Haemoglobinopathies

Major forms of Hb: HbA = 2 Alpha chains & 2 [blank_start]Beta[blank_end] chains HbA2 = 2 Alpha chains & 2 [blank_start]Delta[blank_end] chains HbF = 2 Alpha chains & 2 [blank_start]Gamma[blank_end] chains

The most abundant Hb in the normal human body is [blank_start]HbA[blank_end]

Alpha genes lie on chromosome 16. There are [blank_start]4[blank_end] alpha genes per cell ([blank_start]2[blank_end] on each chromosome) Beta genes lie on chromosome 11. There are [blank_start]2[blank_end] beta genes per cell ([blank_start]1[blank_end] on each chromosome)

Adult levels of HbA are typically achieved by [blank_start]12 months[blank_end] of age

Haemoglobinopathies are hereditary conditions which affect the synthesis of [blank_start]globin[blank_end] chains, thus affecting haemoglobin production.

Haemoglobinopathies whereby there is a decreased rate of globin chain synthesis are called [blank_start]thalassaemias[blank_end]

Reduced rate of production of alpha globin chains is known as [blank_start]alpha thalassaemia[blank_end] Reduced rate of production of beta globin chains is known as [blank_start]beta thalassaemia[blank_end]

Thalassaemias lead to [blank_start]microcytic[blank_end] anaemia

[blank_start]Alpha Thalassaemia Trait[blank_end] = 1 or 2 alpha genes missing (i.e -α/αα OR -α/-α) [blank_start]Haemoglobin H Disease (HbH)[blank_end] = 3 alpha genes missing (i.e. (--/-α) [blank_start]Barts Hydrops Fetalis[blank_end] = All 4 alpha genes missing (i.e. (--/--)

Alpha Thalassaemia Trait is the most severe form of the condition and patients rarely survive past infancy.

HbH disease causes strange 3 beta 1 alpha tetramers to form which can't carry oxygen, thus causing severe anaemia.

The skin of HbH Disease patient may be slightly discoloured as this condition is known to cause a mild [blank_start]jaundice[blank_end]

Extramedullary haematopoiesis in HbH Disease causes the pathological enlargement of which organ? The [blank_start]Spleen[blank_end]

Hb Barts Hydrops Fetalis is a condition whereby HbA cannot be produced due to the inability to synthesize alpha chains. This condition is typically incompatible with life.

[blank_start]Alpha[blank_end] Thalassaemia is considered to be more dangerous that [blank_start]Beta[blank_end] Thalassaemia as the former affects HbA, HbA2 & HbF whereas the latter only affects HbA

β+/β or β0/β = Beta Thalassaemia [blank_start]Trait[blank_end] β+/β+ or β0/β+ = Beta Thalassaemia [blank_start]Intermedia[blank_end] β0/β0 = Beta Thalassaemia [blank_start]Major[blank_end]

Beta Thalassaemia Trait = [blank_start]Asymptomatic[blank_end] Beta Thalassaemia Intermedia = [blank_start]Occasional Transfusions Required[blank_end] Beta Thalassaemia Major = [blank_start]Lifelong Transfusions Required[blank_end]

Beta thalassaemia major present around 6-24 months of age as the individual's [blank_start]HbF[blank_end] falls

Children with beta thalassaemia major will typically present with which two key clinical signs?

Beta thalassaemia major can be separated from Alpha thalassaemia by looking at the child's blood - there will be an abundance of HbF in young beta thalassaemia patients.

Regular transfusion of patients with beta thalassaemia major aims to keep the Hb level at around [blank_start]95-105[blank_end]g/L

The main cause of mortality in beta thalassaemia major patients who are well treated is [blank_start]iron[blank_end] overload from the regular blood transfusions

Beta thalassaemia major patient with iron overload are typically treated via venesection

Sickle cell disease is caused by a [blank_start]point[blank_end] mutation in codon 6 of the [blank_start]beta[blank_end] globin gene that substitutes glutamine to value producing Beta Globin S

When you have one normal (B) and one abnormal (BS) gene this is known as sickle [blank_start]trait[blank_end]. This is asymptomatic and makes you a carrier of sickle cell disease (not affected by the condition).

Sickle cell anaemia follows which kind of inheritance pattern? Autosomal [blank_start]Recessive[blank_end].

Sickle Cell Anaemia causes [blank_start]Hyposplenism[blank_end] due to repeated splenic infarcts

A patient with known HbSS is out with friends hiking. He progressively develops chest pain, shortness of breath, headache and skin pallor. He is likely experiencing a [blank_start]sickle crisis[blank_end]

Sickle cells can become stuck in arteries leading to sickle vaso-occlusion. This can cause a patient extreme [blank_start]pain[blank_end]

Which of the following are common causes of sickle crises in HbSS patients?

A Sickle Crisis should be managed by providing analgesia (if pain present, which it likely will be), hydration, oxygen and rest.

Long term management of Sickle Cell Disease includes: - [blank_start]Folic Acid[blank_end] supplementation to increase RBC turnover - Hydroxycarbamide to induce produce of [blank_start]HbF[blank_end]

Due to the risk of occlusion, sickle cell anaemia patients are at a significantly higher risk of experiencing a stroke.

Raised HbA2 is diagnostic of which type of Thalassaemia? [blank_start]Beta Thalassaemia Trait[blank_end]

HPLC blood testing is normal in [blank_start]alpha[blank_end] thalassaemia trait and thus DNA testing is necessary to confirm the condition.