Paediatric haematology Flashcards
What kind of anaemia can sickle cell disease lead to?
Haemolytic anaemia
How many units makes up heamoglobin?
4
What subunits make up adult haemoglobin?
2 alpha and 2 beta
What subunits make up fetal haemoglobin?
2 alpha and 2 gamma
What does the difference in structure of fetal haemoglobin allow it to do?
Has a higher affinity for oxygen so oxygen binds more easily and releases less easily
What is on the axis of oxygen dissociation curve?
y-axis is saturation of oxygen and x-axis is partial pressure of oxygen
Which is further to the right on the oxygen dissociation curve, adult or fetal and why?
Adult as adult requires higher partial pressure of oxygen for the molecule to fill with oxygen compared to fetal
How much haemoglobin is fetal at birth?
About half
What abnormality causes sickle cells?
A genetic abnormality in the beta subunit coding
Why can you not get sickled fetal haemoglobin?
Because fetal haemoglobin doesn’t have beta subunits
What can be used to increase the production of fetal haemoglobin in patients with sickle cell anaemia?
Hydroxycarbamide
What does hydroxycarbamide protect against?
Sickle cell crises and acute chest syndrome
At what week of gestation does HbF start to decrease?
32-36 weeks
What kind of genetic condition is sickle cell anaemia?
Autosomal recessive
What gene is abnormal in sickle cell disease and where is it?
The gene for beta- globin and it is found on chromosome 11
How does having one copy of the sickle cell gene act as a selective advantage?
Reduces the severity of malaria
How is sickle cell disease diagnosed?
With the newborn screening heel prick test at 5 days of age
What are some complications of sickle cell disease?
Anaemia
Increased risk of infection
Stroke
Avascular necrosis
Pulmonary HTN
Painful and persistent penile erection
CKD
Sickle cell crisis
Acute chest syndrome
What is given as prophylaxis against infection in sickle cell disease?
Penicillin V (phenoxymethypenicillin)
What drug can be used to stimulate production of foetal haemoglobin in people with sickle cell disease?
Hydroxycarbamide
What can sickle cell crisis be triggered by?
infection, dehydration, cold or significant life events
What are the symptoms of vaso-occlusive crisis in sickle cell disease?
Dehydration, raised haematocrit, pain and fever and can cause priopism
What is aplastic crisis in sickle cell disease?
temporary loss pf the creation of new blood cells
What kind of infection most commonly triggers aplastic disease in sickle cell anaemia?
Paravirus B19
What can splenic sequestrian crisis lead to in sickle cell disease?
Severe anaemia and circulatory collapse
What is anaemia?
low level of haemoglobin
What are the causes of haemolytic anaemia in infancy?
Physiologic
Anaemia of prematurity
Blood loss
Haemolysis
Twin-twin transfusion
What are the causes of haemolysis in infancy?
Haemolytic disease of the newborn
Hereditary spherocytosis
G6PD deficiency
When is there a dip in haemoglobin levels naturally and why?
6-9 weeks
High oxygen at birth results in lower haemoglobin production
Who are most likely to become anaemic in infancy?
Premature babies
What are the causes for anaemia in prematurity?
Less time in utero receiving iron from the mother
Red blood cell creation cannot keep up with the rapid growth in the first few days
Reduced erythropoietin levels
Blood tests remove a significant portion of the circulating powers
What causes haemolysis of the newborn?
incompatibility between rhesus antigens
What are the main symptom of haemolysis of newborn?
Jaundice (high bilirubin) and anaemia
How does rhesus D difference cause haemolysis of the newborn?
A woman who is rhesus D negative may have a rhesus D positive baby. She will produce antibodies to the rhesus D antigen which will attack in a secondary pregnancy
What might causes a rhesus D problem in a first pregnancy?
Antepartum haemorrhage
What is the test for immune haemolytic anaemia?
Direct Coombs test which will be positive in haemolytic disease
What are the common causes of anaemia in older children?
Iron deficiency anaemia and blood loss due to menstruation
What are the rarer causes of anaemia in children?
Sickle cell anaemia
Thalassemia
Leukaemia
Hereditary spherocytosis
Hereditary elliptocytosis
Sideroblastic anaemia
What is helminth infection and what does it cause?
Infection with roundworms, hookworms or whipworms
What is helminth infection treated with?
Albendazole or mebendazole
What are the causes of microcytic anaemia?
TAILS
Thalassemia
Anaemia of chronic disease
Iron deficiency anaemia
Lead poisoning
Sideroblastic anaemia
What are the causes of Normocytic anaemia?
3A + 2H
Acute blood loss
Anaemia of chronic disease
Aplastic anaemia
Haemolytic anaemia
Hypothyroidism
What are the two types of macrocytic anaemia?
Megaloblastic or normoblastic
What is megaloblastic anaemia the result of?
Impaired DNA synthesis preventing the cell from dividing normally; it divides into a large abnormal cell. This is caused by vitamin deficiency.
What is megaloblastic anaemia caused by?
B12 deficiency
Folate deficiency
What is normoblastic macrocytic anaemia caused by?
Alcohol
Reticulocytes
Hypothyroidism
Liver disease
Drugs such as azathioprine
What are the generic symptoms of anaemia?
Tiredness
Shortness of breath
Headaches
Dizziness
Palpitations
Worsening of other conditions
What symptoms are specific to iron deficiency anaemia?
Pica- dietary cravings for abnormal things such as dirt
Hair loss
What are the generic signs of anaemia?
Pale skin
Conjunctival pallor
Tachycardia
Raised respiratory rate
What signs are specific to iron deficiency anaemia?
Koilonychia
Angular cheilitis
Atrophic glossitis
Brittle hair and nails
What sign is specific to haemolytic anaemia?
Jaundice
What sign is specific to thalassemia?
Bone deformities
What are the initial investigations for anaemia?
Full blood count for haemoglobin and MCV
Blood film
Reticulocyte count
Ferritin (low in iron deficiency)
B12 and folate
Bilirubin (raised in haemolysis)
Direct Coombs test
Haemoglobin electrophoresis (for haemaglobinopathies)
What does a high level of reticulocytes in the blood indicate?
active production of red blood cells to replace lost cells- haemolysis or blood loss
What can cause iron stores to be too low?
Dietary insufficiency
loss of iron (heavy menstruation)
Inadequate iron absorption
Where is iron mainly absorbed?
duodenum and jejunum
How can medications such as proton pump inhibitors interfere with iron absorption?
Acid in the stomach keeps iron in the soluble ferrous form. Less acid in the stomach changes it to the insoluble ferric form.
What conditions can interfere with iron absorption and why?
Conditions that result in inflammation of the duodenum and jejunum such as ceoliac or crohn’s
How does iron travel round the body?
As ferric irons bound to a carrier protein called transferrin
What is TIBC?
Total iron binding capacity
What is the formula for transferrin saturation?
Serum Iron/ Total Iron Binding Capacity
What is ferritin?
The form iron takes when it is deposited and stored in cells
When is extra ferritin released from cells?
When there is inflammation such as infection or cancer
What measure of iron is not very good as it fluctuates?
Serum iron
What is the normal range for TIBC?
54-75
What is the normal range for serum ferritin?
12-200
What can give the impression of iron overload?
Supplementation with iron
Acute liver damage
What can iron be supplemented with?
Ferrous sulphate
Ferrous fumarate
What are the side effects of oral iron?
Constipation
Black stools
What is the most common type of leukaemia in children?
Acute lymphoblastic leukaemia
What is the second most common type of leukaemia in children?
Acute myeloid leukaemia
What leukaemia is rare in children?
Chronic myeloid leukaemia
When does ALL peak in children?
2-3 years
When does AML peak in children?
under 2 years
What is leukaemia?
excessive production of a single type of cell can lead to suppression of the other cell lines causing underproduction of other cell types resulting in pancytopenia
What is pancytopenia?
Low red blood cells-anaemia
Low white blood cells- leukopenia
Low platelets- thrombocytopenia
What are the risk factors for leukaemia?
Radiation- abdominal z ray during pregnancy
Down’s syndrome
Kleinfelter syndrome
Noonan syndrome
Fanconi’s syndrome
What is the presentation of leukaemia?
Persistent fatigue
Unexplained fever
Failure to thrive
Weight loss
Night sweats
Pallor (anaemia)
Petechiae and abnormal bruising
Unexplained bleeding
Abdominal pain
Generalised lymphadenopathy
Unexplained or persistent bone or joint pain
Hepatosplenomegaly
What should be done if leukaemia is suspected with non-specific signs and symptoms?
full blood count within 48 hours
What investigations should be done for leukaemia and results?
FBC- anaemia, leukopenia, thrombocytopenia and high numbers of the abnormal WBCs
Blood film-blast cells
Bone marrow biopsy
Lymph node biopsy
What tests can be done for staging of leukaemia?
Chest xray
CT scan
Lumbar puncture
Genetic analysis and immunophenotyping
What is the management of leukaemia?
Chemotherapy
Radiotherapy
Bone marrow transplant
Surgery
What are the complications of chemotherapy?
Failure to treat the leukaemia
Stunted growth and development
Immunodeficiency and infections
Neurotoxicity
Infertility
Secondary malignancy
Cardiotoxicity
What is the prognosis of ALL?
Cure rate is 80%
What is ITP?
Idiopathic thrombocytopenic purpura- Spontaneous low platelet count causing a purpuric rash (non-blanching rash)
What type of hypersensitivity reaction is ITP and what does it usually follow?
Type II hypersensitivity reaction caused by production of antibodies that target and destroy platelets usually triggered by a viral infection
What is a a key differential diagnosis of a non-blanching rash?
ITP
When does ITP normally present?
usually under 10 years
How fast is the onset of symptoms of ITP and what are the symptoms?
24-48 hours
Bleeding
Bruising
Petechial or purpuric rash caused by bleeding under the skin
What are the types of non-blanching lesions?
Petechiae- pin-prick spots
Purpura- larger spots of bleeding under the skin
Ecchymoses- large area of blood under the skin
What is the test for ITP?
urgent FBC for the platelet count. Other values on the FBC should be normal
What should you exclude when diagnosing ITP?
Heparin induced thrombocytopenia
Leukaemia
What is the management for ITP?
Usually no treatment is required and patients are monitored
Around 70% of patients will remit spontaneously within 3 months
What is the treatment for actively bleeding ITP or severe thrombocytopenia (platelets under 10)
Prednisolone
Iv immunoglobulins
Blood transfusions if required
Platelet transfusions
Why do platelets only work temporarily in ITP?
Antibodies against platelets will begin destroying the transfused platelets as soon as they are infused
What is key advice for people with thrombocytopenia?
Avoid contact sports
Avoid IM injections and lumbar punctures
Avoid NSAIDs, aspirin and blood thinning meds
Advice on managing nosebleeds
What are the complications of ITP?
Chronic ITP
Anaemia
Intracranial and subarachnoid haemorrhage
Gastrointestinal bleeding
What is thalassaemia?
genetic defect in the protein chains that make up haemoglobin
What is the genetic heritsbility of thalassaemia?
Autosomal recessive
Why do patients with thalassaemia get splenomegaly?
RBCs are more fragile and break down more easily and the spleen collects the destroyed RBCs
Why do you get susceptability to fractures in thalassaemia?
Bone marrow expands to produce RBCs to compensate for chronic anaemia
What facial features do you have in thalassaemia?
Pronounced features and malar eminences
What are potential signs and symptoms of thalssaemia?
Microcytic anaemia
Fatigue
Pallor
Jaundice
Gallstones
Splenomegaly
Poor growth and development
Pronounced forehead and malar eminences
How do you diagnose thalassaemia?
FBC- microcytic anaemia
Haemoglobin electrophoresis- globin abnormalities
DNA testing
Who are offered thalassaemia screening tests?
Pregnant women
What does Iron overload occur due to in thalassaemia?
faulty creation of RBCs, recurrent transfusions and increased absorption of iron in the gut in response to anaemia
What do you monitor in thalassaemia?
Serum ferritin for iron overload
What can iron overload in thalassaemia cause?
Effects similar to haemachromotosis:
Fatigue
Liver cirrhosis
Infertility
Impotence
Heart failure
Arthritis
Diabetes
Osteoporosis and joint pain
How do you manage iron overload in thalassaemia?
Limiting transfusions and performing iron chelation
What are the types of thalssaemia?
Alpha and Beta
Where is the defect in alpha thalassemia globin chain found?
Chromosome 16
What is the management for alpha thalssemia?
Monitoring FBC
Monitoring complications
Blood transfusions
Splenectomy may be performed
Bone marrow transplant can be curative
Where is the defect in beta thalassemia globin chain found?
Chromosome 11
What types can beta-thalassemia be split into?
Thalassaemia minor
Thalassaemia intermedia
Thalassaemia major
What is the gene defect in thalassaemia minor?
carriers of an abnormally functioning beta globin gene. They have one abnormal and one normal gene
What does thalassaemia minor cause?
mild microcytic anaemia
monitoring and no active treatment
What is the gene defect in thalassaemia intermedia?
two abnormal copies of the beta globin gene. This can either be two defective genes or one defective gene and one deletion gene
What does thalassaemia intermedia cause?
more significnat microcytic anaemia. Patients require monitoring and occasional blood transfusions. When they require more transfusions they may require iron chelation
What is the gene defect in thalassaemia major?
homozygous for the deletion genes. They have no functioning beta globin genes at all
What does thalassaemia major cause?
severe microcytic anaemia
splenomegaly
bone deformities
What is the management for thalassameia major?
regular transfusions
iron chelation
splenectomy
bone marrow transplant can potentially be curative
What is hereditary spherocytosis?
a condition where the red blood cells are sphere shaped, making them fragile and easily destroyed when passing through the spleen
What is the most common inherited haemolytic anaemia in Northern Europeans?
Hereditary spherocytosis
How is hereditary spherocytosis inherited/
Autosomal dominant
What is the presentation of hereditary spherocytosis?
Jaundice
Anaemia
Gallstones
Splenomegaly
What is haemolytic crisis caused by in hereditary spherocytosis?
Infections
What infection triggers aplastic crisis in hereditary spherocytosis?
parvovirus
What can infection with parvovirus trigger in hereditary spherocytosis?
Aplastic crisis
What is aplastic crisis?
There is increased anaemia, haemolysis and jaundice, without the normal response from the bone marrow or creating new red blood cells. Usually the bone marrow will respond to haemolysis by producing red blood cells faster, demonstrated by extra reticulocytes (immature red blood cells) in the blood. There is no reticulocyte response
How is hereditary spherocytosis diagnosed?
Family History
Clinical features
Spherocytes on the blood film
Reticulocytes raised
Mean corpuscular haemoglobin concentration is raised on a full blood count
What is the management of hereditary spherocytosis?
Folate supplementation and splenectomy
Removal of the gallbladder if gallstones are a problem.
Transfusions in acute crisis
What is hereditary elliptocytosis?
red blood cells are ellipse shaped. It is also autosomal dominant
In whom is G6PD deficiency most common in?
Mediterranean, Middle Eastern and African patients, Males
How is G6PD deficiency inherited and who does this therefore affect?
X-linked recessive so it usually only affects males
What are G6PD deficiency crisis triggered by?
Infections, medications(e.g. antimalarials) and fava beans (broad beans)
What is the G6PD enzyme responsible for?
helping protect cells from damage by reactive oxygen species (ROS). Particularly important in red blood cells.
What are reactive oxygen species?
reactive molecules that contain oxygen, produced during normal cell metabolism and in higher quantities during stress on the cell.
What does a G6PD enzyme deficiency result in?
Cells are more vulnerable to ROS, leading to heamolysis in red blood cells.
What is the presentation of G6PD deficiency?
neonatal jaundice
Anaemia
Intermittent jaundice
Gallstones
Splenomegaly
How is G6PD deficiency diagnosed?
Heinz bodies on blood film (these are denatured haemoglobin)
G6PD enzyme assay
What medications can trigger G6PD deficiency?
Primaquine (antimalarial)
Ciprofloxacin
Nitrofurantoin
Trimethoprim
Sulfonylureas (e.g. gliclazide)
Sulfasalazine and other sulphonamide drugs
