The most appropriate provisional diagnosis is aplastic anemia. To diagnose: - Perform a bone marrow biopsy which will show hypoplastic/aplastic bone marrow. - Check for pancytopenia - low RBC, WBC, platelet counts. To manage: - Blood transfusions to manage anemia and thrombocytopenia. - Antibiotics for any infections given low WBC. - Consider immunosuppressive therapy like ATG or look for a HLA matched sibling donor for hematopoietic stem cell transplant which can cure severe aplastic anemia.

2. Agranulocytosis: Aplastic anaemia
Presented by:
Dr. Md. Ahsan Habib
Assistant Professor(Dept.of Medicine)
Shahid Ziaur Rahman Medical College and
Hospital,Bogura

3. Agranulocytosis
• Agranulocytosis is an acute condition involving a severe
and dangerous lowered white blood cell count
(leukopenia, most commonly of neutrophils) and thus
causing a neutropenia in the circulating blood
• It may be asymptomatic, or may clinically present with
sudden fever, rigors and sore throat , rapidly progressive
pneumonia, urinary tract infection etc.

4. Agranulocytosis(Contd):
• The terms agranulocytosis, granulocytopenia and
neutropenia are sometimes used interchangeably
Agranulocytosis implies a more severe deficiency than
granulocytopenia. Neutropenia indicates a deficiency of
neutrophils only
• To be precise, neutropenia is the term normally used to
describe absolute neutrophil counts (ANCs) of less than
500 cells per microlitre, whereas agranulocytosis is
reserved for cases with ANCs of less than 100 cells per
microliter

5. Agranulocytosis(Contd):
• To formally diagnose agranulocytosis, other
pathologies with a similar presentation must be
excluded, such as aplastic anemia, paroxysmal
nocturnal hemoglobinuria, myelodysplasia and
leukemias.

6. Causes:
Mainly due to idiosyncreatic reaction to certain drugs:
• Antiepileptic drugs: Carbamazapine, Na valporate
• Anti thyroid drugs: Carbimazole, propylthiouracil
• Antibiotics: Penicillin, chloramphenicol, Cotrim
• H2 blocker: Cimetidine, ranitidine,famotidine

7. Causes(Contd):
• Analgesics: Indomethacine, naproxen
• Antidepressant: Mitrazapine
• Antipsychotic: Clozapine
Although the reaction is generally idiosyncreatic rather
than proportional, it is recommended that all patient
using these drugs should be told about the symptoms of
agranulocytosis related infections such as sore throat
and fever

8. Scenario:
A 30-year- old lady came with generalized weakness,
lassitude, palpitation for 1 month, sore throat for 2 weeks
and excess menstrual bleeding for 3 months. She has no H/O
weight loss, cough or bony or any joint pain. There was no
lymphadenopathy or organomegaly, but some reddish
palpable lesion without pain in different parts of body.
Q. What is the most appropriate provisional diagnosis?

9. Aplastic anaemia
Key features for diagnosis:
• Pancytopenia.
• No abnormal hematopoietic cells seen in blood or
bone marrow.
• Hypocellular bone marrow.
Aplastic anemia is a condition of bone marrow failure
that arises from suppression of, or injury to, the
hematopoietic stem cell. The bone marrow becomes
hypoplastic, fails to produce mature blood cells, and
pancytopenia develops.

10. Contd:
• Patients come to medical attention because of the
consequences of bone marrow failure
• The basic problem is failure of the pluripotent stem
producing hypoplasia of the bone marrow with a
pancytopenia in the blood
• This is a rare disorder in Europe and North America
• Much more common in other parts of the world, e.g.
east Asia

11. Types:
• Primary idiopathic aplastic anaemia: No cause
is found
• Secondary aplastic anaemia
• Rare congenital causes: Fanconi’s anaemia,
Pure red cell aplasia

12. Causes of secondary aplastic anaemia:
 Drugs:
• Cytotoxic drugs
• Antibiotics – chloramphenicol, sulphonamides
• Antirheumatic agents – penicillamine, gold,
phenylbutazone, indometacin
• Antithyroid drugs – carbimazole, propylthiouracil
• Anticonvulsants
• Immunosuppressants – azathioprine

13. Contd:
• Chemicals:
 Benzene, toluene solvent misuse – glue-sniffing
 Insecticides – chlorinated hydrocarbons (DDT),
organophosphates
 Carbamates
• Radiation
• Viral hepatitis
• Pregnancy
• Paroxysmal nocturnal haemoglobinuria

14. Clinical features
• Anemia: Tiredness, Lightheadedness, Breathlessness
• Neutropenia : Vulnerability to bacterial or fungal
infections
• Thrombocytopenia: Gum and mucous membrane
bleeding, skin bleeding
• Physical examination may reveal signs of pallor,
purpura, and petechiae, bruises, Fundal haemorrhage.
• No hepatosplenomegaly, lymphadenopathy, or bone
tenderness

15. Laboratory findings
The hallmark of aplastic anemia is pancytopenia. However,
early in the evolution of aplastic anemia, only one or two
cell lines may be reduced.
• Estimation of haemoglobin : Reduced, may be as low as
3gm/dl
• WBC : Reduced
• Platelet count : Reduced

16. Contd:
• ESR : Very high
• Res cell indices : MCV, MCH, MCHC are normal.
• Reticulocyte count : low or absent.
• Peripheral blood film:
Red cells are normochromic and normocytic, leukopenia,
neutropenia with relatively lymphocytosis, no abnormal cell,
platelets are reduced but morphologically normal.

17. BM findings:
• Cellularity: Decreased, Dry tap,Increased reticulin and
fibrous tissue
• ME ratio : Normal
• Erythropoiesis : Depressed but normoblastic
• Granulopoiesis : Reduced
• Megakaryopoiesis : Reduced

18. Criteria of severe aplastic anemia
• Bone marrow cellularity less than 20%
• Neutrophil count of less than 500/mcL
• Platelets less than 20,000/mcL
• Reticulocytes less than 1%

19. Treatment
Mild cases of aplastic anemia : Supportive care
• Red blood cell transfusions
• Antibiotics are used to treat infections
• Platelet transfusions
• Erythropoietic stimulation by (epoetin or
darbepoetin) or myeloid series stimulation (filgrastim )
may be used

20. Severe aplastic anemia:
Less than 35 years of age:
• HSCT- Curative treatment.
• If HLA matched sibling donor - 75–90% chance of long-
term cure.

21. Contd:
In older patients and those without a suitable donor:
Immunosuppressive therapy (IST) :
• Anti-thymocyte globulin (ATG)
• Ciclosporin
• Eltrombopag often added to ATG and ciclosporin

22. Prognosis:
The prognosis of severe aplastic anaemia managed
with supportive therapy only is poor and more than
50% of patients die, usually in the first year.

23. Scenerio
A 30-year- old lady came with generalized weakness,
lassitude, palpitation for 1 month, sore throat for 2 weeks.
Excess menstrual bleeding for 3 months. She has no H/O
weight loss, cough or bony pain. There was no
lymphadenopathy or organomegaly, but some reddish
palpable lesion without pain in different parts of body. Hb-
5gm/dl, Platelet count 15000/cmm.
Q. What is the most appropriate provisional diagnosis?
Q. How will u diagnose and manage her?