PATHOLOGY NOTES by Dr.

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

→ Used for Bone Marrow Aspirate

Side screw: Salah Needle

Longitudinal screw: Klima Needle

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

Fat cells replace hematopoietic cells in the bone marrow. Pancytopenia, no

hepatosplenomegaly, Associated with Parvo B19 infection. Fat in marrow.
 PATHOLOGY NOTES by Dr. Sara
→ Stages of RBC development

➢ Hb first appears on LM in: Intermediate/ Polychromatic Erythroblast

➢ During erythroblast maturation: ↓ cell and Nucleus size
➢ Reticulocytes (Polychromatophil)
➢ Reticulocyte count is an indicator of erythropoietic activity of the bone marrow
▪ ↓: Hypoproliferative Anemia
▪ ↑: Hemolytic Anemia
➢ They are immature RBC’s

Supravital staining

Contains Ribosomal RNA (imparts bluish color)

 PATHOLOGY NOTES by Dr. Sara
→ Normal Peripheral Blood Smear (PBS)

RBC Indices
MCV (Mean cell volume): It is the average volume (in femtolitres) of a red blood cell (normal value is
82-96 f1)

MCV MCH MCH RDW

(Mean cell volume) (Mean corpuscular (Mean corpuscular (Red cell
hemoglobin) hemoglobin) distribution width)
80-100 fl 27-33 pg 33-37 g/dl 11.5-14.5
 PATHOLOGY NOTES by Dr. Sara
RBC Morphology

Acanthocytes (Spur cells) Echinocytes (Burr cells)

Seen in Liver disease, Vitamin E deficiency.

Projections of varying sizes at irregular intervals
Dacrocytes (Tear Drop RBC’s)
Uniform distribution of projections on the
surface of the cell. Seen in pyruvate kinase
deficiency, Liver disease.
Schistocytes (Helmet cells)

Fragmented RBC’s. Seen in MAHAH Eg: DIC,

Seen in Myelofibrosis TTP/HUS. HELLP syndrome etc.

Degmatcytes (Bite cells) Elliptocytes

Seen in G6PD deficiency

Seen in Hereditary Elliptocytosis caused by a

mutation in Alpha Spectrin
 PATHOLOGY NOTES by Dr. Sara

Classification of Anaemias according to MCV

Microcytic Macrocytic

Sideroblastic Anaemia Liver disease (Alcoholics)

Iron deficiency Anaemia Hypothyroidism

Thalassemia Megaloblastic Anaemia

Anaemia of chronic (B9 & B12 deficiency)

disease
Cytotoxic drugs (Methotrexate, Phenytoin)

Normocytic

Anemia of Chronic Disease

Aplastic Anemia
 PATHOLOGY NOTES by Dr. Sara

Based on Mechanism

Blood loss: ↑RBC Destruction ↓RBC production

Acute: Trauma
(Hemolytic Anemia) Nutritional Anemias
Chronic: Gi Lesions
I. Membrane defect IDA
Megaloblastic Anemia
Hereditary Spherocytosis
Sideroblastic Anemia
Paroxxysmal Nocturnal Hematuria
Myelopthisic Anemia

II. Enzyme defect

G6PD

III. Immune mediated

Autoimmune Hemolytic Anemia

IV. Hb Defect:

Qualitative: Sickle Cell Anemia

Quantitative: Thalessemia
 PATHOLOGY NOTES by Dr. Sara
Haemolytic Anemia’s

Types

Intravascular Hemolysis Extravascular Hemolysis

Hemolysis occurs inside a blood vessel Hemolysis occurs outside the blood vessel

Eg: Liver, Spleen

No Hepatosplenomegaly Hepatosplenomegaly, Jaundice

Serum Haptoglobin ↓ -

Hemoglobinuria, Hemosiderinuria -

Intracorpuscular Defects Extracorpuscular Defects

Membrane defects: Hereditary Spherocytosis, Immune mediated:
Hereditary Elliptocytosis Autoimmune Hemolytic Anemia
Enzyme defects: G6PD Deficiency, Pyruvate Non-Immune mediated:
Kinase deficiency, Hexokinase deficiency Infections like Malaria
Hemoglobinopathies: Sickle cell Anemia,
Thalassemia
Acquired: PNH

Intravascular Hemolysis Extravascular Hemolysis

PNH Membrane defects

MAHA Hemoglobinopathies

AIHA (warm)
Enzyme defects
 PATHOLOGY NOTES by Dr. Sara
Hereditary Spherocytosis

Autosomal Dominant

Band 2 Glycophorin A
2

Membrane

Actin
Ankyrin

Spectrin

Spectrin: The chief protein component responsible for biconcave shape

2. Ankyrin and band 4.2: Binds spectrin to band 3
3. Band 3: A transmembrane ion transport protein.
4. Band 4.1: Binds spectrin to glycophorin A, a transmembrane protein. \

Pathogenesis:

Reduced life span of RBCs in (HS) (10-20 days compared to the normal 120 days).

Increased osmotic fragility of RBCs is a characteristic feature in HS

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.

OSMOTIC FRAGILITY TEST

Screening test
This test is a measure of RBC resistance to haemolysis by osmotic stress.
Patient’s RBCs are suspended in decreasing concentrations of normal saline.

HS patients have ↑ osmotic fragility, Graph shifts towards right.

In thalassemia patients, RBCs are resistant, graph shifts towards left.
 PATHOLOGY NOTES by Dr. Sara
Complications:
Aplastic crisis in HS is triggered by acute Parvovirus infections.

Splenectomy – Definitive treatment. Spherocytes are still present but extravascular haemolysis
does not occur.

Conditions with spherocytosis

Autoimmune hemolytic anemias: MC (Coomb’s test positive)

G6PD deficiency, Hereditary spherocytosis (Coomb’s Test Negative)

Burns, Infections (Malaria)

G6PD Deficiency

XLR, M>>F

Hexose monophosphate shunt (HMP Shunt)

Deficiency of G6PD

↑H2O2 thereby ↑ oxidative stress in a cell

Denaturation of Hb: Heinz bodies Eaten by splenic macrophages:

membrane loss: Bite cells

Increased Intravascular Hemolysis

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:

Heinz bodies, seen on Bite cells Blister cells

supravital staining
(Brilliant cresyl blue)

Paroxysmal Nocturnal Hemoglobinuria (PNH)

➢ Acquired Intracorpuscular defect in PNH.
➢ Hemoglobin eliminated in urine at night.
➢ PIGA gene on X chromosome produces GPI anchors.
➢ Anchors (CD55, CD59, C8 binding protein, Leukocyte Alkaline Phosphate) control complement
system.
Pathogenesis:
➢ Respiratory rates slightly reduce at night.
➢ Reduced pH activates complement system (controlled by CD55, CD59).
➢ PIGA gene defect, anchors (CD55, CD59) are absent in PNH.
➢ Uncontrolled complement system leads to RBC breakdown.
➢ Broken RBCs eliminated in urine.
Investigation of choice for PNH: Flow Cytometry
Detects CD59 and CD55.
Treatment
 PATHOLOGY NOTES by Dr. Sara
➢ Eculizumab (C5 Inhibitor):
Prevents RBC breakdown by inhibiting complement activation.
➢ Replacement of defective stem cells (HSCT)

Hemoglobinopathies

Sickle Cell Anemia & Thalassemia

Haemoglobin (Hb) is a four-part molecule (tetramer) made up of 2 alpha and 2 beta chains.

Normal Hb (HbA) α2β2 chains: 95%

HbA2: α2 δ2 chains: <3%

HbF (Fetal Hemoglobin): α2γ2: <1%

Sickle Cell Anemia (SCA)

AR

Sickle Cell Anemia

Sickle cell trait Sickle cell disease HbSS

>>90%
HbAS

HbA 60%

HbS 40%

Missence point Mutation: At β 6 subunit Glutamic Acid changes to Valine

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.

HbC (at β6): Glutamic acid is replaced by lysine

Clinical Features

Pallor, splenomegaly, and jaundice result from extravascular hemolysis.

Vaso-Occlusive Crisis (Most commonly seen in adults)

Bones: Can be at a risk of developing osteomyelitis caused by Salmonella

Vertebra: Characterized by fish mouth appearance

Long bones: Avascular necrosis

Small bones: Exhibits acute dactylitis (Hand foot syndrome)

Brain: Stroke, TIA

Heart: Ischemia, MI

Lungs: Prone to acute chest syndrome.

 PATHOLOGY NOTES by Dr. Sara
Other Crises:

➢ Aplastic Crisis: Linked to parvovirus B19 infection.

➢ Sequestration Crisis:
➢ Pooling of blood in the spleen
➢ Damages the spleen, first increase in size then leading to multiple splenic infarcts.
➢ Results in decreased spleen size, known as auto-splenectomy.
➢ Lab Values:

Hb: ↓

Reticulocyte count: ↑

ESR: ↓↓ (d/t RBC do not get packed and settle down)

Sickling test

➢ Done when no sickle cells are found on PBS

➢ 2% Sodium metabisulfite added to a drop of blood to remove oxygen: cell converts to sickle
shape.

Hemoglobin Gel Electrophoresis

 PATHOLOGY NOTES by Dr. Sara
Treatment: Hydroxyurea: ↑ Fetal Hb: Treats Hypoxia by ↑ oxygen affinity, Oxygen, IV fluids,
analgesics

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%

Types of Beta Thalasemia

Beta Thalassemia Major: β0 β0

Beta Thalassemia Trait/ Minor: β+ β

 PATHOLOGY NOTES by Dr. Sara
The diminished production of beta chains

Reduced α2β2→Reduced HbA: α2 chains combine with γ2: Increase in HbF:

Microcytic Hypochromic Anemia Erythropoiesis
α chains form tetramers:
Ineffective erythropoiesis

Extramedullary Erythropoiesis Rbc’s destroyed in spleen

Crew cut/ Hair on End Appearance Extravascular hemolysis
Chimpunk faces

Increase load on Bone marrow: Erythroid Hyperplasia

Increase in iron absorption from GIT
Repeated blood transfusion: ↑ Iron levels→ Iron overload

Feature β Thalassemia β Thalassemia β Thalassemia

Major (Cooley’s Intermedia Minor
Anemia)
β chains are not Some β chains present One β chains is normal
produced
Clinical Features H/O repeated Blood Pallor, Jaundice, Usually,
transfusion Hepatosplenomegaly asymptomatic
Hepatosplenomegaly
Jaundince, Pallor
Hb 3-5 gm% 5-8 gm% 8 gm%
RBC indices ↓MCV, MCH, MCHC, ↓MCV, MCH, MCHC, Asymptomatic
RDW: Normal RDW: Normal
Iron profile ↑ iron Normal Normal
Hb electrophoresis, ↑HbF Both↑ ↑HbA2 >3.5
HPLC

Hb HPLC: 2nd Best investigation after Globin gene sequencing

 PATHOLOGY NOTES by Dr. Sara

Microcytic Hypochromic RBC

Codocytes/ Target cells
Nucleated RBC’s

Crew cut/ Hair on End appearance Chipmunk Facies

Seen in both Thalassemia & Sickle Cell Anemia Maxillary prominence is seen

Thalassemia Minor/ Trait

Incidental finding
Mild Microcytic Hypochromic Anemia
No H/O blood transfusion
Hb Electrophoresis/ HPLC: ↑ HbA2
Differentiates between Thalassemia trait and IDA

Patterns of Hb Electrophoresis
 PATHOLOGY NOTES by Dr. Sara

Screening test:

NESTROF/ Naked Eye Single Tube Red RBC Osmotic Fragility test

Iron Deficiency Anemia Β Thalassemia Trait

RDW: Increases RDW: Normal

Mentzer Index: > 13 < 13

(MCV/RBC count)

HbA2 <3.5% 3.5%

RBC: Less More

Iron Profile: Abnormal Normal

α Thalassemia

Due to gene deletion

Ch16 → 4 α genes (α α/ α α → Normal)

 PATHOLOGY NOTES by Dr. Sara

Categorization into four types based on the quantity of deleted genes

1 α gene deleted 2 α gene deleted 3 α gene deleted 4 α gene deleted

α α/ α- α α/ -- α -/ -- - -/ --
Silent Carrier Thalassemia trait Formation of β 4 Gamma 4 tetramers
tetramers are formed
HbH disease Hb Bart’s
Hydrops fetalis (IUD)

HbH Disease:

Golf ball inclusions

New Methylene blue

Autoimmune Hemolytic Anemia

Type II HSN

Has two major types :

Warm antibody AIHA (37°c)- IgG

MC

Causes: Idiopathic (MC)

Autoimmune disorders: SLE

B-Cell Leukemia:CLL

IgG antibodies are produced against P antigen of RBC

IgG is a potent opsonin

Engulfed by splenic macrophages: EVH

Cold antibody AIHA (4°c)

 PATHOLOGY NOTES by Dr. Sara

Cold Agglutinin disease Cold Hemolysin type

Causes: Infections: Mycoplasma, Formation of IgG

Malignancies (Waldenstorm macroglobulinemia) AKA Paroxysmal Cold Hemoglobinuria

IgG is AKA: Donath Landsteiner antibody

IgM → ‘I’ Antigen of RBC Activates complement system

Binds to RBC at cold temperature Lysis of RBC (IVH)

Clumping/ agglutination of RBC

IgM→ Complement proteins→ c3b attachment→

destruction of RBCs by hepatic macrophages:
EVH

Lab tests:

➢ Peripheral blood smear: Spherocytes

➢ Coomb’s test positive
➢ RBC clumps (agglutination) in cold antibody

Intravascular Hemolysis Extravascular Hemolysis

G6PD Deficiency G6PD deficiency

Plasmodium Falciparum Hereditary Spherocytosis

Microangiopathic Hemolytic Anemias Sickle cell Anemia

(MAHA)

AIHA (PCH) AIHA

Micrcocytic Hypochromic Anemia

Iron Deficiency Anemia

 PATHOLOGY NOTES by Dr. Sara
Most common Nutritional Anemia

Physiology of Iron Metabolism

Iron metabolism happens in three crucial steps: Absorption, Transport, and Storage.

Iron Absorption: Iron exists in two forms — Fe2+ (ferrous) and Fe3+ (ferric).

Site of Iron absorption (Fe2+): Duodenum

↑ Iron absorption: Acids like HCl and Ascorbic acid, Acidic pH

↓ Iron absorption: Phytates, Carbonates, Tannates, Tea, Coffee and drugs like tetracyclines.

Role of Transporters:

→ DMT1: Responsible for transporting Fe2+.

→ Cytochrome b Reductase: Convert Fe2+ to Fe3+, and the resulting Fe3+ is transported by

DMT1.

→ Ferroportin: Transports Fe2+ into the body.

 PATHOLOGY NOTES by Dr. Sara
Oxidation Process: Hephaestin and ceruloplasmin play crucial roles in oxidizing Fe2+ to Fe3+

Hepcidin: Produced by liver, Inhibits Ferroportin, Master regulator of Iron

Iron Transport via Transferrin:

→ 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:

1. % Transferrin Saturation: 33%

2. Serum Iron: 100-120 mg/dL

3. TIBC (Total Iron Binding Capacity): 300-360 mg/dL

4. Serum Ferritin: Key indicator of iron storage; inversely proportional to TIBC.

Causes of Iron Deficiency Anemia (IDA):

→ Infants: Breastmilk (poor source of iron)

→ Children: Growing child, nutritional deficiency, worm infestation (Hookworm)
→ Adults: Chronic Peptic ulcer disease, piles; Females more susceptible than males
→ Elderly: Chronic blood loss (GI cancer, colon cancer, genitourinary cancer), history of
gastrectomy, malabsorption disorder, celiac sprue

Plummer-Vinson Syndrome:

Triad of IDA, glossitis, and esophageal webs.

 PATHOLOGY NOTES by Dr. Sara

Clinical Features of IDA:

1. Fatigue, stunted growth

2. Dyspnea, palpitations

3. Koilonychia (spoon-shaped nails)

4. Hair loss, pica (craving for non-nutritive substances)

Stages of IDA

1. Decrease in Iron storage: ↓ S. Ferritin

2. Iron deficient erythropoiesis
3. RBCs affected, Now KA IDA: Microcytic Hypochromic Anemia. PBS findings is seen here

Anisocytosis
Poikilocytosis (including pencil cells)

Diagnosis:

Gold Standard: Bone Marrow Examination, Prussian blue staining.

Blood ↓Hb ↓MCH ↓MCV ↓MCHC ↑RDW

Iron Profile ↓ S. Ferritin ↓ S. Iron ↓T Saturation ↑TIBC

 PATHOLOGY NOTES by Dr. Sara
↑↑Free erythrocyte protoporphyrin

Treatment: Iron supplementation: Oral/ Parenteral

Anemia of Chronic Disease

It is most commonly Normocytic Normochromic but can also be Microcytic Hypochromic

Pathogenesis:

Chronic Disorder (RA)

Release of Cytokine IL 6→Acts on liver→ Increase in Hepcidin

Hepcidin: Inhibits Fe absorption

Inhibits the levels of Fe from Ferritin: ↑ Ferritin: ↓TIBC

Iron Profile ↓ S. Fe ↓T. Saturation ↑Ferritin ↓TIBC

Treatment: Treat the underlying cause

Sideroblastic Anemia

Opposite to iron profile study in IDA

Sider is iron & blastic is immature precursors, this is an iron overload (↑↑Iron)

Causes: Congenital: Enzyme Defect (ALA synthase etc.)

Acquired: Alcohol, Vitamin B6 deficiency, Anti TB drug (Isoniazid), Lead poisoning

Pathogenesis

Hb synthesis pathway:

Hb: Heme + globin

Heme is made up of Iron and Protoporphyrin

Succinyl Co A

ALA synthase (Rate Limiting)

 PATHOLOGY NOTES by Dr. Sara

Porphobilinogen

By many reactions

Protoporphyrin Iron
(Occurs in Mitochondria)

Ferrochelatase

Heme

Peripheral Blood smear

Stained with
Aggregates of Fe
Perl’s Prussian
known as
Blue
Pappenheimer
bodies
 PATHOLOGY NOTES by Dr. Sara
Bone Marrow Aspiration

Ringed Sideroblasts are seen

(At least 5 granules of iron covering 1/3 of nucleus)

Feature IDA AOCD Sideroblastic Anemia Thalessemia

S. Iron ↓ ↓ ↑ N
Transferrin ↓ ↓ ↑ N
Saturation
Ferritin ↓ ↑ ↑ N
S. TIBC ↑ ↓ ↓ N
P/S Pencil Cells, Ringed Sideroblasts
Coarse Basophilic
stippling
Extra RDW↑ ESR↑ Mentzer
Mentzer >13 Index <13

Megaloblastic Anemia

→ B12 and Folic Acid Deficiency Anemia

→ Vitamin B12
→ Absorbed at the terminal Ileum
→ Source: Animal food (Milk & Meat), (Usaully deficient in Vegetarian/ Vegan people)
 PATHOLOGY NOTES by Dr. Sara
Vitamin B12 from food HAPTOCORIN
(Produced by salivary gland)

B12 Haptocorin complex

Haptocorin is separated from B12 by pancreatic enzymes

B12 binds with Intrinsic factor

(Produced by parietal cells of the stomach)

B12-IF complex moves to terminal ileum

Cubulin receptors of T. Ileum absorb B12

Transcobalamine 2

Transported to other parts of the body

Uses of Vitamin B12

Thymidine production: Important for nuclear maturation

Nuclear Cytoplasmic Asynchrony

Patients with Vitamin B12: N:C Asynchrony (Nuclear membrane is not matured & cytoplasm is
matured)

B12 is a coenzyme for 2 reactions

 PATHOLOGY NOTES by Dr. Sara
In B12 deficiency ↑Methyl Malonyl levels are seen. ↓ Succinyl CoA level leads to deficiency of
myelin production; Neurological symptoms

Causes of Vitamin B12 Deficiency

Vegans

Infections: Diphyllobothrium latum (Fish tapeworm)

↑Requirement: Pregnancy, Children, Lactation

At Stomach level: Gastrectomy/ Pernicious Anemia

At Pancreas level: Pancreatitic insufficiency

At Ileum level: Malabsorption disorders, GIT TB, Crohn’s disease

Clinical Features

Bone Marrow Findings: Pancytopenia, Hypercellular BM (Ineffective erythropoiesis)

Howell jolly bodies (DNA remnants) Hypersegmented neutrophil >5% with 5 or more
Seen in Megaloblastic Anemia and Post nuclei
splenectomy RBC abnormalities: Macro-ovalocytes

Cabot rings composed

of Arginine rich mitotic
spindle.
 PATHOLOGY NOTES by Dr. Sara

Hyperpigmented of knuckles due to Beefy tongue

increased tyrosinase activity

Diagnosis:

1. S. Homocysteine ↑
2. S. Methyl Malonyl ↑
3. Blood: ↑MCV, ↑MCH, MCHC normal and unaffected
4. S. B12↓

Pernicious Anemia

Type 2 Hypersensitivity

Autoimmune, patients have auto-Ab

Type of Auto-Ab

I. Type 1 Ab: ↓IF (Inhibits B12 binding to IF)

II. Type 2 Ab: Ileal (Inhibits binding of B12-IF to iliac cubulin)
III. Type 3 Ab: Ab against Parietal cells (IF not released)

Atrophic gastritis: Risk for Gastric Adenocarcinoma

Clinical Features: Atrophic tongue + Chronic Gastritis

Tx: B12 supplementation (Parenteral in Pernicious Anemia)

Folate Deficiency

Site for folate absorption: Jejunum

Causes: Drugs: Phenytoin, OCP’s, Methotrexate, Alcholics, Pregnancy (NTD’s)

Clinical Features: Megaloblastic Anemia with NO neurological symptoms.

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

Q5. Which of the following statements is false about reticulocytes?

a) They are nucleated
b) They contain ribosomal RNA
c) They are larger in size than red cells
d) Their normal count is 0.5-1.5%

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

Q7. Which of the following is not increased in intravascular hemolysis?

a) Lactate dehydrogenase
b) Free hemoglobin
c) Methemoglobin
d) Haptoglobin

Q8. Which of the following does not cause intravascular hemolysis?

a) Paroxysmal nocturnal hemoglobinuria
b) Thrombotic thrombocytopenic purpura
c) Infection
d) Thalassemia

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

Q13. Osmotic fragility is increased in

a) Sickle-cell anemia
b) Thalassemia
c) Hereditary spherocytosis
d) Chronic lead poisoning
 PATHOLOGY NOTES by Dr. Sara
Q14. The most common trigger for hemolysis in G6PD deficiency is _
a) Infection
b) Drugs
c) Fava beans
d) Alcohol

Q15. Heinz bodies are seen in

a) Hereditary spherocytosis
b) Sickle-cell anemia
c) Megaloblastic anemia
d) G6PD deficiency

Q16. Hb Barts is a tetramer of

a) Alpha chains
b) Beta chains
c) Gamma chains
d) Delta chains

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

Q18. NESTROF test is used to diagnose

a) Sickle cell anemia
b) Thalassemia
c) Hereditary spherocytosis
d) PNH

Q19. CD-59 is involved in

a) Paroxysmal nocturnal hemoglobinuria
b) Chediak-Higashi syndrome
 PATHOLOGY NOTES by Dr. Sara
c) Essential thrombocythemia
d) Primary myelofibrosis

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

Q21. In which of the following conditions is macrocytic anemia seen?

a) Thalassemia
b) Anemia of chronic disease
c) Sideroblastic anemia
d) Liver disease

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

Q23. Supravital stains are used in the identification of all except?

a) Reticulocytes
b) Copper in tissue
c) Heinz bodies
d) Ribosomal RNA
 PATHOLOGY NOTES by Dr. Sara
Q24. A 24-year-old male patient arrives with a case of anemia. Both his father and paternal aunt
experienced a similar illness and were effectively treated with splenectomy. The patient's
peripheral blood smear resembles the one depicted in the accompanying illustration. What other
abnormalities can be anticipated?

a) Decreased osmotic fragility

b) Decreased reticulocytes
c) Heinz bodies
d) Howell-jolly bodies

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

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