inherited HA: red cell memb defect+hemoglobinopathies

Question 1

hereditary spherocytosis

Answer 1

A genetic disorder where red blood cells (RBCs) become sphere-shaped (spherocytes) instead of their normal disc shape. These cells are fragile and get destroyed too early in the spleen, leading to anemia.

Question 2

genetic mutation in hereditary spherocytosis

Answer 2

Genetic mutation affecting proteins that maintain RBC shape (spectrin, ankyrin, band 3, protein 4.2).
• Autosomal dominant in most cases (runs in families).

Question 3

what happens in hereditary spherocytosis

Answer 3

1. RBCs lose flexibility → Can’t squeeze through the spleen.
2. Splenic macrophages destroy them → Extravascular hemolysis (in the spleen).
3. Anemia develops (low RBC count).
4. Body tries to compensate by making more RBCs → High reticulocyte count.

Question 4

symptoms of hereditary spherocytosis

Answer 4

• Jaundice (yellow skin, high bilirubin).
• Splenomegaly (big spleen due to overwork).
• Pigmented gallstones (from excess bilirubin).
• Fatigue, pallor (due to anemia).

Question 5

blood test in hereditary spherocytosis

Answer 5

CBC =microcytic anemia (mild) and reticulocytosis
• BF = spherocytes, ­high retics (because these patients are trying to compensate for the destruction of red blood cells).

Question 6

what is coombs test in hereditary spherocytosis

Answer 6

Negative direct Coombs test—helps to distinguish hereditary spherocytosis (HS) from AIHA (also characterized by spherocytes)

Question 7

hereditary elliptocytosis

Answer 7

RBCs elliptical in shape. Milder clinically, doesn’t require splenectomy

• caused by mutations in genes encoding RBC membrane proteins (e.g., spectrin, protein 4.1); usually asymptomatic, genetic mutations result in weakness of the cytoskeleton of the cell, leading to deformation of the cell.

Question 8

what is diff btwn direct and indirect coombs test

Answer 8

1. Direct Coombs Test (DCT) – “Is there an attack happening now?”
   • Detects antibodies or complement proteins that are already attached to RBCs.
   • Used to diagnose autoimmune hemolytic anemia (AIHA) and hemolytic reactions.
2. Indirect Coombs Test (ICT) – “Are there dangerous antibodies in the plasma?”
   • Detects free antibodies in the plasma that can bind to RBCs in the future.
   • Used for blood compatibility testing before transfusions and in pregnancy screening.

Question 9

what is coombs test

Answer 9

The Coombs test is a blood test used to detect antibodies that attack red blood cells (RBCs), leading to hemolysis (destruction of RBCs).

Question 10

inherited hemolytic anemia examples

Answer 10

red cell membrane defects
hb abnormalities
metabolic defects enzyme

Question 11

normal hemoglobin chain is

Answer 11

2a and 2b chains

Question 12

what is the possibilty of inheritance in hemoglobin abnormalities

Answer 12

(Autosomal recessive): If both parents are carriers, 25% of offspring will be affected, 50% carriers, and 25% normal

Question 13

in alpha thalasemia there is decrease in what

Answer 13

Alpha thalassemia occurs when one or more of the four alpha-globin genes (HBA1, HBA2) are missing or mutated.

• More missing genes = more severe disease.

Question 14

what is a silent carrier in alpha thalasemia

Answer 14

1 alpha gene is affected no symptoms normal blood test

Question 15

what is the diagnosis if 2 alpha genes are missing asymptomatic and mild microcytic anemia

Answer 15

alpha thalassmia trait (minor)

Question 16

what is the electrophosis shown in alpha thalassmia trait

Answer 16

(97% HbA, 2% HbA2, 1% HbF)

Question 17

what is the diease when 3 alpha genes are missing

Answer 17

Hbh

Question 18

what is the presentation of anemia in a pt with Hbh disease

Answer 18

Severe microcytic hypochromic anemia, hemolyAc anemia, splenomegaly —> splenectomy if requiring frequent blood transfusions are needed

Question 19

electrophoresis in Hbh

Answer 19

Hbh

Question 20

what is hydrops fetalis (Hb barts)

Answer 20

Complete absence of alpha = fatal at birth (hydrops fetalis)

Question 21

b thalasemia is most common in who

Answer 21

Mediterranean, Middle Eastern, and Indian ancestry

Question 22

what does Hb electrophoresis in B-thalassmia minor show

Answer 22

high HbA2

Question 23

is b thalassmia minor transfusion dependent

Answer 23

NO

Question 24

what type of b thalassmia is moderate anemia doesn’t require blood transfusion in childhood, but many will become transfusion-dependent in adulthood with two partially functioming alleles

Answer 24

b thalasemia intermedite

Question 25

Hb electrophoresis in B thalassmia intermediate

Answer 25

high HbF

Question 26

what time of b thalassmia causes Massive hepatosplenomegaly (due to extramedullary hematopoiesis & extravascular hemolysis)

Answer 26

Beta thalasemia major (cooleys anemia)

Question 27

when does B thalasemia major occur

Answer 27

1st yr of life = Severe anemia, failure to thrive, recurrent infections

Question 28

what do u see in xray in B thalasemia

Answer 28

Bone abnormalities due to hypertrophy of ineffective bone marrow -enlarged maxilla -prominent frontal & parietal bones (skull x-ray: hair on end appearance) (result in “crew-cut” appearance on skull X-ray)

Question 29

what do u look for to differ btwn thalassmia and IDA

Answer 29

Mentzer index: MCV/RBC count If <13: thalassemia (decreased MCV & ­ RBC). If >13: IDA

Question 30

what is the blood film of thalasemia

Answer 30

-microcytic hypochromic RBCs -basophilic nucleated RBCs -target cells -anisopoikilocytosis

Question 31

main tx of thalasemia

Answer 31

blood transfusion or best bone stem cell transplant

Question 32

Sickling is precipitated by anything that shifts the oxygen dissociation curve to the right:

Answer 32

hypoxia, dehydration, infection, acidosis, cold weather

Question 33

what is Autosomal recessive disorder resulting from the inheritance of two HbS genes (homozygous), causing normal Hb A to be replaced by the mutant Hb S

Answer 33

sickle cell anemia

Question 34

what causes sickle cell anemia mutation where

Answer 34

This results in a glutamic acid (hydrophilic) being replaced by valine (hydrophobic) at position 6 of the beta-globin chain. • The mutated hemoglobin is called Hemoglobin S (HbS).

Question 35

what is the reason of the sickle shape

Answer 35

When HbS is deoxygenated it becomes insoluble and polymerizes --> increased rigidity and sickle shape

Question 36

what is a complication of sickle cell

Answer 36

--> hemolysis & premature destruction of RBCs and vaso-occlusion (obstruction of micro-circulation) leading to tissue infarction bcs stuck

Question 37

when do signs and symptoms of sickle cell pt start

Answer 37

after 6 months of age (before then HbF is normal) • HbF does not sickle and prevents red blood cells from becoming rigid. • It reduces the effects of sickle hemoglobin (HbS).

Question 38

how does the spleen look like in sickle cell

Answer 38

o Auto-splenectomy = splenic atrophy from repeated infarction--> patient susceptable to infections with capsulated organisms (pneumococcus, salmonella, Hemophilus) (The spleen is large in childhood but is no longer palpable by 4 years of age)

Question 39

signs and symptoms of sickle cell

Answer 39

S – Splenomegaly/Infections (initially enlarged spleen, then shrinks due to repeated infarctions, leading to functional asplenia and increased infections). I – Infarctions (vaso-occlusion can cause strokes, MI, bone infarcts). C – Crisis (Painful Episodes) (due to blocked blood flow, especially in bones, chest, and abdomen). K – Kidney Disease (renal papillary necrosis, hematuria, inability to concentrate urine). L – Liver and Gallbladder Issues (bilirubin gallstones, liver dysfunction). E – Eye Problems (retinopathy, retinal detachment). C – Chest Syndrome (acute chest syndrome = fever, cough, chest pain, pulmonary infarcts, life-threatening). E – Erectile Dysfunction/Priapism (prolonged, painful erections due to vaso-occlusion). L – Leg Ulcers (poor circulation leads to chronic ulcers). L – Low RBCs (Anemia) (chronic hemolytic anemia, fatigue, pallor).

Question 40

hb electrophoresis in sickle

Answer 40

80-90% HbSS, absent HbA (most accurate test) (HbS travels slower on electrophoresis bcz of less charge)

Question 41

management of sickke cell

Answer 41

1) folic acids 2) hydroxyurea 3) oxygen 4) hydration

Question 42

most common cause of death in sickle cell

Answer 42

acute chest syndrome and multiorgan failure

Question 43

what ia sickle cell trait

Answer 43

60% HbA (normal), 40% HbS • No symptoms except if extreme circumstances such as hypoxia • Normal CBC and blood film • Only manifestatiom is isosthenuria (a defect in the ability to concentrate urine, paAents will have a constant osmolality on urinalysis testing)

Question 44

what is the one advantage in patiemts with sickle cell trait

Answer 44

Protection Against Malaria: People with sickle cell trait have a survival advantage against Plasmodium falciparum malaria, as infected RBCs are cleared more quickly.