Blood pathology

Thalassaemia

Defect in synthesis of either the alpha or beta globin chains in haemoglobin.

Beta Thalassaemia

• Caused by gene mutations
• If heterozygous, usually asymptomatic.
• In homozygous, large amounts of HB A2 and Hb F. Not as good an normal Hb A, but can cope, though in severe cases regular 6 week transfusions will be required – can lead to iron overload.

Alpha Thalassaemia

• Caused by gene deletions
• If all four are deleted you get Hb Barts which isn't compatible with life. Children are stillborn or die shortly after birth.
• If three are deleted some Hb A is present, and usually transfusion are not necessary.
• If 2 or less are deleted. Often not noticeable.

Anaemias

For more, see the pages on anaemia and causes of anaemia.

Sickle cell anaemia

• A base mutation
• No Hb A, just Hb S and Hb F in homozygous
• Carriers (heterozygous) will have sickle cell trait, with some signs of illness.
• Often presents with acute pain in hands and feet, due to vaso-occlusion of small vessels.
• Pigment stones can occur due to rapid haemolysis.
• Anaemia is present since sickle cells are broken down quickly. This can present with jaundice, due to increased levels of bilirubin getting released.

Aplastic anaemia

• Non functioning bone marrow
• Dangerous but uncommon.
• Can be caused by some chemicals and drugs (especially anticancer ones), radiation, infections and pregnancy (where it has 90% mortality).
• Leads to pancytopenia – a reduced red, white and platelet cell count.

Haemolytic anaemia

• Excessive rate of erythrocyte breakdown.
• Causes jaundice (due to excess bilirubin)
• Associated with blood transfusion mismatch.
• Haemolytic anaemia of the newborn (when the mother is Rhesus – and the baby Rhesus + sometimes there can be a sever complication)
• Increased young cells, reticulocytes due to high turnover.

Megaloblastic anaemia

• Maturation of the normoblast needs vitamin B12 and folate.
• Without this it leads to formation of abnormally large megaloblasts which become macrocytes.
• Number of red cells is greatly reduced and the rate of destruction increased.
• Folate defiency is usually related to poor diet, B12 is malabsorbtion

Pernicious Anaemia

• B12 deficiency, with defective absortion in the ileum.
• Caused by diet, or autoimmune disease where antibodies attack gastric parietal cells, so intrinsic factor can't be made.
• Treatment by B12 intramuscular injections till sorted then every 3 months for life.

Purpura

• A skin rash due to capillaries bleeding into the skin.
• Easy bruising
• Can be due to capillary defects, platelet deficiency or malabsorbtion (eg. Vitamin K)

Non Muco-Cutaneous

(Haemophilias, with bleeding into joints and muscles)

Haemophilia A

• Level of factor VIII is reduced, but vWF is normal.
• Sex linked on the X chromosome.
• Rare 1 in 10000

Haemophilia B

• Same as A, except factor IX is reduced.
• Very rare, 1 in 50000

Muco-Cutaneous

vWD and platelet disorders.

Von Willebrand's disease (vWD)

• Autosomnal dominant.
• There is defective platelet function as well as factor VIII:C deficiency.
• Leads to longer extrinsic pathway.

Platelet disorders

• Pretty rare.
• Drug effect more common.

Vitamin K deficiency

• Needed for factors II, VII, IX and C and proteins C and S.
• It is a fat soluble vitamin needing bile for absorption – so in obstructive jaundice you get malabsorbtion.
• PT is prolonged.
• Warfarin is a Vitamin K inhibitor
• Neonates tend to have deficiency due to lack of gut bacteria and low conc of K in milk.

DIC

(Disseminated Intravascular Coagulation)

• Widespread generation of fibrin within the blood.
• Caused by diffuse endothelial damage, generalised platelet aggregation.
• Causes 1 sepsis, 2 obstetric, 3 malignancy – assume sepsis and treat for this.
• Also, burns, liver disease, trauma, malignant disease, septicaemia, haemolytic transfusion errors.