Paediatrics - Haematology Flashcards
Reading Hb Oxygen Dissociation curves
Fetal haemoglobin (HbF) has two alpha and two gamma subunits. Adult haemoglobin (HbA) has two alpha and two beta subunits.
Compare the saturation of fetal and adult Hb at the same partial pressure of oxygen?
The structure gives fetal haemoglobin a greater affinity to oxygen than adult haemoglobin. Oxygen binds to fetal haemoglobin more easily and is more reluctant to let go. This is important, as fetal haemoglobin needs to “steal” oxygen away from the mother’s haemoglobin when nearby in the placenta. If the fetal and maternal haemoglobin had the same affinity for oxygen, there would be no incentive for the oxygen to switch from the maternal blood to fetal blood.
The affinity of fetal and adult haemoglobin with oxygen can be illustrated with the oxygen dissociation curve. This is an exam favourite. Along the x-axis is the partial pressure of oxygen, which is how much oxygen is crammed into a space. The higher the partial pressure, the more oxygen is in the area. On the y-axis is the percentage of the haemoglobin molecule that is bound to oxygen. This is how “full” the haemoglobin molecule is.
As the partial pressure of oxygen goes up, more oxygen will be bound to haemoglobin.** Adult haemoglobin requires a higher partial pressure of oxygen for the molecule to fill with oxygen compared with fetal haemoglobin.**
This card is mainly for understanding - just memorise that adult haemoglobin requires a higher partial pressure of oxygen to become saturated. I.e. at a lower partial pressure of oxygen, fetal Hb is more saturated
Causes of anaemia in infancy
Causes of Anaemia In Infancy
Physiologic anaemia of infancy causes most cases of anaemia in infancy - high fetal Hb causes high oxygen delivery, negative feedback leads to reduced EPO production and low Hb at 6-9 weeks - normal
The other causes of anaemia in infants are:
- Anaemia of prematurity (rapid growth and lacking in-utero iron)
- Blood loss
- Haemolysis - test yourself on causes (answer below)
- Twin-twin transfusion, where blood is unequally distributed between twins that share a placenta
Haemolysis is a common cause of anaemia in infancy. There are a number of causes of haemolysis in a neonate:
- Haemolytic disease of the newborn (ABO or rhesus incompatibility) - A direct coombs test can check for immune haemolytic anaemia
- Hereditary spherocytosis
- G6PD deficiency
SIDE NOTE - SLIGHTLY SEPERATE BUT REMEMBER THAT PHYSIOLOGICAL NEONATAL JAUNDICE OCCOURS AFTER THE FIRST 24 HOURS (BEFORE THIS IS PATHOLOGICAL) AND IS DUE TO THE FETAL HB BEING MORE FRAGILE AND BREAKING DOWN AND THEN LESS DEVELOPED LIVER FUNCTION LEADING TO A HIGH BLOOD CONC OF UNCONJUGATED (BY THE LIVER) BILLIRUBIN.
What are the main two causes of anaemia in older children
Causes of Anaemia in Older Children
The key causes of anaemia in older children are:
Iron deficiency anaemia secondary to dietary insufficiency. This is the most common cause overall.
Blood loss, most frequently from menstruation in older girls
Rarer causes of anaemia in children include:
Sickle cell anaemia
Thalassaemia
Leukaemia
Hereditary spherocytosis
Hereditary eliptocytosis
Sideroblastic anaemia
Worldwide, a common cause of blood loss causing chronic anaemia and iron deficiency is helminth infection, with roundworms, hookworms or whipworms. This can be very common in developing countries and those living in poverty. It is more unusual in the UK. Treatment is with a single dose of albendazole or mebendazole.
Causes of Microcytic Anaemia
A helpful mnemonic for understanding the causes of microcytic anaemia is TAILS.
T – Thalassaemia
A – Anaemia of chronic disease
I – Iron deficiency anaemia
L – Lead poisoning
S – Sideroblastic anaemia
What is Haemolytic disease of the newborne?
What is the Ix?
Haemolytic disease of the newborn is a cause haemolysis (red blood cells breaking down) and jaundice in the neonate. It is caused by incompatibility between the rhesus antigens on the surface of the red blood cells of the mother and fetus. The rhesus antigens on the red blood cells vary between individual. This is different to the ABO blood group system.
Within the rhesus group, there are many different types of antigens that can be present or absent depending on the person’s blood type. The most important antigen within the rhesus blood group system is the rhesus D antigen.
When a woman that is rhesus D negative (does not have the rhesus D antigen) becomes pregnant, we have to consider the possibility that the fetus will be rhesus D positive (has the rhesus D antigen). It is likely at some point in the pregnancy the blood from the fetus will find a way into her bloodstream. When this happens, the fetal red blood cells display the rhesus D antigen. The mother’s immune system will recognise the rhesus D antigen as foreign and produce antibodies to the rhesus D antigen. The mother has then become sensitised to rhesus D antigens.
Usually, this sensitisation process does not cause problems during the first pregnancy (unless the sensitisation happens early on, such as during antepartum haemorrhage). During subsequent pregnancies, the mothers anti-D antibodies can cross the placenta into the fetus. If that fetus is rhesus positive, these antibodies attach themselves to the red blood cells of the fetus and causes the immune system of the fetus to attack its own red blood cells. This leads to haemolysis, causing anaemia and high bilirubin levels. This leads to a condition called haemolytic disease of the newborn.
A direct Coombs test (DCT) can be used to check for immune haemolytic anaemia. This will be positive in haemolytic disease of the newborn.
It is treated with phototherapy for the hyperbilirubinemia (prevent kernicturus) and blood tranfusion for the anaemia
3 most common causes of iron deficiency in children
management?
The bone marrow requires iron to produce haemoglobin. There are several scenarios where iron stores can be used up and the patient becomes iron deficient:
1.Dietary insufficiency. This is the most common cause in children.
2.Loss of iron, for example in heavy menstruation
3.Inadequate iron absorption, for example in Crohn’s disease
Iron is mainly absorbed in the duodenum and jejunum. It requires the acid from the stomach to keep the iron in the soluble ferrous (Fe2+) form. When there is less acid in the stomach, it changes to the insoluble ferric (Fe3+) form. Therefore, medications that reduce the stomach acid, such as proton pump inhibitors (lansoprazole and omeprazole) can interfere with iron absorption. Conditions that result in inflammation of the duodenum or jejunum such as coeliac disease or Crohn’s disease can also cause inadequate iron absorption.
Management
Management involves treating the underlying cause and correcting the anaemia. In children the underlying cause is usually dietary deficiency, so input from a dietician can be helpful.
Iron can be supplemented with ferrous sulphate or ferrous fumarate. This slowly corrects the iron deficiency. Oral iron causes constipation and black coloured stools. It is unsuitable where malabsorption is the cause of the anaemia.
Blood transfusions are very rarely necessary. Children are generally able to tolerate a low haemoglobin well and can be given time to correct their anaemia.
How does Idiopathic thrombocytompenic purpura present?
What causes it?
Ix?
Rx?
TOM TIP: ITP is worth remembering as it is a key differential diagnosis of a non-blanching rash.
It normal presents in children under 10 with bleeding, brusing, a non-blanching rash
ITP is caused by a type II hypersensitivity reaction. It is caused by the production of antibodies that target and destroy platelets. This can happen spontaneously, or it can be triggered by something, such as a viral infection.
Remeber it is idiopathic so the cause of the type II hypersensitivity reaciton is not known.
The condition can be confirmed by doing an urgent full blood count for the platelet count. Other values on the FBC should be normal. Other causes of a low platelet count should be excluded, for example heparin induced thrombocytopenia (HIT antibodies) and leukaemia.
Usually no treatment is required and patients are monitored until the platelets return to normal. Around 70% of patients will remit spontaneously within 3 months.
Treatment may be required if the patient is actively bleeding or severe thrombocytopenia (platelets below 10):
Prednisolone
IV immunoglobulins
Blood transfusions if required
Platelet transfusions only work temporarily - the antibodies against platelets will begin destroying the transfused platelets as soon as they are infused.
Some key education and advice is necessary:
Avoid contact sports
Avoid intramuscular injections and procedures such as lumbar punctures
Avoid NSAIDs, aspirin and blood thinning medications
Advice on managing nosebleeds
Seek help after any injury that may cause internal bleeding, for example car accidents or head injuries
Complications
Chronic ITP
Anaemia
**Intracranial and subarachnoid haemorrhage
**Gastrointestinal bleeding
Sickle cell anaemia is a genetic condition that causes sickle (crescent) shaped red blood cells.
The abnormal shape makes the red blood cells more fragile and easily destroyed, leading to haemolytic anaemia. Patients with sickle cell anaemia are prone to various sickle cell crises.
- inheritance pattern?
Sickle cell crisis refers to a spectrum of acute exacerbations caused by sickle cell disease. These range from mild to life-threatening. They can occur spontaneously or triggered by dehydration, infection, stress or cold weather.
- Management of a sickle cell crisis?
- what causes a painful crisis?
- what is a splenic sequestration crisis and how is it managed?
- what is acute chest syndrome?
Sickle cell anaemia is an autosomal recessive condition affecting the gene for beta-globin on chromosome 11. One abnormal copy of the gene results in sickle-cell trait. Patients with sickle-cell trait are usually asymptomatic. They are carriers of the condition. Two abnormal copies result in sickle-cell disease.
There is no specific treatment for sickle cell crisis. They are managed supportively, with:
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)
Vaso-occlusive Crisis
Vaso-occlusive crisis (VOC) is also known as painful crisis and is the most common type of sickle cell crisis. It is caused by the sickle-shaped red blood cells clogging capillaries, causing distal ischaemia.
It typically presents with pain and swelling in the hands or feet but can affect the chest, back, or other body areas. It can be associated with fever.
It can cause priapism in men by trapping blood in the penis, causing a painful and persistent erection. Priapism is a urological emergency, treated by aspirating blood from the penis.
Splenic Sequestration Crisis
Splenic sequestration crisis is caused by red blood cells blocking blood flow within the spleen. It causes an acutely enlarged and painful spleen. Blood pooling in the spleen can lead to severe anaemia and hypovolaemic shock.
Splenic sequestration crisis is considered an emergency. Management is supportive, with blood transfusions and fluid resuscitation to treat anaemia and shock.
Splenic sequestration crisis can lead to splenic infarction, leading to hyposplenism and susceptibility to infections, particularly by encapsulated bacteria (e.g., Streptococcus pneumoniae and Haemophilus influenzae).
Splenectomy prevents sequestration crises and may be used in recurrent cases.
Aplastic Crisis
Aplastic crisis describes a temporary absence of the creation of new red blood cells. It is usually triggered by infection with parvovirus B19.
It leads to significant anaemia (aplastic anaemia). Management is supportive.
Acute Chest Syndrome
Acute chest syndrome occurs when the vessels supplying the lungs become clogged with red blood cells. A vaso-occlusive crisis, fat embolism or infection can trigger it.
Acute chest syndrome presents with fever, shortness of breath, chest pain, cough and hypoxia. A chest x-ray will show pulmonary infiltrates.
Acute chest syndrome is a medical emergency with high mortality. It requires prompt supportive management and treatment of the underlying cause:
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 with oxygen, non-invasive ventilation or mechanical ventilation
Sickle cell 2
What is involved in the general management of sickle cell disease?
General Management
A specialist MDT will manage sickle cell disease. The general principles are:
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
Hydroxycarbamide works by stimulating the production of fetal haemoglobin (HbF). Fetal haemoglobin does not lead to the sickling of red blood cells (unlike HbS). It reduces the frequency of vaso-occlusive crises, improves anaemia and may extend lifespan.
Crizanlizumab is a monoclonal antibody that 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.
A patient becomes jaundice and anaemic after eating broad beans, developing an infection or being treated with antimalarial medications
What is the likely diagnosis and background pathphysiology
G6PD deficiency is a condition where there is a defect in the G6PD enzyme normally found in all cells in the body.
It is more common in Mediterranean, Middle Eastern and African patients. It is inherited in an X linked recessive pattern, meaning it usually affects males, as they have only a single copy of the gene on their single X chromosome. It causes crises that are triggered by infections, medications or fava beans (broad beans).
The G6PD enzyme is responsible for helping protect cells from damage by reactive oxygen species (ROS). ROS are reactive molecules that contain oxygen, produced during normal cell metabolism and in higher quantities during stress on the cell. The G6PD enzyme is particularly important in red blood cells. A deficiency in G6PD makes cells more vulnerable to ROS, leading to haemolysis in red blood cells. Periods of increased stress, with a higher production of ROS, can lead to acute haemolytic anaemia.
Diagnosis can be made by doing a G6PD enzyme assay.
It is a cause of neonatal jaundice
Thalassaemia is related to a genetic defect in the protein chains that make up haemoglobin. Normal haemoglobin consists of 2 alpha and 2 beta globin chains. Defects in the alpha globin chains lead to alpha thalassaemia. Defects in the beta globin chains lead to beta thalassaemia.
How does thalasemmia affect the spleen and bones?
What is the inheritence pattern of alpha and beta thalasemia?
What type of anaemia does it cause?
How is diagnosis made?
Seperate card on minor vs major stuff…
In patients with thalassaemia the red blood cells are more fragile and break down more easily. 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.
The bone marrow expands to produce extra red blood cells to compensate for the chronic anaemia. This causes a susceptibility to fractures and prominent features, such as a pronounced forehead and malar eminences (cheek bones).
Both conditions are autosomal recessive.The overall effect is varying degrees of anaemia, depending on the type and mutation.
Potential Signs and Symptoms
Microcytic anaemia (low mean corpuscular volume)
Fatigue
Pallor
Jaundice
Gallstones
Splenomegaly
Poor growth and development
Pronounced forehead and malar eminences
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Diagnosis:
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
Pregnant women in the UK are offered a screening test for thalassaemia at booking.
Key Complication of thalassemia?
Iron overload occurs in thalassaemia 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.
Patients with thalassaemia have serum ferritin levels monitored to check for iron overload. Management of iron overload involves limiting transfusions and performing iron chelation.
Iron overload in thalassaemia causes effects similar to haemochromatosis:
Fatigue
Liver cirrhosis
Infertility
Impotence
Heart failure
Arthritis
Diabetes
Osteoporosis and joint pain
What are the 4 types of Thalasemia and how do they present?
Genetic cause of each?
Management for each? (3 for major)
Alpha-Thalassaemia
Alpha-thalassaemia is caused by defects in alpha globin chains. The gene coding for this protein is on chromosome 16.
Management:
Monitoring the full blood count
Monitoring for complications
Blood transfusions
Splenectomy may be performed
Bone marrow transplant can be curative
Beta-Thalassaemia
Beta-thalassaemia is caused by defects in beta globin chains. The gene coding for this protein is on chromosome 11.
The gene defect can either consist of abnormal copies that retain some function or deletion genes where there is no function in the beta globin protein at all. Based on the type of defect, beta-thalassamia can be split into three types:
Thalassaemia minor
Thalassaemia intermedia
Thalassaemia major
(Beta) Thalassaemia Minor
Patients with beta thalassaemia minor are carriers of an abnormally functioning beta globin gene. They have one abnormal and one normal gene.
Thalassaemia minor causes a mild microcytic anaemia and usually patients only require monitoring and no active treatment.
(Beta) Thalassaemia Intermedia
Patients with beta thalassaemia intermedia have two abnormal copies of the beta globin gene. This can be either two defective genes or one defective gene and one deletion gene.
Thalassaemia intermedia causes a more significant microcytic anaemia. Patients require monitoring and occasional blood transfusions. When they require more transfusions, they may require iron chelation to prevent iron overload.
(Beta) Thalassaemia Major
Patients with beta thalassaemia major are **homozygous for the deletion genes. **They have no functioning beta globin genes at all. This is the most severe form and usually presents with severe anaemia and failure to thrive in early childhood.
Thalassaemia major causes:
Severe microcytic anaemia
Splenomegaly
Bone deformities
Management involves regular transfusions, iron chelation and splenectomy. Bone marrow transplant can potentially be curative.
I think you really need to learn 1A1N, 2A or 1A1D - intermedia , and 2D - major
Von Willebrand and Haemophilia:
- protein affected
- inheritence pattern
- management
Von Willebrand disease (VWD) is the most common inherited cause of abnormal and prolonged bleeding. There are many underlying genetic causes, most of which are autosomal dominant.
In von Willebrand disease, there is a deficiency, absence or malfunctioning of a glycoprotein called von Willebrand factor (VWF). Von Willebrand factor is important in platelet adhesion and aggregation in damaged vessels.
It causes nosebleeds, bleeding gums, easy bruising
Von Willebrand disease does not generally require daily treatment. Management is needed in response to significant bleeding or trauma (to stop bleeding) or in preparation for operations (to prevent bleeding). Options include:
Desmopressin (stimulates the release of vWF from endothelial cells)
Tranexamic acid
Von Willebrand factor infusion
Factor VIII plus von Willebrand factor infusion
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Haemophilia is a lot less common but alot more severe - epitaxis but also GI, GU, Intercranial bleeding
Haemophilia A and B are severe inherited bleeding disorders. Haemophilia A is caused by a deficiency of factor VIII. Haemophilia B (also known as Christmas disease) is caused by a deficiency in factor IX.
Both haemophilia A and B are X-linked recessive diseases. ROYAL BOYS
Most cases present in neonates or early childhood. It can present with intracranial haemorrhage, haematomas and cord bleeding in neonates.
The affected clotting factors (VIII or IX) can be given by intravenous infusion, either regularly or in response to bleeding.
Exam Q: The coagulation cascade and Ix in Coagulopathies:
PT and APTT - what do they each test for?
What factors affect each of these (write out the coagulation cascade)
Vitamin K dependant clotting factors?
FBC- for thrombocytopenia (normal APTT and PT!)
Low fibrinogen - DIC
Clotting factor assays - 8 and 9, and vwf
Prothrombin Time (PT)
- Assesses the extrinsic pathway (Factors VII, X, V, II, fibrinogen).
- Prolonged PT suggests a deficiency or dysfunction in these factors.
Activated Partial Thromboplastin Time (APTT)
- Assesses the intrinsic pathway (Factors XII, XI, IX, VIII, X, V, II, fibrinogen).
- Prolonged APTT indicates defects in these factors, commonly seen in hemophilia or von Willebrand disease.
Haemophilia will thereofre affect only the APTT
Vitamin K def will affect both! because 1972 = 10 , 9 7, 2
Mnemononics
apTT = table tennis is inside so intrinsic
pT = tennis is outside so extrinsic
Coagulation cascade:
1 X 2 X 5 = 10 - common pathway
3 + 7 = 10 - Extrinsic
12 to 8 - Intrinsic pathway, excluding factor 10 which is a part of common pathway
NOTE GOT THIS MIXED UP IN THE EXAM TISSUE FACTOR IS EXTRINSIC
