Anaemia + haemoglobinopathies

What causes microcytic anaemia?

Reduced rate of haemoglobin synthesis

• Iron deficiency (affects haem synthesis)

• Thalassemia (affects globin synthesis)

• Chronic inflammation/ malignancy

What are chronic inflammatory conditions characterised by?

• low serum iron

• Normal/ raised serum ferritin

• Bone marrow iron storage is normal

• Reduced TIBC

• High levels of IL-6 → unregulates hepcidin→ decreased iron absorption + increased iron retention → less iron available

• IL-1 + TNa→ decrease EPO → reduced half life of RBC

What is iron deficiency anaemia characterised by?

• Reduced serum iron

• Reduces serum ferritin

• No bone iron stored in bone marrow

• Raises TIBC (total iron binding capacity)

What is the iron transporter called?

Transferrin

What is sideroblastic anaemia?

Rare inherited microcytic anaemia → due to defect in haem synthesis (mutation in ALAS-gene , X chromosome )

Rings of iron form in RBC

** high serum iron and serum ferritin

name some causes of normocytic anaemia

• anaemia of chronic disease

• Renal failure

• Acute blood loss

• Endocrine failure (hypothyroidism, hypopituitarism)

What are the 2 different normocytic anaemia?

Hypoproliferative (normal/ decreased reticulocyte count): due to chronic disorders, liver disease, leukaemia

Hyperproliferative (high reticulocytes count): due to blood loss , haemolytic anaemia)

What does haemolytic anaemia cause?

Increased RBC destruction

→ can be due to: autoimmune, infections (eg. malaria), hereditary (eg. G6PD deficiency, Pyruvate kinase deficiency, spherocyrosis, elliptocytosis)

How do people with haemolytic anaemia present?

Pallor of mucous membranes

Fluctuating jaundice and splenomegaly

High reticulocytes count

How do you test for acquired (autoimmune) haemolytic anaemia?

Direct antiglobulin test (DAG) = Coombs test

Warm/ cold autoimmune disease (antibody reacts better at warm/ cold)

How does an alloimmune haemolytic anaemia occur?

Alloimmune- antibodies produced by 1 individual react with the RBC of another

Can occur in blood transfusion/ pregnancy

Pregnancy:

1. Has a Rh+ baby when she is RH-

2. Blood cross over during birth → has anti-Rh antibodies in her blood

3. Antibodies attack her next baby if Rh+

What are come causes of macrocytic anaemia?

Megaloblastic: low B12 + folate

Non-megaloblastic: alcohol, liver disease, pregnancy, smoking

Mutation in sickle cell

GAG → GTG on chromosome 11

Glutamic acid → valine

Symptoms of sickle cell anemia

• jaundice + gallstones

• Splenic atrophy due to splenic infarction due to infection with strep pneumonia / meningitis

• Sickle cell crisis:

→ Hand foot syndrome (painful dactylic caused by infarcts of small bones in hands)

→ If they block the blood vessels → infection: pooling of blood

What do patients with sickle chest syndrome present with and how do you treat it?

• dyspnoea

• Falling arterial PO2

• Chest pain

• Pulmonary infiltrates on chest x-ray

  treatment: analgesia, oxygen

How is Alpha Thalassemia caused?

Deletion/ kids of function of 1 or more of the 4 alpha glob in chains

What is Bart’s disease?

No alpha chain in haemoglobin

What are Alpha Thalassemia traits caused by and how is

Loss of 1 or 2 genes that are not associated with anaemia

MCV + MCH are now

Haemoglobin electrophoresis is normal + need a DNA analysis using PCR

What is the difference between between beta Thalassemia major, intermedia and minor?

Major: transfusion dependent (no beta chains)

Intermedia: non-transfusion dependent but moderate anaemia

Minor: carrier with not many symptoms

Symptoms of beta Thalassemia major

• severe anaemia at 3-6 months, failure to thrive, swollen abdomen

• Hepatosplenomegaly

• Expansion of bones due to intense marrow hyperplasia

• Thalassaemic face

• Infections

• Liver disease

Symptoms of beta Thalassemia intermedia

• bone deformity

• Enlarged liver and spleen

• Leg ulcers

• Gall stones

• Osteoporosis

• Venous thrombosis

Why does sickle cell lead to jaundice?

Sickled RBC survive 30 days

Normal RBC survive 120 days

More haemolysis of sickle cells → increased bilirubin released