Red Cells and Congenital Anaemia Flashcards
What is anaemia and Sx
The reduction in red cells or their haemoglobin content
Sx Pallor Fatigue SOB Chest pain
What can cause anaemia
Blood loss
Increased destruction of red cells
Lack of production or defective production
What substances are required for definite red cell production
Iron
B12
Folic acid
Erythropoeitin
What are substances are needed for red cell production
Copper Cobalt Manganese Thiamine Vit B,C,E A GM-CSF Androgens Thyroxine
Where are red cells broken down
In the reticuloendothelial system extravacular
Can be done intravascular if damaged
Spleen = majority
Liver / LN / lungs
What are red cells (haem + globe) broken down into
Globin -> AA
Haem -> bilirubin (bound to albumin in plasma)
Iron is reutilised and binds to transferrin
Stored as ferritin in the liver
Is bilirubin conjugated or unconjugated
Unconjugated as not passed through liver
What are congenital causes of anaemia
Defects in Red cell membrane Metabolic enzymes and pathways Haemoglobin production (haemoglobinopathy) Leads to haemolysis
What pathways are involved in RBC formation and what enzymes are affected
Glycolysis to produce energy
Pentose phosphate shunt to prevent oxidative damage
G-6PD enzyme + pyruvate kinase
What diseases are associated with red cell membrane issues
Hereditary spherocytosis
Hereditary elliptocysos
Heriditary pyropoikilocytosis
What is hereditary spherocytosis
Autosomal dominant defects in structural proteins so removed faster by the spleen
What proteins are affected
Ankyrin / Band 3
What is the presentation of hereditary spherocytosis
What would cause abdominal pain
Variable
FTT
Anaemia
Jaundice + pigment gallstones due to increased bilirubin
- Can present with abdominal pain due to gall stone / splenic rupture
Splenomegaly
Chronic Sx but can have crisis e.g. in infection / parvovirus
If aplastic crisis = no increase in reticulocyte count
How do you Dx
Typical Hx, FH + spherocytes on film = Dx
Osmotic fragilited= +Ve
Raised unconjugated bilirubin
Reticulocytes + blurbing will be high
Electrophoresis / EMA binding test if atypical
How do you treat hereditary spherocytosis / follow up
Body compensates with lower Hb
Folic acid - higher requirement due to turnover
Transfusion if haemolysis increased in intercurrent illness
Splenectomy as main site of destruction
Follow up
- FBC, SBR
- Spleen size
- USS gall bladder
- general health
What does G6PD deficiency lead too
G6PD protects haemoglobin from oxidative damage so Increased oxidative damage
Protection against malaria
What type of inheritance of G6PD deficiency
X-linked
How do you diagnose G6PD
FBC
G6PD assay
Blood film - blister and bite cells / Heinz bodies
How does G6PD deficiency present
Intravascular haemolysis as structural damage in circulation
Anaemia
Jaundice + gallstones
Splenomehaly
Wha will intravascular haemolysis lead too
Haemoglobinuria which can damage kidneys
What are triggers to haemolysis in G6PD deficiency
Infection Acute illness e.g. DKA Broad beans Anti-malarial drug - check G6PD level Other drugs - sulphonamide / ciprofloxacin / trimethoprim / nitrofurantoin
What other enzyme deficiency is there and what does it cause
Pyruvate kinase
Leads to reduced ATP and increased 2,3-DPH
Anaemia / jaundice / gall stones
What is haemoglobin made up of
Haemo = carries o2
Globin chains = determine type of Hb
2 alpha chains - 4 alpha genes so if mutation in one can still make good chain
2 beta chains - 2 beta genes so if mutation can’t make beta
Delta / gamma chains can take over if genes missing
What does the haem in our blood look like
HbA (aaBB) = 97%
HbA2 (aaDD) = 2% - make if lose beta chains
HbF (aaYY) = <1% (high in fetal)
Should have NO sickle (aaSS)
What leads to haem binding more oxygen
Exercise
Acidosis
Hyperthermia
Hypercapnia
What has highest affinity fro oxygen
HbF as need to take oxygen from mother’s blood
What is the function of haemoglobin
Delivery 02 to tissue and co2 to the lungs
What are the haemoglobinopathies and how do you Dx
Autosomal RECESSIVE disorders of haemoglobin
Absent or reduced chain production but normal structure - thalassaemia
- Beta absent or reduced
- Alpha absent or reduced
Structutrally abnormal chains due to point mutation - sickle cell
Dx = electrophoresis
What is sickle cell disease and what types can you get
Beta gene of HbA has sickle cell mutation leading to abnormal protein - HbS
Homosygotes have sickle cell disease
Heterozygoutes have trait (protective against malaria) which is why more common in Africa has selective advantage - asymptomatic unless at high altitude etc.
Hb in blood
- HbA = 0%
- HbA2 = 2%
- HbF = 20%
- HbS = 8-90%
Homozygous - HbSS
- Inherited two abnormal copy of sickle
- Classic sickle
Compound heterozygous - HbSc
- Inherited one abnormal sickle but also another mutated recessive
- Less severe
Combined thalassaemia
- Inherited sickle gene (HbS) but also have beta-thalassaemia
- Abnormal structure and reduced production
What happens in sickle cell
When deoxygenated fully / placed under stress, sickle cell RBC polymerises and forms aggregated and keep sickle shape
Increased risk of haemolyis = haemolytic anaemia
Broken parts of RBC can get stuck in vessel = occlusion
RBC removed by spleen much faster - 20 instead of 120
Damage to blood vessel due to RBC breakdown and blockage
What is the sickle cell crisis
Endothelial activation Inflammation Coagulation acitvated Vasodilators - NO Vaso-occlusion / blockage of small blood vessel
Wha does sickle cell crisis cause and long term
Major = vaso-occlusion + haemolytic
Vaso-occlusive painful crisis causing ishchaemia (pain / fever = main Sx)
- Bone - AVN
- Hand and feet if <3 = dactylitis
- CNS - STROKE IN CHILDREN etc (can be ischaemic or haemorrhage due to damaged vessel)
- Priaprism
- Acute chest syndrome
- Renal infarction
Severe anaemia - normocytic normochromic
- Jaundice / fatigue
Severe infections
Sequestrian
- Sickling when spleen / lungs cause pooling of blood
- Can lead to hypovolaemic shock / abdominal pain / splenomegaly but as get older more likely atrophy
- Enlarged liver and spleen as blood pools
Aplastic crisis - parovirus (Sudden fall in Hb)
Haemolytic crisis (rare)
Long term
- Chronic multi-organ damage due to occlusion / damage
- Chronic haemolytic normocytic anaemia
- Splenic infarction and atrophy in early childhood so don’t get splenomegaly
- Increased risk of infection / sepsis
- Growth
- Chronic renal failure
- Gall stones
- Lung damage
- Stroke due to damage
- Retinopathy
- Pulmonary hypertension due to microvascular damage
What does acute chest syndrome present with
Either due to infection or vase-occlusive crisis Pulmonary infiltrates on CXR Dyspnoea Low sats Fever Chest pain
What causes increased infection and what type
Hyposplenism
Usually encapsulated organisms
Salmonella = typical but rare in real life
What can precipitate crisis
Hypoxia Infection Dehydration Cold exposure Pregnancy can stress more Can be well in between
How do you Rx painful thrombotic crisis
ADMIT Analgesia - often use high strength Bloods - FBC + relic, U+E, LFT - X-match - Sepsis screen / culture ECG + CXR + ABG Fluid Oxygen to stop polymerisation process Consider Ax or try to treat precipitant
Blood transfusion if Hb or reticulocyte fall sharply - guided by haematologist
Exchange transfusion if neuro complications
How do you Rx chest crisis
Resp support O2 Ax - macrolide and cephalosporin IV fluid Analgesia May need ventilation May need exchange transfusion
If someone comes in want to know
- Sickle % and baseline Hb
- Any recent complication / admission
- Any disease modifying / exchange transfusion
What is given as life long prophylaxis
Vaccinations as hyposplenism
Penicillin prophylaxis
Pneumococcal vaccine 5 yearly
Folic acid
How do you Dx sickle cell
Most Dx at new-born screen
Hb electrophoresis
- Indirct to look for sickled Hb
Can do direct sequence of beta global gene to look for mutation
What is general management
Avoid trigger
Ensure vaccines up to date
Ax prophylaxis
Blood transfusion
Disease modifying drug - hydroxycarbamiade / hydroxyurea - increases HbF which cannot sickle as no BB and improve RBC life-space
ALLOGRAFT bone marrow transplant can be indicated in young patient with specific complication e.g. stroke
Gene therapy
Have a low threshold for admission as hyposplenism can led to severe infections
- Temp >38
- Child with mild to mod pain
- Chest Sx
What is thalassaemia
Reduced or absent global chain production due to mutations or deletions in alpha or B genes
Thalassaemia minor or trait if one or 2 chains missing
Major if 3 or all chains missing
Leads to chronic haemolytic and microcytic anaemia
Hb in blood
- HbA = 0%
- HbA2 = 2%
- HbF = 95%
What are 4 types of thalassaemia
Homozygous alpha zero if mutation in all 4 alpha gene
Beta thalassaemia major (homozygous betA) if mutation in both beta genes
Non transfusion depedent
Beta thalassaemia trait / minor if mutation in one
Major = no chain produced Minor = reduced amount
How does homozygous alpha zero present
Hydrops fettles Incompatible with life as no alpha chains
What is Beta thalassaemia major
Absence of beta chain as not inherited
Still have alpha which can joint with delta or gamma to make foetal haemoglobin
Most severe
When do you become transfusion dependent / symptomatic
When fatal Hb drops and gamma exchanged for beta at around 4 months
How does it present
Microcytic anaemia with symptoms quite severe FTT Expansion of ineffective marrow to compensate for chronic anaemia leading to - Bone deformities - Fractures - Skull and facial bossing HSM as spleen deals with RBC's Jaundice Gall stones Can cause heart failure
How do you Dx
Screen in pregnancy
FBC, MCV, film
Film = target cell
Reticulocyte = raised but not enough to be normocytic
Hb electrophoresis - low HbA or HbF = DIAGNOSTIC
Ferritin levels normal
How do you Rx
Monitor FBC / complications
Chronic transfusion 4-6 weeks
Splenectomy
Bone marrow transplant = curative
What is risk of transfusion and how do you monitor
Iron overload - present like haemochromatosis
Cause heart / liver / endocrine failure
Monitor with ferritin levels
How do you Rx
Iron chelation - deferoxamine
What is beta thalassaemia minor / trait
Carrier state- AR
Usually no symptoms
Microcytic anaemia with mild Sx
What is seen on film
Hypochromic Microcytic
What are all congenital anaemia’s
Haemolytic so increased reticulocyte count
Sickle cell RBC lifespan can be as small as 5 days
If have splenectomy what is needed
Flu and pneumococcal immunisation
Penicillin
Alert
