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1. Group Discussion No:
Hematology Unit/ Internal
Medicine Department
Rotation Medicine 1 (MED-314) for
third year medical students
2021-2022

2. Aplastic anemia

3. •Chief Complaint
•Fatigue,
• recurrent upper respiratory infections,
• and frequent bruising

4. History and Physical Examination
•A 25-year-old woman comes to the clinic because of
progressive fatigue over the last 6 months.
•She has also noticed frequent colds and several sinus
infections, which she never experienced in the past.
•Over the last 2 months she notes multiple bruises on her
arms and legs without a history of obvious trauma.
•Her periods have also been particularly heavy, lasting 7
days.

5. •She denies recurrent fever and weight loss (toxic symptoms
sugessting malignancy or chronic debilitating disease).
• Her appetite is intact, and she has no abdominal pain or fullness
(may suggest the presence of organomegaly).
• occupation: The patient currently is unemployed but had worked
as a painter for several years.
• Drug Hx: She takes no medications.
•Upon physical examination her
•temperature is 38 C (100.4 F),
•blood pressure 100/70 mm Hg,
•and pulse 100/min (proportionate Tachycardia ). Every rise in
tepm 1degree associated with increase of pulse about 10:15b/M
•Genaral Examination
•She appears pale. With the exception of multiple bruises seen on
her extremities, the remainder of the physical examination is
normal.

7. •From this history and examination we suggest
3 blood elements affection what we called
pancytopenia
•So the initial order is CBC

8. Differential Diagnosis: Pancytopenia
•Primary BM diseases peripheral destruction
•Aplastic anemia. (cong, acquired ) SLE
• Infiltration (Acute leukemia) Drugs
•marrow suppression secondary to nutritional deficiency
(vitamin B12, folate). Viral infection
•PNH. Hypersplenism
•Drug( irreversible with idiosyncrasy and reversible with dose
dependent)
• toxin-induced marrow failure
•Myelofibrosis.
•MDs
•infection (tuberculosis, HIV ).

9. •Initial Management:
•Setting: emergency department
•Diagnostic/Therapeutic Plan:
• CBC and Peripheral smear
• TLC including (Absolute neutrophil count )
•HIV test
•Chest x-ray,
•urinalysis,
•blood cultures
•ANA
•B12 and folate

10. •Test Results:
•Peripheral smear: no immature forms seen, no
increase in reticulocytes (why?),
•mean corpuscular volume 100 fL (normal 80–100 fL)
•TLC
•Absolute neutrophil count: 500/mm
3
( critically low)
• HIV: negative
•Chest x-ray, urinalysis, blood cultures normal
•ANA negative
•B12 and folate :normal

11. DD of macrocytic anemia
•Macrocytic anaemia:
- Megaloblastic: vit B12 or folate deficiency
- Non megaloblastic: -alcohol
- liver disease
- hypothyrodism
- reticulocytosis(in hemolysis)
-myelodysplastic syndrome
-aplastic anemia patient has a
normochromic, normocytic (or slightly macrocytic)
anemia

12. •All patients with anemia should have a
peripheral smear.
•A smear is most useful in macrocytic anemia
and hemolysis.

13. •Assessment
•The differential diagnosis for pancytopenia is extensive and
includes premature destruction of cells due to
• hypersplenism or
•autoimmune disease,
•marrow suppression secondary to nutritional deficiency
(vitamin B12, folate),
•infection (tuberculosis, HIV),
•drugs (trimethoprim- sulfamethoxazole, chloramphenicol),
Drug-induced pancytopenia is usually dose-dependent and
reversible A rare idiosyncratic reaction to chloramphenicol
is associated with irreversible marrow failure.
•
•malignant infiltration..

14. •Paroxysmal nocturnal hemoglobinuria may also present
with a hypocellular marrow, although it is more commonly
associated with hyperplasia of red blood cell precursor
populations.
•Myelodysplasia may also yield a hypocellular biopsy but is
usually associated with a hypercellular specimen with
abnormal features of maturation and characteristic findings
(deletion of chromosomes 5 or 7).
•Other potential etiologies for a dry aspirate include hairy
cell leukemia, myelofibrosis, and M7 (megakaryocyte)
acute myeloblastic leukemia (AML).
• Hairy cell leukemia is associated with characteristic
abnormalities on immunophenotyping

15. •There are no abnormal white blood cell forms
on peripheral smear. The most likely cause is
aplastic anemia, which may be related to her
exposure to paints.

16. •Further Management Plan/Results
Bone marrow biopsy:
•Unable to aspirate; biopsy profoundly
hypocellular with fat replacing most
hematopoietic elements
•No increase in reticulin fibers seen
•Bone marrow for AFB stain and fungal forms
negative

19. •Discussion:
•Aplastic anemia is characterized by pancytopenia, thought to be
due to stem cell injury.
•This can be acquired or congenital.
• In the acquired form, a known insult (such as one of the above
toxins), drug, or infection is found in about 50% of cases.
•
•Several drugs are associated with aplasia, such as indomethacin
(analgesic), gold, phenylbutazone (NSAIDs), sulfonamides
(antibiotic), phenytoin (antiepilptic), nifedipine (anti HTN), and
quinacrine (antimalarial).
•Chloramphenicol is associated with a dose-related pancytopenia
and with an idiosyncratic, rare, profound, pancytopenia not
related to dose.

20. •Other causes of marrow aplasia include:
•
Toxins such as benzene, arsenic, toluene found in
glue, insecticides, paint thinners, and lacquers
•Infections such as hepatitis C and infectious
mononucleosis
•Radiation and chemotherapeutic agents
•Occasionally, HIV and parvovirus (usually cause
red cell aplasia but occasionally can cause aplastic
anemia)

21. •A careful history of prior toxin exposure is crucial because
removal of the offending agent may reverse the disease.
•In some cases, aplastic anemia is thought to arise from
immune-mediated injury of stem cells.
•This is supported by the finding that some patients have
been shown to respond to immunosuppressants such as
antithymocyte globulin (ATG) and cyclosporine.

•Bone marrow transplant is often only successful when
preceded by high-dose chemotherapy to eradicate the
existing host immunity prior to transplant.
•Bone marrow transplant is also curative and is the best
therapy in patients age <70 in good health and with an
HLA-matched donor.

22. •The clinical presentation includes bleeding, anemia,
and recurrent infections.
• The latter is of particular concern in patients with
neutrophil count <500/mm
3
, who are at risk for nadir
sepsis.
•The first principle in treatment is removal of the
offending toxin or agent.
•Those patients who are fit and have HLA-matched
siblings should undergo bone marrow transplantation.
•If possible, patients should not be transfused prior to
transplant to avoid sensitization and rejection of the
future graft.
•Those patients who are elderly or have no donor are
given trials of immunosuppressive agents.

23. •Follow-up Management:
•Removal of offending toxin if one is present
•Hematology consult to consider bone marrow
transplantation in those age <50 with a matched donor
•Trial of immunosuppressive therapy with anti-thymocyte
globulin and cyclosporine if transplant is not an option
•Alternate immunosuppressive medications are
mycophenolate or cyclophosphamide
•
•Final Diagnosis
•Pancytopenia, aplastic anemia

25. •Aplastic anemia is a Disease of Nill:
•No splenomegaly
•No hepatomegaly
•No lymphadenopathy
•No abnormal cells in peripheral blood smear