Haematology Flashcards
What is the structural difference between adult and foetal haemoglobin ?
Adults - 2 alpha and 2 beta subunits
Foetal - 2 alpha and 2 gamma subunits
What are some causes of anaemia in infancy ?
Physiological anaemia of infancy
Anaemia of prematurity
Blood loss
Haemolysis
Twin-twin transfusion where blood is unequally distributed between twins that share a placenta.
Haemolytic disease of the newborn
Hereditary spherocytosis
G6PD deficiency
What is physiological anaemia of infancy ?
There is a normal dip in haemoglobin around 6 to 9 weeks of age in healthy term babies.
High oxygen delivery to the tissues caused by the high haemoglobin levels at birth cause negative feedback. Production of EPO by the kidneys is suppressed causing reduced Hb by the bone marrow.
What are some reasons for anaemia in premature neonates ?
-Less time in utero receiving iron from the mother
-Red blood cell creation cant keep up with rapid growth in the first few weeks
-reduced EPO levels
-blood tests remove a significant portion of their circulating volume
What is the direct Coombs test ?
Can be used to check for immune haemolytic anaemia.
What are some causes of anaemia in older children ?
Iron deficiency anaemia
Blood loss
Sickle cell anaemia
Thalassaemia
Leukaemia
What is microcytic anaemia ?
Low MCV indicating small RBC
What is normocytic anaemia ?
Normal MCV indicating normal sized RBC
What is macrocytic anaemia ?
Large MCV indicating large RBC
What are some causes of microcytic anaemia ?
Thalassaemia
Anaemia of chronic disease
Iron deficiency anaemia
Lead poisoning
Sideroblastic anaemia
What are some causes of normocytic anaemia ?
Acute blood loss
Anaemia of chronic disease
Aplastic anaemia
Haemolytic anaemia
Hypothyroidism
What are the 2 types of macrocytic anaemia ?
Megaloblastic
Normoblastic
What is megaloblastic anaemia ?
The result of impaired DNA synthesis preventing the cell from dividing normally. Rather than it dividing it keeps growing into a large abnormal cell.
This is caused by vitamin deficiency.
What causes megaloblastic anaemia ?
B12 deficiency
Folate deficiency
What is normoblastic macrocytic anaemia ?
Alcohol
Reticulocytosis
Hypothyroidism
Liver disease
Drugs such as azathioprine
What are some symptoms of anaemia ?
Tiredness
SOB
Headaches
Dizziness
Palpitations
Worsening of other conditions
What are some symptoms specific to iron deficiency anaemia ?
Pica - dietary cravings for abnormal things like dirt
Hair loss - indicate iron deficiency anaemia
What are some generic signs of anaemia ?
Pale skin
Conjunctival pallor
Tachycardia
Raised RR
What are some signs that indicate iron deficiency anaemia ?
Koilonychia ( spoon shaped nails )
Angular chelitis
Atrophic glossitis ( smooth tongue due to atrophy of the papillae )
Brittle hair and nails
What are some initial investigations when suspecting anaemia ?
FBC
Blood film
Reticulocyte count
Ferritin
B12 and folate
Bilirubin
Direct Coombs test
How is severe anaemia treated ?
Blood transfusions
How is iron deficiency anaemia managed ?
Iron supplements
What are the types of leukaemia ?
Acute lymphoblastic leukaemia
Acute myeloid leukaemia
Chronic myeloid leukaemia
When do the types of leukaemia peak ?
Acute lymphoblastic leukaemia - 2-3 years old
Acute myeloid leukaemia - under 2 years old
What is the main environmental risk factor for leukaemia ?
Radiation exposure - abdominal X-ray during pregnancy
What conditions are associated with developing leukaemia ?
Down’s syndrome
Klinefelter’s syndrome
Noonan syndrome
Fanconi’s anaemia
How does leukaemia present ?
Persistent fatigue
Unexplained fever
Failure to thrive
Weight loss
Night sweats
Pallor
Petechiae
Unexplained bleeding
Abdominal pain
Generalised lymphadenopathy
Unexplained or persistent bone or joint pain
Hepatosplenomegaly
What investigations should be performed to establish a diagnosis of leukaemia ?
FBC
Blood film
Bone marrow biopsy
Lymph node biopsy
What further tests may be required for staging leukaemia ?
CXR
CT scan
Lumbar puncture
Genetic analysis and immunophenotyping
What is the management of leukaemia ?
Chemotherapy
Radiotherapy
Bone marrow transplant
Surgery
What are some complications of chemotherapy ?
Failure to treat leukaemia
Stunted growth and development
Immunodeficiency and infections
Neurotoxicity
Infertility
Secondary malignancy
Cardio toxicity
What is idiopathic thrombocytopenic purpura ?
A condition characterised by idiopathic ( spontaneous ) thrombocytopenia ( low platelet count ) causing a purpurin rash ( non-blanching rash ).
What causes ITP ?
Caused by a type 2 hypersensitivity reaction.
It is caused by the production of antibodies that target and destroy platelets.
How does ITP present ?
Under 10 years old
Often recent viral illness
Bleeding ( from gums, epistaxis or Menorrhagia )
Bruising
Petechial or purpuric rash
What are some treatment options if someone with ITP is actively bleeding ?
Prednisolone
IV immunoglobulins
Blood transfusions
Platelet transfusions - only temporary
Why is platelet transfusions only temporary in the treatment of ITP ?
Antibodies against platelets will begin destroying the transfused platelets as soon as they are transfused.
What are some key eduction and advice for ITP patients ?
Avoid contact sports
Avoid IM injections and procedures such as LP
Avoid NSAIDs, aspirin and blood thinning medications
Advice or managing nosebleeds
Seek help after any injury that may cause internal bleeding.
What are some complications of ITP ?
Chronic ITP
Anaemia
Intracranial and subarachnoid haemorrhage
GI bleeding
What is sickle cell anaemia ?
A genetic condition that causes sickle ( crescent ) shaped red blood cells.
The abnormal shape makes the red blood cells more fragile and easily destroyed leading to haemolytic anaemia.
What is the pathophysiology of sickle cell disease ?
Autosomal recessive condition affecting the gene for beta-globin on chromosome 11.
Patients with one abnormal copy of the gene results in sickle cell trait.
How does sickle cell disease relate to malaria ?
Having one copy of the gene ( sickle cell trait ) reduces the severity of malaria.
As a result , patients with sickle cell trait are more likely to survive malaria and pass on their genes.
When is sickle cell disease screened ?
Newborn blood spot test at day 5
What are some complications of sickle cell disease ?
Anaemia
Increased risk of infection
CKD
Sickle cell crises
Acute chest syndrome
Stroke
AVN
Pulmonary HTN
Gallstones
Priapism
What can trigger a sickle cell crisis ?
Dehydration
Infection
Stress
Cold weather
What is the management of sickle cell crisis ?
Low threshold for admission to hospital
Treating infection that may have been the trigger
Keep warm
Good hydration
Analgesia
How does sickle cell disease cause vaso-occlusive crisis ?
Caused by the sickle-shaped red blood cells clogging capillaries, causing distal ischaemia.
How does vaso-occlusive crisis present ?
Pain and swelling in the hands or feet but can affect the chest, back or other body areas.
Associated with fever
What causes splenic sequestration crisis ?
Red blood cells blocking blood flow within in the spleen. It causes an acutely enlarged and painful spleen. Blood pooling in the spleen can lead to severe anaemia and hypovolaemic shock.
What can splenic sequestration crisis cause ?
Splenic infarction leading to hyposplenism and susceptibility to infections - encapsulated bacteria.
How is a splenic sequestration crisis managed ?
Supportive - blood transfusions and fluid resus to treat
Splenectomy can prevent a sequestration crises
What is an aplastic crisis ?
Describes a temporary absence of the creation of new red blood cells. It is usually triggered by infection with parvovirus B19. It leads to significant anaemia.
What is the management of an aplastic crisis ?
Supportive - blood transfusions if necessary
Resolves spontaneously within a week
What is acute chest syndrome ?
Occurs when the vessels supplying the lungs become clogged with red blood cells. Medical emergency
What can trigger acute chest syndrome ?
Vaso-occlusive crisis
Fat embolism
Infection
How does acute chest syndrome present ?
Fever
SOB
Chest pain
Cough
Hypoxia
How does acute chest syndrome present on an X-ray ?
Pulmonary infiltrates
How is acute chest syndrome managed ?
Analgesia
Good hydration - IV fluids
Antibiotics or antivirals
Blood transfusions
Incentive spirometry
Respiratory support with oxygen, non-invasive ventilation or mechanical ventilation.
How is sickle cell disease managed ?
Avoid triggers for crises
Up to date vaccinations
Antibiotic prophylaxis - penicillin V
Hydroxycarbamide - stimulates HbF
Crizanlizumab
Blood transfusions
Bone marrow transplant
How does crizanlizumab work in sickle cell disease ?
A monoclonal antibody that targets P-selection.
It prevents red blood cells from sticking to the blood vessel wall and reduces the frequency of vaso-occlusive crises.
What is thalassaemia ?
Related to a genetic defect in the protein chains that make up haemoglobin.
Defects in the alpha globin chains lead to alpha thalassaemia and defects in the beta globin chains lead to beta thalassaemia.
Autosomal recessive
How does thalassaemia cause splenomegaly ?
The red blood cells are more fragile and break down more easily.
The spleen acts as a sieve to filter the blood and remove older blood cells.
In patients with thalassaemia the spleen collects all the destroyed red blood cells resulting in splenomegaly.
What are some potential signs and symptoms of thalassaemia ?
Microcytic anaemia
Fatigue
Pallor
Jaundice
Gallstones
Splenomegaly
Poor growth and development
Pronounced forehead and malar eminences
How does thalassaemia cause a pronounced forehand and Malar eminences ?
Bone marrow expands to produce extra red blood cells to compensate for the chronic anaemia. This causes a susceptibility to fractures and prominent features.
How is a diagnosis of thalassaemia made ?
FBC
Haemoglobin electrophoresis
DNA testing
How does iron overload occur in thalassaemia ?
As a result of the faulty creation of red blood cells recurrent transfusions and increased absorption of iron in the gut in response to anaemia.
what can iron overload in thalassaemia cause ?
Fatigue
Liver cirrhosis
Infertility
Impotence
Heart failure
Heart failure
Arthritis
Diabetes
Osteoporosis and joint pain
Which chromosome is affected in alpha thalassaemia ?
Chromosome 16
What is the management of alpha thalassaemia ?
Monitor FBC and for any complications
Blood transfusions
Splenectomy
Bone marrow transplant
What chromosome is affected in beta thalassaemia ?
Chromosome 11
What are the 3 types of thalassaemia ?
Thalassaemia minor
Thalassaemia intermedia
Thalassaemia major
What is thalassaemia minor ?
They are carriers of an abnormally functioning beta globin gene. They have one abnormal and one normal gene.
Causes mild microcytic anaemia
What is thalassaemia intermedia ?
Patients with beta thalassaemia intermedia have 2 abnormal copies of the beta globin gene.
This can either be 2 defective genes or one defective and one deletion gene.
More significant microcytic
What is the management of thalassaemia intermedia ?
Occasional blood transfusions
May require iron chelation to prevent iron overload
What is thalassaemia major ?
Homozygous for the deletion genes.
Most severe and causes failure to thrive
What can thalassaemia major cause ?
Severe microcytic anaemia
Splenomegaly
Bone deformities
What is the management for thalassaemia major ?
Regualr trasnfusions
Iron chelation
Splenectomy
Bone marrow can be 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.
Autosomal dominant
How does hereditary spherocytosis present ?
Jaundice
Anaemia
Gallstones
Splenomegaly
Episodes of haemolytic anaemia
Aplastic crisis
How is a diagnosis of hereditary spherocytosis ?
Is diagnosed by family history and clinical features along with spherocytes on the blood film.
The mean corpuscular haemoglobin concentration is raised on FBC.
Reticulocytes will be raised due to rapid turnover of red blood cells.
What is the management of hereditary spherocytosis ?
Folate supplementation and splenectomy
Removal of gall bladder
Transfusions in acute crisis
What is G6PD deficiency ?
A condition where there is a defect in the G6PD enzyme normally found in all cells in the body.
X linked recessive - males more likely to be affected
What triggers a crises in G6PD deficiency ?
Infections
Medications - anti malarial
Fava beans
What is the pathophysiology of G6PD deficiency ?
The G6PD enzyme is responsible for helping protect cells from damage by reactive oxygen species.
ROS are reactive molecules that contain oxygen produced during cell metabolism.
A deficiency in the G6PD enzyme makes the cell vulnerable to ROS leading to haemolysis.
How does G6PD present ?
Neonatal jaundice
Anaemia
Gallstones
Splenomegaly
How does G6PD present on a blood film ?
With heinz bodies due to the denatured haemoglobin within the red blood cells
What is the management of G6PD ?
Avoid fava beans
Avoid certain medications :
- primaquine
- Ciprofloxacin
- nitrofurantoin
- trimethoprim
- sulfonylurea
- sulfasalazine
