Sickle Cell and Haemoglobinopathies Flashcards
What is normal Hb?
HbA
Adult haemoglobin
What is adult Hb made up of?
4 globin chains
- 2 alpha
- 2 beta
4 haem molecules, one bound to each chain
Define haemoglobinopathies
Structural Abnormalities affecting globin chains in Hb molecules
Example of haemoglobinopathy
Sickle cell disease
Presence of HbS in beta chain due to mutation
Causes of thalassaemia?
- reduced/absent production of beta or alpha chain = ineffective erythropoiesis
- effects of anaemia
- effects of iron overload in transfused patients
Cause of sickle cell
HbS
Glutamate substituted by valine in position 6 of beta gene
Inheritance of sickle cell
- autosomal recessive
- mendelian mode of inheritance
- carries = asymptomatic
Pathophys of sickle cell
- polymerisation = sickling
- this results in vaso-occlusion/infarction AND haemolysis
- precipitated by hypoxia, HbS conc/dehydration, acidosis
Clinical diagnosis of sickle cell
FH
Recurrent pain
Lab diagnosis of sickle cell
- anaemia
- haemolysis (high bilirubin, high LDH, raised reticulocytes, undetectable haptoglobin)
- blood film
- haemoglobin electrophoresis/sickle solubility test
Sickle solubility test
- negative = can see lines behind tube
- positive = cannot see lines behind tube
Emergency presentations/complications of sickle cell
1) pain/acute painful crisis
2) splenic sequestration
3) aplastic crisis
4) overwhelming sepsis
5) acute chest syndrome
6) fat embolism syndrome/mutli organ failure
7) priapism (splenic sequestration mechanism)
8) acute infarct
What can an acute infarct cause?
Stroke
MI
Acute visual loss
Acute renal failure
Presentation of painful sickle cell crisis
- rapid onset
- bone pain
- bone marrow infarction
- hours-weeks variable
- fever, bone tenderness, swelling, hypertension, tachycardic, tachypnoea
Precipitating factors of painful sickle cell crisis
- infections
- skin cooling
- dehydration
- deoxygenation
- stress
Analgesia procedures for sickle cell crisis
- within 30min of presentation
- parenteral opiates
- re-assess and repeat as necessary
What to monitor in sickle cell crisis?
- vital signs
- temp
- fluid intake
- analgesia use and pain score
- sedation/urinary retention/restlessness
Investigations in sickle cell crisis
- FBC and reticulocytes
- U&E/LFT
- LDH
- CRP
- Blood cultures
- CXR
What is acute chest syndrome?
- acute illness
- new infiltrate on CXR
- respiratory syndromes
Triggers of acute chest syndrome
- surgery/anesthesia
- pregnancy
- increased risk of chronic lung disease
- increased risk of death
Sickle cell positive feedback symptoms
hypoxi, inflammation and acidosis = vaso-occlusion within pulmonary microvasculature = fat embolism and pulmonary thrombi
BUT vaso-occlusion causes more hypoxia/inflammation/acidosis
Management of sickle cell crisis
- analgesia
- incentive spirometry = reduces ACS
- O2 therapy
- fluids
- AB
- transfusion
Which transfusion to give in sickle cell crisis
- TUT = mild ACS
- ExTx gen = moderate/severe ACS
Overwhelming hyposplenic sepsis cause
Pneumococcal
Meningococcal
Haemophilus influenzae
Overwhelming hyposplenic sepsis symptoms
Febrile
Coma
Altered sensorium
Seizures
Overwhelming Hyposplenic sepsis treatment
Urgent AB treatment
Prophylactic Pen V
Vaccination
Overwhelming Hyposplenic sepsis who?
<3 years
splenic auto-infarction from very young age = functional asplenia
Sequestration define
- acute deterioration of anaemia
- painful enlargement of spleen
- drop in Hb>2g/L
Sequestration who?
- children
- <2years
Sequestration management
- early detection
- parental education
- urgent blood transfusion
- splenectomy
Sequestration prognosis
- recurrence = 50%
- mortality = 12%
Aplastic crisis cause
infection with HPV B19
- infection of red cell precursors in bone marrow = pure red cell aplasia = low reticulocytes
- Hb nadir 15 days post infection
Aplastic crisis who
- childhood illness common
- slapped cheek disease
Aplastic crisis management
Urgent blood treatment
Inheritance of thalassaemia
- autosomal recessive
- mutations = deletion of alpha globin or beta globin genes
- carries asymptomatic = thalassaemia minors
What anaemia do you get with thalassaemia?
microcytic hypochromic
with haemolysis
Beta thalassaemia major define
- deletion of beta globin gene
- lack of production of beta chains
- homozygous
How to treat beta thalassaemia major?
- transfusion dependent
- get secondary iron overload
Clinical features of beta thalassaemia major?
- severe anaemia
- growth failure
- HF as high output
- bone marrow expansion
- death in 1st and 2nd decade without transfusion
- regular transfusions from early to maintain Hb>10
Consequences of bone marrow expansion in beta thalassaemia major?
- thalassaemic facies
- poor dentition
- interdental separation
- hair on end appearance on skull x-ray
- bone disease
- extramedullary haemopoiesis
Haemosiderosis
- tranfusional iron overall
- without chelation
- effects appear by end of first decade
Clinical features of iron overload
- impaired growth
- infertility
- hypoparathyroidism
- cardiomyopathy
- cardiac failure
- hepatic cirrhosis
- diabetes mellitus
- hypogonadism
- sudden arrhythmia = death in teens/early 20s
How to assess iron status?
- liver biopsy (invasive)
- serum ferritin (non specific)
- cardiac/liver MRI
Gold standard to assess iron status for iron overload
cardiac/liver MRI
Iron chelating agents
- desferoxamine (continuous infusion)
- deferiprone (oral)
- deferassirox (oral)
- combination
Which thalassaemia is worse
Beta worse than alpha
Alpha thalassaemia prevalent areas
China
SE Asia
Eastern Mediterranean
Middle East
Inheritance of alpha thalassaemia
2 sets of genes located on chromosome 16
2 inherited from each parent
Alpha thalassaemia minor
- asymptomtic
- mild microcytic anaemia
- 2 from 1 parent or 1 from both
Hb H disease
- symptomatic
- haemolytic and microcytic anaemia
- splenomegaly
- 3, 2 from 1 parent, 1 from other
Alpha thalassaemia major
- 2 from each parents
- incompatible with life
- hydrops fetalis
Thalassaemia Intermedia
- anaemia
- not transfusion dependent
- risk of iron overload as increased absorption
- Beta thalssaemia major with alpha thalassaemia trait
- beta thalssaemia trait with triplicate alpha chains
- e.g. delta-beta thalassaemia
- e.g. HbE beta thalassaemia
Antenatal Screening
Heel Prick test
- identify all pregnancies with haemoglobinopathy risk
- offer partner screening
- genetic counselling to affected
Children at birth with sickle cell management?
- pencillin prophylaxis
- immunisation
- parent education
