DRUG-INDUCED APLASTIC ANEMIA

A Case Study Presented to the

Faculty of Medical Laboratory Science of Department
San Pedro College, Davao City

In Partial Fulfillment of the Requirements for the Degree

Bachelor in Medical Laboratory Science

Facturan, Raphael
Ferolin, Jules Tyrell
Nipangue, Regine April
Orig, Larah Mae

March 7, 2017
Objectives
To diagnose the patient based on her data.
To identify the pathophysiology of the suspected diagnosis.
To correlate the laboratory results with the patients symptoms.

Chapter I.

Introduction
A 28-year-old woman was admitted to the hospital because of severe menstrual
bleeding. She presented numerous petechiae and some purpura. She was a religious
missionary who had recently returned from a 2-year assignment. Six months ago, she
developed a severe lower respiratory infection. She was treated by a local physician at
that time but was not hospitalized because of the lack of medical facilities on the area.
She had refused to return home for further treatment at that time. Initially, she received
a cephalosporin-type antibiotic. Her symptoms persisted and she later received
chloramphenicol. At the time of admission, she showed no evidence of a respiratory
disorder. However, she had recently discontinued the chloramphenicol that she had taken
continuously for 5 months. Upon admission, the following tests were ordered: CBC,
platelet count, cold agglutinin antibody screen, urinalysis, and chest radiograph. Thirty-
six hours after admission the patient died of a massive cerebral hemorrhage. Tests
performed on specimens obtained at autopsy revealed that the patients bone marrow
showed an almost total absence of hematopoiesis. A blood culture was positive for the
Gram-negative rod Proteus vulgaris.

Chapter II.

Patients Data:

Age: 28 years old

Sex: Female

Patients history:
Severe lower respiratory infection
Severe menstrual bleeding

Laboratory results:
Hemoglobin 5.5 g/dL
Hct 18%
RBC 1.85 1012 /L

The RBC indices were as follows:

MCV 97.2 fL
MCH 29.7 pg
MCHC 31 g/dL

Her WBC count was 1.1 109 /L. On the peripheral bloodsmear, the RBCs had a
normochromic, normocytic appearance. Platelets were severely diminished on the blood
film. Her platelet count was 2.5 x 109 /L. The result of the screening test for cold
agglutinins was negative. Urinalysis results were normal.
Chapter III.

A. Definition of the Case

The 28-year-old woman was admitted due to a severe menstrual bleeding. She had
numerous petechiae which appears when capillaries bleed, leaking into the skin. She also
had purpura which is a rash on the skin caused by internal bleeding from small blood
vessels. She was a missionary and returned from a 2- year assignment and developed a
severe lower respiratory infection 6 months ago and was treated by a local physician.
She was not hospitalized at that time because of lack of medical facilities in the area and
did not returned home for further treatment. She was initially given a cephalosphorin-
type antibiotic. Cepahlosporins are bacterial agents and have the same mode of action
as other beta-lactam antibiotics. They inhibit enzymes in the cell wall of susceptible
bacteria, disrupting cell synthesis. But after taking it, her symptoms still persisted so she
was given chloramphenicol which is also an antibiotic used to kill bacteria by allowing it
to diffuse through the bacterial cell membrane since it is a lipid-soluble drug. Here were
no signs of a respiratory disorder during her admission. However, she had recently
discontinued the chloramphenicol that she had taken continuously for 5 months. Thirty-
six hours after admission the patient died of a massive cerebral hemorrhage, a type of
intracranial bleed that occurs within the brain tissue or ventricles. Tests performed on
specimens obtained at autopsy revealed that the patients bone marrow showed an
almost total absence of hematopoiesis which is a process of creating new blood cells in
the body. A blood culture was positive of Proteus vulgaris, a gram negative rod-shaped,
indole positive, catalase positive, and hydrogen sulfide-producing bacterium that inhabits
the intestinal tract of humans and animals. It causes nosocomial infections and can be
easily isolated from individuals in long-term care facilities and hospitals dorm patients
with underlying diseases or compromised immune systems.

B. Anatomy/Physiology and Pathophysiology

Bone Marrow

Bone marrow is the soft, spongy, gelatinous

tissue found in the hollow spaces in the
interior of bones. The average weight of this
tissue is about 4% of the total body weight, or
2.6 kg in an adult weighing 65 kg. Progenitor
cell (stem cell) lines in the bone marrow
produce new blood cells and stromal cells.

Bone marrow consists of stem cells, which are

large, "primitive," undifferentiated cells
supported by fibrous tissue called stroma.
There are 2 main types of stem cells and,
therefore, the bone marrow consists of 2 types
of cellular tissue. One type of stem cell is
involved in producing blood cells and the
other is involved in producing stromal cells,
which are responsible for the supporting stroma.

All types of blood cells are derived from 1 common stem cell. Stem cells exist throughout
the life of an individual. The common stem cell produces 2 other stem cells, the myeloid
stem cell and the lymphoid stem cell. These stem cells divide to eventually give rise to
red blood cells, platelets, and most white blood cells in the red marrow. Bone marrow
thus contains blood cells at varying stages of development.

The rate of blood cell production is controlled by the body's needs. Normal blood cells
last for a limited time. Red blood cells last for about 120 days. These cells must be
replaced constantly. When the oxygen content of body tissues is low, if there is loss of
blood or anemia, or if the number of red blood cells decreases, the kidneys produce and
release erythropoietin, a hormone that stimulates the bone marrow to produce more red
blood cells.

Pathophysiology

Aplastic anemia develops when damage occurs to your bone marrow, slowing or
shutting down the production of new blood cells. Bone marrow suppression is the
decrease in production of white blood cells, red blood cells, and platelets. It is a serious
side effect of chemotherapy and certain drugs affecting the immune system such as
chloramphenicol. The decrease in blood cells counts that are already in the bloodstream
does not happen at the start of drug intake. Instead, the drug affects the new blood cells
being made by the bone marrow. Drug toxicity on hematopoietic cells is usually mediated
through metabolites that bind to proteins and DNA to cause bone marrow failure.
Chloramphenicol is an antibiotic for bacterial infections. Its common side effects includes
bone marrow suppression that is dose dependent and reversible because it has a direct
toxic effect of the drug on human mitochondria leading to a defective hematopoiesis.
Chloramphenicol is the prototype drug for idiosyncratic mechanism. Idiosyncratic drug
reaction means an aberrant or hypersensitivity to a substance without connection to the
pharmacology of the drug. The idiosyncratic mechanism is believed to result from
abnormal metabolism of the drug which has constituents or by product that affects the
human blood cells causing chromosomal damage that could lead to cell death. Based on
the woman's peripheral blood smear, the morphology of the red blood cells were just
normal since the drug would not affect the blood cells that are already present in the
bloodstream since its target are the new cells that are still being made by the bone
marrow. Intracranial or cerebral hemorrhage is a fatal complication of aplastic anemias
and it might be because of excessive thrombocytopenia. Since the patient has decreased
white blood cells to protect herself from infections, she is unable to produce enough
antibodies to protect herself from pathogens. She is already immunosuppressed due to
the effects of chloramphenicol so opportunistic pathogens could easily enter her body.
What caused her death was septicemia caused by Proteus vulgaris which is an
opportunistic pathogen.
Chapter IV.

Presentation of the Data

Parameters Result Normal values Rationale

Hemoglobin 5.5 g/dL 12.1-15.1 g/dL Low- Anemia
Hematocrit 18% 40-60% Low- Anemia
RBC 1.85 x 10^12/L 4.00-6.00 x Low- Anemia,
10^12/L pancytopenia due
to bone marrow
failure induced
my
chloramphenicol
MCV 97.2 fL 80.0-94.0 fL Normal
MCH 29.7 pg 27.0-31.0 pg Normal
MCHC 31 g/dL 32-36 g/dL Low- Anemia
WBC 1.1 x 10^9/L 5.00-10.00 x Low-
10^9/L pancytopenia due
to bone marrow
failure induced
my
chloramphenicol
Platelet count 2.5 x 10^9/L 150-450 x 10^9/L Low-
pancytopenia due
to bone marrow
failure induced
my
chloramphenicol
Cold agglutinin Negative <1:64 No cold agglutinin
detected that
would cause
hemolytic anemia
since the cause
of a decreased
RBC count is due
to a defective
hematopoiesis
Urinalysis Normal No renal disease
or urinary tract
infection
Peripheral blood RBC: Platelets maybe
smear normochromic, severely
normocytic diminished
Platelets: severely because of
diminished excessive
bleeding
Blood culture Positive of Proteus No growth of Nosocomial
vulgaris organism infection due to
immunosuppressi
on

Treatment
 Drug-induced aplastic anemia must be quickly diagnosed and treated. The goal is
to improve peripheral blood counts, limit the requirement for transfusions, and minimize
the risk for infections. There is a need for transfusion support with red blood cells and
platelets to avoid severe bleeding. Antimicrobial prophylaxis is also needed to avoid
further infections since it causes immunosuppression. Broad spectrum IV antibiotics
should be started if there is severe neutropenia. For patients with disease requiring
treatment, the two major treatment options for patients are allogeneic HSCT
(Hematopoietic Stem Cell Transplantation) and immunosuppressive therapy. Allogeneic
HSCT from an HLA-matched sibling is preferred in children, while immunosuppressive
therapy is preferred for adults since allogeneic HSCT has higher mortality rate for them.
Cyclosporine is an example of an immunosuppressive therapy for aplastic anemia.

Chapter V.
Summary (LARAH)
Conclusion(JULES)
The patient is suffering from pancytopenia because of the effects of prolonged use
of the drug chloramphenicol, which can depress bone marrow activity at high dosage
level. Based on this findings, our diagnosis for the case is drug- induced aplastic anemia.
The patient died because of septicemia cause by Proteus vulgaris. Due to the
pancytopenia specifically the leukopenia, the body was so weak to effectively counter the
massive bacterial infection.
Recommendations(LARAH AND JULES)
Stop using the chloramphenicol and treat the pancytopenia first.
Give antibiotics to counter act the septicemia
Chapter VI.

References

http://www.emedicinehealth.com/hemoglobin_levels/page4_em.htm
https://en.wikipedia.org/wiki/Proteus_vulgaris
https://en.wikipedia.org/wiki/Intracerebral_hemorrhage
https://en.wikipedia.org/wiki/Intracerebral_hemorrhage
https://labtestsonline.org/understanding/analytes/cold-agglutinins/tab/test/
http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/8992
https://en.wikipedia.org/wiki/Chloramphenicol#Bone_marrow_suppression
http://www.mhpharmacotherapy.com/0071800530/online_pdfs/24_Dipi_Web_Ch24_359-
374.pdf