Agranulocytosis

Agranulocytosis

1. AGRANULOCYTOSIS SUNIL KUMAR.P Dept.of TMAIH St.John’s Medical college Hospital Bangalore 1 SUNIL KUMAR.P

2. Introduction Definition Epidemiology Classification Etiology Pathogenesis Clinical Manifestation Diagnosis 2 SUNIL KUMAR.P

3. AGRANULOCYTOSIS Also known as: NEUTROPENIA, AGRANULOSIS, GRANULOPENIA, GRANULOCYTOPENIA 3 SUNIL KUMAR.P

4. AGRANULOCYTOSIS The term "agranulocytosis" (Shultz syndrome) is used when neutropenia occurs as a reaction (most probably immunologic) to drugs. 4 SUNIL KUMAR.P

5. DEFINITION Neutropenia/ agranulocytosis is the term when neutrophil count is <2.5 x 10 9 /L and children and < 1.5 x 10 9 /L. Mild -when the count is 1000-1800/mm 3 Moderate - when the count is 500- 1000/mm 3 Severe -When the ANC is below 500 /mm 3 5 SUNIL KUMAR.P

6. EPIDEMIOLOGY Frequency : The exact frequency of agranulocytosis is unknown. The estimated frequency of agranulocytosis is 1.0 -3.4 cases per million population per year. Race : Agranulocytosis has no racial predilection 6 SUNIL KUMAR.P

7. Sex: Agranulocytosis occurs slightly more frequent in women than in men, possibly because of their increased rate of medication usage. Whether this higher frequency is related to the increased incidence of autoimmune disease in women is unknown. 7 SUNIL KUMAR.P

8. Age : Agranulocytosis occurs in all age groups. The congenital forms are most common in childhood. Acquired agranulocytosis is most common in the elderly population 8 SUNIL KUMAR.P

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10. Causes of Neutropenia ( Agranulocytosis) 1. Drug Induced 2.Autoimmune diseases 3.Infections 4.Viral 5.Protozoal 6.Miscellaneous 10 SUNIL KUMAR.P

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13. PATHOGENESIS Pathogenesis of neutropenia can be divided into following categories 1. Inadequate or ineffective formation of granulocytes. 2.Accelerated destruction of neutrophils 3.Decreased production 4.Decreased survival 13 SUNIL KUMAR.P

14. 1. Inadequate or ineffective formation of granulocytes. This can be due to bonemarrow failure such that occurs in aplastic anaemia, several leukaemias and chemotherapeutic agents. There can also be isolated neutropenias where only differentiated granulocyte precursors are affected as in the case of neoplastic proliferation of cytotoxic T cells or NK Cells 14 SUNIL KUMAR.P

15. 2.Accelerated destruction of neutrophils Immune mediated reactions to neutrophils which can be caused by drugs. An enlarged spleen can lead to splenic sequestration and accelerated removal of neutrophils. Utilization of neutrophils can occur in infection. 15 SUNIL KUMAR.P

16. Decreased Production Congenital Dyskeratosis congenita Kostmanns ’ syndrome Schawchmann Diamond syndrome 16 SUNIL KUMAR.P

17. Decreased Production Acquired Drug-induced Chemicals, e.g. benzene Infections Acquired aplastic anaemia Myelodysplastic syndrome Acute leukaemia Hairy cell leukaemia Malignant infiltration of bone marrow, e.g. lymphoma, carcinomatosis 17 SUNIL KUMAR.P

18. Decreased survival Autoimmune neutropenia Felty’s syndrome Systemic lupus erythematous Drugs 18 SUNIL KUMAR.P

19. CLINICAL FEATURES OF NEUTROPENIA The manifestations of neutropenia depend upon the degree of neutropenia and of compensatory monocytosis. The manifestations are generally due to severe bacterial infections. 19 SUNIL KUMAR.P

20. Asymptomatic High Grade Fever Rigors Sore Throat Oral ulcers Abscesses Poor wound healing 20 SUNIL KUMAR.P

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23. Laboratory Diagnosis 1. peripheral blood examination 2.Bone marrow examination 23 SUNIL KUMAR.P

24. Peripheral Blood Complete blood examination is required to rule out various causes of pancytopenia Hb : Normal TLC: Decreased DLC: Neutropenia with neutrophils being 0-20% . ANC: < 0.5 X 10 9 /L 24 SUNIL KUMAR.P

25. Bone marrow Examination BM is essential to rule other causes of neutropenia like……. sub leukemic/ aleukemic leukemia Megaloblastic anemia Aplastic anemia 25 SUNIL KUMAR.P

26. Cellularity : Normal Erythropoiesis: Normoblastic Myelopoiesis: Myelopoiesis in No. of cases manifests maturation arrest at promyelocytes / myelocyte stage. In some cases there is depletion of the cells of myeloid series. Megakaryopoiesis : Normal 26 SUNIL KUMAR.P

27. THANK YOU 27 SUNIL KUMAR.P