Week 33- Diseases of the blood

• Coagulation disorders


  • Clotting factor disorders
  • Platelet disorders
• Clotting factor disorders


  • Include Haemophilia A and B and Von Willebrand's disease
  • Patients will bruise easily (in mild cases) or may bleed without warning throughout the body in severe instances
• Platelet disorders


  Thrombocytopenia is a disease where there is an insufficient number of platelets
• Inherited coagulation disorders


  • Include the A and B haemophilia
  • For classic haemophilia (Type A) there is a lack of one subunit of clotting factor VIII
  • Type A is found in 80% of cases and is X-linked and recessive
  • Type B (also known as Christmas disease) is a defect in factor IX production and is also X-linked
  • There is a delay in the formation of fibrin in both A and B haemophilia
• Von Willebrands' disease


  • Is a lack of clotting factor (Von Willebrand's factor) and also of a VIII subunit
  • Is autosomal dominant
  • Is needed for the clumping of platelets, so this disease may prevent a platelet plug from being formed properly and strongly
• Thrombocytopenia


  A coagulation disorder where there is insufficient numbers of platelets in the blood
• Acquired coagulation disorders


  • Vitamin K deficiency bleeding (VKDB) is now the term used for haemorrhagic disease of the newborn (HDN)
  • This is due to deficiency of clotting factors due to a lack of Vitamin K
  • Vitamin K is needed for producing clotting factors II, VII, IX and X
  • It is present in some vegetables and is also synthesised by some E. coli bacteria found in the large intestine
• Warfarin


  • An anti-clotting agent also called coumarin
  • Prevents thrombosis and embolism in patients with "sticky blood" by inhibiting the activation of vitamin K
  • It is called a "blood thinner"
• Thrombosis


  The formation of clots in veins or arteries
• Embolism


  The obstruction of an artery by a clot of blood (from the Greek: "embolos" meaning wedge or plug)
• How warfarin works


  1. Warfarin competitively inhibits the vitamin K epoxide reductase complex 1 (VKORC1), which is an essential enzyme for activating the Vitamin K available in the body

  2. Through this mechanism, warfarin can deplete functional Vitamin K reserves and therefore reduce the synthesis of active clotting factors
• Types of Leukocyte Disorders

  • Leukopenia
  • Leucocytosis
  • Leukemias
• Leukopenia


  Deficiency in leukocytes, usually neutrophils which can lead to an increased risk of infection due to a lack of phagocytosis of bacteria
• Leucocytosis


  An abnormal increase in leukocytes leading to many inflammatory diseases and occurs after chronic infection with a microorganism
• Leukemias


  Tumours of the immune system (sometimes called blood cancer) that are classified as either lymphomas or leukemias
• Types of Leukemia


  • Acute leukemias (arise from less mature cells, called acute lymphocytic leukemia (ALL) or acute myelogenous leukemia (AML))
  • Chronic leukemias (sub-divided into chronic lymphocytic leukemia (CLL) and chronic myelogenous leukemia (CML))
• Types of Anaemias


  • Aplastic anaemia
  • Iron-deficiency anaemia
  • Sickle cell anaemia
  • Haemolytic anaemia
  • Pernicious anaemia
• Aplastic anaemia


  There has been a bone marrow defect or the patient has been exposed to chemicals such as arsenic or high doses of radiation
• Iron-deficiency anaemia


  Inadequate iron intake or excess blood loss in menstruating women can be the cause
• Sickle cell anaemia


  There is an amino acid abnormality in the haemoglobin molecule beta chain (a form referred to as HbS), forming an abnormal crescent shape in the erythrocytes
• Haemolytic anaemia


  Red blood cells rupture at a high rate due to a defective cytoskeleton, such as in hereditary spherocytosis
• Pernicious anaemia


  An autoimmune disease where there is little or no Vitamin B12 absorption from the gut after a meal, due to a lack of a protein called intrinsic factor
• Pernicious anaemia


  • Antibodies are made to intrinsic factor so Vitamin B12 cannot be absorbed from the gut
  • Vitamin B12 is needed to make healthy red blood cells
• Sickle-cell Anaemia


  • An autosomal recessive blood disorder and carried by 8-11% of the African-American population
  • When oxygen levels are low, red blood cells of homozygous patients collapse into a sickle shape
  • An A->T mutation, (glutamic acid -> valine amino acid substitution) at position 6 in the β-globin protein is responsible. This form of haemoglobin is called haemoglobin S
  • Under conditions of low blood oxygen, haemoglobin S comes out of solution and cross-links to become a paracrystalline gel within the red blood cells
  • This makes the cells adopt a sickle shape which makes them much less flexible and much more fragile
  • These cells can then block small blood vessels and cause organ ischaemia (lack of oxygen in the organ)
• How sickle cell anemia affects the body

  1. Red blood cells with healthy haemoglobin have a disc-shaped structure. This makes them very flexible, allowing them to carry oxygen throughout the bloodstream to organs and tissues

  2. Red blood cells with haemoglobin S become rigid, making it difficult for them to get through smaller blood vessels. This prevents or slows blood flow

  3. Pain develops when sickle-shaped red blood cells block blood flow through tiny blood vessels to the chest, abdomen and joints, causing inflammation and episodes of sudden and severe pain, known as pain crises

  4. Another consequence of poor oxygen delivery is damage to major organs, including the brain, eyes, lungs, liver, heart, spleen and kidneys

  5. Red blood cells with hemoglobin S usually die much quicker than healthy cells. Their typical lifespan is 10 to 20 days, versus 90 to 120 for normal red blood cells