**Question:** Haemoglobin F is raised in -

**Core Concept:** Haemoglobin F, also known as fetal haemoglobin, is the normal haemoglobin present in fetal circulation until birth. It is composed of two alpha and two gamma globin chains, as opposed to the two alpha and two beta chains in adult haemoglobin (HbA). Haemoglobin F levels typically decrease after birth and remain low in adults unless certain conditions are present.

**Why the Correct Answer is Right:** Haemoglobin F is raised in individuals with sickle cell trait (HbAS) due to the presence of both fetal and adult haemoglobin. In these individuals, there is a balance between the production of fetal and adult haemoglobin. However, the increased production of fetal haemoglobin in sickle cell trait counteracts the abnormal polymerization of deoxygenated adult haemoglobin that leads to sickle cell crisis.

**Why Each Wrong Option is Incorrect:**

A. Beta-thalassemia trait: Haemoglobin F levels are not raised in beta-thalassemia trait due to the reduced production of adult haemoglobin and increased production of abnormal alpha chains, which leads to poor development of beta chains.

B. Sickle cell disease: Haemoglobin F levels are not raised in sickle cell disease (HbSS) due to the increased production of abnormal haemoglobin, which leads to polymerization and sickling of red blood cells, rather than the counteraction of polymerization by increased fetal haemoglobin.

C. Beta-thalassemia major: Haemoglobin F levels are not raised in beta-thalassemia major due to the reduced production of both alpha and beta chains, leading to severe anaemia and compensatory increase in fetal haemoglobin levels.

D. Sickle cell trait: Haemoglobin F levels are not raised in sickle cell trait (HbAS) due to the presence of both normal adult haemoglobin and abnormal alpha chains, which results in an imbalance between fetal and adult haemoglobin production.

**Clinical Pearl:** The presence of haemoglobin F can be an important clue for the diagnosis of sickle cell trait in individuals with normal haematocrit and microcytic anaemia. Further genetic testing is required for definitive diagnosis.

**Correct Answer:** D. Sickle cell trait (HbAS)

**Explanation:** Haemoglobin F levels are raised in individuals with sickle cell trait due to the presence of both normal adult haemoglobin (HbA) and abnormal alpha chains (HbS) which results in an imbalance between fetal and adult haemoglobin production. This leads to an increase in haemoglobin F as the body tries to compensate for the abnormal alpha chains. In sickle cell trait, the individual is a heterozygous carrier for both HbA and HbS, resulting in a 50:50 ratio of fetal:adult haemoglobin. This leads to a microcytic anaemia and a characteristic red cell morphology in peripheral blood smear.

**Why not other options:**

A. Beta-thalassemia trait (HbAS): Although the individual has microcytic anaemia, the abnormal alpha chains (HbS) are not in the correct balance with normal