This case presentation describes a 24-year-old female patient who was admitted to the hospital with symptoms of weakness, shortness of breath, fever, and recurrent nosebleeds. Laboratory tests showed very low blood cell counts. A bone marrow examination found a markedly hypocellular marrow with few hematopoietic cells. The patient was diagnosed with aplastic anemia based on pancytopenia, low bone marrow cellularity, and no evidence of damage to stem cells or dysplasia. Aplastic anemia is a rare disease caused by damage to or decrease in bone marrow stem cells resulting in bone marrow failure and replacement with fat.

1. Case Presentation
Diagnostic Hematology
Ahmad Adel A.

2. • Patient A, a 24-year old female, was admitted to hospital with
complaints of recurrent epistaxis, progressive weakness and
shortness of breath with minimal physical effort. she has experienced
recurrent fever reaching 38.2°C.
• Upon physical examination she showed a pale skin, good nutritional
status and no acute distress.
• There's no lymphadenopathy or hepatosplenomegaly.
• Many petechial hemorrhages cover her chest and legs.
• Several bruises are found on her legs and thighs.
• The patient denies sinus congestion, throat pain, cough, nausea,
emesis, melena, or hematuria.

3. • For the past 3 months, patient A's family physician has been following
her recovery from viral hepatitis. her recovery was uneventful.
• Her liver enzyme levels returning to normal within two months.
• She has no past medical history, and there's no family history of
hematological disorders.
• Laboratory tests were ordered on admission.

4. • Blood cells count showed a peripheral pancytopenia:
- Hemoglobin 5.2 g/dl,
- White cell count 1200/mmc (neutrophils 570; lymphocytes 540,
monocytes 80),
- Platelets 5,000/mmc,
- Reticulocytes < 1 %.

5. • CBC : Parameters result normal
RBC 3.32 x 1012/L 4.7 to 6.1 x 1012/L
HB 5.2 g/dL 13.0-18.0 g/dL
HCT 14.8% 40-52 %
MCV 98 Fl 80-97 fl
MCH 28 pg 27-31 pg
MCHC 33.6 g/dL 32-36 %
RDW 14 % 13 ± 15 %
WBC 1200 /μL 4,5-11 /μL
Neutrophil 570 /mm3 1500-8000 /mm3
PLT 5000 /μL 150 - 400 x 103/μL

6. Blood smear
Normal

7. Blood smear
Pancytopenia and reticulocytopenia

8. • Patient A was referred to a hematologist who ordered a bone marrow
examination.
• The aspirate obtained was inadequate for evaluation.
• Only a single site could be aspirated.
• Preps made from the aspirate showed a markedly hypo-cellular
marrow with very few hematopoietic cells.
• Cells present consisted of lymphocyte, plasma cells, and stromal cells.
• There's no malignant cells present.

9. Bone
marrow

10. Bone marrow
Normal marrow

11. Bone marrow
Hypocellular with
increased fat spaces
Severely Reduced
Hematopoietic Stem Cell
Precursors In Bone
Marrow
Bone marrow cellularity <
25%.

12. Diagnosis
Involves low counts in 2 of 3 cell lines:
red blood cells (RBC), white blood cells (WBC), platelets.
• Bone marrow cellularity is too low.
• No evidence of damage or mutation to the stem cell pool
(NORMAL cytogenetic).
• No dysplasia.
** (If dysplasia or abnormal cytogenetic seen, think myelodysplastic
syndrome (MDS)).

13. Diagnosis
Aplastic Anemia

14. Aplastic Anemia
• Aplastic Anemia is a rare disease caused by a
decrease in or damage to marrow stem cells,
damage to the microenvironment within the
marrow, and replacement within the marrow
with fat.
• The precise etiology is unknown, but it's
hypothesized that the body's T-cell mediate
inappropriate attack against the bone marrow,
result in bone marrow aplasia .

15. Classification
• Severe Aplastic Anemia
• Patient must meet the following criteria:
(a) Bone marrow cellularity < 25%
Or
30-50% with < 30% residual
hematopoietic cells
(b) Two of three of the following:
(1) Neutrophils < 0.5 x 109/L
(2) Platelets < 20 x 109/L
(3) Reticulocytes < 1%
• Very Severe Aplastic Anemia
• Patient must meet the criteria
for severe aplastic anemia and
have:
Neutrophils < 0.2 x 109/L

16. Causes
• In about 50% of cases, aplastic anemia is considered to be idiopathic,
meaning that the cause of the disease is unknown.
• Acquired aplastic anemia (environmental factors and physical
conditions):
- radiation or chemotherapy.
- medications: chloramphenicol, sulfonamides.
• Genetic (Inherited) disorders: Fanconi anemia.
• Autoimmune diseases.
• Viruses: EBV, HIV, and Hepatitis virus.

18. Fanconi anemia
Fanconi anemia (FA) is a rare genetic disease resulting in impaired
response to DNA damage.
FA is the result of a genetic defect in a cluster of proteins responsible
for DNA repair.
Among those affected, the majority develop cancer, most often acute
myelogenous leukemia, and 90% develop bone marrow failure by age
40.
About 60–75% of people have congenital defects, commonly short
stature, abnormalities of the skin, arms, head, eyes, kidneys, and ears,
and developmental disabilities. Around 75% of people have some
form of endocrine problems, with varying degrees of severity.

19. • FA is primarily an autosomal recessive genetic disorder.
• This means that two mutated alleles (one from each parent) are
required to cause the disease.
• Scientists have identified 17 FA or FA-like genes: FANCA, FANCB,
FANCC, FANCD1 (BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI,
FANCJ (BRIP1), FANCL, FANCM, FANCN (PALB2), FANCP (SLX4), FANCS
(BRCA1), RAD51C and XPF.