Explain the normal types of haemoglobin in adult?
HbA (a2b2) 90%
HbA2 (a2d2) 3%
HbF (a2g2) 1%
Neonates has majority HbF but some HbA (25%)
What are the main causes of haemolytic anaemia in the newborn?
-Blood group incompatibility (Rh or ABO)
-Red cell membrane disorders e.g. hereditary spherocytosis
-Red cell enzyme disorders (G6PD deficiency)
Abnormal haemoglobin (thalassaemia major)
What is beta-thalassaemia?
How is it inherited?
Who normally gets it?
- Affects the PRODUCTION of haemoglobin (reduced or none)
- Globin part not heme part (like IDA and Achronic disease)
- AUTOSOMAL RESSESIVE MUTATION
- Typically people on the Indian Sub-Continent, Mediterranean and the middle east
What is the consequence of beta-thalassaemia on the Hb conformity?
Beta-thalassaemia
- reduced HbA
- increased HbF (doesn’t contain beta chain)
- increased HbA2 (doesn’t contain beta chain)
-Severity of the disease depends on how much HbF resides
What will the clinical presentation be of beta-thalassaemia major?
- Extra medullary haematopoiesis leads to hepatosplenomegaly
- Classic ‘rodent’ face- overaction of the bone marrow leads to classical bossing of skull and forehead and maxillary overgrowth and malocclusion of teeth
- Neonatal jaundice (heamolysis)
- Anaemia signs (pallor, heart murmurs, FTT
What is beta thaleaseamia B Major (homozygous) ?
- both beta chains are effected (all alpha)
- HbA cannot be produced at all so blood transfusion are necessary for survival (to prevent Extramedullary hemopoiesis and bone deformities)
Explain the genetics of alpha thalesemia
Alpha thalassemia (genetic DELETION)
• Inherit 1 alpha gene-asymptomatic
• Inherit 2 alpha genes-trait
• Inherit 3 alpha genes-marked anemia
• Inherit all 4 alpha genes-Hb BARTS
-death in utero>hydrops fetalisWhat is the management for thalesmias?
They will need intervention if severe:
- regular blood transfusions with iron chelation (to prevent heamatomachrosis)
- folate supplementation (heamolysis causes deficiency)
- splenectomy may be indicated to prevent heamolysis of RBC
- How common is sickle cell?
- Who is most likely to get sickle cell disease?
- How can we diagnose?
Sickle Cell anaemia
- the most common inherited genetic condition in UK
- most common in afro-Caribbean population
- diagnosed by blood smear
Describe the pathophysiology of sickle cell anaemia
How do these RBC cause disease?
- AUTOSOMAL RECESSIVE
- There is a point mutation in codon six on the beta chain of haemoglobinA meaning there is an amino acid swap (missence glut acid>valine)
RBC cause disease due to:
1) Heamolysis
2) Vasoocclusion
What triggers an acute sickle cell episode?
- Cold, low oxygen and dehydration (think about being on a mountain)
- Infection
- Stress
- acidosis also reduces affinity for Hb for oxygen
Explain the 4 types of sickle cell?
1/ SICKLE CELL ANAEMIA (Homozygous)
- HbSS (virtually all their Hb is HbS)
- They have small amount of HbF and NO HbA
- Most severe
2/ HbSC DISEASE (combined heterozygous)
- Affected children inherit HbS from one parent and HbC from another (HbC is a different point mutation on the beta-globin chain).
- They also have no HbA
3/ SICKLE TRAIT:
- Single copy of HbS (inheritance of Hbs from one parent but normal HbA genes from the other)
- Asymptomatic carriers
- Small amounts of HbF
4/ SICKLE BETA THALASSEMIA
- HbS/beta thalaseamia
- affect structure AND production
- Affected children inherit HbS from one parent and beta-thalassemia from another.
- They have no normal B-globin genes and so most patients can make no HbS
Long term treatment of sickle cell disease?
PREVENTION
1) AVOID TRIGGERS (dehydration, altitude)
2) LONG TERM ANTIBIOTICS
- Daily phenoxypenecillin (Pen v)
3) FULLY IMMUNISED
- autosplenectomy
- especially encapsulated organisms (Salmonella, HiB, strep pneumonia)
4) HYDROXYUREA (Hydroxycarbamide)
- increases fatal haemoglobin
COMPLICATIONS
- Once daily folic acid (increased demand for folic acid due to increased hemolytic anemia)
- Bone marrow transplant/gene therapy as well
How should we manage a sickle cell crisis?
- Management with OXYGEN AND FLUIDS improves the following triggers:
○ Hypoxia
○ Acidosis
○ Dehyration - OPIODS-pain releif
- ANTIBIOTICS (treat underlying bacterial infection from acute chest syndrome)
-BLOOD TRANFUSION in ACS, stroke or priapism
Whats the function of factor VIII (8) and factor IX (9)?
8 and 9 combine to activate factor 10
What are the most commonly inherited coagulation disorders? How are they inherited?
Haemophilias A and B
They are X-linked (passed down to boys through the maternal line)
What is haemophilia B and how will it present?
- Factor IX deficiency
- usually presents as bleeding into joints and muscles that will lead to crippling arthritis
What is haemophilia A and how will it present?
- Heamophillia A is Factor VIII deficiency
- Will usually only present when they start to walk/crawl -covered in bruises (A first then B)
Other presentations might include intra-cranial bleeding in the neonatal period, excessive bleeding after circumcision, heel prick test or venipuncture
How should we manage acute haemophilia bleed?
Acute bleed
• Treatment with RECOMBINANT clotting factors given IV
- FVIII (8) for haemophilia A
- FIX (9) for haemophilia B
- Tranexamic acid (orally) can reduce bleeds
- Physio for any bleed related arthritis
Can we treat haemophilia A prophylactically?
YES - definitely with haemophilia A (treat with prophylactic FVIII that is given through a portocath)
DESMOPRESSIN can also be given to stimulate endogenous release of FVIII and vWF
Give Emicizumab subcut
Investigations of haemophilia?
INVESTIGATIONS
Investigations of haemophilia
-FBC (low heamatocrit and Hb if recent bleed)
-Prothombin time (extrinsic and common), fibrinogen levels and vW factor should be normal
-Activated partial thromboplastin time (APTT) should be prolonged (intrinsic (8,9) and common)
-Then look for specific factors
-Genetic mutation tests
-LFTs
What should you council patients about haemophilia?
- ***all IM injections, aspirin and NSAIDs should be avoided in patients with haemophilias
- check before vaccines-give subcut instead
- Avoid contact sports
What are the 2 types of heamaglobinopathies?
Heamaglobin variants (affect STRUCTURE) -HbS -HbC -HbE Thalaseamias (affect PRODUCTION)
can get both
Symptoms of sickle cell aneamia?
Symptoms of sickle cell aneamia -Infection -Severe anemia (SOB, palpatations) -Vaso-occlusive phenominom • acute pain episodes • stroke (heamorragic and ischemic) • acute chest syndrome • AKI (papillary necrosis) • Avascular necrosis • priapsim (4+ hours is med emergency)
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PRRAPID10
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RESPIRATORY90
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Cardiology51
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Iron Deficiency Anaemia10
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GI (medical)60
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Infections92
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Immunisations12
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GI (Surgical)71
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Neurology65
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Malignancy36
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Growth metabolic endocrine95
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Development and malnutrition33
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Dysmorphia16
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Urology48
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Dermatology - Rashes22
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Neonatal93
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Haematology30
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CAMHS27
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Intro week-normal child48
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Intro week-PPRAPID14
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Intro week-febrile child25
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Intro week-normal growth29
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Intro week-safeguarding10
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intro week-peads radiology32
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intro week-prescribing6
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Intro week- Paediatric surgery38
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Intro week-newborn4
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Respiratory87
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Nutrition13
