Pathology of Aplastic_Anemia for undergraduate students

Aplastic anemia

1. Aplastic Anemia Dr. Nirmalya Chakrabarti MD (Path) Malda Medical College, Malda

2. Competencies: After end of the class the students should be able to: PA17.1.1: Enumerate the causes of aplastic anemia PA17.1.2: Enumerate the pathogenesis of aplastic anemia PA17.1.3: Enumerate the bone marrow findings in aplastic anemia PA17.2.1: List the types of bone marrow study PA17.2.2: List the indications and contraindications for bone marrow study PA17.2.3: Describe the bone marrow findings with specific examples of involvement

3. Definition: Aplastic anemia is a disorder of hematopoiesis in which there are pancytopenia in peripheral blood and decreased cellularity of bone marrow along with there should be N O abnormal infiltrate (leukemic, cancerous, or other) or increase in reticulin in bone marrow .

4. Epidemiology: More common in East Asia and other developing countries Uncommon in Western countries Two peaks of presentations of acquired aplastic anemia : ( i ) between 15 and 25 years of age (ii) > 60 years of age

5. Causes of Aplastic Anemia : Acquired: 2/3 rd cases Constitutional: 1/3 rd cases Idiopathic 1. Fanconi Anemia 2. Drugs ( dose dependent action : Cytotoxic drugs; idiosyncratic reaction : Sulfonamide , Chromalphenicol , Phenylbutazone , Diclofenac , Indomethacin, Gold, Penicillamine , Phenytoin, Carbamazepine, Ticlopidine ) 2. Dyskeratosis Congenita 3. Chemicals: Benzene, Organophosphates, Organochlorines 3. Schwachman -Diamond syndrome 4. Viral infections: viral hepatitis, CMV, EBV 4. Diamond- Blackfan syndrome 5. PNH 5. Congenital amegakaryocytic thrombocytopenia 6. GVHD 7. Pregnancy

6. Pathogenesis: Inhibition of hematopoiesis by immunological mechanisms: Major mechanism haematopoietic stem cells are first antigenically altered by exposure to the causative agents Activation and proliferation of cytotoxic T cells Liberation of TNF- α and Interferon- γ TNF - α mediated upregulation of Fas receptors leading to apoptosis of stem cells

7. Pathogenesis Contd … 2. Reduction in number of stem cells in bone marrow 3. Defective stem cells: The causative agent affects the capacity of self-renewal, proliferation , and differentiation of stem cells. Shortened telomeres were o bserved. Mutations in telomerase related genes (TERT and TERC). 4. Defective hematopoietic microenvironment 5. Deficiency of factors stimulating hematopoiesis

8. Clinical features: Signs and symptoms of pancytopenia: Bleeding – due to thrombocytopenia ; petechiae , ecchymoses , nasal or G.I bleeding. Infections – due to neutropenia Weakness, easy fatigability, pallor, dyspnoea – due to anemia THERE SHOULD BE NO LYMPHADENOPATHY OR HEPATOSPLENOMEGALY

9. Laboratory features: Peripheral blood examination : pancytopenia Hemoglobin < 10g / dL Absolute Neutrophil Count < 1500 / cu mm Platelet count < 50,000 / cu mm RBC – normocytic normochromic Reticulocyte count – low Granulocytes and monocytes – reduced Predominant WBC in PBS - lymphocytes

10. Laboratory features contd … Bone marrow aspiration cytology: Cellularity – markedly decreased. Most of the particles show fat cells Erythropoiesis – decreased Granulopoiesis – decreased Megakaryocytes - often absent Lymphocytes and Plasma cells – increased Bone Marrow Trephine Biopsy: Hypocellularity Predominance of fat cells Sparse hematopoietic elements No abnormal cellular infiltrate No increase in reticulin

11. Differential diagnosis: D/D of Aplastic Anemia includes disorders causing pancytopenia.

12. Thank you