Haematology Flashcards
Adult vs Fetal haemoglobin.
Fetal haemoglobin has a higher affinity for oxygen than adult haemoglobin, meaning oxygen preferentially crosses the placenta to perfuse the fetus.
What changes occur to haemoglobin at birth?
From 32 weeks gestation, the production of HbF decreases; HbA production increases.
At the time of birth, HbF:HbA is 1:1.
By 6 months of age, most haemoglobin is HbA.
Causes of anaemia in infancy.
- physiological anaemia
- anaemia of prematurity
- blood loss
- haemolysis
- twin-twin transfusion syndrome
Causes of haemolysis in neonates.
- haemolytic disease of the newborn
- hereditary spherocytosis
- G6PD deficiency
What is physiological anaemia of infancy?
There is a normal dip in haemoglobin around 6-9 weeks of age in healthy term babies.
High oxygen delivery to the tissues caused by high haemoglobin levels at birth cause negative feedback, suppressing the production of erythropoietin by the kidneys.
Subsequently, there is a reduced production of haemoglobin in the bone marrow.
What are the reasons for anaemia of 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 weeks
- reduced erythropoietin levels
- blood tests remove a significant portion of circulating volume
Pathophysiology of haemolytic disease of the newborn.
What test is used to check for haemolytic disease of the newborn?
Direct Coombs test (DCT)
Causes of anaemia in older children.
- iron deficiency anaemia
- blood loss
- sickle cell anaemia
- thalassaemia
- leukaemia
- hereditary spherocytosis
- sideroblastic anaemia
Causes of microcytic anaemia.
TAILS:
Thalassaemia
Anaemia of chronic disease
Iron deficiency anaemia
Lead poisoning
Sideroblastic anaemia
Causes of normocytic anaemia.
AHAHA:
Acute blood loss
Haemolytic anaemia
Anaemia of chronic disease
Hypothyroidism
Aplastic anaemia
Causes of macrocytic anaemia.
FAT RBC
Fetus (pregnancy)
Alcohol
Thyroid disease
Reticulocytosis
B12 deficiency
Cirrhosis / chronic liver disease
Symptoms of anaemia.
- tiredness
- shortness of breath
- headaches
- dizziness
- palpitations
- worsening of other conditions
Specific symptoms of anaemia.
Pica - dietary cravings for abnormal things such as dirt can signify iron deficiency.
Hair loss.
Signs of anaemia.
- pale skin
- conjunctival pallor
- tachycardia
- tachypnoea
- koilonychia (?iron deficiency)
- angular chelitis (?iron deficiency)
- glossitis (?iron deficiency)
- brittle hair (?iron deficiency)
- jaundice (?haemolysis)
How should anaemia be initially investigated.
- FBC
- blood film
- reticulocyte count
- ferritin
- B12 and folate
- bilirubin
- DCT
- haemoglobin electrophoresis
Management of anaemia in children.
Establish the underlying cause and directing treatment accordingly.
Iron deficiency can be treated with iron supplementation.
Severe anaemia may require blood transfusions.
Where is iron usually absorbed?
Duodenum and jejunum
Understanding tests for iron deficiency:
a) serum ferritin
b) serum iron
c) total iron binding capacity
a) the form that iron takes when it is deposited and stored in cells, but can be artificially raised in inflammation;
b) serum iron varies significantly throughout the day, therefore isn’t a useful measure alone;
c) a marker for how much transferrin is in the blood, increasing in iron deficiency;
Management of iron deficiency anaemia.
Treat the underlying cause - usually dietary deficiency.
Iron can be supplemented with ferrous sulphate or ferrous fumarate.
Oral iron can cause constipation and black coloured stools; it’s unsuitable where malabsorption is the cause of the anaemia.
What are the most common types of leukaemia to affect children?
- acute lymphoblastic leukaemia
- acute myeloid leukaemia
- chronic myeloid leukaemia
Pathophysiology of leukaemia.
Genetic mutation of one of the precursor cells in the bone marrow leads to excessive production of a single type of white blood cell.
The excessive production of a single type of cell can lead to suppression of the other cell lines, resulting in pancytopenia:
- anaemia
- leukopenia
- thrombocytopenia
Risk factors for leukaemia.
- radiation exposure
- Down’s syndrome
- Kleinfelter syndrome
- Noonan syndrome
Presentation of leukaemia.
- failure to thrive
- night sweats
- unexplained fever
- petechiae
- unexplained bleeding
- generalised lymphadenopathy
- bone or joint pain
- hepatosplenomegaly
Diagnostic workup for leukaemia.
- FBC (?anaemia, leukopenia, thrombocytopenia, raised WBCs)
- blood film (?blast cells)
- bone marrow biopsy
- lymph node biopsy
For staging:
- CXR
- CT
- LP
- genetic analysis and immunophenotyping of abnormal cells
Management of leukaemia.
MDT:
- chemotherapy
- radiotherapy
- bone marrow transplant
- surgery
Complications of chemotherapy.
- failure to treat the leukaemia
- stunted growth and development
- immunodeficiency
- neurotoxicity
- infertility
- secondary malignancy
- cardiotoxicity
Prognosis of leukaemia.
ALL ~80%
Other types of leukaemia are less favourable.
What is idiopathic thrombocytopenic purpura (ITP)?
Type II hypersensitivity reaction caused by the production of antibodies that target and destroy platelets.
This causes a spontaneous thombocytopenia, causing a purpuric rash.
This can happen spontaneously, or it can be triggered by viral infection.
Presentation of ITP.
Presents in children under the age of 10, with onset of symptoms within 48 hours:
- bleeding
- bruising
- petechial or purpuric rash
Diagnostic work up of ITP.
- FBC (?thrombocytopenia)
- blood film (?exclude leukaemia)
Management of ITP.
Usually no treatment is required and patients are monitored until the platelets return to normal - 70% of patients will remit spontaneously within 3 months.
Treatment may be required if the patient is actively bleeding or severe thrombocytopenia:
- prednisolone
- IV immunoglobulins
- blood transfusions
- platelet transfusions
Why is the use of platelet transfusion in ITP limited?
Platelet transfusions only work temporarily because the antibodies against platelets will begin destroying the transfused platelets as soon as they are infused.
Discharge advice following ITP episode.
- avoid contact sports
- avoid IM injections / LPs
- avoid NSAIDs, aspirin
- advice on managing nosebleeds
- seek help after any injury that may cause internal bleeding.
Management of a nosebleed.
First aid measures 10-15 minutes of pressure to the nostrils.
A topical antiseptic such as Naseptin cream may be applied to prevent re-bleeding.
Management of recurrent or prolonged epistaxis.
Admission to hospital and nasal packing or nasal cautery.
Complications of ITP.
- chronic ITP
- anaemia
- intracranial or subarachnoid haemorrhage
- gastrointestinal bleeding
Inheritance pattern of sickle cell anaemia.
Autosomal recessive condition affecting the HBB gene.
Pathophysiology of sickle cell anaemia.
Mutation of HBB gene causes a sickle-shaped haemoglobin molecule to accumulate called HbS.
In sickle cell disease, there is no sickling of HbF as there is no beta subunit in the structure; HbA has a beta subunit so will sickle. Therefore, presentation of sickle cell anaemia may be delayed.
Relationship between sickle cell anaemia and malaria.
Sickle cell disease is more common in patients from areas that are traditionally affected by malaria (e.g. Africa, India, Middle East, Caribbean).
Having one copy of the gene (sickle cell trait) reduced the severity of malaria - making it more likely to survive malaria and pass on their genes.
It is therefore a selective advantage to have sickle cell trait in areas of malaria, making it more common.
Sickle cell screening.
Newborn blood spot screening test at around day 5.
Pregnant women at high risk of being carriers of the sickle cell gene are offered testing.
Complications of sickle cell anaemia.
- anaemia
- increased risk of infection
- CKD
- sickle cell crises
- acute chest syndrome
- stroke
- avascular necrosis (ie. hip)
- pulmonary hypertension
- gallstones
- priapism
What is sickle cell crisis?
An acute exacerbation of sickle cell disease.
Causes of sickle cell crisis.
- spontaneous
- dehydration
- infection
- stress
- cold weather
Presentation of sickle cell crisis.
- skeletal pain
- abdominal pain
- fever
- chest pain
- cough
- shortness of breath
- headache
- seizures
- focal neurological signs
- visual impairment
- AKI
- priapism
Management of sickle cell crisis.
Supportive management:
- admission
- treating infections that have triggered the crisis
- keep warm
- IV fluids
- analgesia (avoid NSAIDs)
What is vaso-occlusive crisis (VOC)?
Painful crisis caused by the sickle-shaped red blood cells clogging the capillaries, causing distal ischaemia.
Presentation of vaso-occlusive crisis.
Pain and swelling in the hands, feet, chest or back.
Fever.
Priapism.
What is splenic sequestration crisis?
Type of sickle cell crisis caused by red blood cells blocking blood flow within the spleen.
Presentation of splenic sequestration crisis.
Acutely enlarged and painful spleen.
Severe anaemia.
Hypovolaemic shock.
Complications of splenic sequestration crisis.
Splenic infarction, leading to hyposplenism and susceptibility to infections.
Particularly by encapsulated bacteria (ie. Streptococcus pneumoniae, Haemophilus influenzae).
Management of splenic sequestration crisis.
Management is supportive:
- blood transfusions
- fluid resuscitation
Splenectomy prevents sequestration crises and may be used in recurrent cases.
What is aplastic crisis?
Temporary absence in the creation of new red blood cells, triggers by parvovirus B19.
Leads to significant anaemia.
Trigger of aplastic crisis.
Infection with Parvovirus B19.
Management of aplastic crisis.
Supportive:
- blood transfusions
Spontaneously resolves within around a week.
What is acute chest syndrome?
The vessels supplying the lungs become clogged with red blood cells, presenting with:
- fever
- shortness of breath
- cough
- hypoxia
- chest pain
CXR of acute chest syndrome.
Pulmonary infiltrates.
Management of acute chest syndrome.
Medical emergency with high mortality:
- analgesia
- IV fluids
- antibiotics / antivirals
- blood transfusions
- respiratory support (ie. oxygen, NIV, mechanical ventilation).
General management of sickle cell anaemia.
MDT:
- avoid triggers
- up-to-date vaccinations
- antibiotic prophylaxis
- hydroxycarbamide
- crizanlizumab
- blood transfusions
- bone marrow transplant (?curative)
What is the role of hydroxycarbamide in sickle cell anaemia?
Stimulates the production of HbF, which does not sickle as it has no beta subunit.
This reduces the frequency of vaso-occlusive crises, improves anaemia and may extend lifespan.
What is the role of crizanlizumab in sickle cell anaemia.
Monoclonal antibody that targets P-selectin.
P-selectin is an adhesion molecule on endothelial cells.
Disruption of P-selectin prevents red blood cells from sticking to the blood vessel wall and reduces the frequency of vaso-occlusive crises.
What is thalassaemia?
A genetic defect in the protein chains that make up haemoglobin.
Alpha thalassaemia = alpha globin chains affected.
Beta thalassaemia = beta globin chains affected.
Inheritance pattern of thalassaemia.
Alpha-thalassaemia = autosomal recessive.
Beta-thalassaemia = autosomal recessive.
Signs and symptoms of thalassaemia.
- microcytic anaemia
- fatigue
- pallor
- jaundice
- gallstones
- splenomegaly
- poor growth and development
- pronounced forehead and malar eminences
Why is splenomegaly a feature of thalassaemia?
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.
Why is pronounced forehead and malar eminences a feature of thalassaemia?
Bone marrow expands to produce extra red blood cells to compensate for the chronic anaemia.
Diagnostic workup for thalassaemia.
- FBC (?microcytic anaemia)
- haemoglobin electrophoresis
- DNA testing
- serum ferritin (?iron overload)
Why is iron overload a feature of thalassaemia.
Iron overload occurs 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.
Management of iron overload in thalassaemia.
Limiting transfusions and performing iron chelation.
Complications of iron overload in thalassaemia.
- fatigue
- liver cirrhosis
- infertility
- impotence
- heart failure
- arthritis
- diabetes
- osteoporosis
Management of alpha thalassaemia.
- monitoring of FBC
- monitoring for complications
- blood transfusions
- splenectomy
- bone marrow transplant (?curative)
What are the types of beta thalassaemia.
- thalassaemia minor
- thalassaemia intermedia
- thalassaemia major
What is thalassaemia minor?
A subtype of beta thalassaemia, where the patient is a carrier of an abnormally functioning beta globin gene. They have one normal and one abnormal gene.
Thalassaemia minor causes a mild microcytic anaemia.
What is thalassaemia intermedia?
A subtype of beta thalassaemia, where the patient has two abnormal copies of the beta globin gene.
This causes a more significant microcytic anaemia, with patients requiring monitoring and blood transfusions.
When iron transfusions are frequently required, they may require iron chelation to prevent iron overload.
What is thalassaemia major?
A subtype of beta thalassaemia, where the patient is homozygous for the deletion genes. This means they have no functioning beta globin genes at all.
Presentation of thalassaemia major.
- severe microcytic anaemia
- splenomegaly
- bone deformities
- failure to thrive
Management of thalassaemia major.
- regular transfusions
- iron chelation
- splenectomy
- bone marrow transplant (?curative)
What is hereditary spherocytosis?
A condition where the red blood cells are sphere shapes, making them fragile and easily destroyed when passing through the spleen.I
Inheritance pattern of hereditary spherocytosis.
Autosomal dominant.
Presentation of hereditary spherocytosis.
- jaundice
- anaemia
- gallstones
- splenomegaly
Trigger for aplastic crisis in hereditary spherocytosis.
Parvovirus B19 infection - causes an increased anaemia, haemolysis and jaundice.
Diagnostic workup of hereditary spherocytosis.
Family history and clinical features.
Blood film (?spherocytes)
FBC (?raised MCHC / ?raised reticulocytes)
Management of hereditary spherocytosis.
Folate supplementation and splenectomy.
Cholecystectomy may be required if gallstones are a problem.
Transfusions may be required during acute crises.
What is hereditary elliptocytosis?
Similar to hereditary spherocytosis - red blood cells are elipse shaped.
Autosomal dominant inheritance pattern.
Inheritance pattern of G6PD deficiency.
X-linked recessive inheritance pattern - more commonly affects males.
What are the triggers of G6PD crises?
- fava beans (broad beans)
- antimalarial medications
- infections
Pathophysiology of G6PD deficiency.
G6PD enzyme is responsible for helping to protect cells from damage by reactive oxygen species (ROS).
A deficiency in G6PD makes cells more vulnerable to ROS, leading to haemolysis of red blood cells.
Periods of increased stress, with higher production of ROS, can lead to acute haemolytic anaemia.
Presentation of G6PD deficiency.
- neonatal jaundice
- anaemia
- intermittent jaundice
- gallstones
- splenomegaly
Blood film findings consistent with G6PD deficiency.
Heinz bodies - blobs of denatured haemoglobin within the red blood cells.
Gold standard for G6PD deficiency diagnosis.
G6PD enzyme assay.
Management of G6PD deficiency.
Patients should avoid triggers to acute haemolysis where possible - including avoiding fava beans and antimalarial medications.
Medications that trigger haemolysis in G6PD deficiency.
- primaquine
- ciprofloxacin
- nitrofurantoin
- trimethoprim
- sulfonylureas
- sulfasalazine
