This document discusses agranulocytosis, which is a severe neutropenia (low neutrophil count) that can have various causes. It defines agranulocytosis and classifies its severity. The document covers the epidemiology of agranulocytosis, including its estimated frequency in the population. It also discusses the potential causes of agranulocytosis including drugs, autoimmune diseases, infections, and other miscellaneous factors. The pathogenesis involves inadequate neutrophil formation, accelerated neutrophil destruction, decreased production, or decreased survival. Clinical manifestations depend on the degree of neutropenia and can include fever, infections, and poor wound healing. Diagnosis involves blood and bone marrow examinations to evaluate the

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

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

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

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

5. DEFINITION
• Neutropenia/ agranulocytosis is the term
when neutrophil count is <2.5 x 109/L and
children and < 1.5 x 109/L.
Mild -when the count is 1000-1800/mm3
Moderate- when the count is 500-
1000/mm3
 Severe -When the ANC isbelow 500/mm3
5SUNIL 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
6SUNIL 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.
7SUNIL 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
8SUNIL KUMAR.P

9. 9SUNIL KUMAR.P

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

11. 11SUNIL KUMAR.P

12. 12SUNIL KUMAR.P

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
13SUNIL 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
14SUNIL 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.
15SUNIL KUMAR.P

16. Decreased Production
• Congenital
• Dyskeratosis congenita
• Kostmanns’ syndrome
• Schawchmann Diamond syndrome
16SUNIL 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
17SUNIL KUMAR.P

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

19. CLINICALFEATURESOFNEUTROPENIA
• The manifestations of neutropenia depend
upon the degree of neutropenia and of
compensatory monocytosis.
• The manifestations are generally due to severe
bacterial infections.
19SUNIL KUMAR.P

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

21. 21SUNIL KUMAR.P

22. 22SUNIL KUMAR.P

23. Laboratory Diagnosis
• 1. peripheral blood examination
• 2.Bone marrow examination
23SUNIL 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 109/L
24SUNIL KUMAR.P

25. Bone marrow Examination
• BM is essential to rule other causes of
neutropenia like…….
• sub leukemic/
• aleukemic leukemia
• Megaloblastic anemia
• Aplastic anemia
25SUNIL 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
26SUNIL KUMAR.P

27. THANK YOU
27SUNIL KUMAR.P