Red Cells 2: acquired anaemias Flashcards
(37 cards)
Definition of Anaemia
Low haemoglobin
However this has to be below the normal range for their age / sex
What happens to your Hb as you get older?
There is a drop in your Hb
Reference ranges for Hb in M and F
- Male 12-70 (140-180)
- Male >70 (116-156)
- Female 12-70 (120-160)
- Female >70 (108-143)
Lower levels of Hb in menstruating females due to drop in iron
General symptoms/features of anaemia (caused by reduced O2 delivery to tissues)
- Tiredness/pallor
- Breathlessness
- Swelling of ankles
- Dizziness – on standing up too quickly etc
- Chest pain – myocardial ischaemia
These depend on age, speed of onset and Hb level
Common underlying causes of anaemia
- If evidence of bleeding
- Menorrhagia
- GI bleeding - Dyspepsia
- PR bleeding
- Symptoms of malabsorption - GI symptoms - unable to absorb things necessary to make blood i.e B12
- Diarrhoea
- Weight loss
- Jaundice - haemolysing
- Splenomegaly/lymphadenopathy - haemotolgical condition
Anaemia pathophysiology
Understanding blood count results
When you get a blood count you get Hb level and a whole lot of indices telling you all about the size, number and shape of the RBCs. The most important ones are:
- MCH = mean cell haemoglobin (amount of Hb in the cells)
- MCV = mean cell volume (cell size)
From this you can give a morphological description of anaemia – and a clue as to cause! Machines cannot tell you shape of blood but it can tell you whether there is an abnormal average size and amount of Hb in cells even if they are misshapen under microscope
How do we describe anaemias? (3)
- Hypochromic microcytic anaemia – small, pale cells
- Normochromic normocytic – normal size, normal colour
- Macrocytic anaemia – big cells and are usually pale (not hyperchromic – as this would mean they have lots of Hb)
Once you have looked at the blood results and find out it is hypochromic microcytic anaemia. What test will you do next to confrim this?
Serum ferritin test
Iron deficiency is the commonest cause of hypochromic microcytic and ferritin is a measure of the body’s iron stores.
- If your serum ferritin is low = iron deficiency
- If your serum ferritin is normal or increased then there can be other things going on. It can go up if you have inflammation or liver damage.
- Thalassaemia has normal ferritin but small cells. They can develop iron deficiency too from GI bleed etc.
- Secondary anaemia
Once you have looked at the blood results and find out it is normochromic normocytic anaemia. There are lots of causes of this so what test will you do next to investigate it further / confrim this?
A reticulocyte count
This can tell you if your bone marrow is working or not.
Why might you have a normal or low reticulocyte count?
Low:
- Secondary anaemia / anaemia of chronic disease - renal impairment - kidneys don’t make erythropoietin (EPO) which tells bone marrow to make RBCs
- Marrow infiltration - aplastic anaemia - cells appear normal but just aren’t enough of them - can be caused by malignancy etc
Why might you have a raised reticulocyte count in Normochromic normocytic anaemia?
High:
- In acute blood loss - it takes a long period of bleeding to empy body’s iron stores so in acute blood loss you just become anaemic but you wouldn’t be iron deficient by then because your body would still have iron stores. In acute blood loss you get normochromic anaemia and body responds by making reticulocytes to compensate for loss of RBCs
- Haemolysis - increased breakdown of cells => reduced Hb => compensation by bone marrow => increased retic count
What is Secondary anaemia / anaemia of chronic disease?
Inability to use iron efficiently - increased hepcidin in inflammation blocks ferroportin and so Fe is stuck in places where it shouldn’t be and not being used efficiently for erythropoeisis. Your ferritin stores may be normal or even raised if underlying inflammatory process as Fe is an acute phase reactant.
- 70% normochromic normocytic
- Very chronic secondary anaemias where there is a lot of inflammation causes abnormal Fe utilisation (remember it plas important role in protecting body from microorganisms) that cells become microcytic = 30% hypochromic microcytic
Once you have looked at the blood results and find out it is macrocytic anaemia. What tests will you do next to investigate it further / confrim this?
- B12/folate
- Bone marrow
The commonest cause of a macrocytic anaemia is B12 or folate deficiency. If your B12/folate results are normal then you are looking at a problem with the bone marrow such as malignancies
Look
There is no pathway for excretion of excess iron = you need iron chelation therapy/drugs
What forms of iron do you get from your diet?
- Haem iron - get this from blood - meat sources - more readily absorbed than non-haem iron
- Non-haem iron - dietary sources
There are different ways of absorbing these types of iron
Key proteins in iron metabolism
Ferroprotin - carries Fe across basement membranes to all the cells it needs around the body
Transferrin - binds Fe and carries it through the circulation - transfers it to different organs
Ferritin - iron stores in liver and a little in bone marrow
What is Hepcidin and why is it important?
- Hepcidin = hormone that is made in the liver
- It’s produced when you have sufficient amount of Fe for haematopoeisis
- Hepcidin binds to ferroportin and inactivates it, stopping you from absorbing any more Iron and stops it being mobilised from ferritin stores
- You excrete any more iron that comes in through the diet by just not absorbing it
- This is dynamic process as your iron in diet changes etc
- It is also made in the context of inflammation as iron levels increase in inflammation
What is the commonest cause of anaemia worldwide?
Iron deficiency - this is not a diagnosis and you must find out the cause of their iron deficiency
Common causes specifically for Iron deficiency anaemia?
- Dyspepsia - GI bleeding
- Other bleeding, eg menorrhagia
- Diet (NB children and elderly)
- Increased requirement - pregnancy
Management of iron deficiency
Correct the deficiency
- Oral iron usually sufficient
- IV iron if intolerant of oral
- Blood transfusion is rarely indicated
Correct the cause!
- Diet
- Ulcer therapy
- Gynae interventions
- Surgery - if they have a tumour
Extravascular vs intravascular haemolysis
Intravascular haemolysis - is not normal - RBCs burst within your circulation resulting in free Hb which is toxic to the kidneys. You also get free iron in the circulation which produces free radicals as a result. Examples include SCD or G6PD deficiency (inherited)
Extravascular haemolysis - happens in the reticuloendothelial system where RBCs are being removed - this is a normal process of RBC breakdown that keeps our bilirubin levels at a normal level but this can increase in some forms of haemolysis. If RBC is detected as abnormal shape for example in hereditary spherocytosis the liver/spleen/macrophages will remove those faster than normal
Acquired reasons for Haemolysis?
Acquired extravascular haemolysis:
- Autoimmune haemolytic anaemia - exaggerated removal of RBCs from the circulation
Acquired intravascular haemolysis (usually happens in sick people):
- Mechanical e.g artificial valve that is leaking - RBCs get smashed apart as they pass over the valve
- Severe infection / Disseminated intravascular coagulation
- Pre-eclampsia (PET) - hypertension / Hemolytic uremic syndrome / TTP
If you suspect an auto-immune haemolysis which test should you do that will confirm this?
DAT - direct antiglobulin test - a +ve DAT test implies there is an autoimmune basis for the haemolysis
How? The DAT test detects either antibody or complement on the surface of the red blood cell membrane.
- Involves a blood test - the patient’s own plasma and unbound antibodies are removed from the RBCs and then incubated with an anti-antibody = IgG (“Coombs reagent”).
- If the patient has antibodies on their RBCs against their own RBCs or maybe someone else’s (transufsion reaction) then the reagent will cause the red cells to cross-link and agglutinate = direct Coombs test is positive.
- +ve DAT = antibodies against own RBCs are present
- -ve DAT = its not immune mediated
