Paeds Haematology Flashcards
Adult Hb vs Fetal Hb
Fetal Hb picks up O2 from the Placenta stealing it from mother.
The Hb concentration is high at birth (>14 g/dl)
but falls to its lowest level at 2 months of age.
Fetal Hb: 2 Alpha 2 Gamma
Adult: 2 Alpha 2 Beta
HbF strucutre = greater affinity for O2 therefore creating that dynamic in the womb where it takes more O2 from the mother’s womb
From 32wk Gestation HbF down and HbA up by 6mths very little HbF remains
Adult haemoglobin requires a higher partial pressure of oxygen for the molecule to fill with oxygen compared with fetal haemoglobin.
Epidemiology & Pathophysiology of Iron Deficient Anaemia
- Common in infants because additional iron is required for increase in blood volume accompanying growth.
- Bone marrow requires Iron to produce Hb for blood exchange -> lack of dietary iron = less for Hb production
Evidence that IDA may be detrimental to behaviour and intellectual function.
Causes of Iron Deficient Anaemia
- Inadequate Iron intake (including breast milk)
- Malabsorption
- Blood loss
Cow’s milk poor source compared to breast & formula milk
Signs and Symptoms of Iron Deficient Anaemia
Assymptomatic until Iron below 60-70g/L
- Tiredness (infants feed more slowly)
- Headaches, Diziness, Palpitations
- Pallor
- Palmar creases
- Kolonychia
- Angular Chealitis
- Pica
- Britle hair and nails
- Atropic Glossitis
Investigations and Management of IDA
Serum Iron alone not a useful measure
What is the role of a certain Vitamin..
- Low MCV and MCH & Ferritin
- Management: Dietary advice and supplementation
- Vit C given to aid Iron absorption
Ferritin is the form that iron takes when stored in cells – a patient with a normal ferritin can still have IDA, particularly in cases where they may have a raised ferritin normally such as infection.
Epidemiology & Causes of Thalassaemia
chromosomes & areas commonly seen
- Autosomal Recessive
- Chromosome 16: Alpha
- Chromosome 11: Beta
- Commonly seen in people from Indian Subcontinent/Mediteranean/Middle East
Chromosome 16
Alpha Thalassaemia Pathophysiology
Alpha Major, trait and HbH disease.
Healthy individuals have 2 Beta globin chains and 4 Alpha globin chains
Major: Deletion of all 4 genes -> no HbA or HbF (Hb Barts hydrops fetalis)
HbH: 3 genes deleted
Trait: Deletion of 1 or 2 genes
Signs and Symptoms of Thalassaemia
Beta Major, B Intermedia, Alpha Major, HbH
Beta Major: Severe Anaemia, Jaundice, faltering growth, extramedullary haemopoiesis prevented by transfusions - Hepatosplenomegaly, bone marrow expansion (skull bossing and maxilary overgrowth)
Intermedia: Usually asymptomatic
Alpha Major: Fatal in utero or within hours of delivery
HbH: Mild/Moderate Anaemia Symptoms
Trait are usually asymptomatic or minor anaemia symptoms
Complications of Thalassaemia: Iron Overload similar symptoms of Haematomachrosis: Fatigue, liver cirrhosis, infertility, HF, arthritis, diabetes. Perform Iron Chealation
Investigation and Management of Thalassaemia
- Hypochromic Microcytic Anaemia with Normal Serum Ferritin
- Hb electrophoresis then performed for diagnosis
- Trait: Monitor
- Intermedia: Monitor + Occasional Transfusion
- Major: Lifelong transfusion
GIVE CHEALATION WITH TRANSFUSION TO PREVENT IRON OVERLOAD
In Alpha you can perform splenectomy or BM Transplant
Chromosome 11
Beta Thalassaemia Pathophysiology
Beta Minor, Intermedia, Major
Healthy individuals have 2 Beta globin chains and 4 Alpha globin chains
Minor: One gene affected one normal
Intermedia: One defected and One deleted gene - Small production of HbA and HbF
Major: Both affected: non functioning = no HbA produced
Risk factors for Haemolytic Disease of the Newborn
Neonatal Jaundice
Caused by incompatibility between the rhesus antigens on the surface of the red blood cells of the mother -ve and fetus +ve. Most important antigen within the rhesus blood group system is the rhesus D antigen.
- Maternal Sensitisation to RhD antigen
- History of delivery of Rh+ve Fetus to Rh-ve mother
- Feto-maternal haemorrhage
- Invasive Foetal procedures
- Placental Trauma
- Multiparity
- Abortion
- No Rh Immunoprophylaxis
Pathophysiology of Haemolytic Disease of the Newborn
& Complications
- During first pregnancy Rh-ve mother receives Rh+ve blood from fetus during cross over
- Rh-ve then form IgM antibodies to Rh+ve blood
- Subsequent pregnancy IgM becomes IgG which can cross placenta
- These IgG cross placenta and cause Haemolysis
- Haemolysis = excess bilirubin from breakdown = Jaundice
Complications: Kernicterus if deposition of bilirubin in basal ganglia or Hydrops fetalis when there’s Hb Deficit
Investigating Haemolytic Disease of the Newborn
& Management
After birth the baby may have pallor from anaemia, jaundice due to the high levels of bilirubin from RBC haemolysis. There may also be hepatosplenomegaly.
- Coomb’s Test: +ve
Test is only +ve in antibody mediated anaemias. - Pregnant Women (RhD-ve) given anti D immunoprophylaxis at wk 28 + if baby is positive then another dose given at birth.
- Affected baby: Phototherapy and potential transfusion.
Anti D immunoprophylaxis destroys foetal RhD+ve which crosses over.
Causes of Neonatal Jaundice
- Haemolytic Disease of the Newborn
- G6PD deficiency
- Spherocytosis
- Congential Infections
- ABO incompatibility: Group O women have IgG anti-A in the blood that can cross placenta occasionally anti-B too
RFs and Causes of Sickle Cell Disease
Sickle Cell: Formation of abnormal Hb chain: HbS
- Autosomal Recessive -> Abnormal Beta Globlin on Chromosome 11
- Most common inherited disorder in Europe
- Common in Tropical Africa, Caribbean & ME
- 1 in 2000
HbAA is normal
Pathophysiology Sickle Cell Disease
HbSS, HbSC, Sickle Beta Thalassaemia, Sickle Trait
- Substitution of Glutamine (polar) to Valine (non polar) in Hb protein leading to HbS (sickle)
- HbS polymerises within RBC deforming cells into irreversible Sickle shape, which have reduced lifespan and may be trapped in microcirculation
- HbSS - Sickle Cell Anaemia. Pts are homozygous for the mutation leading to all Hb being HbS
- HbSC - Mild form of Sickle Cell. HbS from one parent and HbC (point mutation in beta globin) from ther other
- HbAS - Sickle Cell trait: Asymptomatic Carriers.
- Sickle Cell Beta Thalassaemia: Inherit HbS from one parent and Beta Thalassaemia from the other.
Sickle cells are fragile and haemolyse; they block small blood vessels and cause infarction
Signs and Symptoms of Sickle Cell Disease
Symptoms in homozygotes don’t tend to develop until 4-6 months when the abnormal HbSS molecules take over from fetal haemoglobin.
- Anaemia
- Infections due to hyposplenism (Chronic sickling and microinfarctions in spleen)
- Painful Crises: Vaso-occulsive crises causing pain and can affect many different organs - bones of limbs common site. Triggered by cold, dehydration, hypoxia
- Splenomegaly in young children.
Complications of Sickle Cell Anaemia
- Acute Chest Syndrome: Lead to severe hypoxia and need for mechanical ventilation
-
Acute Anaemia Crisis
1. Splenic Sequestration Crisis (RBC block flow within spleen -> enalrged painful spleen -> severe anaemia and hypovalemic shock)
2. Aplastic Crisis: B19 virus leads lack of RBC creation. Anaemia - Priapism (need ASAP treatment or leads to impotence)
Investigations & Management of Sickle Cell Anaemia
Neborn: Heel prick test
Definitive Diagnosis: Hb Electrophoresis
- Prophylactic Infection: AbX (penicillin)
- Avoid VasoOcclusive triggers.
- Treat crisis with IV analgesia and good hydration
- Daily Folic Acid
- Hydroxycarbamide for Pts constantly in hospital.
- BM transplant when irresponsive to hydroxycabamide
Haemohilia A vs Haemophilia B
Most common inherited coagulation disorders
Both are X-Linked Recessive inheritance disorders.
Haemophila A
- Clotting factor 8 deficiency
- 1 in 5000 males
Haemohilia B
- Clotting factor 9 deficiency
- 1 in 30,000 males
- aka Christmas Disease
Up to 10-15% of patients with haemophilia A develop antibodies to factor 8 treatment
Signs & Symptoms Haemophila
& Complications
- Haemoarthroses: Bleeding into joints and muscles -> leads to arthritis (Severe arthropathy) if not treated
- Haematomas
- Prolonged bleeding after trauma
Most children present towards end of 1Y when walking/crawling.
Neonal detection only if there’s a intracranial haemorrhage, post-circumcision bleed.
Investigations Haemophilia
- Normal prothrombin/thrombin/bleeding time
- Raised partial thromboplastin time APTT
- Prenatal test using DNA analysis
Management Haemophilia
Recombinant Factor VIII and IX given via IV whenver there is bleeding
- Prophylactic Conc given to Haeophilia A to prevent chronic joint damage.
- Desmopressin in Haemophilia A to stimulate release of clotting factors.
Aetiology of vWD
Platelet disorder
- Autosomal Dominant bleeding disorder
- Mutations in the vWF gene
- Most common inherited bleeding disorder
Pathophysiology of vWD
Platelet disorder
Role of vWF: promotes platelet adhesion to damaged endothelium
- Quantitative or Qualitative deficiency of vWF
- Defect in platelet plug formation
- vWF also carrier protein for clotting factor VIII
Signs and Symptoms of vWD
Platelet disorder
3 subtypes
1. partial reduction in vWF (80%)
2. Abnormal vWF
3. Total lack of vWF.
Epistaxis and Menorrhagia are common whilst haemoarthroses and muscle haematomas are rare
- Excessive bleeding post trauma
Investigations vWD
- Raised APTT
- Prolonged bleeding time
- Low vWF antigen
Management vWD
- Tranexamic acid for mild bleeding
- Desmopressin (DDAVP): raises levels of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells
- Factor VIII concentrate
Intramuscular injections, aspirin and NSAIDs should be avoided in these patients.
Causes of Immune Thrombocytopenia ITP
Immune-mediated reduction in the platelet count
- Type II Hypersensitivity rxn producing antibodies which target and destroy platelets
- Spontaneous or triggered by viral infection
Signs and Symptoms of ITP
& Complications
Immune-mediated reduction in the platelet count
- Presents in U10s, onset post viral infection
- Bleeding from gums, epistaxis, menorrhagia
- Bruising easily
- Petechial (Smaller) /Purpuric (larger) Rash
- Profuse bleeding is uncommon
Complications: Intracranial, GI bleeding
Investigations ITP
Immune-mediated reduction in the platelet count
FBC should demonstrate an isolated thrombocytopenia
- BM examination performed if atypical features like failure to resolve, splenomegaly, lymph enlargement
Management ITP
Immune-mediated reduction in the platelet count
- Self limiting (within 6-8wks)
Chronic ITP Treatment options are: - Prednisolone orally
- IV immunoglobulins
Avoid contact sports or trauma inducing scenarios.
Platelet transfusions are reserved for life-threatening haemorrhage as they only raise the platelets for a few hours.
Features of Fanconi Anaemia
Most common inherited aplastic anaemia
Autosomal Recessive
- Majority have congenital abnormalities: short stature, abnormal radii and thumbs, renal
malformations, microphthalmia and pigmented skin
lesion - Present with any of above anomalies & signs of BM failure
- Appear at 5-6Y
Neonate Fanconi: Normal blood count
Test in nenonates: Increased chromosomal
breakage of peripheral blood lymphocytes.
Aetiology and Pathophysiology of Hereditary Spherocytosis
Most common inherited haemolytic anaemia in Northern Europeans.
- Autosomal dominant defect of red blood cell cytoskeleton
- The normal biconcave disc shape is replaced by a sphere-shaped red blood cell
- Red blood cell survival reduced as destroyed by the spleen
Signs and Symptoms of Hereditary Spherocytosis
Most common inherited haemolytic anaemia in Northern Europeans.
- Jaundice
- Anaemia signs and symptoms – usually mild but can be severe during infections
- Splenomegaly – generally mild or moderate
- Gallstones commonly
- Failure to thrive
Complications of Hereditary Spherocytosis
Aplastic crisis which is often triggered by infection by parvovirus B19.
Haemolytic crisis may occur with infections commonly, where the haemolysis, anaemia and jaundice are significantly worse.
Investigations and Management of Hereditary Spherocytosis
FH indicates investigations
Blood Film: Spherocytes (round, lack of central pallor)
Test: EMA binding test
Acute haemolytic crisis:
treatment is generally supportive
transfusion if necessary
Longer term treatment:
Folate replacement
Splenectomy
Epidemiology G6PD Deficiency
- Most common red cell enzymopathy in the world
- High prevalence in Central Africa, Mediterranean, Middle East, and Far east
- X linked (affects males)
Pathophysiology G6PD
↓ G6PD → ↓ reduced _____ → ↓ _______ → ______ susceptibility to ________
Glucose-6-phosphate-dehydrogenase is the rate-limiting enzyme in the pentose phosphate pathway and is essential for preventing oxidative damage to the red cells. These cells will be susceptible to oxidant-induced haemolysis.
damage by oxidants such as superoxide anion O2- and hydrogen peroxide
↓ G6PD → ↓ reduced NADPH → ↓ reduced glutathione → increased red cell susceptibility to oxidative stress
Signs & Symptoms G6PD
Triggers & Symptoms of Acute Haemolytic Crisis
- Neonatal Jaundice
- Splenomegaly
Acute Haemolytic Crisis triggers - Infection, the most common precipitating factor
- Certain drugs – co-trimoxazole, ciprofloxacin, nitrofurantoin convey definite risk; others include quinine, chloroquine, aspirin, sulphonylureas
- Fava beans/broad beans – other beans do not cause
- Naphthalene in mothballs
These acute episodes present as fever, malaise, abdominal pain and the passage of dark urine. Hb also often falls rapidly.
Investigations & Management of G6PD
- RBC Destruction: Bite cells
- Raised Reticulocytes
- Denatured Hb: **Heinz Bodies **
- Diagnosis is made by using a G6PD enzyme assay
levels should be checked around 3 months after an acute episode of hemolysis to avoid false readings
Management: Avoid Triggers, Give Folate in Chronic Haemolysis
