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Sara
CHAPTER 1. HEMATOLOGY
The most common site preferred for bone marrow biopsy: PSIS (Posterior Superior Iliac Spine)
In children: Anteromedial surface of the Tibia
Jamshidi Needle (Trephine Biopsy Needle) for Bone Marrow Biopsy. It is T-shaped
PATHOLOGY NOTES by Dr. Sara
→ Normal Bone Marrow Biopsy
In a biopsy a child would have 75% of cells and only 25% of Fat. An elderly person would have
25% cells and 75% fat. An adult has 50% cells and 50 % fats.
→ Aplastic Anemia
Supravital staining
RBC Indices
MCV (Mean cell volume): It is the average volume (in femtolitres) of a red blood cell (normal value is
82-96 f1)
Microcytic Macrocytic
Normocytic
Aplastic Anemia
PATHOLOGY NOTES by Dr. Sara
Based on Mechanism
G6PD
IV. Hb Defect:
Quantitative: Thalessemia
PATHOLOGY NOTES by Dr. Sara
Haemolytic Anemia’s
Types
Serum Haptoglobin ↓ -
Hemoglobinuria, Hemosiderinuria -
MAHA Hemoglobinopathies
AIHA (warm)
Enzyme defects
PATHOLOGY NOTES by Dr. Sara
Hereditary Spherocytosis
Autosomal Dominant
Band 2 Glycophorin A
2
Membrane
Actin
Ankyrin
Spectrin
Pathogenesis:
Reduced life span of RBCs in (HS) (10-20 days compared to the normal 120 days).
Main clinical findings in HS include Pallor jaundice, splenomegaly, and the formation of gallstones.
PATHOLOGY NOTES by Dr. Sara
Lab features:
Haemoglobin – ↓
MCV –↓ due to Membrane loss
MCHC** –↑ due to dehydration resulting from the loss of potassium (K+) and water.
RDW: ↑
Reticulocyte count: ↑
PBS shows micro spherocytes without central pallor
Pincer cell or mushroom cell is seen in Hereditary spherocytosis associated with Band 3 deficiency.
Splenectomy – Definitive treatment. Spherocytes are still present but extravascular haemolysis
does not occur.
G6PD Deficiency
XLR, M>>F
Deficiency of G6PD
Extravascular hemolysis
PATHOLOGY NOTES by Dr. Sara
Precipitating Factors
→ Fava beans (Mediterranean region), Fever, Infection, Antimalarial drugs
→ G6PD provides protection against plasmodium falciparum
→ Clinical features: Episodic Pallor, Jaundice, Hemoglobinuria (only when oxidative stress
→ No splenomegaly and gallstones
PBS findings:
Hemoglobinopathies
Haemoglobin (Hb) is a four-part molecule (tetramer) made up of 2 alpha and 2 beta chains.
AR
HbA 60%
HbS 40%
Sickle cell trait (HbAS) carriers have 60% HbA and 40% HbS.
Sickle cell disease (HbSS) individuals lack HbA, having a2ßS2 exclusively.
HbS (sickle hemoglobin) is less soluble and prone to forming polymers and take a sickle shape,
especially in dehydration, Hypoxia, Less PH.
PATHOLOGY NOTES by Dr. Sara
Rehydration can reverse sickling, but persistent hypoxia leads to sickled RBCs getting trapped in
the spleen, causing Hemolytic Anemia.
Sticky sickled RBCs adhere to blood vessels, causing blockages (vaso-occlusion) and damage to
organs.
HbA and HbF inhibit sickling, so sickle cell anemia symptoms typically start after the first six
months of life.
Clinical Features
Heart: Ischemia, MI
Hb: ↓
Reticulocyte count: ↑
Sickling test
Thalassemia
Quantitative Disorder of Hb
α Thalassemia β Thalassemia
Gene for Alpha chains is on chromosome 16 Gene for Beta chain is on chromosome 11
Alpha gene deletion Beta gene mutation
Beta Thalassemia
Normal Adult: HbA (α2β2) 95%, HbF (α2γ2) 1%, HbA2 (α2 δ2) 3%
Patterns of Hb Electrophoresis
PATHOLOGY NOTES by Dr. Sara
Screening test:
NESTROF/ Naked Eye Single Tube Red RBC Osmotic Fragility test
α Thalassemia
HbH Disease:
Type II HSN
MC
B-Cell Leukemia:CLL
Lab tests:
(MAHA)
Iron metabolism happens in three crucial steps: Absorption, Transport, and Storage.
Iron Absorption: Iron exists in two forms — Fe2+ (ferrous) and Fe3+ (ferric).
↓ Iron absorption: Phytates, Carbonates, Tannates, Tea, Coffee and drugs like tetracyclines.
Role of Transporters:
→ Cytochrome b Reductase: Convert Fe2+ to Fe3+, and the resulting Fe3+ is transported by
DMT1.
→ Transferrin has 6 iron attachment sites, yet only 2 are utilized by iron.
→ Normal transferrin saturation: 33%
→ It facilitates the transfer of iron from the bloodstream to macrophages in organs like the liver
and bone marrow. Erythroblasts express the transferrin receptor (T). ↑Transferrin receptors
present on early erythroid precursors. Late normoblast release all its receptors
→ Marker of erythropoiesis: S. Transferrin Receptors
Iron Storage:
Two primary forms store iron—ferritin and hemosiderin. Ferritin, in its condensed form known as
hemosiderin, tightly packs iron.
Iron Profile:
Plummer-Vinson Syndrome:
2. Dyspnea, palpitations
Stages of IDA
Anisocytosis
Poikilocytosis (including pencil cells)
Diagnosis:
Pathogenesis:
Sideroblastic Anemia
Sider is iron & blastic is immature precursors, this is an iron overload (↑↑Iron)
Pathogenesis
Hb synthesis pathway:
Succinyl Co A
Porphobilinogen
By many reactions
Protoporphyrin Iron
(Occurs in Mitochondria)
Ferrochelatase
Heme
Stained with
Aggregates of Fe
Perl’s Prussian
known as
Blue
Pappenheimer
bodies
PATHOLOGY NOTES by Dr. Sara
Bone Marrow Aspiration
Megaloblastic Anemia
Transcobalamine 2
Patients with Vitamin B12: N:C Asynchrony (Nuclear membrane is not matured & cytoplasm is
matured)
Vegans
Clinical Features
Howell jolly bodies (DNA remnants) Hypersegmented neutrophil >5% with 5 or more
Seen in Megaloblastic Anemia and Post nuclei
splenectomy RBC abnormalities: Macro-ovalocytes
Diagnosis:
1. S. Homocysteine ↑
2. S. Methyl Malonyl ↑
3. Blood: ↑MCV, ↑MCH, MCHC normal and unaffected
4. S. B12↓
Pernicious Anemia
Type 2 Hypersensitivity
Type of Auto-Ab
Folate Deficiency
Lets Revise !
PATHOLOGY NOTES by Dr. Sara
Q1. In a patient with suspected Plummer-Vinson syndrome, which of the following is least likely to
be observed?
a)
c)
b)
d)
Q2. In a 35-year-old woman presenting with body pain and easy fatigability, investigations reveal a
hemoglobin level of 7 gm/dL. The peripheral smear is given in the image below. Further tests
indicate elevated serum levels of homocysteine and methylmalonic acid. This condition may also
lead to:
a) Syringomyelia
b) Progressive multifocal leukoencephalopathy
c) Subacute combined degeneration of the spinal cord
d) Central pontine myelinolysis
Q3. In a pediatric patient with a history of recurrent chest infections and abdominal pain, along with
icterus and mild splenomegaly, and electrophoresis showing increased HbA2, HbF, and S spike,
what is the likely diagnosis?
a) Beta thalassemia
b) HbC disease
c) Sickle cell disease
d) Acute coronary disease
PATHOLOGY NOTES by Dr. Sara
Q4. A 20-year-old female presents with fatigue and weakness. Laboratory tests reveal hemoglobin
of 9 gm%, MCV of 55 fl, and RBC count of 4.5 million/mm³. There is no history of blood
transfusion. What is the most likely diagnosis?
a) Thalassemia major
b) Thalassemia minor
c) Iron deficiency anemia
d) Anemia of chronic disease
Q6. In a patient with microcytic hypochromic anemia, red cell distribution width was measured.
What is this parameter used to identify?
a) Anisocytosis
b) Poikilocytosis
c) Anisochromia
d) Biconcavity
Q9. Which of the following pairs of mutation and involved genes describes paroxysmal nocturnal
hemoglobinuria?
PATHOLOGY NOTES by Dr. Sara
a) AD inheritance - UMOD
b) Acquired genetic mutation - PIGA
c) AR inheritance - MUC1
d) Acquired genetic mutation - GPI
Q10. A 37-year-old man presents with a history of dark-colored urine in the morning for 2 months.
His lab investigations are given below. What is the curative therapy for this condition?
Hb level - 3 g/dL
RBC - 3 million/mm3
TLC - 1500 /mL
Platelet - 15,000 /uL
a) Eculizumab
b) Immunosuppressants
c) Blood transfusion
d) Hematopoietic stem cell transplant
Q11. A 12-year-old girl presents with fever and severe pain in her hands and feet. There is no history
of trauma. Her lab reports reveal Hb to be 8.2 g/dL and peripheral smear as shown below. Which
of the following parasitic infections is this condition protective against?
a) P. falciparum
b) P. vivax
c) P. ovale
d) Babesia
Q12. What is the most common protein deficiency associated with hereditary spherocytosis?
a) Spectrin
b) Ankyrin
c) Band 3
d) Glycophorin A
Q17. A Punjabi couple presents to you fearing that their child may have thalassemia because both
their families have a history of thalassemia. You ordered HPLC for both husband and wife, and it
shows Hb A2 levels of 2% and 4.9% for them, respectively. What is the percentage chance of their
child to get thalassemia major?
a) 0
b) 25
c) 50
d) 75
Q20. Which of the following correctly represents the effect of the mutation causing sickle cell
anemia?
a) Glutamate by valine at the 6th position
b) Valine by glutamate at the 6th position
c) Glutamate by valine at the 5th position
d) Valine by glutamate at the 5th position
Q22. A female patient presented with fatigue and a history of piles. Routine complete blood count
analysis showed hemoglobin of 9 g/dL, MCV 60 fL, and RBC count of 5.2 million. A peripheral
smear is given below. Which of the following is the next best investigation for this patient?
a) HbA2 levels
b) Serum ferritin levels
c) Serum folate levels
d) Serum homocysteine levels
Essential snippets
➢ Erythropoiesis in organs follows the sequence of yolk sac, liver, and then bone marrow.
➢ Best indicator of anisocytosis: RDW
➢ Hereditary spherocytosis is the only important anemia with increased MCHC.
➢ Biconcave shape of RBC is due to Spectrin.
➢ Most common defect in hereditary spherocytosis is Ankyrin (most common) followed by Band 3
(2nd MC). Others include defective spectrin and Band 4.2
➢ Most common cause of spherocytes: Immune hemolytic anemia.
➢ Young female with spherocytes, investigation to be done: Coomb's test (to rule out immune
hemolytic anemia).
➢ Bite cells and Heinz body are seen in G-6PD deficiency.
➢ Sickle cell anemia is due to a Point mutation (and not deletion).
➢ Sickling is affected by: Concentration of HbS (most important), deoxygenation and pH, duration
of deoxygenation in microcirculation.
➢ Best investigation for hemoglobinopathies is HPLC.
➢ On Hb electrophoresis: HbS moves slower than HbA towards the positive electrode.
➢ Sickle cell trait provides protection against: Falciparum malaria.
➢ Gamna Gandy bodies are seen in Sickle cell anemia, chronic myeloid leukemia, and cirrhosis.
➢ Mutation in thalassemia: Mainly point mutation (missense mutation) causing aberrant splicing.
➢ HbA, is raised (> 3.5%) in thalassemia trait whereas HbF is highly raised in thalassemia major
(Cooley's anemia).
PATHOLOGY NOTES by Dr. Sara
➢ HBH disease is due to three alpha genes deletion whereas Barts Hb is due to four gene deletions.
➢ Hair on end (Crew cut appearance) appearance on skull x-ray: Thalassemia, SCA, HS, G6PD
deficiency.
➢ Paroxysmal nocturnal hemoglobinuria is due to Acquired defect in red cell PIG-A gene leading
to defective (GPI)-linked proteins CD 55, CD 59. It is best diagnosed by flow cytometry.
➢ M/C collagen vascular disorder causing Coomb's positive hemolytic anemia is SLE whereas the
leukemia causing Coomb's positive test is CLL.
➢ Donath-Landsteiner antibody is seen in: Paroxysmal cold hemoglobinuria.
➢ Important causes of microcytic hypochromic anemia: Iron deficiency, sideroblastic anemia,
thalassemia, anemia of chronic disease.
➢ Mentzer index < 13: Thalassemia minor whereas Mentzer index > 13 is seen in iron deficiency
anemia.
➢ M/C anemia in chronic renal failure is Normocytic normochromic anemia.
➢ Sideroblastic anemia is having production of Ringed sideroblasts and its causes include collagen
vascular disorders (SLE), lead (lead poisoning leads to Inhibition of enzymes involved in heme
synthesis like ferrochelatase and aminolevulinic acid dehydratase), porphyria, myelofibrosis, iron
overload, alcoholism, myelodysplasia.
➢ Triad of megaloblastic anemia: Oval macrocytes (earliest finding), hypersegmented neutrophils,
Howell-Jolly bodies.
THE FUTURE BELONGS TO
THOSE WHO BELIEVE IN THE
BEAUTY OF THEIR DREAMS.
ELEANOR ROOSEVELT
ARISE-Chennai ARISE-Delhi
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