Paeds Haem 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 ITP?
- Type II hypersensitivity reaction
- Antibodies are produced that destroy the platelets
- Can occur spontaneously or as a result of a VIRAL INFECTION
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
- Leukopenia
- Thrombocytopenia
Give 4 genetic syndromes that predispose to a higher risk of developing leukaemia
Down’s syndrome
Kleinfelter syndrome
Noonan syndrome
Fanconi’s anaemia
