aplastic anemia.pptx

Aplastic anemia

1. Aplastic Anemia Download more documents and slide shows on The Medical Post [ www.themedicalpost.net ] Dr. Kalpana Malla MD Pediatrics Manipal Teaching Hospital

2. DEFINTION ETIOLOGY PATHOLOGY CLASSIFICATON CLINICAL FEATURES DIAGNOSIS DIFFERENTIAL DIAGNOSIS 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 chlo r amphe n i c ol antiepileptics Viruses: CMV EBV Hep B, C,D HIV Immune diseases: eosinophilic fascitis thymoma Pregnancy PNH Marrow replacement: leukemia myelofibrosis myelodysplasia

8. P a thology: Absent or defective stem cells (marrow failure) Abnormal marrow microenvironment Inhibition by abnormal clone of hematopoietic cells 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. P a th o logy: 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 BM : dry aspirate, hypocellular with fat (>70% yellow marrow)

15. Liver function tests Viral studies Hepatitis CMV HIV RA factor ANA, anti-dsDNA Chromosomal breakage analysis- Fanconi anemia

16. DIFFERENTIAL DIAGNOSIS ITP LEUKEMIA MYELOID METAPLASIA

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

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

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

20. Management: Identification and elimination of underlying cause Supportive therapy: Blood transfusion Iron chelation to treat iron overload Antibiotics Growth factors

21. 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.

22. 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

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

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

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

26. 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

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

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

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

30. 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

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

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

33. Thank you Download more documents and slide shows on The Medical Post [ www.themedicalpost.net ]