Paediatric haematology Flashcards
What is ferritin ?
Stored iron in cells
What does low ferritin suggest ?
Iron deficiency
What does high ferritin suggest ?
- Inflammation
- Ferritin is released from cells when there is inflammation such as with infection or cancer
What happens to the TIBC and transferrin levels in IDA?
Increased
How is IDA treated ?
- Ferrous sulphate or ferrous fumarate
- Blood transfusions if necessary
what causes Immune thrombocytopenic purpura ?
- Type II hypersensitivity reaction
- Antibodies are produced that destroy the platelets
- Can occur spontaneously or as a result of a VIRAL INFECTION or vaccination
How does ITP present ?
- Usually a history of a viral illness
- Onset of symptoms is 24-48hrs
- Bruising
- Petechial or purpuric rash
- Bleeding : gums, epistaxis or menorrhagia (less common)
Who does ITP usually effect ?
-Children <10
How is ITP diagnosed ?
-FBC for platelet count = isolated thrombocytopenia
Give 3 causes of low plts
- ITP
- Heparin induced thrombocytopenia
- Leukaemia
How is ITP treated if patient is actively bleeding or if plt levels are severe (<10)
- Usually resolves on own
- Prednisolone
- IV immunoglobulins
- Platelet transfusion (if required)
Why would a plt transfusion for ITP only work temporarily ?
-The antibodies will destroy the transfused plts
What key education is given in ITP?
- Avoid contact sports
- Avoid IM injections
- Avoid NSAIDs, aspirin and other blood thinning meds
Give 4 complications of ITP
- Chronic ITP
- Anaemia
- Intracranial and SAH
- Gastrointestinal bleeding
What is thalassaemia ?
-Autosomal recessive condition causing a genetic defect in the protein chains that make up Hb.
Give 8 potential signs and symptoms of thalassaemia
- Microcytic anaemia
- Fatigue
- Pallor
- Jaundice
- Gallstones
- Splenomegaly
- Poor growth and development
- Pronounced forehead and malar eminences
How is thalassaemia diagnosed ?
- Pregnant screening test
- FBC -> microcytic anaemia
- Haemoglobin electrophoresis -> globin abnormalitis
- DNA testing -> genetic abnormality
Why can thalassaemia cause iron overload?
- Faulty creation of RBC
- Recurrent transfusions
- Increased iron absorption from the gut due to anaemia
Give 8 signs of iron overload
- Fatigue
- Liver cirrhosis
- Infertility
- Impotence
- HF
- Arthritis
- DM
- Osteoporosis and joint pain
How is potential iron overload monitored and then treated ?
- Monitor serum ferritin
- Treat with iron chelation (desferrioxamine) and limit transfusions
What chromosome is involved in alpha thalassaemia ?
-16
- 4 genes, 2 on each chromosome
How is alpha thalassaemia managed ?
- Monitor FBC
- Monitor for complications
- Blood transfusions
- Splenectomy can be performed
- BM transplant can be curative
What chromosome is involved in beta thalassaemia and why is there 3 types ?
11
-Gene defect can either consist of abnormal copies that retian some function or deletion of genese where there is no function :
- Thalassaemia minor
- Thalassaemia intermedia
- Thalassaemia major
What is thalassaemia minor ?
- Carriers of abnormally functioning beta globin gene
- 1 abnormal, one normal
- Causes mild hypochromic microcytic anaemia and pts often only require monitoring and no active treatment
- Raised HbA2
What is thalassaemia intermedia
- 2 defective genese or one defective and one deletion gene
- More significant anaemia
- Need monitoring and occassional blood transfusions
- May require iron chelation to prevent iron overload
What is thalassaemia major ?
- Homozygous for the deletion gene
- Severe : presents with severe anaemia and failure to thrive in early childhood
What are 3 complications of thalassaemia major ?
- Severe microcytic anaemia
- Hepatosplenomegaly in the 1st year of life
- Bone deformities
- Raised HbF and HbA2, absent HbA
What is sickle cell anaemia ?
- Autosomal recessive condition causing crescent shaped RBC’s
- They are more fragile and more easily destroyed = haemolytic anaemia
Explain the pathophysiology behind sickle cell anaemia
- Pts have an abnormal Hb variant
- It is an autosomal recessive condition where there is an abnormal gene for beta-globin on chromosome 11
- One copy = sickle trait and usually asymptomatic (HbAS)
- 2 copies = sickle cell disease (HbSS)
Why is having sickle cell trait a selective advantage in areas affected by malaria ?
- It reduces the severity of malaria
- Makes them more likely to survive malaria and pass on their genes
How is sickle cell disease diagnosed
- Newborn screening heel prick test at 5 days old
or by Hb electrophoresis - Pregnant women at risk of being carriers are offered testing during pregnancy.
What is the general management of sickle cell anaemia ?
- Avoid dehydration and other triggers
- Keep vaccines up to date
- Abx prophylaxis with penicillin V
- Hydroxycarbamide to stimulate HbF production -> protective effect against sickle cell crisis and acute chest syndrome
- Blood transfusion for severe anaemia
- Stem cell transplant can be curative
Give 9 complications of sickle cell disease
- Anaemia
- Avascular necrosis of large joints
- Pulmonary HTN
- CKD
- Sickle cell crisis
- Acute chest syndrome
- Increased risk of infection
- Stroke
- Priapism
Give 4 examples of a sickle cell crisis
- Vaso-occlusive crisis (painful)
- Splenic sequestration
- Aplastic
- Acute chest syndrome
What is a vaso-occlusive crisis
- Precipitated by infection, dehydration or deoxygenation.
- The sickle RBC’s clog capillaries and cause distal ischaemia
- Presents with pain, fever and signs of triggering infection
- Associated with dehydration and raised haematocrit
- Can cause priapism in med which is treated with aspiration of blood from the penis
What is a splenic sequestration crisis ?
- RBC’s block blood flow to the spleen = enlarged and painful spleen
- Pooling of blood in the spleen can lead to severe and anaemia and circulatory collapse (hypovolaemic shock)
- Mx : blood transfusion, fluid resus
- Recurrent crises -> splenectomy as reccurrent crisis can lead to splenic infarct
- Associated with raised reticulocyte count
What is an aplastic crisis ?
- Temporary loss of creation of new blood cells
- Usually triggered by parovovirus B19
- Leads to severe anaemia and is managed with blood transfusion if necessary
- BM supression -> raised reticuloytes
When is acute chest syndrome diagnosed ?
-Fever or resp symptoms with NEW INFILTRATES seen on CXR and low pO2
What causes acute chest syndrome ?
- Infection (pneumonia, bronchiolitis)
- Non-infective (pulmonary vaso-occlussion or fat emboli)
How is acute chest syndrome managed ?
- Abx or antivirals for infection
- Blood transfusions for anaemia
- Incentive spirometry for breathing
- Artifical ventilation with NIV or intubation if required
What is haemophilia and its causative deficiencies
- X linked recessive bleeding disorder
- Haemophilia A : deficiency in factor VIII
- Haemophilia B : deficiency in factor IX
Explain the inheritance of haemophilia
- X linked recessive
- Almost exclusively affects males
How does haemophilia present
- Excessive bleeding in response to trauma or spontaneous haemorrhage
- Usually in neonates or early childhood with intracranial haemorrhage, haematomas and cord bleeding
- E.g. 11mnth -> bruising, painful and swollen joint but no fever
Where can bleeding occur in haemophilia ?
- Joints (haemathrosis) and muscles = severe
- Gums
- GI tract
- Urinary tract -> haematuria
- Retroperitoneal space
- Intracranial
- Following procedures
How is haemophilia diagnosed ?
- 1st line = clotting screen
- Isolated raised APTT
How is an acute episode of bleeding managed in haemophilia ?
- Infusions of the factor
- Desmopressin to stimulate VWF release
- Antifibrinolytics such as tranexamic acid
What is a complication of clotting factor IV infusions
-Abx can be made against the factors
What is the most common inherited cause of abnormal bleeding ?
-Von Willebrand Disease
What is the inheritance pattern of VWD?
- Autosomal dominant
- Involves deficiency, absence or malfunctioning VWF
- 3 types, type 3 most severe (autosommal recessive)
How does VWD present ?
- Hx of unusually easy, prolonged or heavy breathing
- Bleeding gums with brushing
- Epistaxis
- Menorrhagia
- Heavy bleeding during surgical operations
- Fx of heavy bleeding or VWD
How is major trauma treated in VWD?
- Desmopressin to stimulate release of VWD
- VWF infusion
- Factor VIII
What are the 4 subunits of haemoglobin in the foetus (HbF)
- 2 alpha subunits
- 2 gamma subunits
Explain the difference between adult and foetal haemoglobin, in terms of the oxygen dissociation curve
- Fetal HbF has a greater affinity for oxygen that HbA
- HbF binds to oxygen more easilty and is more reliuctan to let go
- It sits further left on the oxygen dissociation curve
When does HbF production being to decrease ?
- From 32 to 36 weeks gestation
- HbA is then produced in greater quantities
What can be given to increase HbF production in patients with sickle cell anaemia ?
-Hydroxycarbamide
What is the most common cause of anaemia in infancy ?
-Physiologic anaemia of infancy
Give 4 other causes of anaemia in infancy?
- Anaemia of prematurity
- Blood loss
- Haemolysis
- Twin Twin transfusion -> blood is unequally distributed between twins that share a placenta
Give 3 causes of haemolysis in neonates
- Haemolytic disease of the newborn (ABO or rhesus incompatibility)
- Hereditary spherocytosis
- G6PD deficiency
What is Physiologic Anaemia of Infancy and when does it occur ?
- Six to nine weeks
- High oxygen delivery to the tissues due to high HbF levels at birth leads to negative feedback
- There is reduced erythropoietin produced by the kidneys leading to reduced HbF by the bone marrow
- High oxygen = lower haemoglobin production
Give 4 reasons why premature neonates become anaemic
- Less time in utero receiving iron from the mother
- RBC creation cannot keep up with rapid growth in the first few weeks
- Reduced erythropoietin levels
- Blood tests remove a significant portion of their circulating volume
What is haemolytic disease of the newborn ?
-Incompatibility between rhesus antigens on the surface of RBC of the mother and fetus
Explain the pathophysiology behind haemolytic disease of the newborn
- In subsequent pregnancies, the mothers anti-D antibodies cross the placenta
- If the fetus is resus positive, the Abx attack the RBC
- This leads to haemolysis, anaemia and high bilirubin levels
How is immune haemolytic anaemic diagnosed ?
Direct coombs test
Give the 2 most common causes of anaemia in older children
- IDA -> secondary to dietary insufficiency (most common cause overall)
- Blood loss -> most commonly menstruation in older girls
Give 6 rarer causes of anaemia in children
- Sickle cell
- Thalassaemia
- Leukaemia
- Hereditary spherocytosis
- Hereditaty eliptocytosis
- Sideroblastic anaemia
What is a common cause of blood loss leading to IDA and chronic anaemia in developing countries ?
-Helminth infection : roundworms, hookworms or whipworms
How is a Helminth infection treated ?
-Single dose of albendazole or mebendazole
Give 5 causes of microcytic anaemia
-TAILS
T: Thalassaemia
A : Anaemia of chronic disease
I : Iron deficiency anaemia
L : Lead poisoning
S : Sideroblastic anaemia
Give 5 causes of normocytic anaemia
-3A’s, 2H’s
A : acute blood loss
A : anaemia of chronic disease
A : aplastic anaemia
H : Haemolytic anaemia
H : hypothyroidism
How can macrocytic anaemia be classified ?
- Megaloblastic : impaired DNA synthesis preventing if dividing normally = continuous growth into a large, abnormal cell. Caused by a vitamin deficiency
- Normoblastic
Give 2 causes of megaloblastic macrocytic anaemia
- B12 deficiency
- Folate deficiency
Give 5 causes of normoblastic macrocytic anaemia
- Alcohol
- Reticulocytosis (from haemolytic anaemia or blood loss)
- Hypothyroidism
- Liver disease
- Drugs such as azathroprine
Give 5 generic symptoms of anaemia
- Tiredness
- SOB
- Headaches
- Dizziness
- Palpitations
Give 2 symptoms specific to IDA
- Pica -> dietary cravings for abnormal things such as dirt
- Hair loss
Give 4 general signs of anaemia
- Pale sign
- Conjunctival pallor
- Tachycardia
- Raised resp rate
Give 4 specific signs of IDA
- Koilonychia -> spoon shaped nails
- Angular stomatitis
- Atrophic glossitis
- Brittle hair and nails
Give 8 initial investigations for anaemia
- FBC for Hb and MCV
- Blood film
- Reticulocyte count (high in anaemia due to haemolysis or blood loss)
- Ferritin (low in IDA)
- B12 and folate
- Bilirubin (raised in haemolysis)
- Direct coombs test (autoimmune haemolytic anaemia)
- Haemoglobin electrophoresis (haemoglobinopathies)
Give 3 causes of iron deficiency
- Dietary insufficiency (most common in children)
- Loss of iron -> heavy menstruation
- Inadequate iron absorption (e.g. crohn’s)
Where is iron absorbed and what is required ?
- Duodenum and jejunum -> any conditions causing inflammation can cause inadequate absorption
- Stomach acid to maintain is soluble ferrous (Fe2+) form. Medications such as PPI’s reduced stomach acid = ferric Fe3+ form = insoluble
What is the total iron binding capacity ?
-Total space on the transferrin molecule for iron to bind
What is the transferrin saturation ?
-Proportion of transferrin molecules that iron is bound to?
How is the transferrin saturation calculated ?
Transferrin saturation = Serum Iron / Total Iron Binding Capacity
What is hereditary spherocytosis and how is it inherited ?
- RBC are sphere shaped = easily destroyed
- Autosomal dominant, along woth hereditary elliptocytosis
How does hereditary spherocytosis present?
- Jaundice
- Anaemia
- Gallstones
- Splenomegaly
What infection can trigger an aplastic crisis in hereditary spherocytosis ?
-Parovirus
What is an aplastic crisis
-Anaemia, haemolysis and jaundice is increased without the BM creating new RBCs
How is hereditary spherocytosis diagnosed and anaged ?
- Blood film : spherocytes, raised MCHC, raised reticulocytes
- Manage : folate and splenectomy
What is. theinheritance pattern of G6PD deficiency and how can a crisis be triggered ?
- X linlked recessive
- Infections, medications, fava (broad) beans
- Exam presentation : jaundice following the triggers above
Explain the pathophysiology behond G6PD deficiency
- Deficiency in G6PD = cells more vulnerable to ROS = haemolysis of RBC
- Period of increased stress = higher production of ROPS = acute haemolytic anaemia
How does G6PD deficiency present ?
- Neonatal jaundice
- Anaemia, intermittent jaundice, gallstones, splenomegaly
What is seen on investigations in G6PD deficiency
- Heinz bodies on blood film
- Diagnosed using G6PD enzyme assay
what is the inheritance of fanconi anaemia
Autosommal recessive
what are the 4 features of fanconi anemia
- Haematological : Aplastic anaemia with increased risk of AML
- Neurological
- Skeletal abnormalities : short stature, thumb/radius abnormalities
- Cafe au lait spots
what is seen on blood results in leukaemia ?
- Pancytopenia, combination of :
- Anaemia : lethargy & pallor
- Leukopenia : frequent / severe infections
- Thrombocytopenia : easy bruising, petechiae
Give 4 genetic syndromes that predispose to a higher risk of developing leukaemia
Down’s syndrome
Kleinfelter syndrome
Noonan syndrome
Fanconi’s anaemia
what can be given to reduce the risk of tumour lysis syndrome secondary to chemo
Allopurinol
what features suggest need for urgent FBC (within 48 hrs) in a person aged 0-24 to investigate leukaemia
Pallor
Persistent fatigue
Unexplained fever
Unexplained persistent infections
Generalised lymphadenopathy
Persistent or unexplained bone pain
Unexplained bruising
Unexplained bleeding
Blood results seen in sickle cell patients
normocytic anaemia with raised reticulocyte count – due to haemolysis
