RBC AND

CASE DISCUSSIONS WBCS

CLINICAL SCENARIO:

A 35-year-old woman presents with fatigue, dizziness, and brittle

nails. She reports heavy menstrual bleeding for the past several
months. CBC shows Hb 8.9 g/dL, MCV 72 fL, and hypochromic
microcytic red cells. Ferritin is low, TIBC is elevated.
QUESTIONS:

a) What are the key laboratory findings that differentiate iron

deficiency anemia from other microcytic anemias?
b) Explain the pathogenesis of iron deficiency anemia.
c) Why is TIBC increased in this condition?
d) Name two clinical signs or symptoms related to epithelial tissue
changes in iron deficiency.
ANSWER KEY:

a) Low serum iron, low ferritin, high TIBC, microcytic hypochromic

RBCs; RDW is often elevated.
b) Iron deficiency → impaired hemoglobin synthesis → smaller RBCs
with less color.
c) TIBC rises because transferrin increases in response to low iron to
maximize iron transport.
d) Koilonychia (spoon nails), glossitis, angular cheilitis, and pica are
common epithelial-related findings.
SCENERIO
A 62-year-old vegetarian woman presents with fatigue, sore
tongue, and tingling in her feet. CBC shows macrocytic anemia
(MCV 118 fL) and hypersegmented neutrophils. Serum B12 is low,
folate is normal.
a) What is the most likely cause of this patient's anemia?
b) Describe the role of vitamin B12 in DNA synthesis and how its
deficiency leads to megaloblastic changes.
c) What are the key peripheral smear findings?
d) Why do neurologic symptoms occur in B12 deficiency but not in
folate deficiency?
ANSWER KEY:

a) Vitamin B12 deficiency, likely due to dietary insufficiency or

pernicious anemia.
b) B12 is needed to regenerate tetrahydrofolate → necessary for
DNA synthesis. Deficiency causes nuclear-cytoplasmic asynchrony →
megaloblastic cells.
c) Macrocytosis, hypersegmented neutrophils, and oval macrocytes.
d) B12 is required for methylmalonic acid metabolism; its buildup
impairs myelin, causing neurologic symptoms—folate doesn’t affect
this pathway.
SCENERIO
A 3-year-old child of South Asian descent presents with pallor,
growth retardation, and frontal bossing. Lab shows severe anemia
with microcytosis. Hemoglobin electrophoresis reveals increased
HbF and HbA2.
QUESTIONS:

a) What is the underlying genetic defect in beta-thalassemia major?

b) Explain how ineffective erythropoiesis contributes to the clinical
features.
c) What skeletal changes are typically seen and why?
d) What is the role of iron overload in this condition and how does it
occur?
ANSWER KEY:

a) Mutations in the β-globin gene reduce or eliminate β-globin

production.
b) Excess unpaired α-chains precipitate → damage erythroblasts →
marrow expansion and anemia.
c) Expansion of marrow causes crew-cut skull and facial bone
deformities (frontal bossing).
d) Repeated transfusions and increased GI absorption → iron
overload → hemosiderosis and organ damage.
CLINICAL SCENARIO:

A 15-year-old African boy is brought to the ER with sudden severe

limb pain. He has a history of multiple similar episodes. CBC shows
normocytic anemia, and peripheral smear reveals sickled cells.
QUESTIONS:

a) What mutation causes sickle cell anemia, and how does it affect
hemoglobin?
b) Explain the mechanism of vaso-occlusive crisis.
c) Name two long-term complications of sickle cell disease.
d) What factors precipitate sickling and how can they be prevented?
ANSWER KEY:

a) Point mutation in β-globin gene (Glu→Val at position 6) → HbS

polymerizes under deoxygenation.
b) Sickled RBCs block small vessels → ischemia → pain and organ
damage.
c) Avascular necrosis (e.g., femoral head), autosplenectomy, stroke,
leg ulcers.
d) Precipitating factors: hypoxia, dehydration, acidosis, cold.
Prevention: hydration, avoiding high altitudes, hydroxyurea.
CLINICAL SCENARIO:

A 12-year-old girl presents with mild jaundice and splenomegaly. Her

MCHC is elevated, and the osmotic fragility test is positive.
Peripheral smear shows spherocytes.
QUESTIONS:

a) What is the molecular basis of hereditary spherocytosis?

b) How does the RBC membrane defect lead to hemolysis?
c) What are the characteristic lab findings in this condition?
d) Why is splenectomy considered a treatment option?
ANSWER KEY:

a) Defects in RBC membrane proteins like spectrin, ankyrin, band 3

→ decreased membrane stability.
b) Loss of membrane surface area → spherocytes → trapped and
destroyed in spleen.
c) Normocytic anemia, elevated MCHC, reticulocytosis, positive
osmotic fragility test.
d) Splenectomy removes the site of RBC destruction and improves
anemia, though spherocytes persist.
CLINICAL SCENARIO:

A 33-year-old man complains of dark-colored urine in the morning.

Lab tests show anemia, mild leukopenia, and thrombocytopenia.
Flow cytometry shows absence of CD55 and CD59 on RBCs
QUESTIONS:

a) Describe the genetic and molecular defect responsible for PNH.

b) Why is hemolysis more prominent during sleep in PNH?
c) What is the most serious complication of this disease?
d) How is flow cytometry used in diagnosis?
ANSWER KEY:

a) Mutation in PIGA gene → loss of GPI anchor proteins (CD55, CD59)

→ RBCs become complement-sensitive.
b) At night, shallow breathing → mild acidosis → activates
complement → increased intravascular hemolysis.
c) Thrombosis, especially in abdominal veins (e.g., Budd-Chiari
syndrome).
d) Flow cytometry shows absence of CD55/CD59 on RBCs and
leukocytes → confirms diagnosis.
SCENERIO
A 22-year-old man develops jaundice and fatigue two days after
taking an antimalarial drug. Labs show hemolysis. Smear shows
bite cells and Heinz bodies
a) What is the role of G6PD in protecting red cells from oxidative
damage?
b) Explain the mechanism of hemolysis in this patient.
c) What are Heinz bodies, and how do they form?
d) List two common triggers for hemolysis in G6PD deficiency.
ANSWER KEY:

a) G6PD generates NADPH → maintains glutathione in reduced form

→ detoxifies oxidative stress.
b) Without G6PD, oxidative stress causes hemoglobin denaturation
→ membrane damage → intravascular and splenic hemolysis.
c) Heinz bodies are precipitated, oxidized hemoglobin seen inside
RBCs → removed by splenic macrophages → bite cells.
d) Triggers: antimalarials (e.g., primaquine), sulfa drugs, fava beans,
infections.
CLINICAL SCENARIO:

A 55-year-old man presents with fatigue, recurrent infections, and

spontaneous gum bleeding. On examination, there is no
lymphadenopathy or splenomegaly. CBC shows anemia,
thrombocytopenia, and high WBC count with circulating
myeloblasts. Auer rods are noted on peripheral smear.
QUESTIONS:

a) What is the diagnostic significance of Auer rods in this patient’s

smear?
b) Describe the pathogenesis of AML and the cell of origin.
c) What are the typical laboratory findings in AML?
d) Name two common cytogenetic abnormalities seen in AML and
their prognostic implications.
ANSWER KEY:

a) Auer rods are pathognomonic of AML, particularly seen in

myeloblasts; they are composed of fused lysosomes and azurophilic
granules.
b) AML is caused by acquired mutations in myeloid progenitor cells,
leading to blocked differentiation and proliferation of immature
myeloblasts.
c) Lab findings: anemia, thrombocytopenia, leukocytosis with
myeloblasts, elevated LDH, and DIC in acute promyelocytic
leukemia (APL).
d) t(15;17) in APL (favorable, responsive to ATRA); t(8;21) (also
favorable); complex karyotype or monosomy 7 (poor prognosis).
CLINICAL SCENARIO:

A 7-year-old boy presents with fever, bone pain, and generalized

lymphadenopathy. He also has petechiae and pallor. CBC shows
pancytopenia with numerous lymphoblasts. Flow cytometry shows
TdT and CD10 positivity.
QUESTIONS
a) What is the most likely diagnosis and its most common age
group?
b) Describe the origin and key immunophenotypic markers of
lymphoblasts in ALL.
c) Why is bone pain a common symptom in children with ALL?
d) Mention two important prognostic factors in pediatric ALL.
ANSWER KEY:

a) Diagnosis: Acute lymphoblastic leukemia (ALL), most common in

children aged 2–10 years.
b) Lymphoblasts originate from immature B or T lymphoid
precursors; markers include TdT+, CD10+, CD19+ (B-cell); CD3+ (T-
cell).
c) Bone pain is due to leukemic infiltration and expansion of the
marrow cavity.
d) Favorable factors: age 2–10 years, low WBC count, early response
to therapy; poor prognosis with CNS involvement or adverse
cytogenetics (e.g., t(9;22)).
CLINICAL SCENARIO:

A 45-year-old male presents with fatigue, weight loss, and early

satiety. On examination, spleen is palpable 6 cm below the costal
margin. CBC shows elevated WBC count (120,000/μL) with increased
neutrophils, myelocytes, metamyelocytes, basophils, and
eosinophils. LAP score is low.
QUESTIONS:

a) What genetic abnormality is characteristic of CML and how is it

detected?
b) Explain the mechanism of leukocytosis in CML.
c) How is CML distinguished from leukemoid reaction?
d) What is the significance of progression to blast crisis in CML?
ANSWER KEY:

a) Philadelphia chromosome t(9;22) → BCR-ABL fusion gene →

detected via PCR or FISH.
b) BCR-ABL is a constitutively active tyrosine kinase → promotes
unchecked myeloid cell proliferation.
c) CML: low LAP, presence of basophils, BCR-ABL+; Leukemoid
reaction: high LAP, reactive left shift, no basophils or BCR-ABL.
d) Blast crisis is the terminal phase of CML resembling acute
leukemia; poor prognosis and resistance to therapy.
CLINICAL SCENARIO:

A 65-year-old man is found to have lymphocytosis on routine blood

tests. He reports mild fatigue but no other symptoms. Peripheral
smear shows numerous small, mature lymphocytes and smudge
cells. Flow cytometry shows CD5 and CD23 positivity.
QUESTIONS:

a) What are the key diagnostic features of CLL on smear and flow
cytometry?
b) Why are smudge cells commonly seen in CLL?
c) List two potential complications of advanced CLL.
d) How does CLL typically progress over time in most patients?
ANSWER KEY:

a) Smear shows mature small lymphocytes and smudge cells; flow

cytometry: CD19+, CD5+, CD23+ B-cells (aberrant expression).
b) Smudge cells result from mechanical fragility of the CLL
lymphocytes during slide preparation.
c) Complications: hypogammaglobulinemia → infections;
autoimmune hemolytic anemia; Richter transformation to DLBCL.
d) CLL often has an indolent course; may not need treatment for
years. Progression is slow but may evolve to more aggressive
disease in some.