Drug induced Neutropenia

1. Drug induced Neutropenia
Presented by :-
Ayesha Ambereen,
PharmD,
Sultan ul Uloom college of pharmacy,
Banjara hills, Hyderabad.
Guided by :-
Dr. S P Srinivas Nayak,
Assistant professor,
SUCP, HYD.

2. Introduction :
Neutrophils play an essential role in immune defenses because they
ingest, kill, and digest invading microorganisms, including fungi and
bacteria. Failure to carry out this role leads to immunodeficiency,
which is mainly characterized by the presence of recurrent
infections.Defects in neutrophil function can be quantitative, as seen in
neutropenia or qualitative, as seen in neutrophil dysfunction. The
standard circulating neutrophil count is above 1.5 x 10/L. Neutropenia
can be classified in asymptomatic (mild), moderate, and severe, and
thus, the progression to infection concerning the number.

3. Neutrophils formation :
.

4. .● Neutrophils (also known as neutrocytes or heterophils) are the
most abundant type of granulocytes and make up 40% to 70% of
all white blood cells in humans.

5. What is Neutropenia?
● Neutropenia is a blood condition characterized by low levels of neutrophils,
which are white blood cells that protect your body from infections.
● Without enough neutrophils, your body can’t fight off bacteria. Having
neutropenia increases your risk for many types of infection.
● TYPES OF NEUTROPENIA : 4 types
1. Congenital :
● Congenital neutropenia is present at birth. Severe congenital neutropenia is also
called Kostmann syndrome. It causes very low neutrophil levels and in some
cases, complete lack of neutrophils. This puts infants and young children at risk
for serious infections.

6. .2. Cyclic :
● Cyclic neutropenia is present at birth and causes neutrophil counts to vary
in a 21-day cycle. A period of neutropenia may last a few days, followed
by normal levels for the rest of the cycle. The cycle then begins again.
3. Autoimmune :
● With autoimmune neutropenia, your body makes antibodies that fight your
neutrophils. These antibodies kill the neutrophils, causing neutropenia.
● Autoimmune neutropenia is most common in infants and young children,
with the average age of diagnosis between 7 and 9 months.
4. Idiopathic :
● Idiopathic neutropenia develops any time in life and can affect anyone. The
cause is unknown.

7. Symptoms of Neutropenia:
● Neutropenia symptoms can range from mild to severe. The lower the level of
neutrophils, the more intense the symptoms.
● Typical symptoms include: fever, pneumonia, sinus infections, otitis media
(ear infection), gingivitis (gum inflammation), omphalitis (navel infection), skin
abscesses, etc.
● Severe congenital neutropenia can have serious symptoms. The symptoms
often include bacterial infections. These infections can grow on the skin and
in the digestive and respiratory systems.
● The symptoms of cyclic neutropenia recur in 3-week cycles. Infections can
increase when neutrophil levels fall.
● The symptoms of autoimmune and idiopathic neutropenia include infections.
They’re usually not as severe as those in congenital forms.

8. Diagnosing Neutropenia :
● Complete blood count (CBC). This test measures neutrophil counts.
Intermittent CBC tests can help your doctor check for changes in
neutrophil count three times per week for 6 weeks.
● Antibody blood test. This test checks for autoimmune neutropenia.
● Bone marrow aspirate. This procedure tests bone marrow cells.
● Bone marrow biopsy. This involves testing a piece of the bony part of
bone marrow.
● Cytogenetic and molecular testing. This testing helps your healthcare
provider study the structures of the cells.

9. Some Drugs which causes Neutropenia:
● Chloramphenicol
● Cotrimoxazole
● Penicillins
● Cephalosporins
● Glycopeptides
● Quinine
● Rifabutin
● Ganciclovir ...etc,.

10. Chloramphenicol :
● Chloramphenicol is the most prominent cause of bone marrow
depression, which is if two forms :
● (a) Non dose related idiosyncratic reaction : unpredictable, but
serious, often fatal, if they survive, develop leukemia later.
● (b) Dose and duration of therapy related myelosuppression :
predictable and probably due to inhibition of mitochondrial
enzyme synthesis in the erythropoietic cells.

11. .

12. Cotrimoxazole :
● Cotrimoxazole causing Neutropenia is dose dependent.
● High dose cotrimoxazole causes bone marrow hypoplasia.
● Elderly patients are at greater risk of bone marrow toxicity, leading to
myelosuppression.
● Myelosuppression — also referred to as bone marrow suppression is a
decrease in bone marrow activity resulting in reduced production of blood
cells.
Bone marrow
hypoplasia

13. Penicillins :
● Drug-induced neutropenia occurs in a patient receiving a semisynthetic
penicillin for two weeks or more. The cause is believed to be either a
hypersensitivity reaction or a toxic dose-related suppression of white blood
cell precursors. Most patients improve after discontinuation of the drug.
● Low-molecular-weight compounds are immunogenic only when linked
covalently to a carrier protein, in which state they can induce the formation of
drug (hapten)–specific antibodies.
● The drug became coupled in vivo to certain membrane proteins that were
then recognized as “foreign” by the immune system, leading to the
production of drug-specific antibodies. On subsequent administration, the
drug could then reassociate with the membrane protein to create a target for
antibody, leading to blood cell destruction.

14. Cephalosporins :
● The exact mechanism for neutropenia and thrombocytopenia is not
fully known, but this is likely caused by direct bone marrow
suppression.
● Bone marrow suppression occurred because of mitochondrial damage
in hematopoietic cells and maturation arrest within the granulocyte
cell lines,, all which disappeared and was reversed after cessation of
the offending antibiotics.
● Cefazolin, ceftazidime, etc are some Drugs that induces Neutropenia.

15. Glycopeptides :
● The mechanism of glycopeptides-induced neutropenia is an
immunological rather than a direct toxic effect of the drug on
granulocytes. The likely cause is an antibody-mediated destruction of
neutrophils, as observed in patients with the positive test for
antineutrophil antibody. Bone marrow findings in affected patients
shows normal or increased cellularity. A hypersensitivity mediated
mechanism was thought to be a cause of neutrophil destruction in a
neutropenic patient who presented with eosinophilia and rash

16. Quinine :
● It is characterized by drug-dependent antibodies (DDAbs) that
bind to platelets and cause their destruction when the
responsible drug is ingested or injected.
● Less often, drug-induced antibodies target erythrocytes or
neutrophils and cause immune hemolytic anemia or
neutropenia.

17. Rifabutin :
● Rifabutin induced Neutropenia is caused by myelotoxicity.
● Which leads to“abnormal myeloid maturation with
minimal number of myelocytes”, interpreting as
hypoplastic bone marrow.

18. Ganciclovir :
● Neutropenia is caused by dose limiting toxicity.
● Which leads to bone marrow toxicity.
● It is reversible upon discontinuing the drug.

19. Thank you
.