Agranulocytosis is a condition characterized by a severe lack of neutrophils in the blood which leaves the immune system highly vulnerable to infection. It can be either acquired, such as from drug exposure, or hereditary due to genetic mutations. Symptoms include sudden fever, chills, mouth sores, and bleeding gums that can progress to life-threatening sepsis if untreated. Treatment focuses on identifying and removing the cause, administering antibiotics to fight infection, and using colony-stimulating factors to shorten the duration of neutropenia. With prompt treatment, the risk of death from agranulocytosis is low.

1. AGRANULOCYTOSIS
Presented by:-
Dinoosh De livera
Group 49
5th year
International Students Faculty
VSMU
Ministry of Education Republic of Belarus
Vitebsk Order of Peoples’ Friendship Medical University
Department of Internal Medicine No:2

2. DEFINITION
Agranulocytosis, also known as agranulosis or granulopenia, is an acute condition involving a
severe and dangerous leukopenia (lowered white blood cell count), most commonly of
neutrophils causing a neutropenia in the circulating blood.
It is a severe lack of one major class of infection-fighting white blood cells.
People with this condition are at very high risk of seriousinfections due to their suppressed
immune system.
In agranulocytosis, the concentration of granulocytes (a major class of white blood cells that
includes neutrophils, basophils, and eosinophils) drops below 500 cells/mm³ of blood.

3. DEFINITION
Agranulocytosis is characterized by a greatly decreased number of circulating
neutrophils. Severe neutropenia is the term usually applied to patients with fewer than
500 neutrophils per microliter (μL) (including bands).
Agranulocytosis usually refers to patients with fewer than 100 neutrophils/μL.
The reduced number of neutrophils makes patients extremely vulnerable to infection.
Cardinal symptoms include fever, sepsis, and other manifestations of infection. Causes
can include drugs, chemicals, infective agents, ionizing radiation, immune
mechanisms, and heritable genetic aberrations.

4. CLASSIFICATION
• Agranulocytosis may be broadly divided into 2 groups: hereditary disease due to genetic mutations and acquired
disease.
Hereditary disease due to genetic mutations
Many hereditary disorders are due to mutations in the gene encoding neutrophil elastase, or ELA2. Several alleles are
involved. The most common mutations are intronic substitutions that inactivate a splice site in intron 4. Genes other
than ELA2 are also involved.
A strong family history of recurrent infections, usually beginning in childhood, is strongly indicative of a genetic
defect.
Acquired disease
Acquired agranulocytic disease may be due to drugs, chemicals, autoimmunity, infectious agents, or other causes.
Drugs or chemical is the most common cause of agranulocytosis. About one half of patients have a history of
medication or chemical exposure. The patient's history must be carefully taken to elicit this information.
Bone marrow and peripheral blood are the organ systems affected. Agranulocytosis is characterized by inadequate
production of neutrophils, excessive destruction of neutrophils, or both. The resulting infections tend to involve the
oral cavity, mucous membranes, and skin. Systemic life-threatening sepsis may ensue. The most common infecting
organisms are staphylococci, streptococci, gram-negative organisms, and anaerobes. Fungi are also commonly
involved as secondary infective agents.
The occurrence of infection depends on the degree and duration of neutropenia. When the ANC (absolute neutrophil
countis) persistently fewer than 100/µL for longer than 3-4 weeks, the incidence of infection approaches 100%.

5. PATHOGENESIS
Pathogenesis of neutropenia can be divided into two categories;
1) Inadequate or ineffective formation of granulocytes. This can be due to bone marrow
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
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 infections

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.
Sex
Agranulocytosis occurs slightly more frequently 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.
Age
Agranulocytosis occurs in all age groups.
The congenital forms are most common in childhood.
Acquired agranulocytosis is most common in the elderly population.

7. SIGNS & SYMPTOMS
The early symptoms of agranulocytosis may include:
• sudden fever
• chills
• sore throat
• weakness in your limbs
• HIGH FEVER
• mouth ulcers
• bleeding gums
Other signs and symptoms of agranulocytosis can include:
• fast heart rate
• rapid breathing
• low blood pressure
• skin abscesses

8. SIGNS & SYMPTOMS - HISTORY
• Patients with agranulocytosis usually present with the following:
Sudden onset of malaise
• Sudden onset of fever, possibly with chills and prostration
• Stomatitis and periodontitis accompanied by pain
• Pharyngitis, with difficulty in swallowing
• If treatment is not promptly instituted, the infection progresses to generalized sepsis, which may become life
threatening.
• Patients often report a history of a new drug being used or a recent change in medication.
• Occupational or accidental exposure to chemicals or physical agents (eg, ionizing radiation) may have
occurred.
• The patient may have experienced a recent viral infection, although such infections are rarely associated with
severe neutropenia. Certain bacterial infections may also precede agranulocytosis.
• A history of periodically recurring infections is suggestive of cyclic neutropenia.
• A history of autoimmune diseases may be associated with antineutrophil antibodies. Such antibodies may
also be the only manifestation of autoimmune disease. A number of test methods are available, but none is
widely used.
• A strong family history of recurrent infections, usually beginning in childhood, is strongly indicative of a
genetic defect.

9. SIGNS & SYMPTOMS - PHYSICAL
• Fever may be present (temperature often 40 º C or higher).
• Rapid pulse and respiration may be evident.
• Hypotension and signs of septic shock if infection has been present
• Painful aphthous ulcers may be found in the oral cavity.
• Swollen and tender gums may be present.
• Usually, purulent discharge is not present, because not enough neutrophils exist to
form pus.
• Skin infections are associated with painful swelling, but erythema and suppuration
are usually absent.

10. DIFFERENTIAL DIAGNOSIS
• Large granular lymphocyte leukemia
• Autoimmune diseases
• Chronic myelomonocytic leukemia
• Congenital neutropenia
• Cyclic neutropenia
• Drug-induced neutropenia
• Large granular lymphocytic leukemia
• Pseudoneutropenia

11. TREATMENT – GENERAL CARE
• Medical care for patients with neutropenia is mostly supportive and based on the
etiology, severity, and duration of the neutropenia. Fever and infections occurring as
complications of neutropenia require specific treatment.
• Removal of any offending drugs or agents is the most important step in most cases
involving drug exposure; if the identity of the causative agent is not known, stop
administration of all drugs until the etiology is established
• Use careful oral hygiene to prevent infections of the mucosa and teeth; control oral and
gingival lesion pain with saline and hydrogen peroxide rinses and local anesthetic gels
and gargles
• Avoid rectal temperature measurements and rectal examinations
• Administer stool softeners for constipation
• Use good skin care for wounds and abrasions; skin infections should be managed by
someone with experience in the treatment of infection in neutropenic patients

12. TREATMENT - DRUGS
• Antibiotics
Start specific antibiotic therapy to combat infections. This often involves the use of
third-generation cephalosporins or equivalents
Colony-Stimulating Factor Therapy
Myeloid growth factors—specifically, granulocyte colony-stimulating factors (G-CSFs)
and granulocyte-macrophage colony-stimulating factor (GM-CSFs)—may shorten the
duration of neutropenia
Granulocyte Transfusion
Neutrophil (granulocyte) transfusions have undergone a cycle of popularity followed
by disfavor. These transfusions are accompanied by many complications, including
severe febrile reactions. Their use is controversial.

13. PROGNOSIS
• If agranulocytosis is untreated, the risk of dying is high. Death results from
uncontrolled sepsis.
• If the condition can be reversed with treatment, the risk of dying is low. Antibiotic
and antifungal medications can cure the infection if the ANC rises.
Morbidity is entirely due to infections that complicate agranulocytosis. The
infections may be superficial, involving mainly the oral mucosa, gums, skin, and
sinuses, or they may be systemic, with life-threatening septicemia.

14. THANK YOU FOR YOUR ATTENTION!
QUESTIONS?