Haematology Flashcards
What is adult haemoglobin made up of?
Two alpha and two beta subunits
What is Fetal haemoglobin made up of?
Two alpha and two gamma subunits
What is the difference between adult and fetal haemoglobin?
FbH has greater affinity to oxygen (binds more easily and more reluctant to let go)
What are on the x and y axis of the oxygen dissociation curve?
X= partial pressure of oxygen Y= percentage of Hb bound to O2
At what gestation does HbF production begin to decrease?
32-36 weeks
At birth, what proportion of haemoglobin is HbF and HbA?
50% HbA
50% HbF
By what age do blood cells contain mainly HbA?
6 months
What is anaemia?
Low level of haemoglobin in the blood
What is the most common cause of anaemia in infancy?
Physiologic anaemia of infancy
What are the other causes of anaemia in infancy?
Anaemia of prematurity Blood loss Haemolysis Twin-twin transfusion (unequal distribution) Haemolysis
What are the most common causes of haemolysis in infancy?
Haemolytic disease of the newborn (ABO or rhesus incompatibility)
Hereditary spherocytosis
G6PD deficiency
What is physiologic anaemia of infancy?
The normal dip in haemoglobin around 6-9 weeks of age in healthy term babies
What causes physiologic anaemia of infancy?
High oxygen levels (caused by high haemoglobin levels at birth) cause negative feedback which suppresses erythropoietin production in the kidneys. This reduces the production of haemoglobin in the bone marrow.
Why are premature neonates more likely to become anaemic?
Less time receiving iron from mother
RBC creation cannot keep up with rapid growth in first few weeks
Reduced EPO levels
Blood tests remove large proportion of blood
What test can be done to look for haemolytic disease of the newborn?
Direct Coombs test
What are the key causes of anaemia in older children?
Iron deficiency Blood loss (menstruation)
What are other causes of anaemia in older children?
Sickle cell anaemia Thalassaemia Leukaemia Hereditary spherocytosis/ eliptocytosis Sideroblastic anaemia
What is a common cause in developing countries of blood loss causing chronic anaemia?
Halminth infection (roundwormds, hookworms, whipworms)
How is helminth infection treated?
Single dose of albendazole or mebendazole
What are the three types of anaemia?
Microcytic
Normocytic
Macrocytic
What are the causes of microcytic anaemia?
TAILS: Thallasaemia Anaemia of chronic disease Iron deficiency Lead poisoning Sideroblastic anaemia
What are the causes of normocytic anaemia?
3A's, 2H's: Anaemia of chronic disease Acute blood loss Aplastic anaemia Haemolytic anaemia Hypothyroidism
What are the two types of macrocytic anaemia?
Megaloblastic
Normoblastic
What is the cause of megaloblastic anaemia?
Impaired DNA synthesis preventing cell from dividing normally
What causes megaloblastic anaemia?
B12 or folate deficiency
What causes normolastic macrocytic anaemia?
Alcohol Reticulocytosis Hypothyroidism Liver disease Drugs (azathioprine)
What are the symptoms of anaemia?
Tiredness SOB Headaches Dizziness Palpitations Worsening of other conditions
What symptoms are specific to iron deficiency anaemia?
Pica (strange dietary cravings)
Hair loss
What are the generic signs of anaemis on examination?
Pale
Conjunctival pallor
Tachycardia
Raised resp rate
What signs of iron deficiency anaemia may be found on examination?
Koilonychia
Angular chelitis
Atrophic glossitis
Brittle hair/ nails
What initial investigations are done into anaemia?
FBC Blood film Reticulocyte count Ferritin B12/ Folate Bilirubin Direct Coombs test Haemoglobin electrophoresis
What is haemoglobin electrophoresis?
Test that measures the different types of haemoglobin in the blood
What are reticulocytes?
Immature red blood cells
What does a high level of reticulocytes in the blood indicate?
Anaemia is due to haemolysis or blood loss (active production of RBC’s to replace lost cells)
How is anaemia managed?
Establish underlying cause (e.g. iron supplements, blood transfusions)
What are the 3 categories of causes of iron deficiency?
Dietary insufficiency
Loss or iron
Inadequate absorption
Where is iron mainly absorbed?
In duodenum and jejunum
What keeps iron in its soluble ferrous (Fe2+) form?
Stomach acid
What happens when there is less acid in the stomach?
Soluble ferrous turns into its insoluble ferric (Fe3+) form
What medications can interfere with iron absorption and why?
PPIs as they reduce the stomach acid, changing iron into its insoluble form
What conditions can cause inadequate absorption of iron?
Those that cause inflammation of the duodenum or jejunum= Coeliac or Crohn’s
In what form does iron travel around the body?
Ferric ions (Fe3+) attached to transferrin
What is transferrin?
Carrier protein
What is the total iron binding capacity?
The total space on transferrin molecules for iron to bing
What is the transferrin saturation?
The proportion of transferrin molecules that are bound to iron
How do you calculate transferring saturation?
Serum iron/ Total iron binding capacity
What form does iron take when it is stored in cells?
Ferritin
When is extra ferritin released from cells?
When there is inflammation (infection or cancer)
What does it suggest if there is low ferritin in the blood?
Iron deficiency
Can a person with normal blood ferritin levels still have iron deficiency?
Yes- may be raised due to infection ect
Why is serum iron on its own not a very useful measure?
It varies significantly throughout the day
What happens to both TIBC and transferrin levels in iron deficiency?
Increase
What does the transferrin saturation give a good indication of?
Total iron in the body
In an adult, what is the normal transferrin saturation?
30%
What is the easiest/ best test to look for iron deficiency?
Total iron binding capacity
What are the types of leukaemia that affect children (most–> least common)?
- Acute lymphoblastic laeukaemia
- Acute myeloid leukaemia
- Chronic myeloid leukaemia
What age does ALL peak?
2-3 years
What age does AML peak?
<2
What cells does leukaemia affect?
Stem cells of the bone marrow
What does leukaemia cause?
Excessive production of a single type of abnormal white blood cell
What does excessive production of a single type of cell in leukaemia lead to?
Pancytopenia (anaemia + Leukopenia + thrombocytopenia)
What are the risk factors for developing leukaemia?
Radiation exposure furing pregnancy Down's syndrome Kleinfelter syndrome Noonan syndrome Fanconi's anaemia
What may symptoms of leukaemia include?
Fatigue Fever Failure to thrive Weight loss Night sweats Anaemia Bruising Bleeding Lymphadenopathy Bone/ joint pain Hepatosplenomegaly
What red flags would cause a child to have immediate specialist assessment for leukaemia?
Unexplained petechiae or hepatomegaly
If leukaemia is suspected what initial investigation should be done?
FBC within 48 hours
What investigations can be done to diagnose leukaemia?
FBC
Blood film
Bone marrow biopsy
Lymph node biopsy
What will FBC show in leukaemia?
Anaemia
Leukopenia
Thrombocytopenia
High numbers of abnormal WBC’s
What may blood film show in leukaemia?
Blast cells
What further tests may be done into leukaemia?
CXR
CT
LP
Genetic analysis
How is leukaemia primarily treated?
Chemotherapy
What are the complications of chemotherapy?
Failure Stunted growth/ development Immunodeficiency/ infections Neurotoxicity Infertility Secondary malignancy Cardiotoxicity
What is the prognosis for ALL?
80% cure rate
What is ITP?
Idiopathic thrombocytopenic purpura
What is idiopathic thrombocytopenic purpura?
Condition that causes idiopathic low platelet count causing a non-blanching rash
What is ITP caused by?
Type II hypersensitivity reaction that causes antibodies to destroy platelets
What age does ITP usually present?
Children under 10
What might trigger ITP?
Idiopathic or viral infection
What are the main symptoms of ITP?
Bleeding (gums, nose, menorrhagia)
Bruising
Petechial or purpuric rash
What are petechiae?
Pin-prick spots (1mm) of bleeding under the skin
What are purpura?
Larger (3-10mm) spots of bleeding under the skin
What is ecchymoses?
Large area of blood (>10mm) collected under the skin
Is the rash in ITP blanching?
Non-blanching
How is ITP diagnosed?
Urgent FBC for platelet count
What other causes of thrombocytopenia should be excluded when diagnosing ITP?
Heparin induced thrombocytopenia
Leukaemia
How is ITP usually managed
Usualy no treatment required and patients monitored until platelets return to normal
What percentage of patients remit spontaneously with ITP and how quickly?
70% within 3 months
What treatments should be given for severe ITP or if the patient is actively bleeding?
Prednisolone
IV immunoglobulins
Blood transfusions
Platelet transfusions
Why do platelet transfusions only work temporarily when treating ITP?
Antibodies against platelets will begin destroying the transfused platelets
What key advice should be given to patients with ITP?
Avoid contact sports
Avoid IM injections
Avoid NSAIDs, aspirin and anticoagulants
Seek help after any injury that may cause bleeding
What are the complications of ITP?
Chronic ITP
Anaemia
Intracranial and subarachnoid haemorrhage
GI bleed
What is sickle cell anaemia?
Genetic condition causing sickle shaped RBC’s
What does sickle cell anaemia cause?
Haemolytic anaemia
What is the pathophysiology of sickle cell anaemia?
Patients have abnormal gene for beta-globin on chromosome 11 which codes for abnormal haemoglobin (HbS) which causes RBCs to become sickle shape
What kind of genetic inheritance is sickle cell anaemia?
Autosomal recessive
What does one copy of the abnormal beta-globin gene cause?
Sickle-cell trait
What do two copies of the abnormal beta-globin gene cause?
Sickle-cell disease
Where is sickle cell disease more common?
Africa, India, Middle East, Caribbean
What are the benefits of sickle cell trait?
Reduces severity of malaria
How is sickle cell anaemia diagnosed?
Women at risk tested during pregnancy
Newborn screening heel prick test
What are the complications of sickle cell disease?
Anaemia Increased risk of infection Stroke Avascular necrosis of large joints Pulmonary hypertension Priapism CKD Sickle cell crises Acute chest syndrome
What is the general management of sickle cell disease?
Avoid crises triggers
Up to date with vaccines
Antibiotic prophylaxis
Blood transfusion (Severe anaemia)
What can be used to protect against sickle cell crises and acute chest syndrome?
Hydroxycarbamide
What is the action of hydroxycarbamide?
Stimulates production of fetal haemoglobin (hbF) which does not lead to the sickling of RBCs
What can be used to cure sickle cell anaemia?
Bone marrow transplant
What may trigger a sickle cell crisis?
Spontaneous Infection Dehydration Cold Significant life events
How are sickle cell crises managed?
Supportively:
Treat infection
Keep warm and hydrated
Simple analgesia
What is priapsim?
Painful and persistent penile erection
What are the different types of sickle cell crisis?
Vaso-occlusive crisis
Splenic sequestration crisis
Aplastic crisis
Acute chest syndrome
What causes a vaso-occlusive crisis?
Sickle shaped blood cells clogging capillaries and causing distal ischaemia
What is haematocrit?
Measurement of the proportion of blood which is made up of cells (Packed cell volume)
What is the usual cause of a vaso-occlusive crisis?
Dehydration
What are the symptoms of a vaso-occlusive crisis?
Pain
Fever
How is priapism treated?
Aspiration of blood from penis
What is a splenic sequestrian crisis?
When RBCs block flow in the spleen, causing it to become acutely enlarged and painful
What can pooling of blood in the spleen lead to?
Severe anaemia
Hypovolaemic shock
How is a splenic sequestrian crisis managed?
Supportive
Blood transfusions
Fluid resuscitation
What may be done if there are recurrent splenic sequestration crises?
Splenectomy
What is an aplastic crisis?
Temporary loss of the creation of new blood cells
What is the most common trigger of an aplastic crisis?
Infection with parvovirus B19
How is aplastic crisis managed?
Supportive with blood transfusions as necessary
Usually resolves within a week
What is acute chest syndrome?
Medical emergency caused by sickled cells causing pulmonary infarction/ emboli
What must be seen to make a diagnosis of acute chest syndrome?
Fever or respiratory symptoms
New infiltrates on CXR
What can cause acute chest syndrome?
Infection (pneumonia or bronchiolitis)
Non-infective (pulmonary vaso-occlusion or fat emboli)
How is acute chest syndrome managed?
Treat underlying cause: Antibiotics or antivirals Blood transfusions Incentive spirometry Artificial ventilation
What causes thalassaemia?
Genetic defect in protein chains that make up haemoglobin
What are the two types of thalassaemia?
Alpha and beta
What genetic inheritance is thalassaemia?
Autosomal recessive
What does thalassaemia cause?
RBCs to be more fragile and break down more easily, leading to anaemia and splenomegaly
Why do you get splenomegaly in thalassaemia?
The spleen collects all the destroyed red blood cells and there are lots
What happens to the bone marrow in thalassaemia?
It expands to produce extra RBCs to compensate for chronic anaemia
What are the signs and symptoms of thalassaemia?
Microcytic anaemia Fatigue Pallor Jaundice Gallstones Splenomegaly Poor growth/ development Pronounced forehead/ cheekbones
How is thalassaemia diagnosed?
FBC (microcytic anaemia)
Haemoglobin electrophoresis
DNA testing
Pregnancy screening test
What is the key complication of thalassamiea?
Iron overload
Why do you get iron overload in thalassaemia?
Due to faulty creation of RBCs, recurrent transfusions and increased absorption of iron in the gut in response to anaemia
How is iron overload monitored for?
Monitor serum ferritin levels
How is iron overload managed?
Limit transfusions
Iron chelation
What are the symptoms of iron overload?
Fatigue Liver cirrhosis Infertility Impotence Heart failure Arthritis Diabetes Osteoporosis Joint pain
What gene codes for alpha globin?
Chromosome 16
How is alpha thalassaemia managed?
Blood transfusions
Splenectomy
Bone marrow transplant
What chromosome codes for beta globin chains?
Chromosome 11
What are the different types of beta-thalassaemia?
Minor
Intermedia
Major
What is thalassaemia minor?
When patients are carriers of an abnormally functioning beta globin gene (one abnormal, one normal gene)
What does thalassaemia minor cause?
Mild microcytic anaemia
What is thalassaemia intermedia?
When patients have two abnormal copies of the beta globin gene
What are the different genes patients may have in thalassaemia intermedia?
Two defective genes or one defective gene and one deletion gene
What does thalassaemia intermedia cause?
More significant microcytic anaemia
What is thalassaemia major?
When patients have two deletion genes, meaning they have no functioning beta globin genes
How does thalassaemia major usually present?
Severe anaemia
Failure to thrive
Splenomegaly
Bone defomities
How is thalassaemia major managed?
Regular transfusions
Iron chelation
Splenectomy
Bone marrow transplant
What is iron chelation?
Agent (tablet or infusion) given that binds to iron and allows body to excrete the bound particles
What is hereditary spherocytosis?
Condition where RBCs are sphere shaped, making them fragile and easily destroyed
In which population is hereditary spherocytosis most common?
Northern Europeans
What inheritance pattern in Hereditary spherocytosis?
Autosomal dominant
How does hereditary spherocytosis present?
Jaundice
Anaemia
Gallstones
Splenomegaly
What are haemolytic crises?
Periods triggered by infections where haemolysis, anaemia and jaundice are more significant
What may patients with hereditary spherocytosis develop?
Aplastic crisis
What happens in an aplastic crisis?
The body stops producing enough RBCs, leading to anaemia, haemolysis and jaundice
What is the common trigger of an aplastic crisis?
Parvovirus
How is hereditary spherocytosis diagnosed?
By family history and clinical features
Spherocytes on blood film
How is hereditary spherocytosis managed?
Folate supplementation and splenomectomy
What is hereditary elliptocytosis?
Autosomal dominant condition causing RBC;s to be an ellipse shape
What is G6PD deficiency?
Condition where there is a defect in the G6PD enzyme
In which patients id G6PD deficiency more common?
Mediterranean, Middle Eastern and African
What is the inheritance pattern of G6PD deficiency?
X-linked recessive
Who is usually affected by G6PD deficiency and why?
Males because they only have a single copy of the X chromosome
What are the key triggers of a G6PD crisis?
Infections
Medications
Fava beans
What is the action of the G6PD enzyme?
Helps protect cells (especially RBCs) from damage by reactive oxygen species (ROS)
What are ROS?
Reactive molecules that contain oxygen, produced during normal cell metabolism and in higher quantities during stress on the cell
What does a deficiency in G6PD lead to?
Makes cells more vulnerable to ROS, leading to haemolysis in RBCs, and eventually acute haemolytic anaemia
How does G6PD deficiency normally present?
Neonatal jaundice
What are the key features of G6PD deficiency?
Intermittent jaundice
Anaemia
Gallstones
Splenomegaly
How is G6PD deficiency diagnosed?
Blood film
G6PD enzyme assay
What may be seen on blood film of G6PD deficiency?
Heinz bodies (blobs of denatures haemoglobin in RBCs)
How is G6PD deficiency managed?
Avoid triggers to acute haemolysis (fava beans, medications)
