Anaemia Flashcards
What is haemoglobin (Hb)?
A protein found in RBC
what is the function of Hb?
Haemoglobin is responsible for picking up oxygen in the lungs and transporting it to the body’s cells
What is the role of iron in Hb?
Iron is essential in creating haemoglobin and forms part of it’s structure.
What does mean cell volume (MCV) mean?
The mean cell volume (MCV) refers to the size of the red blood cells
Normal Hb ranges for men & women?
Women: 120 – 165 grams/litre
Men: 130 -180 grams/litre
Anaemia is divided into three categories based on the mean cell volume.
What are they?
1) microcytic anaemia (low MCV)
2) Normocytic anaemia (normal MCV)
3) Macrocytic anaemia (large MCV)
What should new onset microcytic anaemia in older patients always be urgently investigated for?
underlying malignancy.
Give some causes of microcytic anaemia
Mneumonic: TAILS
T - thalassaemia
A - anaemia of chronic disease
I - iron deficiency
L - lead poisoning
S - sideroblastic anaemia
Macrocytic anaemia can be megaloblastic or normoblastic.
Name some causes of both
Megaloblastic bone marrow:
- B12 deficiency
- folate deficiency
- e.g. secondary to methotrexate
Normoblastic bone marrow:
- alcohol
- reticulocytosis (usually from haemolytic anaemia or blood loss)
- hypothyroidism
- liver disease
- drugs e.g. aziothioprine
- pregnancy
What is the difference between macrocytic and megaloblastic anaemia?
Megaloblastic anaemia is a type of macrocytic anaemia.
Macrocytes are enlarged RBCs (raised MCV).
Megaloblasts are large RBC precursors due to impaired DNA synthesis, preventing the cells from dividing normally. Rather than dividing, they grow into large, abnormal cells.
What causes the production of megaloblasts?
Impaired synthesis of RBC DNA e.g. folate deficiency
Define reticulocytosis
An increased concentration of reticulocytes (immature red blood cells.
This happens when there is a rapid turnover of red blood cells, such as with haemolytic anaemia or blood loss.
Anaemia of chronic disease often occurs with CKD.
How?
Reduced production of EPO by kidneys (hormone responsible for production of RBCs).
Treatment of anaemia caused by CKD?
erythropoietin
What are the causes of normocytic anaemia?
(3 As and 2 Hs)
A - acute blood loss
A - anaemia of chronic (more likely than microcytic) e.g. CKD
A - aplastic anaemia
H - haemolytic anaemia
H - hypothyroidism
What type of anaemia does CKD cause?
Typically normocytic
What is sideroblastic anaemia?
Sideroblastic anaemia is a disorder where the body produces enough iron but is unable to put it into the haemoglobin (iron levels will be normal/high)
What is the main cause of sideroblastic anaemia?
Alcohol excess
Generic symptoms of anaemia?
- Tiredness
- Shortness of breath
- Headaches
- Dizziness
- Palpitations
- Worsening of other conditions, such as angina, heart failure or peripheral arterial disease
What 2 symptoms are specific to iron deficiency anaemia?
1) Pica (dietary cravings for abnormal things, such as dirt or soil)
2) Hair loss
Generic signs of anaemia?
- pale skin
- conjunctival pallor
- tachycardia
- raised RR
What is koilonychia?
spoon-shaped nails
What can koilonychia indicate?
iron deficiency anaemia
What is angular cheilitis?
a common inflammatory condition affecting the corners of the mouth.
What anaemia can cause angular cheilitis?
Iron deficiency
What is atrophic glossitis?
a smooth tongue due to atrophy of the papillae
What anaemia can atrophic glossitis indicate?
Iron deficiency
What type of anaemia can cause brittle hair and nails?
iron deficiency
What type of anaemia can cause jaundice?
Haemolytic
What type of anaemia cause cause bone deformities?
Thalassaemia
Possible blood tests in anaemia?
1) FBC: Hb & MCV
2) Reticulocyte count (indicates red blood cell production)
3) Blood film for abnormal cells and inclusions
4) Renal profile: for CKD
5) LFTs for liver disease and bilirubin (raised in haemolysis)
6) Ferritin (iron)
7) B12 & folate
8) Intrinsic factor antibodies for pernicious anaemia
9) TFTs for hypothyroidism
10) Coeliac disease serology (e.g., anti-tissue transglutaminase antibodies)
11) Myeloma screening (e.g., serum protein electrophoresis)
12) Haemoglobin electrophoresis for thalassaemia and sickle cell disease
13) Direct Coombs test for autoimmune haemolytic anaemia
What investigations are indicated for unexplained iron deficiency anaemia?
A colonoscopy and oesophagogastroduodenoscopy (OGD).
How can iron deficiency lead to anaemia?
Iron is needed to make the Hb in RBCs, therefore a deficiency of iron leads to a reduction in RBCs/Hb.
Who does iron deficiency have the highest incidence among?
Pre school-age children
What are the 4 most common causes of iron deficiency anaemia?
1) excessive blood loss
- women: menorrhagia
- men & postmenopausal women: GI bleeding (suspect colon cancer)
2) inadequate dietary intake
3) poor intestinal absorption e.g. coeliac
4) increased iron requirements
- growth periods in children
- pregnancy
What can cause anaemia in pregnancy?
1) increased demands during pregnancy as the baby will receive their iron supply from the mother
2) an increase in plasma volume during pregnancy causes iron deficiency anaemia through dilution i.e. the proportion of fluid in comparison to red blood cells increases.
Iron deficiency causes microcytic hypochromic anaemia.
What does microcytic mean?
What does hypochromic mean?
Microcytic: small RBCs with a low MCV
Hypochromic: pale cells due to reduced Hb conc
what are causes of blood loss causing iron deficiency anaemia?
1) menorrhagia
2) GI tract bleeding:
- Cancer (e.g., stomach or bowel cancer)
- Oesophagitis and gastritis
- Peptic ulcers
- Inflammatory bowel disease
- Angiodysplasia (abnormal vessels in the wall)
What is the most common cause of iron deficiency anaemia in children?
Dietary insufficiency - during growth, iron requirements often exceed the dietary intake
What is a common exam presentation for iron deficiency anaemia in children?
Pica (e.g. eating soil or dirt)
Where is iron mainly absorbed?
Duodenum & jejunum
Mechanism of absorption of iron:
1) Iron is mainly absorbed in the duodenum and jejunum.
2) It requires the acid from the stomach to keep the iron in the soluble ferrous (Fe2+) form
3) When the stomach contents are less acidic, it changes to the insoluble ferric (Fe3+) form.
How can PPIs result in iron deficiency?
PPIs reduce stomach acid –> changes iron to the insoluble ferric (Fe3+) form.
How can coeliac disease or Crohn’s disease cause iron deficiency?
Inflammation of the duodenum or jejunum can also reduce iron absorption.
Features of iron deficiency anaemia?
- Fatigue
- Shortness of breath on exertion
- Palpitations
- Pallor
- Nail changes: this includes koilonychia (spoon-shaped nails)
- Hair loss
- Atrophic glossitis
- Post-cricoid webs
- Angular stomatitis
- Pica
Important history aspects in iron deficiency anaemia?
1) changes in diet
2) medication history
3) menstrual history
4) weight loss
5) change in bowel habit & blood
What is transferrin?
Carrier protein for iron (transports iron around the blood)
What is total iron binding capacity (TIBC)?
The space for iron to attach to on all the transferrin molecules combined.
TIBC is directly related to the amount of transferrin in the blood.
What does transferrin saturation refer to?
The proportion of the transferrin molecules bound to iron, expressed as a percentage.
The formula for transferrin saturation is:
Transferrin saturation = serum iron / total iron-binding capacity
How is TIBC and transferrin affected by iron levels?
Iron excess –> TIBC & transferrin decrease
Iron deficiency –> TIBC & transferrin increase
Why is serum iron often not a useful measure on its own?
Serum iron varies significantly throughout the day, with higher levels in the morning and after eating iron-containing meals.
What does transferrin saturation indicate?
Transferrin saturation indicates the total iron in the body.
How do iron levels affect transferin saturation?
Less iron –> transferrin less saturated
More iron –> transferrin more saturated
Why is a fasting sample of transferrin saturation more accurate?
It can temporarily increase after eating a meal rich in iron or taking iron supplements.
What is ferritin?
Ferritin is a protein that stores iron inside cells.
Ferritin is an acute phase protein.
What does this mean?
Ferritin is an acute-phase protein released with inflammation (e.g., in infection or cancer).
What is low ferritin highly suggestive of?
Ion deficiency.
N.B. Normal ferritin does not exclude iron deficiency.
Raised ferritin is difficult to interpret.
What may it be caused by (i.e. what can cause iron overload)?
- Inflammation (e.g., infection or cancer)
- Acute liver damage (the liver contains lots of iron)
- Iron supplements
- Haemochromatosis
When should iron deficiency anaemia be investigated?
New iron deficiency in an adult without a clear underlying cause (e.g., heavy menstruation or pregnancy) should be investigated further, including a colonoscopy and oesophagogastroduodenoscopy (OGD) for malignancy.
What are the 3 options for treating iron deficiency anaemia?
1) Oral iron (e.g., ferrous sulphate or ferrous fumarate)
2) Iron infusion (e.g., IV CosmoFer)
3) Blood transfusion (in severe anaemia)
Typical lab results in iron deficiency anaemia:
1) FBC
2) Serum ferritin
3) TIBC/transferrin
4) Blood film
1) hypochromic microcytic anaemia
2) this will likely be low, as serum ferritin correlates with iron stores (BUT ferritin can be raised during states of inflammation; so a raised ferritin does not necessarily rule out iron deficiency anaemia if the is co-occurring inflammation)
3) high (a high TIBC reflects low iron stores)
4) blood film: anisopoikilocytosis (red blood cells of different sizes and shapes), target cells, ‘pencil’ poikilocytes
What is anisopoikilocytosis?
when you have red blood cells that are of different sizes and shapes.
Common side effects of iron supplementation?
- nausea
- abdo pain
- constipation
- black stools
How long does oral iron take to work?
Oral iron works slowly. A rise in haemoglobin of 20 grams/litre is expected in the first month
What is there a small risk of in iron infusion?
There is a small risk of allergic reactions and anaphylaxis.
Why should iron infusions be avoided during infections?
there is potential for it to “feed” the bacteria.
What is an ‘iron rich diet’?
dark-green leafy vegetables, meat, iron-fortified bread
What type of anaemia does B12 deficiency cause?
Macrocytic
what are the 5 key causes of low B12?
1) pernicious anaemia
2) insufficient dietary B12 (e.g. vegan, alcoholism)
3) medications that reduce B12 absorption e.g. PPIs, metformin
4) gastrectomy
5) atrophic gastritis: 2ary to H. pylori infection
What is pernicious anaemia?
an autoimmune disorder affecting the gastric mucosa that results in vitamin B12 deficiency.
What does ‘pernicious’ mean?
‘Causing harm, especially in a gradual or subtle way’.
The symptoms of signs are often subtle and diagnose is often delayed.
what is the most common cause of B12 deficiency?
pernicious anaemia
What is the role of intrinsic factor?
A protein that is essential for the absorption of vitamin B12 in the distal ileum.
What is intrinsic factor produced by?
The parietal cells of the stomach
Pathophysiology of pernicious anaemia?
1) autoantibodies target parietal cells and/or intrinsic factor:
a) intrinsic factor antibodies: bind to intrinsic factor blocking the vitamin B12 binding site
b) gastric parietal cell antibodies: reduced acid production and atrophic gastritis as well as reduced intrinsic factor production
2) Lack of intrinsic factor and a lack of absorption of vitamin B12.
What are the 2 major roles of vitamin B12?
1) production of RBCs –> megaloblastic anaemia
2) myelination of nerves –> neuropathy
What neurological symptoms can be caused by B12 deficiency?
1) Peripheral neuropathy, with numbness or paraesthesia (pins and needles)
2) Loss of vibration sense
3) Loss of proprioception
4) Visual changes
5) Mood and cognitive changes
What should you always test for in patients presenting with peripheral neuropathy, particularly with pins and needles?
vitamin B12 deficiency and pernicious anaemia
Risk factors for pernicious anaemia?
1) female
2) middle to old age
3) autoimmune diseases e.g. thyroid, T1D, Addison’s, RA & vitiligo
4) blood group A
Features of pernicious anaemia?
1) anaemia features:
- lethargy
- pallor
- dyspnoea
2) may have neuro features:
- peripheral neuropathy; ‘pins and needles’, numbness
- subacute combined degeneration of the spinal cord
- neuropsychiatric features: memory loss, poor concentration, confusion, depression, irritabiltiy
3) others:
- mild jaundice: combined with pallor results in a ‘lemon tinge’
- glossitis –> sore tongue
What is subacute combined degeneration of the spinal cord?
Vitamin B12 deficiency resulting in impairment of the dorsal columns, lateral corticospinal tracts and spinocerebellar tracts.
Features of subacute combined degeneration of the spinal cord?
1) dorsal column involvement
- distal tingling/burning/sensory loss is symmetrical and tends to affect the legs more than the arms
- impaired proprioception and vibration sense
2) lateral corticospinal tract involvement
- muscle weakness, hyperreflexia, and spasticity
- upper motor neuron signs typically develop in the legs first
- brisk knee reflexes
- absent ankle jerks
- extensor plantars
3) spinocerebellar tract involvement
- sensory ataxia –> gait abnormalities
- positive Romberg’s sign
What 2 autoantibodies can be used to diagnose pernicious anaemia?
1) Intrinsic factor antibodies (the first-line investigation)
2) Gastric parietal cell antibodies
Are IF antibodies or gastric parietal cell antibodies more useful in the diagnosis of pernicious anaemia?
IF antibodies
Typical lab results in pernicious anaemia:
1) FBC
2) blood film
3) vit B12 & folate
4) antibodies
1) FBC:
- macrocytic anaemia (30%)
- low WCC and platelets may also be seen
2) blood film:
- hypersegmented polymorphs on blood film
3) low B12 (<200)
4) anti IF antibodies/anti gastric parietal cell antibodies
Initial management of pernicious anaemia?
B12 replacement with intramuscular hydroxocobalamin: initially given to all patients with B12 deficiency, depending on symptoms:
- no neuro symptoms –> 3 times weekly for two weeks
- neuro symptoms –> alternate days until there is no further improvement in symptoms
How often is IM hydroxocobalamin given in pernicious anaemia if there are NO neuro symptoms?
3 times weekly for 2 weeks
How often is IM hydroxocobalamin given in pernicious anaemia if there are neuro symptoms?
alternate days until there is no further improvement in symptoms
Long term management of pernicious anaemia?
2-3 monthly injections of IM hydroxocobalamin for life.
Long term management of diet related B12 deficiency?
Oral cyanocobalamin or twice-yearly injections
Where there is B12 and folate deficiency together, what should be treated first?
Why?
B12:
Giving patients folic acid when they have a B12 deficiency can lead to subacute combined degeneration of the cord, with demyelination in the spinal cord and severe neurological problems.
What cancer does pernicious anaemia increase risk of?
Gastric cancer
What is involved in haemolytic anaemia?
The destruction of RBCs (haemolysis), resulting in low Hb conc (anaemia.
What inherited conditions can cause chronic haemolytic anaemia?
1) hereditary spherocytosis
2) hereditary elliptocytosis
3) thalassaemia
4) sickle cell anaemia
5) G6PD deficiency
Acquired haemolytic anaemias can be subdivided into immune and non-immune causes.
The acquired immune-related causes are ‘Coombs positive’.
What does that mean?
A positive (abnormal) Coombs test means that you have antibodies that can attack your RBCs i.e. autoimmune.
What are the acquired immune causes (Coombs positive) of haemolytic anaemia?
1) Autoimmune haemolytic anaemia
2) Alloimmune haemolytic anaemia (e.g., transfusions reactions and haemolytic disease of newborn)
3) Drugs: methyldopa, penicillin
What are the acquired non-immune causes (Coombs negative) of haemolytic anaemia?
1) Paroxysmal nocturnal haemoglobinuria
2) Microangiopathic haemolytic anaemia e.g. DIC, malignancy, pre-eclampsia
3) Prosthetic heart valves
4) Infections e.g. malaria
What are the 3 key features of haemolytic anaemia?
A result of the destruction of RBCs:
1) anaemia
2) splenomegaly
3) jaundice
Cause of splenomegaly in haemolytic anaemia?
the spleen becomes filled with destroyed red blood cells
Cause of jaundice in haemolytic anaemia?
bilirubin is released during the destruction of red blood cells
What are the 3 key investigations in haemolytic anaemia?
What will they show?
1) FBC: shows a normocytic anaemia
2) Blood film: shows schistocytes (fragments of red blood cells)
3) Direct Coombs test: positive in autoimmune haemolytic anaemia (not in other types)
What is the most common inherited haemolytic anaemia in northern Europeans?
Hereditary spherocytosis
Inheritance of hereditary spherocytosis?
Autosomal dominant
What happens in hereditary spherocytosis?
It causes fragile, sphere-shaped RBCs that easily break down when passing through the spleen.
Presentation of hereditary spherocytosis?
- anaemia
- jaundice
- gallstones
- splenomegaly
- aplastic cris is in the presence of the parvovirus
- likely to be FH
What is an aplastic crisis?
A condition in which the bone marrow of someone with sickle cell disease suddenly stops producing RBCs.
This causes sudden and severe anemia.
What is aplastic crisis usually caused by?
by an infection with parvovirus
3 key investigation findings in hereditary spherocytosis?
1) FBC: Raised mean corpuscular haemoglobin concentration (MCHC)
2) Raised reticulocyte count: due to rapid turnover of red blood cells
3) Blood film: spherocytes
Treatment of hereditary spherocytosis?
1) folate supplementations
2) blood transfusions when required
3) splenectomy
N.B. Gallbladder removal (cholecystectomy) may be required if gallstones are a problem.
Why can hereditary spherocytosis predispose to gallstones?
Many RBCs break down in hereditary spherocytosis, so there’s more bilirubin in the body than normal. The higher level of bilirubin can lead to gallstones.
What is hereditary elliptocytosis?
Hereditary elliptocytosis is similar to hereditary spherocytosis except that the red blood cells are ellipse-shaped.
The presentation and management are the same as hereditary spherocytosis.
Inheritance of hereditary elliptocytosis?
autosomal dominant
What is G6PD deficiency caused by?
G6PD deficiency is caused by a defect in the gene coding for glucose-6-phosphate dehydrogenase (G6PD).
Role of glucose-6-phosphate dehydrogenase (G6PD)?
It is an enzyme responsible for protecting the cells from oxidative damage.
Inheritance of G6PD deficiency?
X linked recessive (where males are more often affected and females are carriers)
Where is G6PD more common?
It is more common in Mediterranean, Asian and African patients.
What are acute episodes of haemolytic anaemia triggered by in G6PD deficiency?
1) infections
2) drugs: ciprofloxacin, sulfonylureas (e.g., gliclazide) and sulfasalazine.
3) fava beans
What 3 drugs are most commonly implicated in acute episodes of haemolytic anaemia in G6PD deficiency?
1) ciprofloxacin
2) sulfonylureas (e.g., gliclazide)
3) sulfasalazine
Presentatino of G6PD deficiency?
1) jaundice (often in neonatal period)
2) gallstones
3) anaemia
4) splenomegaly
5) Heinz bodies on a blood film
How can a diagnosis of G6PD deficiency be made?
G6PD enzyme assay.
When does jaundice often present in G6PD deficiency?
neonatal period
TIP: The critical piece of knowledge for G6PD deficiency relates to triggers.
In your exams, look out for a male patient that turns jaundiced and becomes anaemic after eating fava beans (broad beans), developing an infection or taking antimalarials.
The underlying diagnosis might be G6PD deficiency.
What are the 2 types of autoimmune haemolytic anaemia (AIHA)?
Warm & cold: based on the temperature at which the auto-antibodies destroy red blood cells.
Is warm or cold AIHA more common?
Warm
What does ‘warm’ AIHA mean?
Haemolysis occurs at normal or above-normal temperatures.
Cause of warm AIHA?
idiopathic
What is cold-reactive autoimmune haemolytic anaemia also called?
cold agglutinin disease
What happens in ‘cold’ AIHA?
1) At lower temperatures (e.g., less than 10ºC), the antibodies attach to the red blood cells and cause them to clump together, called agglutination.
2) The immune system is activated, and the red blood cells are destroyed.
What can cold AIHA occur 2ary to?
1) lymphoma
2) leukaemia
3) systemic lupus erythematosus
4) infections e.g. mycoplasma, EBV, CMV, HIV
Management options in AIHA?
1) blood transfusions
2) prednisolone
3) rituximab (a monoclonal antibody against B cells)
4) splenectomy
What temp does the antibody in cold AIHA cause haemolysis best?
4 degrees
Iron deficiency anaemia vs anaemia of chronic disease:
a) serum iron
b) TIBC
c) transferrin saturation
d) ferritin
a)
IDA –> low <8
ACD –> low <15
b)
IDA –> high
ACD –> low
c)
IDA –> low
ACD –> low
d)
IDA –> low
ACD –> high
