnosis

25. Aplastic Anemia – Complications
• Low physical performance and debility
• Frequent Infections and Febrile episodes
• Bleeding and Hemorrhage
• Iron overload due to blood transfusions

26. Aplastic Anemia
Treatment

27. Aplastic Anemia – Supportive Treatment
• Anemia – Packed RBC transfusions
• Hemorrhage – Platelet transfusions
• Infections –
-- Antibiotics
-- Antivirals
-- G-CSF (Colony Stimulating Factor) - cytokine

28. Aplastic Anemia – Specific Treatment
• Immunosuppressive Treatment
Cyclosporin – Immunomodulator
Corticosteroids – Methylprednisolone
Specific Anti-bodies – ATG (anti-thymocyte globulin)
-- ALG (anti-lymphocyte globulin)
• BMT (Bone Marrow Transplant) – HLA matched sibling

29. BMT (Bone Marrow Transplant)

30. Aplastic Anemia
Prognosis

31. Aplastic Anemia – Prognosis
• Aplastic Anemia – Congenital
• Fanconi Anemia – shortened life span
Complications – AML, Squamous cell carcinoma
• Aplastic Anemia - Idiopathic
• Prognosis depends upon severity of disease
• Medical treatment – 50 % cure
• BMT – 80 % cure

32. In the name of Our Creator Allah,
the most Gracious, the most Merciful
(God speaking to Prophet Muhammad (PBUH)
And, indeed, You have a great moral character
Al Quran - surah Qalam 68:5