Hemat: Hemoglobinopathies

Front 1

The commonest genetic defects in the world are

Back 1

Hemoglobinopathies.

Front 2

Which hemoglobin variants confer protection against malaria

Back 2

1) Hb S

2) Hb C

3) Hb E

Front 3

The most commonly inherited Hb disorder is

Back 3

Sickle cell anaemia (HbSS/homozygous)

Followed by HbSC and HbS-Beta thalassemia

Hint 3

HbAS and HbAC aren't disorders.

Front 4

The most common causes of genetic hemoglobin disorder is

Back 4

Point mutation of genes (1st) - makes sense cause HbSS is due to point mutation

Deletion of genes (2nd)

Front 5

Is Beta thalassemia autosomal recessive or dominant?

Back 5

Autosomal recessive (Because it doesn't really show symptoms as other beta-like chains fill in)

Front 6

Beta chain are encoded by how many gene pairs?

Back 6

A single gene pair(2 genes)

Front 7

Mention one feature common to all thalassemia state/combination (whether alpha or beta)

Back 7

Microcytosis (because of reduced in Hb A)

Hint 7

Rule of thumb: Reduced Hb A amounts at any level causes Microcytosis

Front 8

In Beta thalassemia combination, Hb is normal (i.e no anaemia) when?

Back 8

When there is one totally functional gene out of the gene pair that encodes Beta chain i.e B/B+ or B/B° (but there is microcytosis).

It might also be seen in partial production by both genes i.e B+/B+ if amount can be compensated for

Front 9

Which beta thalassemia state is Blood Transfusion dependent

Back 9

Thalassemia Major (B°/B°). No beta chain is produced, Hb A2 and F can no longer compensate so there is severe anaemia.

Front 10

Jaundice in beta thalassemia and SCD, which is worse

Back 10

Jaundice in SCD

Front 11

Hair-on-end appearance in X-ray is observed in

Back 11

Severe cases of anaemia (eg SCD, beta thalassemia)

Front 12

Patients with Beta thalassemia can be sustained by

Back 12

Blood Transfusion (but this poses a serious risk of Iron overload)

Front 13

Target cells are seen under microscope in which conditions

Back 13

• Thalassemia

• Hb C disease

• Post splenectomy

Front 14

The centre darkly stained area in target cell is

Back 14

Hemoglobin (when hemoglobin is little in relation to the volume of RBCs as in thalassemia, the hemoglobin move to the centre of the cell)

Front 15

The chelating agent for Iron are

Back 15

All the Defero-

• Deferoxamine.

• Deferiprone

• Deferasirox

They bind iron and excrete them through urine or faeces

Front 16

Vitamin C and Iron

Back 16

Vitamin C increases iron excretion.

Front 17

Alpha chains are encoded for by how many gene pairs?

Back 17

2 gene pairs (4 genes)

Front 18

What is Hemoglobin H disease

Back 18

It is alpha thalassemia due to 3 gene deletion (a-,--). Here since alpha chain production can no longer keep up with beta chain, the cells become destroyed by spleen causing splenomegaly. There is microcytosis due to reduced Hb A, target cells, polychromasia, poikilocytosis, etc.

Front 19

Alpha thalassemia trait occur when

Back 19

There are 1 or 2 gene deletions of alpha genes (out of 4). Hb and RBC count is still normal, only that there is slight Microcytosis and hypochromia. They can only be distinguished by DNA analysis.

This is possible because 2 left genes from alpha thalassemia can still keep up with the 2 genes for beta chain production, so no much effect is seen.

Hint 19

Trait is presence of disorder but no significant effect

Front 20

A significant feature of Hb H disease is

Back 20

Presence of golf ball cells (due to formation of Beta tetramers). There is formation of beta tetramers because the beta chains are unused so they come together to form this.

Front 21

Alpha thalassemia with 4 gene deletion results in

Back 21

Barts Hydrops fetalis

Front 22

Are there golf-ball cells (Beta tetramers) in Hydrops fetalis

Back 22

No. In Hydrops fetalis there are gamma tetramers.

Front 23

Alpha thalassemia is due to gene deletion, while beta thalassemia is due to

Back 23

Mutation

Front 24

Effects of Iron overload

Back 24

It causes H.E.LL.S(1) Heart problems/damage(2) Endocrine dysfunction, that include:• decreased thyroid function (hypothyroidism)• decreased parathyroid function (hypoparathyroidism)• diabetes mellitus (decreased pancreatic function)• delayed puberty/impotence (decreased gonadal function)• delayed growth (decreased growth hormone)(3) Liver problems and cirrhosis(4) Skin appear slately grey (too much hemosiderin and melanin)

Front 25

What point mutation occurs on give Hb E?

Back 25

Glycine replaced with Lysine on the Beta 26th codon

Front 26

Hb D (Ibadan) is formed by

Back 26

Replacing Threonine with lysine on beta chain at 87th position

Front 27

Hb D (Punjab) is formed by

Back 27

Replacing Glutamate with Glutamine on beta chain 121st position. It is more common than Hb D (Ibadan)

Front 28

Which hemoglobin states cause sickling of RBCs

Back 28

● HbSS (most common)

● HbSC

● HbS-Beta thalassemia

Front 29

What polymer is precipitated by deoxygenated HbS

Back 29

Tactoids

Front 30

Are RBCs deformable/elastic

Back 30

Yes they are

Front 31

Factors that promote Sickling of RBCs

Back 31

● Temperature (extreme cold or heat, but more of cold)

● Acidosis (that causes Hb-O2 curve to move right)

● Dehydration

● Hypoxemia (physical exercise, altitude, etc)

Front 32

Between HbS and HbA which readily gives off O2

Back 32

HbS (that's why it's Hb-O2 curve is to the right)

Front 33

Mention consequences of Hemolysis (destruction of RBCs)

Back 33

● Jaundice

● Anemia

● Gallstones (due to excess bilirubin that clump/build up)

● Vasculopathy (due to release of substances from RBCs that damage endothelium)

Front 34

What crises accompany sickle cell disease

Back 34

(1) Vaso-occlusive crises (more common crises) causes chest pain amongst others

(2) Anaemic crises divided into

• Sequestration

• Aplastic

• Hyperhemolytic

• Megaloblastic

(3) Leg ulcers (reduced O2 for healing)

Front 35

The first presentation of Vaso-occlusive crises in SCD is usually

Back 35

● Hand-foot syndrome (caused by infarcts to small bones from occlusion)

● Priapism

Front 36

Aplastic crises in SCD is caused by

Back 36

Parvovirus

Front 37

In complicated SCD, fish cuddling appearance is seen in

Back 37

Bones (Vertebral bodies)

Front 38

Sickling and solubility test for RBCs and hemoglobin is done with which metabolite

Back 38

Sodium metabisulphite (a reducing agent)

Front 39

In hemoglobin electrophoresis (hydragel Hb), in what order to Hb appear

Back 39

From top to bottom,

HbA, HbF, HbS, HbC

Front 40

Hydroxyurea is a medication used for treatment of

Back 40

1) Sickle cell disease

2) Myelogenous leukaemia

3) Polycythemia vera

Front 41

What does hydroxyurea do in SCD?

Back 41

It increases HbF amounts.

Front 42

Microspherocytes are seen in what Hb disease

Back 42

Hb C