Case 2 - Sickle Cell Anaemia Flashcards
What symptoms did the patient present with?
Joint pain - right knee and ankles Sharp and constant pain ‘Crisis’ = high pain, 8 on a scale of 1 to 10 (came for crisis last Christmas) Difficult to walk Triggered by a run on a cold morning
How does Hb S differ from Hb A?
In sickle cell anaemia the Hb stick together in a line during the deoxygenated state, but in normal red cells, the Hb is free to float around Forms helices when the rod is formed (3D structure)
What are the 3 amino acids that cause Hb S to stick together?
Valine (Position 6) - from one subunit Leucine (position 88) + Alanine (position 78) - in another subunit
Which specific amino acid is different in Hb S to Hb A?
Valine is glutamate
How does the valine cause the Hb S to stick together? (With relation to leucine and alanine)
In Hb A, valine is glutamate. Leucine and alanine are hydrophobic. In Hb A, glutamate is hydrophilic so it doesn’t stick to leucine and alanine. But valine is hydrophobic so it sticks to them
Does the presence of oxygen reverse the sticking of the Hb S?
No, presence of oxygen stops more Hb S sticking together (i.e forming more of the crescent)
Why does Hb A travel further along the gel in electrophoresis than Hb S?
Hb A travels further along the electrophoresis gel towards the positive end as it is more negative Valine is hydrophobic and uncharged Glutamate is hydrophilic and negatively charged
The gel electrophoresis of a 27F with no haemoglobinopathy looks like?
Predominantly Hb A and a little bit of Hb A2 but NO Hb S or Hb F
The gel electrophoresis of an 18F with the sickle cell trait (HbSS) looks like?
Predominantly Hb S, some Hb F, and some HbA2 but NO Hb A
The gel electrophoresis of a 65M with HbAS (carrying the sickle cell trait).
Predominantly, Hb S and Hb A and a little bit of Hb A2, but NO Hb F
What are the normal ranges for Hb, MCV and reticulocyte count?
Males:
Hb : 130 - 168 g/L
MCV : 83.5 - 99.5 fl
Reticulocyte : 20.0 - 92.0
Females:
Hb : 114 - 150 g/L
MCV : 83.5 - 99.5 fl
Reticulocyte : 12.0 - 96.0
Interpret the blood work of the 27F HbA:
Hb 123 g/L (lower end of normal range) MCV 82.3 fL (slightly low) Reticulocyte count 22 10^9/L Slightly anaemic perhaps due to menstruation
Interpret the blood work of the 18F:
Hb 81 g/L MCV 102.1 Reticulocyte count 217
Causes for low Hb Low: iron, B12 or folic acid Bleeding / injury
Causes for high MCV - many reticulocytes, B12 deficiency
Interpret blood work of the 65M:
What would you do to tell apart the 18F and the 65M?
Blood film
Blood film 1 - 18F
Red blood cells spread out - anaemic See the shape of the sickle cell Sickle cell anaemia - spleen function lower May have nuclear content (portion of DNA) in the RBC - Howell-jolly body, the portion of DNA is stained purple in the blood film
Blood film 2 - 27F
Less spread out + paler blood film (less Hb) Smaller cells All indicate slight anaemia
Blood film 3 - 65M
Normal MCV (not spread out) Darker film - more Hb present
Why might someone with sickle cell anaemia experience a bone crisis?
Because crescent shape of the sickle cell makes it difficult for it to fit through the capillaries - causes vast-occlusions. Lack of oxygen reaching the bones = infarction (cell death) Vado-occlusion —> ischemia —> infarction
Treatment of bone crisis
Morphine Rehydrate - IV fluid (high blood volume = wider lumen) Warm - vasodilation Blood thinners - HbSS more likely to blood clot Oxygen Basically trying to prevent Avascular necrosis (double check)
folic acid for healthy RBC production
Patient may complain about joint pain etc.
Why might someone with sickle cell anaemia suffer from Vision Loss?
Sickle cells get trapped in the blood vessels supplying the retina, causes oedema (fluid build up) and glaucoma (high pressure) Retinal detachment Haemorrhages in the eye (bleeding) as blood vessels may burst due to the crescent shapes of the sickle cells. May cause the blood vessels to malform Damage to retina due to ischaemia
Treatment of visual loss
Oxygen Hydration Analgesia (painkillers) Laser surgery to treat haemorrhages (fix the broken blood vessels)
Why might someone with sickle cell anaemia suffer from a Stroke?
Sickle cells get trapped in the blood vessels supplying the brain - vast occlusion Lack of oxygen to a part of the brain - ischaemia Brain cell death - infarction Causes ischaemic stroke Haemorrhagic stroke Patient presents with : with unilateral weakness Slurred Speech / problems finding the words Facial weakness / facial droop Confusion
Treatment of stroke
Brain scan Blood thinner v dangerous of haemorrhagic stroke Local thrombolysis strong blood thinners at site of stroke Locally inject - lack of control in mouth = aspiration so little or no oral medication
Video - what are the triggers, symptoms and management?
Triggers Cold morning - Vaso constriction Last winter - before Christmas Running - more blood deoxygenated = more sickle shapes Running - dehydration Symptoms Achy Difficulty walking Painful joints Funny tummy Management before by doctor Folic acid Morphine Antibiotics - trigger may be infection (doc’s questions e.g. sputum) because infection causes inflammation & dehydration Heparin - deep vein thrombosis (clots) Management by herself at home Ibuprofen Hot water bottles - vasodilation Hydrated - drinking plenty of water Gave up ballet
What is an idea, concern and expectation?
Idea - physical symptoms, possible causes for this Concern - emotional aspect, how it might affect their lives Expectations - what they want the doctors to give them / do for them
Idea for video
I’m in physical pain due to the sickle cell anaemia
Concerns in video?
Will I be able to go to work? Will I ever be able to travel? How much longer? Will it be like this forever? Do I have to completely give up ballet? Unlikely for patient to give their concerns (more likely to just give ideas and some expectations)
Concerns important?
If doctors talk about be concerns, patients open up more Better treat their health as a whole - psychological aspects as well and physical aspects
Expectations in video?
Hope to relieve the pain - morphine
Unless I ask for morphine, the doctor will give me useless, weaker painkillers - Shows patients think doctors aren’t providing them what they need
Want continuity between appointments (this doc had never seen her before)
Ask how she feels / listens to her concerns e.g. how is this affecting your life
Someone cares about them as a whole
Wants someone to believe her - that she is constantly in pain
What are the Central Nervous System (CNS) issues with Sickle Cell Disease (SCD)?
- Acute Pain (number one cause of hospital admissions(
- Cerebrovascular accident
– Transient ischemic attack occurs in ~ 4%
– Overt stroke occurs in ~ 16%
– Silent cerebral infarction occurs in ~ 20% of children
(Screen for vascular disease and stroke starting at age 2 years and continuing until at least age 16 years)
- Retinopathy occurs in ~23%
- Seizures occur in ~12%
What are the Musculoskeletal issues with SCD?
- Bone pain crisis (~30%) is the most common complication of vaso-occlusive pain, and can lead to bone or bone marrow infarction and osteonecrosis
- Avascular necrosis: 21% (Death of bone tissue from lack of blood supply
What are the Cardiopulmonary issues with SCD?
- Acute chest syndrome (ACS) occurs in ~ 75%
- Pulmonary hypertension occurs in ~ 20%
- Left-sided heart disease occurs in ~ 13%
What are the reticuloendothelial issues with SCD?
• Splenic sequestration (detachment), which occurs in ~ 50% of patients who survive their first episode and can worsen anemia
What are some gastrointestinal and urogenital issues with SCD?
Gastrointestinal
- Cholelithiasis (gallstone disease), acute cholecystitis, biliary sludge (bile stroed in the galbladder for too long), and acute choledocholithiasis are common
- Gallstones occur in ~ 75%
Urogenital
- Renal dysfunction begins at an early age, and ~ 30% experience chronic renal failure
- Priapism occurs in ~ 35% of men
What are some cognitive and psychological disorders that SCD patients may also suffer from?
About 20% with lower IQ scores
35% diagnosed with depression
13% experience anxiety
Other cognitive dysfunctions may be due to silent strokes: difficulty communicating, carrying out basic tasks
Other psychological issues may be stigma around SCD, feeling worthless or PTSD
What are some social and professional issues with SCD?
Less than 50% employed, and 17% missing work days due to vaso-occlusive crisis (VOCs)
65% report impaired sexually (due to VOCs mainly)
Other effects: Loss of relationships due to prolonged stay at hospitals etc, social isolation as the disease progresses, iability to travel due to VOCs, missed work days, incomplete education etc/
Other issues:
Many hospitalisations e.g. A&E due to VOCs
Long waiting times for medical care, unreasonable when they are having a crisis
What is the haemoglobin in adults?
Hb A - 2 alpha (141 aa) and 2 beta (146aa) chains
Haem pocket and hydrophilic and hydrophobic surface
HbA2 - 2 alpha and 2 delta (lower case squiggly line) chains
Sickle cell disease vs sickle cell anaemia
SCD = branched term encompassing many sickle cell disorders
SCA = comes under SCD, one type of sickling in cells
What does the sickle cell shape do?
Sticky- polymerisation : occlude blood vessels (blockage) = ischaemia
Rigid and distorted shape - stuck in small blood vessels
dehydrated
short survival - normally RBCs last 120 days; but sickle cell survives for less time
low affinity for oxygen - hypoxic (attach to O2 less easily but release O2 to tissues more easily)
Hetero Vs homo - zygous
Hetero = trait
homo = sickle cell anaemia
recessive disorder - presents after 3 to 6 months because newborns still have high levels of Hb F after birth
Hetero advantageous in Middle East etc. as it decreases the chances of being affected by malaria
Investigations to spot SCA
Rod shaped cells on blood film
SCA = low Hb + high reticulocyte count because RBC inefficient in transporting O2 so body compensated by producing more RBCs
Reticulocytes in blood films show up as nucleated RBCs as they are immature
When a person has the sickle cell trait - normal FBC and red cell shape in blood film
Microcytic = smaller in size (lower Hb / iron levels)
Hypochromic = pale centre (less Hb)
Poikilocytosis = abnormal shapes
What does the blood film look like?
Microcytic = smaller in size (lower Hb / iron levels)
Hypochromic = pale centre (less Hb)
Poikilocytosis = abnormal shapes
How to test for Hb S?
Solubility - Hb S doesn’t dissolve (precipitates out)
Cannot differentiate between Hb AS and HbSS so must do gel electrophoresis after
Acute Vs chronic issues with SCA
Acute :
Dactylitis - pain in joints of hands (normally present in children) - sticky Hb S blocking blood vessels therefore less oxygen supply
sequestration - blood pooled into spleen so sudden drop in Hb in the rest of the tissues (also more likely in the children as the spleen gets damaged with age)
aplastic - sudden drop in bone marrow red cell production
vaso-occlusion - causes pain crises
acute chest syndrome - sudden pain in chest, cough, shortness of breath, fever
sepsis - spleen atrophy causes increased susceptibility to certain bacterial infections
chronic :
gallstones - due to haemolysis
priapism - painful, persistent erection
kidney disease - blockage of blood vessels + Hb released in blood (haemolysis) = block blood vessels
avasculsr necrosis of hips and shoulders - recurrent pain crises and ischaemia damage
Triggers of pain crisis
Hypoxia - deprived of oxygen supply
Infections
Exercise
dehydration
cold
Potential issues with analgesias:
Addiction
Sedation
Tolerance
Treatment for SCA
Hydroxycarbamid - Increases Hb F = inhibit sickles RBCs sticking together
BM transplant e,g, young and good match
transfusions
gene therapy - use CRISPR to correct single nucleotide and insert into patient’s stem cells
What are is her ICE
Ideas - well informed
concerns - frustrated she needs to go through this again, interferes with her life e.g. ballet, travelling, shopping etc.(psychological impact, hiding ballet from friend, avoid telling her mum)
expectations - morphine, antibiotics and folic acid
Comorbid
Have other conditions e.g. psychological ones
When does SCA present and what symptoms can it present with?
After 3 to 6 months, as Hb F is still high after birth
Anaemia
Jaundice - sickle cells dying faster than the liver can filter them out (bilirubin causes yellow tinge)
growth restriction
pain crises
shortness of breath
strokes
splenomagly - sickle cells block blood vessels in the spleen, so blood cells cannot flow out of the spleen
