Haematological conditions

Question 1

Most common haem condition in children

Answer 1

Iron deficiency anaemia

Question 2

What is anaemia?

Answer 2

• Low circulating level of Hb or low circulating RBCs
• Hb F is the major form of Hb in the foetus but production stops at birth and it makes up only a small proportion of Hb in adults
• Abnormities Hb result from mutations in the genes encoding the alpha and beta globin chains that make up Hb can occur e.g. Hb S in sickle cell disease
• Anaemia is a common diagnosis in children, divided into decreased production of Hb or RBCs + increased destruction

Question 3

Iron deficiency anaemia

Answer 3

• Most common cause of anaemia
• Affects up to 25% of population
• Most common cause = inadequate intake
  
  • Found in children who drink non-fortified milk e.g. cow’s milk
  • Teenage girls have to combination of growth + periods = iron deficiency anaemia
  • Malabsorption e.g. in coeliac disease
  • Parasitic worms in developing countries
• Clinical features
  
  • Common for child to be asymptomatic esp. if developed gradually
    
    • Fatigue, pallor, headache, irritability, poor feeding, angular cheilitis, kolionychia, tachycardia, flow murmur, pica
  • Can cause impaired cognitive development
• Diagnosis
  
  • FBC will show low Hb
  • Blood film shows microcytic, hypochromic anaemia
  • Low reticulocyte count
  • Low ferritin = low iron stores
    
    • But remember ferritin is an acute phase reactant meaning it will be high in inflammation
  • Transferrin and total iron binding capacity = high because no iron is bound
  • Important to take a hx to give a clue to the cause e.g. menorrhagia, GI bleed, malabsorption
• Management
  
  • Increase iron rich food intake
  • Limit excessive milk intake
  • Oral iron supplements
    
    • Vitamin C increases absorption
    • Tea/ milk reduces absorption

Question 4

Sickle cell disease

Answer 4

• Leads to vaso-occlusion and haemolytic anaemia
• Autosomal recessive
• Many variants but hose homozygous for HbS are most severely affected
• Most common in Sub Saharan Africa
• 1 in 10 Afro-Caribbeans are carriers
• Affects 1 in 2000 births in England - highest proportion in ethnic groups
• HbS (abnormal form found in sickle cell disease) form a sickle shape when deoxygenated - less able to pass through capillaries
  
  • HbS also prone to premature breakdown
• Clinical features
  
  • Dactylitis (painful, swollen hands) - occurs due to vaso-occlusion in the small capillaries of the hands
  • Pain is also felt in the spleen
  • Patient may also have symptoms of anaemia and jaundice due to haemolysis of the abnormal cells
  • Signs
    
    • Splenomegaly in young children, and older children autosplenectomy occurs were the spleen fibrosis and shrinks due to recurrent vaso-occlusion and infarction
      
      • Results in an increase acceptability to infection with encapsulated organisms such as strep pneumonia – can lead to life-threatening sepsis

Question 5

Diagnosis and management of sickle cell disease

Answer 5

• Diagnosis
  
  • If parents are known carriers disease may be diagnosed antenatally
  • Children with disease identified in neonatal period by newborn screening program, FBC shows normocytic anaemia and high reticulocyte levels
  • Blood film show sickle cells
  • Haemoglobin electrophoresis shows presence of haemoglobin S
• Management
  
  • No cure, manage symptoms and complications
  • What might trigger a vaso-occlusive crisis?
    
    • Cold temperature, dehydration, infection, hypoxia, stress, alcohol consumption
  • Folic acid needed because of high turnover of RBCs and prophylactic penicillin to prevent infection with encapsulated organisms – important for children with sickle-cell to be fully immunised
  • Blood transfusion may be needed for anaemia
  • Hydroxyurea can help reduce complications by increasing production of haemoglobin F thus lowering concentrations of haemoglobin S
  • What are the complications of sickle-cell disease?
    
    • Salmonella osteomyelitis, gallstones, priapism, stroke, renal failure and iron overload due to recurrent transfusion
• Prognosis
  
  • Variable but due to screening and care mean survival has improved and is about 50 years

Question 6

What is thalassaemia?

Answer 6

• Genetic disorder characterised by defects in genes encoding either the alpha or beta globin chain
• Autosomal recessive
• Reduced number of normal globin chains produced leading to varied severity
• 5% world are carriers
• 1 in 7 Cypriots are carriers of b-thalassaemia
• A and B thalassaemia are the two types, B being more common
• Clinical features
  
  • Depend on the severity of the associated anaemia
  • Unless diagnosed at birth children with B-thalassaemia major present at ~6 months with FTT and severe anaemia when F haemoglobin has diminished
  • Hepatosplenomegaly due to extra medullar haematopoiesis
  • Overgrowth of bones due to bone marrow hyperplasia - esp. maxilla and skull leading to thalassaemia facies
  • Mild thalassaemia may be found incidentally

Question 7

Alpha thalassaemia

Answer 7

• Genetic disorder where there is a deficiency in production of the alpha globin chains of haemoglobin
• It is caused by mutations in the alpha genes (of which we have 4) and these mutations are inherited in an autosomal recessive pattern – if a person has two defective alpha genes they have alpha thalassaemia minor which will cause mild symptoms
  
  • 1 mutation = asymptomatic
  • 2 = thalassaemia trait also known as thalassaemia minor
  • 3 = moderate disease, known as haemoglobin H or HBH disease
    
    • HBH disease occurs because there are excessive beta chains which come together and form a new type of haemoglobin called haemoglobin H, HBH causes hypoxia by damaging RBC membrane and HBH has a very high affinity for oxygen and doesn’t release oxygen to the tissues therefore hyperoxia occurs and this tells the bone marrow and spleen to make more red blood cells hence the facial changes and splenomegaly
  • 4 = incompatible with life, no alpha haemoglobin is produced and pregnancy often ends in miscarriage or birth of neonate with hydrops fetalis this is because the haemoglobin produced has such a high affinity for oxygen that it does not release at the tissues – resulting in severe hyperoxia, high output cardiac failure and oedema all over the body known as hydrops fetalis
• Diagnosis
  
  • Initial symptoms of minor and moderate alpha thalassaemia are due to anaemia which cause pallor, shortness of breath and lethargy
  • Bloods will show low haemoglobin levels, decreased MCV and low MCH
  • Blood smear will show microcytic, hypochromic RBCs with target cells
  • In moderate alpha thalassaemia due to accumulation of HBH there may be golf ball RBCs
  • Haemoglobin electrophoresis can be done to see which types of haemoglobin present and genetic testing can look for mutations

Question 8

Beta thalassaemia

Answer 8

• Deficiency in production of beta-globin, mutations lead to absent or reduced number of beta-globin chain synthesis, it is a more recessive
  
  • 1 gene mutation leads to reduced production of beta-globin and they have beta thalassaemia minor
  • 2 = thalassaemia intermediate
  • If no beta-globin is produced patient has thalassaemia major
• Reduce production of beta-globin leads to increased production of free alpha chains in the blood and they clump together and damage red blood cell membrane causing haemolysis and destruction of RBCs in the spleen
• Beta thalassaemia minor is usually a symptomatic but beta thalassaemia major will become symptomatic around six months after which time fetal haemoglobin is no longer being produced
• Signs and symptoms of beta thalassaemia major include anaemia, shortness of breath, lethargy, jaundice, hepato-splenomegaly and growth retardation
• In addition patients will have a large forehead and cheekbones and x-ray of the skull will show a hair on and appearance, hairlike projections radiate from the cranium
• Bloods will show a microcytic anaemia and blood smear will show microcytic and hypochromic RBCs with target cells

Question 9

What are codocytes?

Answer 9

• Liver disease
• Thalassaemia
• Post-splenectomy
• Sickle cell (although in sickle cell its usually Howell-Jolly bodies
  
  • Howell-Jolly bodies = DNA nuclear remnants in RBCs which are normally removed by the spleen, seen post-splenectomy, in sickle cell and in hyposplenism

Question 10

Diagnosis and management of thalassaemia

Answer 10

• Diagnosis of thalassaemia
  
  • Microcytic, hypochromic anaemia with increased reticulocyte count, target cells are present and electrophoresis identifies different haemoglobin types
• Management of thalassaemia
  
  • Mild forms do not require treatment, patients with beta thalassaemia major or HBH type of alpha thalassaemia require regular blood transfusions. Prognosis depends on the type of thalassaemia, death in beta thalassaemia major occurs in 30 is usually due to heart failure

Question 11

Glucose 6–phosphate dehydrogenase deficiency

Answer 11

• Patients are deficient in G6 phosphate dehydrogenase which is needed for red blood cell metabolism and is needed to protect the cell from oxidative damage, lack of this enzyme means RBCs undergo haemolysis due to increased susceptibility to oxidative stress
• X-linked recessive
• Clinical features
  
  • Patients are usually mail and often asymptomatic, higher frequency of neonatal jaundice and symptoms develop as a consequence of haemolysis which is usually acute
  • Haemolysis leads to anaemia and excess bilirubin which leads to jaundice, gallstones and dark urine
  • Acute haemolysis can be caused by infection, use of certain medications and consumption of Father beans a.k.a. broad beans, during a haemolytic crisis patient may be visibly jaundiced, have splenomegaly and have symptoms of anaemia
  • Blood film will show Heinz bodies
• Management: most individuals have a normal life expectancy and only need to avoid precipitance of acute haemolysis, in severe cases blood transfusion may be needed and then until jaundice is treated with phototherapy

Question 12

Immune thrombocytopenia

Answer 12

• Autoimmune disease in which antibodies attached to antigens on platelets and cause platelets to be destroyed in the spleen
• Occurs in 3–5 in 100,000 children and become present at any age but most commonly between the ages of 2–5
• Clinical features
  
  • Easy bruising, particularly, spontaneous nosebleeds or prolonged bleeding after cutting themselves, increased risk of intracranial bleed
• Diagnosis
  
  • Confirmed when thrombocytopenias is found on the FBC
• Management
  
  • Most children do not require treatment and condition resolves spontaneously after 3–6 months. Patients are advised to avoid contact sport or situations which may lead to trauma – platelet transfusions are not helpful as transfused platelets will also be destroyed
  • Chronic immune thrombocytopenia is diagnosed when the condition last for more than one year

Question 13

Haemophilia A

Answer 13

• X linked recessive, affects one in 5000 male births, low levels of clotting factor eight and patient is therefore at risk of prolonged bleeding
• Clinical features
  
  • In children with a family history of haemophilia testing may be done at birth however 30% of cases occur due to spontaneous mutations
  • Clinical features and age at presentation depend on disease severity which is determined by the activity of factor eight
  • Can lead to haemarthrosis because bleeding occurs into a joint and causes damage which results in arthritis
• Management
  
  • If condition is the patient will receive factor eight infusions and if an acute bleed occurs in fact eight is given
  • Mild – moderate disease, desmopressin can be given to boost factor eight levels

Question 14

Haemophilia B

Answer 14

• A.k.a. Christmas disease, acts linked recessive disorder that results in deficiency of factor nine, affects one in 30,000 miles and severity varies
• Treatment is with factor nine concentrate

Question 15

Von Willebrand disease

Answer 15

• Genetic disorder of the von Willebrand clotting factor which is needed for platelet adhesion and stabilisation of factor eight. Inherited in an autosomal dominant manner and is the most prevalent coagulation defect – found in 1% of the population
• Patient will have low levels of von Willebrand factor or they will have normal levels but the factor produced is defective, features depend on the type of von Willebrand disease present ranging from a symptomatic – severe bleeding
• Management depends on severity, desmopressin and factor eight concentrate are given in cases of severe haemorrhage