BCR 9 - Disorders of Red Blood Cells, Platelets and Clotting

What is anaemia defined as?

Low haemoglobin concentration in the blood.

What is the main function of haemoglobin?

Transports oxygen from the lungs to tissues.

Why is anaemia considered a broad clinical topic?

Because it has many different causes and requires understanding of haemoglobin structure, symptoms, classification systems and underlying pathophysiology.

What is the basic structure of haemoglobin?

A tetramer composed of four globin chains, each containing a haem group with iron.

Why is iron essential in haemoglobin?

Iron within each haem group binds oxygen and allows oxygen transport.

What globin chains make up foetal haemoglobin (HbF)?

Two alpha chains and two gamma chains.

What globin chains make up adult haemoglobin HbA1?

Two alpha chains and two beta chains.

What globin chains make up adult haemoglobin HbA2?

Two alpha chains and two delta chains.

How do haemoglobin levels normally change after birth?

They are high at birth, decrease during the first year of life, and then increase again.

Why does less haemoglobin suffice in adult life compared to foetal life?

Adult haemoglobin is more efficient at transporting and releasing oxygen.

Which full blood count parameter directly defines anaemia?

Total haemoglobin concentration.

What does mean corpuscular haemoglobin (MCH) measure?

The average amount of haemoglobin inside each red cell.

What does mean corpuscular haemoglobin concentration (MCHC) measure?

The concentration of haemoglobin within red cells.

Why are MCH and MCHC useful in evaluating anaemia?

They help differentiate types of anaemia by indicating haemoglobin content within red cells.

Why are haemoglobin reference ranges different in children?

Because haemoglobin levels are high at birth, fall in infancy, then rise again as foetal haemoglobin is replaced by adult haemoglobin.

Why are symptoms of anaemia often non-specific?

Because many types of anaemia produce similar symptoms and diagnosis relies on blood test interpretation.

How does speed of onset influence symptoms in anaemia?

Slow onset allows physiological adaptation, whereas rapid onset causes more pronounced symptoms.

How does age affect tolerance to anaemia?

Young individuals tolerate low haemoglobin better, while older patients become symptomatic at higher levels.

Why are patients with cardiac or respiratory disease more symptomatic in anaemia?

Because reduced oxygen delivery worsens underlying organ dysfunction.

What are common symptoms of anaemia?

Breathlessness, fatigue, headaches, palpitations and dizziness.

In which patients is breathlessness more common in anaemia?

In those with severe anaemia or underlying cardiac or respiratory disease.

Why can palpitations occur in anaemia?

Because the heart compensates for reduced oxygen delivery by increasing heart rate.

What are the general physical signs of anaemia?

Pallor, tachycardia, systolic murmur and possible cardiac failure.

Why can prolonged anaemia lead to cardiac failure?

Chronic increased cardiac workload may eventually impair cardiac function.

What is koilonychia and what does it suggest?

Spoon-shaped nails seen in long-standing iron deficiency anaemia.

What is haemolytic anaemia?

a condition where red blood cells are destroyed and removed from the bloodstream faster than they can be replaced by the bone marrow (haemolysis related)

Why does haemolytic anaemia cause jaundice?

Because increased red cell destruction raises bilirubin levels.

What is bilirubin?

a yellowish-brown waste pigment created when the body breaks down old red blood cells

How does raised bilirubin levels cause jaundice?

by building up in the blood and tissues when the body produces more than the liver can process or when the liver can't remove it efficiently

What is thalassaemia?

a severe, inherited blood disorder where the body produces little to no functional hemoglobin, resulting in life-threatening anemia

Which inherited anaemia historically caused bone deformities?

Thalassaemia major.

Why are bone deformities in thalassaemia now rare?

Because modern therapy prevents severe untreated disease.

Which anaemia is associated with leg ulcers?

Sickle cell disease.

Why are leg ulcers not usually the presenting feature of sickle cell disease?

Because they are typically a later complication rather than an initial symptom.

How is anaemia classified based on red cell size?

As microcytic, normocytic or macrocytic according to mean corpuscular volume.

What defines microcytic anaemia?

Low mean corpuscular volume.

What defines normocytic anaemia?

Normal mean corpuscular volume.

What defines macrocytic anaemia?

High mean corpuscular volume.

How is anaemia classified based on haemoglobin content?

As hypochromic or normochromic according to haemoglobin concentration within red cells.

What defines hypochromic anaemia?

Reduced haemoglobin content within red cells.

Why is classification by size and colour alone insufficient?

Because it does not identify the underlying cause of anaemia.

What is the first key clinical reasoning question in anaemia?

Can the bone marrow produce enough red cells?

How is bone marrow production initially assessed in anaemia?

With blood tests such as reticulocyte count.

When is bone marrow biopsy considered in anaemia?

As a second-line invasive test if further investigation is required.

If the bone marrow can produce red cells, what mechanisms may explain anaemia?

Bleeding, increased destruction or pathological consumption of red cells.

How can inherited disorders reduce red cell production?

By genetic defects impairing red cell or haemoglobin synthesis, such as thalassaemia.

Which nutrients are essential for red cell production?

Iron, vitamin B12 and folate.

Why are vitamin B12 and folate essential for red cell production?

Because they are required for DNA synthesis in all bone marrow cell lines.

What hormone regulates red cell production?

Erythropoietin.

How does chronic kidney disease cause anaemia?

By reducing erythropoietin production.

How can infections and drugs reduce red cell production?

By suppressing bone marrow function.

How does bone marrow infiltration cause anaemia?

By replacing normal marrow with cancer or metastatic cells, impairing production.

How do inherited membrane defects cause haemolysis?

By making red cells fragile and prone to rupture.

Which conditions are examples of inherited membrane defects?

Hereditary spherocytosis and elliptocytosis.

How does sickle cell disease increase red cell destruction?

Abnormal haemoglobin causes red cells to deform and rupture.

How do enzyme deficiencies such as G6PD deficiency cause haemolysis?

Metabolic defects make red cells vulnerable to oxidative damage and rupture.

What is autoimmune haemolysis?

Immune-mediated destruction of red cells by antibodies.

How are autoimmune haemolytic anaemias classified?

By the temperature at which antibodies are active, such as warm, cold or biphasic.

What is alloimmune haemolysis?

Red cell destruction due to antibodies formed after exposure to foreign blood, such as transfusion reactions.

How can drugs cause haemolysis?

Either by direct red cell toxicity or by immune-mediated mechanisms.

What is paroxysmal nocturnal haemoglobinuria?

An acquired membrane defect in which red cells are vulnerable to complement-mediated destruction.

What is microangiopathic haemolytic anaemia?

A life-threatening condition where red cells are mechanically fragmented in small vessels.

How can metallic cardiac valves cause haemolysis?

Mechanical shear stress damages circulating red cells.

What is march haemoglobinuria?

Red cell destruction caused by repetitive mechanical trauma, such as long-distance running.

Which systemic diseases can cause haemolysis?

Renal failure, liver failure, malaria and Mycoplasma infection.

What lineage do red cells arise from in haematopoiesis?

The myeloid lineage.

What are the precursors of red cells called?

Erythroblasts.

Why is haemoglobin central to red cell production?

Because it is synthesised during maturation and is essential for oxygen transport.

What is the direct consequence of low haemoglobin?

Reduced oxygen delivery leading to tissue hypoxia.

How can tissue hypoxia from anaemia cause organ damage?

It can cause acute damage if sudden or chronic damage if prolonged.

What determines the severity of tissue damage in anaemia?

The severity of anaemia and the speed of onset.

What key processes occur during erythrocyte maturation?

Haemoglobin synthesis and expulsion of the nucleus.

Why is loss of the nucleus important in red cells?

It increases flexibility and prevents further haemoglobin production.

How does iron deficiency during maturation affect red cell size?

It produces smaller red cells.

How does B12 or folate deficiency during maturation affect red cell size?

It produces larger red cells.

How long do mature red cells normally circulate?

Approximately 3 months.

What are reticulocytes?

Immature red cells released after nucleus loss that still contain ribosomes.

Why are reticulocytes slightly larger than mature red cells?

Because they still contain residual ribosomal material.

What does a low reticulocyte count indicate?

Inadequate bone marrow production.

What does a high reticulocyte count indicate?

Compensatory marrow response such as after bleeding.

When might nucleated erythroblasts appear in peripheral blood?

In newborns or splenectomised patients.

What is the overall structure of haemoglobin?

A tetramer composed of four globin chains.

How many oxygen molecules can one haemoglobin molecule carry?

Four oxygen molecules.

What component within haemoglobin binds oxygen?

Iron within each haem group.

Why does iron deficiency reduce haemoglobin production?

Because iron is required to form haem.

How is iron conserved in the body?

By recycling iron from destroyed red cells.

What is the first clinical reasoning question in microcytic anaemia?

Can the bone marrow produce enough cells?

What are the two most common causes of microcytic anaemia?

Iron deficiency and thalassaemia.

How can red cell count help differentiate thalassaemia from iron deficiency?

Thalassaemia often has high RBC count despite microcytosis, whereas iron deficiency often has low RBC count.

Where is dietary iron primarily absorbed?

In the duodenum.

How is ferric iron converted before absorption?

Ferric iron is reduced to ferrous iron.

What transporters are involved in iron absorption?

DMT1 and haem carrier protein 1.

Why is haem iron absorbed more efficiently than non-haem iron?

Because haem iron absorption is approximately 20 to 25 percent compared to about 5 percent for non-haem iron.

How does the body regulate iron absorption according to need?

Low iron increases transporter expression and high iron reduces it.

What gastrointestinal factors impair iron absorption?

Reduced gastric acid, altered pH, inflammation, resection or inflammatory bowel disease.

In what form is iron stored inside cells?

Ferritin.

How is iron exported from enterocytes into blood?

Via ferroportin.

Why must free iron be bound in plasma?

Because free iron is toxic.

What protein transports iron in plasma?

Transferrin.

How does iron enter target cells from transferrin?

Through transferrin receptor-mediated endocytosis.