Red Cells 2 Flashcards
What are some factors that may influence haemoglobin counts?
Age (young kids may be low, older people low)
Sex
Ethnicity
Time of day
Time to analysis of sample
What is the normal reference range of haemoglobin for males and females? Males and females older than 70?
Males - 140-180
Males > 70 - 166-156
Females - 120-160
Females > 70. - 108-143
What are some of the general symptoms of anaemia?
Tiredness
Pallor
Breathlessness
Ankle oedema
Dizziness
Chest pain
Why is there often a lack of symptoms / presentation of anaemia in patients?
Because the occurence of symptoms may only be present when there is a significant drop in the baseline Hb that the patient has become accustomed to
Eg. those with thalassaemias would be accustomed to a low Hb and so may only show symptoms once their Hb drops even lower
What are some symptoms that may indicate certain causes of anaemia?
Bleeding - menorrhagia, dyspepsia, PR bleeding
Malabsoroption - diarrhoea, weight loss
Jaundice
Lymphadenopathy / Splenomegaly
What are some important red cell indices that help in the deduction of the cause of anaemia?
MCH - Mean cell haemoglobin (colour of the cell can guess at the level of haemoglobin in a red cell)
MCV - Mean cell volume (size of red cells)
What does hypochromic microcytic anaemia refer to?
Hypochromic - reduced colour
Microcytic - smallk size
Small pale red cells
What does normochromic normocytic anaemia refer to?
Machine says that the cells are on average a normal size and contain a normal amount of haemoglobin
What does macrocytic anaemia refer to?
Macrocytic - big cells
Anaemia in which the red cells are of large size
What is the most common cause of hypochromic microcytic anaemia? If these red cell indices are seen what would be a good next test?
Iron deficiency
Serum Ferritin - low ferritin means you’re iron deficient
When will your reticulocyte count be raised?
When you’re producing more red cells
- After bleeding
- If you’re haemolysing
When would reticulocyte count be low?
When bone marrow isn’t functioning normally
Aplastic anaemia
If normochromic normocytic anaemia is suspected what is a good next test?
Reticulocyte count
- Might just be haemolysing / bleeding too much
- Might just not be producing enough red cells but they are normal in character
What is the commonest cause of macrocytic anaemia? What are some other possible causes?
B12 / Folate deficiency
Bone marrow abnormalties (myelodysplasia)
If a patient has hypochromic microcytic cells but a normal ferritin level what is a possible ddx?
Thalassaemia
Smaller cells produced by thalassaemic patients but ferritin levels are not decreased
Secondary anaemia
Normal ferritin but inefficient iron utilization due to inflammation
Sideroblastic anaemia (inherited)
Where is most of the bodies iron stored? How is iron lost?
In haemoglobin
Iron mainly lost through degradation of GI endothelium, and through menstruation in females. Tend to absorb from diet what you lose each day
What membrane protein is responsible for the absorption of iron? Once in the plasma what happens to iron?
Ferroportin transports iron across basement membrane
Once in the plasma iron is bound to trnasferrin
Then stored as ferritin mainly in the liver
What is the role of hepcidin in the metabolism of iron? Where is it synthesized and in response to what?
Hepcidin is synthesized in the hepatocytes in response to high iron levels and inflammation
Hepcidin functions to block ferroportin transport of iron into cells and mobilizes the reticuloendothelial system
Synthesized in inflammation bc iron is needed in inflammation so allows it to be redirected there
What are some important history questions to ask in order to find the cause of iron deficiency anaemia?
- Presence of dyspepsia? (GI Bleeding)
- Other bleeding? (menorrhagia)
- Diet
- Increased iron requirement (pregnancy)
What are some possible differentials for a patient who has normochromic normocytic red cells but normal - low reticulocyte count?
Secondary anaemia
- Reduced renal failure: can’t make erythropoeitin
- Anaemia of chronic disease
Hypoplasia
Bone marrow infiltration
What does the anaemia of chronic disease refer to?
Hepcidin is produced in response to inflammation and blocks ferroportin activity
Iron is not used for haematopoesis as much as it should be and so there is iron deficiency anaemia due to inflammation associated with chronic disease
What determines the severity of anaemia in patients with haemolytic anaemia?
Their ability to compensate for the red cell loss by bone marrow RBC production (seen via high reticulocytes)
What is the difference between intravascular and extravascular haemolysis?
Extyravascular is just a normal physiological process resulting in the breakdown of RBCs, can be a pathological increase of this process
Intravascular is much worse because cells are bursting within circulation and products such as free Hb are toxic to the kidneys and free iron etc. can cause an inflammatory response
What are some causes of acquired haemolytic anaemia?
Extravascular - autoimmune haemolytic anaemia
Intravascular: (non-immune)
- Mechanical (artificial valve)
- Severe infection / DIC
- Eclampsia / toxins / TTP
If immune mediated acquired haemolysis is suspected, what tests may be done?
Direct antiglobulin test (coombs) - detects antibody or complement on red cell membrane
Reagent binds to antibody or complement on red cell surface and causes clumping in-vitro
Reagent contains an anti-antibody that binds to red cells that have antibodies on them. if you are producing antibodies against your own red cells the reagent will bind these antobodies and cause clumping
What does a positive direct antiglobulin test imply?
That haemolytic anaemia is autoimmune mediated
if the patient has had a transfusion it can also be alloantibody mediated
Why are spherocytes often seen on blood film in immune mediated haemolysis?
Because when the spleen detect antibodies on the surface of red cells it absorbs the antibodies and with it some of the red cell membrane
This causes loss of RBC structure and cells become spherical, as in hereditary spherocytosis
What are warm and cold antibodies with regard to haemolytic anaemia?
Warm - cause haemolysis or RBCs at normal body temperature
Cold - cause clumping of RBCs in cold temperatures
What Is seen on blood film with intravascular haemolysis?
Red cell fragments - schistocytes
What are some investigations to tell if a patient is haemolysing?
FBC / reticulocytes / blood film
Serum bilirubin (should be raised)
Serum LDH (should be raised)
Serum haptoglobin (should be low - haptoglobin is a protein that mops up free haemoglobin)
What tests are useful for detecting the mechanism (cause) for why a patient is haemolysing?
Direct antiglobulin test (Coombs) - immune
Urinalysis for haemosiderin / urobilinogen (intravascular)
How is haemolytic anaemia managed?
Folic acid to support bone marrow function
Immunosuppression if autoimmune (steroids)
Splenectomy to remove site of red cell destruction (if chronic)
Treat sepsis / malignancy / valve if intravascular
Consider transfusion if severe anaemia
What is macrocytic anaemia due to folate / B12 deficiency called?
Megaloblastic anaemia
Non-megaloblastic if the macrocytic anaemia is due to a cause other than folate / B12 deficiency
What are some possible causes of non-magaloblastic macrocytic anaemia?
Drugs (methotrexate etc. )
Bone marrow infiltration
Myelodysplasia
Hypothyroidism
Alcohol
Disordered liver function
Why does a B12 / Folate deficiency result in anaemia? What are some other symptoms that may be seen when deficient in either of these?
Because they are both involved in DNA synthesis and repair and so if you are deficient you have reduced erythropoeisis
Neurological symptoms - subacute degeneration of the cord (B12 deficiency)
What are some causes of B12 deficiency?
Pernicious anaemia
Gastric / Ileal disease
What are some causes of folate deficiency?
Dietary
Increased folate requirements (haemolysis)
GI pathology (eg. coeliac disease)
How is vitamin B12 absorbed?
Intrinsic factor is secreted by gastric parietal cells
IF binds B12 and the complex is absdorbed in the terminal ileum
Gastric disease / gastrectomy may mean no IF. Bowel disease such as Crohns with ileal involvement may mean can’t absorb the complex
How does megaloblastic anaemia tend to present?
Lemon-yellow tinge to the skin
- Due to high bilirubin and LDH
What other blood cells are affected by megaloblastic anaemia?
Thrombocytes - may have thrombocytopenia
White cells - hypersegmentation of neutrophils
What is pernicious anaemia?
Autoimmune disease where there are antibodies against intrinsic factor
Means you can’t absorb B12
Takes a while to present (1-2 years sometimes) due to the relatively high stores of B12
How do you treat pernicious anaemia? B12 deficiency? Folate deficiency?
Pernicious anaemia: IM injections of B12
B12 def: oral B12 supplementation
Folate deficiency - oral folate supplementation
