Paeds Haematology + Oncology + Genetics Flashcards
what is Anaemia
low level of haemoglobin in the blood
what is Haemoglobin
protein found in red blood cells.
responsible for picking up oxygen in the lungs and transporting it to the cells of the body
what is MCV
mean cell volume (MCV)
This is the size of the red blood cells
what is normal Haemoglobin range at birth
150 – 235 grams/litre
what is normal Haemoglobin range after 12 yrs Female
120 – 160 grams/litre
what is normal Haemoglobin range after 12 yrs male
130 -160 grams/litre
what are causes of anaemia in infancy
Physiologic anaemia of infancy
Anaemia of prematurity
Blood loss
Haemolysis
Twin-twin transfusion
What are causes of Haemolysis in neonates
Haemolytic disease of the newborn (ABO or rhesus incompatibility)
Hereditary spherocytosis
G6PD deficiency
when does normal dip in haemoglobin occur in babies
2 to 6 months of age
why does haemoglobin dip in babies
High oxygen delivery to the tissues caused by the high haemoglobin levels at birth cause negative feedback.
EPO production suppressed by kidneys = reducded haemoglobin by BM
what casues 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 their circulating volume
what is Haemolytic Disease of the Newborn
incompatibility between the rhesus antigens on the surface of the red blood cells of the mother and fetus.
what is most important antigen within the rhesus blood group
rhesus D antigen
when does Haemolytic disease of the newborn occur (rhesus group)
if mother = rhesus D negative
and
baby = rhesus D positive
what does rhesus D positive mean
HAS the rhesus D antigen
what happens in subsecent pregancy in a mother who has been sensitised to rhesus D antigens
- mothers anti-D antibodies can cross the placenta into the fetus.
- these antibodies attach themselves to the red blood cells of the fetus
- causes the immune system of the fetus to attack its own red blood cells.
What can happen to baby in haemolytic disease of the newborn
haemolysis, causing anaemia and high bilirubin level
how can haemolytic disease of the newborn be tested
direct Coombs test (DCT)
Detects antibodies that are already attached to red blood cells
what are key causes of anaemia in older children
Iron deficiency anaemia secondary to dietary insufficiency.
Blood loss
what is common cause of aneamia worldwide eg developing countries
helminth infection, with roundworms, hookworms or whipworms.
how are helminth infection treated
single dose of albendazole or mebendazole.
what are subdivsions of aneamia
Microcytic anaemia (low MCV indicating small RBCs)
Normocytic anaemia (normal MCV indicating normal sized RBCs)
Macrocytic anaemia (large MCV indicating large RBCs)
what are causes of microcytic anaemia
TAILS
T – Thalassaemia
A – Anaemia of chronic disease
I – Iron deficiency anaemia
L – Lead poisoning
S – Sideroblastic anaemia
what are causes of normocytic anaemia
3 As and 2 Hs for normocytic anaemia:
A – Acute blood loss
A – Anaemia of Chronic Disease
A – Aplastic Anaemia
H – Haemolytic Anaemia
H – Hypothyroidism
what is Megaloblastic anaemia the result of
result of impaired DNA synthesis preventing the cell from dividing normally. Rather than dividing it keeps growing into a large, abnormal cell. This is caused by a vitamin deficiency.
what are causes of Megaloblastic anaemia
B12 deficiency
Folate deficiency
what are causes of Normoblastic macrocytic anaemia
Alcohol
Reticulocytosis (usually from haemolytic anaemia or blood loss)
Hypothyroidism
Liver disease
Drugs such as azathioprine
what are symptoms of anaemia
Tiredness
Shortness of breath
Headaches
Dizziness
Palpitations
Worsening of other conditions
what are symptoms specific to iron deficiency anaemia:
Pica
Hair loss
what are signs of anaemia
Pale skin
Conjunctival pallor
Tachycardia
Raised respiratory rate
what are specific signs of iron deficiency
Koilonychia
Angular chelitis
Atrophic glossitis
Brittle hair and nails
what are initial investigations for anaemia
- Full blood count for haemoglobin and MCV
- Blood film
- Reticulocyte count
- Ferritin (low iron deficiency)
- B12 and folate
- LFT –> Bilirubin (raised in haemolysis)
- Direct Coombs test (autoimmune haemolytic anaemia)
- Intrinsic factor antibodies for pernicious anaemia
- Haemoglobin electrophoresis for thalassaemia and sickle cell disease
- coeliac disease serology (e.g., anti-tissue transglutaminase antibodies)
what do high Reticulocytes indicate
anaemia is due to haemolysis or blood loss.
name iron supplements
ferrous sulphate or ferrous fumarate.
what are SE of oral iron
constipation and black coloured stools
what are dietary sources of iron
red meat
beans
nuts
what is Thalassaemia
caused by a genetic defect in the protein chains that make up haemoglobin.
alpha-globin and beta-globin chains.
what is the inheritance pattern of Thalassaemia
autosomal recessive
what happens to RBC in Thalassaemia
red blood cells are more fragile and break down easily, causing haemolytic anaemia.
what are features of Thalassaemia
Microcytic anaemia (low mean corpuscular volume)
Fatigue
Pallor
Jaundice
Gallstones
Splenomegaly
Poor growth and development
Pronounced forehead and malar eminences
what happens to BM in Thalassaemia
bone marrow expands to produce extra red blood cells to compensate for the chronic anaemia
how is thalassaemia diagnosed
Full blood count shows a microcytic anaemia.
Haemoglobin electrophoresis is used to diagnose globin abnormalities.
DNA testing can be used to look for the genetic abnormality
what can thalassaemia show on FBC
microcytic anaemia
Raised ferritin suggests iron overload.
what causes iron overload in thalassaemia
faulty creation of red blood cells
recurrent transfusions
increased absorption of iron in the gut in response to anaemia.
how is iron overload managed
limiting transfusions and performing iron chelation (deferoxamine)
what are effects of iron overload in thalassaemia
Fatigue
Liver cirrhosis
Infertility
Impotence
Heart failure
Arthritis
Diabetes
Osteoporosis and joint pain
what chromosome codes of alpha globin chains.
16
how is Alpha-Thalassaemia managed
Monitoring the full blood count
Monitoring for complications
Blood transfusions
Splenectomy may be performed
Bone marrow transplant can be curative
what chromosome codes of beta globin chains.
11
what is beta Thalassaemia Minor
carriers of an abnormally functioning beta globin gene.
one abnormal and one normal gene.
mild microcytic anaemia monitoring no Tx
what is beta Thalassaemia intermedia
two abnormal copies of the beta globin gene
two defective genes or one defective gene and one deletion gene
how is beta Thalassaemia intermedia managed
Patients require monitoring and occasional blood transfusions
what is beta Thalassaemia major
homozygous for the deletion genes. They have no functioning beta globin genes at all.
what does Thalassaemia major cause
Severe microcytic anaemia
Splenomegaly
Bone deformities
how is Thalassaemia managed
regular transfusions, iron chelation and splenectomy. Bone marrow transplant can potentially be curative.
what are abnormal features relating to bone changes in Thalassaemia major
Frontal bossing (prominent forehead)
Enlarged maxilla (prominent cheekbones)
Depressed nasal bridge (flat nose)
Protruding upper teeth
what is sickle cell anaemia
autosomal recessive condition that causes sickle (crescent) shaped red blood cells.
chromosome 11
how does sickle cell anaemia lead to haemolytic anaemia
abnormal shape makes the red blood cells more fragile and easily destroyed,
what is the pathophysiology of sickle cell anaemia
Patients with sickle-cell disease have an abnormal variant called haemoglobin S (HbS). HbS results in sickle-shaped red blood cells.
One abnormal copy of the gene results in sickle-cell trait. Patients with sickle-cell trait are usually asymptomatic
Two abnormal copies result in sickle-cell disease.
at what point in gestation does fetal haemoglobin (HbF) production decrease and adult haemoglobin (HbA) increase
32-36 weeks gestation
what what age is baby 50:50 fetal haemoglobin (HbF) and adult haemoglobin (HbA
at birth
what what age is very little fetal haemoglobin (HbF) produced and RBC contain entirely adult haemoglobin (HbA
6 months
how is sickle cell anaemia tested
newborn blood spot screening test at around five days of age.
what are complications of sickle cell aneamia
Anaemia
Increased risk of infection
Chronic kidney disease
Sickle cell crises
Acute chest syndrome
Stroke
Avascular necrosis in large joints such as the hip
Pulmonary hypertension
Gallstones
Priapism (painful and persistent penile erections)
what is a sickle cell crisis
a spectrum of acute exacerbations caused by sickle cell disease. These range from mild to life-threatening.
what can trigger a sickle cell crisis
spontaneous or triggered by dehydration, infection, stress or cold weather
how are sickle cell crisis managed
Low threshold for admission to hospital
Treating infections that may have triggered the crisis
Keep warm
Good hydration (IV fluids may be required)
Analgesia (NSAIDs should be avoided where there is renal impairment)
what is a Vaso-occlusive Crisis
known as painful 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 area
fever
how is Priapism treated
aspirating blood from the penis
what is Splenic Sequestration Crisis
red blood cells blocking blood flow within the spleen.
enlarged and painful spleen
what can pooling of blood in spleen lead to
severe anaemia and hypovolaemic shock.
how can Splenic Sequestration Crisis be managed
Management is supportive, with blood transfusions and fluid resuscitation to treat anaemia and shock.
what are complications of Splenic Sequestration Crisis
splenic infarction, leading to hyposplenism and susceptibility to infections, particularly by encapsulated bacteria (e.g., Streptococcus pneumoniae and Haemophilus influenzae).
what is definitive management of Splenic Sequestration Crisis
Splenectomy
what is Aplastic Crisis
temporary absence of the creation of new red blood cells
what can trigger Aplastic Crisis
parvovirus B19
what is Acute Chest Syndrome
vessels supplying the lungs become clogged with red blood cells
what can trigger Acute Chest Syndrome
aso-occlusive crisis, fat embolism or infection
how does Acute Chest Syndrome present
fever, shortness of breath, chest pain, cough and hypoxia
what does Xray show for Acute Chest Syndrome
pulmonary infiltrates.
how is Acute Chest Syndrome managed
medical emergency
- Analgesia
- Good hydration (IV fluids may be required)
- Antibiotics or antivirals for infection
- Blood transfusions for anaemia
- Incentive spirometry using a machine that encourages effective and deep breathing
- Respiratory support
what are the general priciples of sickle cell management
- Avoid triggers for crises, such as dehydration
- Up-to-date vaccinations
- Antibiotic prophylaxis to protect against infection, typically with penicillin V (phenoxymethylpenicillin)
- Hydroxycarbamide (stimulates HbF)
- Crizanlizumab
- Blood transfusions for severe anaemia
- Bone marrow transplant can be curative
what is Hydroxycarbamide
Antineoplastic
how does Hydroxycarbamide work in sickle cell
stimulating the production of fetal haemoglobin (HbF).
HbF does not sickle
what is Crizanlizumab
monoclonal antibody
how does Crizanlizumab work in sickle cell anaemia
targets P-selectin.
P-selectin is an adhesion molecule found on endothelial cells on the inside walls of blood vessels and platelets.
It prevents red blood cells from sticking to the blood vessel wall and reduces the frequency of vaso-occlusive crises.
what is Disseminated intravascular coagulation
systemic activation of the clotting cascade, platelet consumption, and subsequent exhaustion of clotting factors that leads to widespread thrombosis and hemorrhage.
what would blood picture show for DIC
PT: Prolonged
APTT: prolonged
Bleeding time: prolonged
Platelet: low
fibrinogen: low
Fibrin degradation products = raised
D-dimer = ELEVATED
What causes DIC
sepsis
trauma
obstetric complications
malignancy
ALL
what is the critical mediator of DIC
release of a transmembrane glycoprotein (tissue factor =TF)
How is DIC investigated
D-dimer, blood film, coag screen
what does activated TF bind with
coagulation factors that then triggers the extrinsic pathway (factor 8) which triggers the intrinsic pathway (12 to 11 to 9) of coagulation.
what does the activation of the coagulation cascade yield
thrombin that converts fibrinogen to fibrin
fibrin = final product of hemostasis
what does the activation of the fibrinolytic system generate
plasmin, responsible for the lysis of fibrin clots
The breakdown of fibrinogen and fibrin results in polypeptides (fibrin degradation products)
what is Fanconi anemia
A hereditary form of aplastic anemia caused by an autosomal recessive resulting in impaired response to DNA damage
what does Fanconi anemia cause
bone marrow failure
how is DIC treated
fresh frozen plasma, platelet concentrate, antithrombin III, and heparin.
- replace clotting factors
- cryoprecipitate (Fresh frozen plasma to replace fibrinogen)
- Platelet transfusion
+ RBC transfusion if bleeding
what is Haemophilia A
severe inherited bleeding disorders caused by a deficiency of factor VIII
what is Haemophilia B
severe inherited bleeding disorders caused by a deficiency of factor IX
what is the inheritance pattern of Haemophilia
X-Linked Recessive
how does Haemophilia present
bleed excessively in response to minor trauma and are at risk of spontaneous bleeding without any trauma
how can Haemophilia present in neonates
intracranial haemorrhage, haematomas and cord bleeding in neonates.
what is haemarthrosis
bleeding into joints
can lead to joint damage and deformity
what can bleeding into muscles cause
compartment syndrome
how is Haemophilia investigated on blood tests
FBC
Clotting Studies
LFT
Factor VIII and IX assays
Von Willebrand factor antigen testing.
how is Haemophilia investigated besides blood tests
US
Joint Xray
CT?MRI
How does Haemophilia show on clotting studies
prolonged APTT (activated partial thromboplastin time)
bleeding time, thrombin time, prothrombin time normal
what is difference between APTT and PT
PT is a measure of the extrinsic pathway, whereas aPTT is a measure of intrinsic pathway.
how is Haemophilia managed
haemophilia A = coagulation factor VIII replaced
haemophilia B = coagulation factor IX replaced
by IV infusion
what is a complication of supplementing clotting factors
formation of antibodies (called inhibitors) against the treatment, resulting in it becoming ineffective.
what is Von Willebrand disease
MC inherited cause of abnormal and prolonged bleeding.
auto dom
deficiency, absence or malfunctioning of a glycoprotein called von Willebrand factor (VWF).
