Haematology Flashcards
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)
What is acute chest syndrome?
What are symptoms?
Acute chest syndrome
- Complication of sickle cell anemia
- Fever with (or without) respiratory symptoms
- SOB, chest pain, pulmonary infiltrates, low pO2
What are investigations (and results) of acute chest syndrome?
- Chest X ray (pulmonary infiltrates)
- ABG (hypoxia)
Treatment of acute chest syndrome?
- IV AB, oxygen, hydration
- exchange transfusion can be used to treat acute chest syndrome in hypoxic patient
What is the most common haematological abnormality in the newborn?
Haemolysis of the newborn
Either due to antibody destroying fetal blood cells or an intrinsic abnormality in the baby’s blood cells themselves
What type of anaemia does thalassaemia cause?
Thalaseamias cause microcytic anaemia (if a suspicion IDA doesn’t respond to treatment think thalasseamia)
What are the causes of microcytic aneamia?
1) Iron deficiency anaemia
2) Thalaseamias
3) Anaemia of chronic disease (normocytic first)
4) Sideroblastic anaemia
