Haematological Disease Flashcards
Define Anaemia in:
- Neonates
- 1 month to 12 month olds
- 1 yr to 12 yr olds
- Neonate: Hb < 140 g/L
- 1-12 month: Hb < 100 g/L
- 1-12 yrs: Hb < 110 g/L
What are the mechanisms behind iron deficiency anaemia?
Main causes of iron deficiency are
o Inadequate intake
▪ Common in infants as additional iron is required for the increased in blood volume accompanying growth
▪ A 1 year old infant requires an intake of iron of ~ 8mg/day (adult male: 9mg/day, adult female: 15mg/day)
o Malabsorption
o Blood loss
What are the sources of iron?
Sources of iron
o Breast milk iron
▪ Low iron content but high absorption (50%)
o Infant formula
o Cow’s milk
▪ Higher iron content but low absorption (10%)
o Solid introduced at weaning e.g. cereals (1% absorption)
Dietary sources of iron
o High in iron
▪ Red meat: beef, lamb
▪ Liver, kidney
▪ Oily fish
o Average iron
▪ Pulses, beans, peas
▪ Fortified cereals with added vitamin C
▪ Wholemeal products
▪ Dark green vegetables: broccoli, spinach
▪ Dried fruit: raisins, sultanas
▪ Nuts and seeds
o Foods to avoid in excess in toddlers
▪ Cow’s milk
▪ Tea: tannin inhibits iron uptake
▪ High-fibre foods: phytates inhibit absorption e.g. in chapatti
o Iron absorption is increased when eaten with food rich in vitamin C
What are the clinical features of iron deficiency anaemia?
Asymptomatic until Hb drops below 60 g/L
Fatigue
Infants will feed more slowly
Explore symptoms of malabsorption
Pale
Pica (inappropriate eating of non-food materials such as soil, chalk and gravel)
What are the clinical features of iron deficiency anaemia?
- Asymptomatic until Hb drops below 60 g/L to 70 g/L
- Fatigue
- Infants will feed more slowly
- Explore symptoms of malabsorption or blood loss
- Pale (tongue, conjunctivae, palmar creases) - unreliable
- Pica (inappropriate eating of non-food materials such as soil, chalk and gravel)
There is evidence the iron anaemia may be detrimental to behaviour and intellectual function
What are the investigations of iron deficiency anaemia?
- Blood
- Low Hb
- Microcytic Hypochromic anaemia (low MCV + MCH)
- Low serum ferritin
- Other main causes of microcytic anaemia
- Beta thalassaemia - request haematinics
- Anaemia of chronic disease e.g. due to CKD
- Note: alpha thalassaemia trait (usually African or Far Eastern ethnicity)- causes microcytic hypo chromic picture but not anaemia
How do we treat iron deficiency anaemia?
- Dietary Advice
- Supplementation with oral iron
- Monitor
What sort of advice should you give for iron deficiency anaemia?
- Dietary advice (increase intake of iron-rich food e.g. dark green vegetables, iron-fortified bread, meat, apricots, prunes and raisins) and consider dietician referral
• ADVICE
o They may experience adverse effects (e.g. dark stools, constipation, diarrhoea, faecal impaction, GI irritation, nausea)
o Discomfort could be minimised by taking the iron supplement with food or reducing dose frequency
o Explain the monitoring requirements
What iron supplements are used in iron deficiency anaemia?
Supplementation with oral iron
o Oral ferrous sulphate 200 mg tablets (2/3 per day)
▪ Should be continued for 3 months after iron deficiency is corrected to allow
stores to be replenished
▪ If not tolerated, consider oral ferrous fumarate or ferrous gluconate
o Monitor to ensure there is an adequate response to treatment
o If failure to respond to treatment, consider other causes
Lissauer’s: Sytron - sodium iron edetate
Niferex - polysaccharide iron complex
How often do we monitor iron deficiency anaemia? How long should treatment last?
Monitoring
o Recheck haemoglobin levels (FBC) after 2-4 weeks of iron supplement treatment
▪ Hb should rise by 10g/L/week
o If the level has risen sufficiently, check again at 2-4 months to ensure that Hb level has normalised
o If it has NOT risen sufficiently, address compliance issues
Once haemoglobin and red cell indices are normal:
▪ Continue iron treatment for 3 months to replenish iron stores
▪ Monitor FBC every 3 months for 1 year
▪ Recheck after another year
What patients should be given a prophylactic dose for iron supplementation?
▪ Recurring anaemia
▪ Iron-poor diet (e.g. vegans)
▪ Malabsorption
▪ Menorrhagia
▪ Gastrectomy
Define red cell aplasia
No red cell production
What are the causes of red cell aplasia?
Causes in children
o Congenital red cell aplasia (Diamond-Blackfan anaemia)
▪ Rare
▪ Family history in 20%, sporadic 80%
▪ Specific gene mutations in ribosomal protein genes implicated in some cases
▪ Most present at 2 months – 3 months age, some present at birth
o Transient erythroblastopenia of childhood
▪ Usually triggered by viral infections
▪ Usually recovers within weeks
o Parvovirus B19 infection
▪ Only causes red cell aplasia in children with inherited haemolytic anaemias
What are the clinical features of Diamond-Blackfan anaemia?
o Symptoms of anaemia
o Some have other congenital anomalies e.g. short stature, abnormal thumbs, microcephaly, cataracts/glaucoma
What are the investigations for red cell aplasia? What results would be expected?
Low reticulocyte count despite low Hb
Normal bilirubin
Negative direct antiglobulin test (Coombs test)
Absent red cell precursors on bone marrow examination
What is the management of red cell aplasia?
• Diamond-Blackfan anaemia
o Oral steroids
o If not responsive to steroids, monthly RBC transfusion
o Some may need stem cell transplantation
• Transient erythroblastopenia of childhood usually recovers
What are the main causes of haemolytic in children? (haemolytic anaemia)
o Immune-mediated haemolytic anaemias are uncommon in children (unlike neonates)
o In children, main causes are intrinsic abnormalities of the red cells
▪ Red cell membrane disorders e.g. hereditary spherocytosis
▪ Red cell enzyme disorders e.g. G6PD deficiency
▪ Haemoglobinopathies e.g. beta-thalassemia major, sickle cell disease
What are the consequences of haemolysis?
o Anaemia
o Hepatosplenomegaly
o Increased unconjugated bilirubin
What are the investigations of haemolysis?
o High reticulocyte count (may appear as polychromasia)
o Unconjugated hyperbilirubinaemia
o High urinary urobilinogen
o Abnormal appearance of red cells on film (e.g. sickle cells, spherocytes)
o Increased red blood cell precursors in the bone marrow
o Positive Coomb’s test if immune cause
How common is hereditary spherocytosis?
1 in 5000 births in caucasians
What is the inheritance pattern of hereditary spherocytosis? What is the mutation?
AD but in 25% no FH
Mutation in genes which encode important red cell membrane proteins such as spectrin or ankyrin.
In HS, the RBCs become spherical in shape because the red cell loses part of its membrane each time it passes through the spleen
How are spherocytes different to normal red blood cells?
Spherocytes are less deformable than normal RBCs and are therefore destroyed prematurely in the spleen
What are the clinical features of hereditary spherocytosis?
Often suspected based on family history
May be asymptomatic
Jaundice
o Usually during childhood
o Intermittent
• Anaemia
o Mild anaemia in childhood
o Hb may fall during infections
Splenomegaly
Aplastic crisis
o Uncommon
o Transient (2-4 weeks)
o Due to parvovirus B19 infections
• Gallstones (due to increase bilirubin excretion)
What are the investigations for hereditary spherocytosis?
• FBC
o Hb:lowornormal
o MCV:lowornormal
o Platelet and WBC: normal
o Raised reticulocytes
Blood film
o Spherocytes
Specific tests
o Dye binding assay
o Osmoticfragility
• Tests for autoimmune haemolytic anaemia (DAT test) as this is also associated with
spherocytes
o Negative in hereditary spherocytosis
What is the management of hereditary spherocytosis?
• Neonates
o Supportive +/- red blood cell transfusion
o Folic acid supplementation
▪ As they have a raised folate requirement secondary to increased RBC production
o Consider phototherapy or exchange transfusion if the baby also has jaundice
• Infants, children and adults
o Supportive care +/- red blood cell transfusion
o Folic acid supplementation (2-5 mg oral OD)
o Splenectomy may be considered with a pre-operative vaccination regimen for encapsulated bacteria (H. influenzae, meningitis C and S. pneumoniae)
▪ Considered if poor growth or troublesome symptoms of anaemia
o Cholecystectomy may be performed because gallstones are common in HS
o Pneumococcal prophylaxis (oral penicillin)
• Aplastic crisis caused by parvovirus B19 requires blood transfusions
What is the prevalence of SCD in England?
1 in 2000 live births
What is the inheritance pattern of SCD? What is the mutation?
AR
HbS forms as a result of a point mutation in codon 6 of the beta globes gene which causes a change in the amino acid encoded from glutamic acid to valine.
Where is SCD the most common?
tropical Africa or the Caribbean, Central India, Middle East
What are the 3 main forms of SCD?
o Sickle cell anaemia(HbSS)
▪ Homozygous for HbS
▪ Have small amounts of HbF and no HbA
▪ Most severe form
o HbSC disease
▪ Inherited HbS from one parent and HbC from the other
▪ HbC mutation is amino acid change from lysine to glutamate at 6th position of beta globin chain
▪ No HbA
o Sickle beta-thalassemia
▪ Inherited HbS from one parent and beta-thalassemia trait from the other
▪ Most patients make no HbA hence have symptoms similar to SCA
▪ In these patients, a mutation of the beta gene blocks production of the normal beta globin chain (beta 0) or reduces its production (beta+)
o Carrier(sickle trait)
▪ Inherited HbS from one parent and a normal beta-globin gene from the other
▪ Approx. 40% of Hb will be HbS
▪ Asymptomatic
Describe the pathogenesis of SCD.
o HbS polymerises within red blood cells forming rigid tubular spiral bodies which deform the RBCs into a sickle shape
o These cells have a reduced life span and are prone to haemolysis, contributing to anaemia
▪ As this haemolysis happens within the vasculature, it is called intravascular haemolysis
▪ Recycling of the haem leads to high levels of unconjugated bilirubin→jaundice
o They can also get stuck in microcirculation resulting in vaso-occlusion and hence ischaemia of an organ
o This is exacerbated by low oxygen tension, dehydration and cold
o Severity can vary based on how much HbF the patient is able to produce (this has some genetic variation)
▪ HbF consists of two alpha and two gamma globin chains so does not include the mutated beta globins
o To counteract the anaemia, bone marrows increases number of reticulocytes produced
▪ This can lead to new bone formation and medullary cavities of the skull can expand outward causing enlarged cheeks and ‘hair-on-end’ appearance on skull X-ray
▪ Extramedullary haematopoiesis can also occur – usually in liver
RBCs can over time clog up the spleen leading to infarction and splenic sequestration
▪ Over time, this can lead to an auto-splenectomy (when spleen scars up with fibrosis)→spleen becomes non-functional
▪ Encapsulated bacteria are normally opsonised and phagocytosed by macrophages in the spleen→become susceptible to these
What are the clinical features of SCD?
Manifests as HbF synthesis reduces ~ 6 months of age
Anaemia
o All have moderate anaemia (Hb 60-100g/L) with clinically detectable jaundice from chronic haemolysis
• Infection
o Susceptible to infection from encapsulated organisms e.g. pneumococci, H influenzae, N meningitidis, Salmonella sp.
o Increased risk of osteomyelitis due to Salmonella
• Painful vaso-occlusive crises
o Cause pain in many organs of the body
o Acute crises can be precipitated by cold, dehydration, excessive exercise or stress, hypoxia or infection
o In late infancy, often presents as hand-foot syndrome
▪ Dactylitis with swelling and pain of the fingers and/or feet from vaso- occlusion
o Acute chest syndrome
▪ Severe form of crises which can lead to severe hypoxia and can require mechanical ventilation and emergency transfusion
o Avascular necrosis of femoral head
• Acute anaemia
o Sudden drop in Hb due to
▪ Haemolytic crises
▪ Aplastic crises
• Parvovirus infection causes temporary cessation of RBC production
▪ Sequestration crises
• Sudden splenic or hepatic enlargement, abdominal pain and circulatory collapse from accumulation of sickled cells in spleen
• Priapism
o Due to vasoocclusion
o Requires prompt treatment with transfusion as it can lead to fibrosis of the corpora cavernosum and erectile impotence
• Splenomegaly
o Common in young children but less frequent in older children
What are the long term problems associated with SCD?
o Short stature and delayed puberty o STROKE and cognitive problems
▪ 1 in 10 children with SCD have a stroke
▪ Can have subtle issues like poor concentration
o Adenotonsillar hypertrophy
▪ Causes sleep apnoea syndrome leading to nocturnal hypoxaemia which can lead to vaso-occlusive crises or stroke
o Cardiac enlargement from chronic anaemia
o Heart failure from uncorrected anaemia
o Renal dysfunction
o Pigment gallstones due to increased bile pigment production
o Leg ulcers (uncommon in children)
o Psychosocial issues
What are the investigations for SCD?
Screened for in newborn blood spot screen
FBC
o Anaemia
o High reticulocytes
• Blood film
o Sickle cells
o Nucleated RBCs
o Howell-Jolly bodies due to hyposplenism
Protein electrophoresis
If presenting with acute chest syndrome take ABCDE approach
o FBC
o CXR
o Oxygen saturation
o ABG
o Blood cultures
What is the prophylaxis of SCD?
o Immunisation against encapsulated organisms (e.g. S. pneumoniae and H. influenzae type B)
o Daily oral penicillin
o Daily oral folic acid
o Vaso-occlusive crises should be minimised by avoiding exposure to cold, dehydration, excessive exercise, undue stress or hypoxia
What are the complications of treatment of haemophilia?
What are the typical bleeding patterns for plt disorder and coagulation factor disorders
