Red Cells 2 Flashcards
what are some factors influencing the normal range of haemaglobin?
Age
Sex
Ethnic origin
Time of day sample taken
Time to analysis
what are the Reference ranges of haemaglobin? (vary with age and sex)
- Male 12-70 (140-180)
- Male >70 (116-156)
- Female 12-70 (120-160)
- Female >70 (108-143)
As you get older there is a physiological drop in hemoglobin
Male different due to effect of testosterone
what are the clinical features of anaemia?
General features due to reduced oxygen delivery to tissues:
- Tiredness/pallor
- Breathlessness
- Swelling of ankles (degree of heart failure)
- Dizziness
- Chest pain
what do the lcinical features of anaemia depend upon?
Depend on age, speed of onset and Hb level
Will depend on a fall from the baseline that the patient is used to
what are some anaemia clinical features that are related ot the underlying cause?
Evidence of bleeding: Menorrhagia, Dyspepsia, PR bleeding
Symptoms of malabsorption - Diarrhoea, Weight loss
Jaundice
Splenomegaly/Lymphadenopathy
Anaemia Pathophysiology:
What is A
Cellularity
Stroma
Nutrients
Anaemia Pathophysiology:
What is B
Membrane
Haemaglobin
Enzymes
Anaemia Pathophysiology:
What is C
Blood loss
Haemolysis
Hypersplenism
Red cell indices - Automated measurement of red cell size and haemoglobin content
what are 2 important measurements?
MCH = Mean cell haemoglobin
MCV = Mean cell volume (cell size)
Can give a morphological description of anaemia – and a clue as to cause!!
what are the different morphological descriptions in anaemia?
Hypochromic – less colour
Microcytic – small
Small pale cells
Normochromic normocytic – normal amount of haemaglobin and on average they are a normal size. Many anaemias have this form. May have sickle cell and machine cant say what shape
Macrocytic – big red cells, usually less haemaglobin in them
what is shown here?
5 different patients
Don’t need to remember reference ranges
- Got bigger cells so got less cells and on average have more in it
What investigation is A?
serrum ferritin
Most common cause is Iron deficiency – do a serum ferritin
What investigation is B?
Reticulocyte count
Lots of causes so blood film important there to see what it looks like, reticulocyte count can be important, last stage of red cell development and if bleeding your reticulocyte count will go up to compensate and same in haemolysis. Reticulocyte count can be low in aplastic anaemia and tells if bone marrow is working or not
What investigation is C?
B12/FOlate
Bone Marrow
Commonest cause if B12/folate deficiency and if these are normal then may. Be a problem in the bone marrow
what is shown here?
Hypochromic, microcytic anaemia
Area of central pallor is about normal in the left photo
Right photo - RBC should be same size as a lymphocyte as seen in dark purple, more pale in the middle
in Hypochromic microcytic anaemia, if serum ferritin is low, then what is it likely to be?
iron deficiency
in Hypochromic microcytic anaemia, if serum ferritin is normal or increased, then what is it likely to be?
Thalassaemia
Secondary Anaemia
Sideroblastic anaemia (a disorder where the body produces enough iron but is unable to put it into the haemoglobin)
iron metabolism:
- Dietary intake ________ by loss
- Most of the body’s iron is in __ - And is “recycled”
Absorbed iron - bound to mucosal ______ and sloughed off Or transported across the basement membrane by ________
Then - bound to _________ in plasma
Stored as Ferritin - mainly in _____
balanced
Hb
ferritin
ferroportin
transferrin
liver
Ferratin is a measure of what?
iron stores
what is hepcidin?
Hepcidin synthesised in hepatocytes in response to ↑iron levels and inflammation – blocks ferroportin so reduces intestinal iron absorption and mobilisation from reticuloendothelial cells
(Transported from enterocytes and macrophages by ferroportin)
epcidin inhibits iron transport by binding to the iron export channel ferroportin
what is the Commonest cause of anaemia worldwide?
iron deficiency anaemia
Description not a diagnosis – establish cause!
what would appear in the history and examination of a patient with iron deficiency anaemia?
History:
- Dyspepsia, GI bleeding
- Other bleeding, eg menorrhagia
- Diet (NB children and elderly)
- Increased requirement - pregnancy
Examination:
- Signs of iron deficiency
- Abdominal and rectal
what are clinical features of iron deficiency?
what are the causes of iron deifiency?
GI blood loss
Menorrhagia (menstrual periods with abnormally heavy or prolonged bleeding)
Malabsorption:
- gastrectomy
- coeliac disease
what is the management of iron deficiency?
Correct the deficiency:
- Oral iron usually sufficient
- IV iron if intolerant of oral
- Blood transfusion rarely indicated
Correct the cause:
- Diet
- Ulcer therapy
- Gynae interventions
- Surgery
in Normochromic normocytic anaemia, if reticulocyte count is increased, what may the cause be?
Acute blood loss
Haemolysis
in Normochromic normocytic anaemia, if reticulocyte count is normal or low, what may the cause be?
Secondary anaemia
Hypoplasia
Marrow infiltration
what is secondary anaemia?
“Anaemia of chronic disease”
70% normochromic normocytic - 30% hypochromic microcytic
Defective iron utilisation - Increased hepcidin in inflammation, Ferritin often elevated
Identifiable underlying disease - infection, inflammation, malignancy
what is haemolytic anaemia?
Accelerated red cell destruction (Decrease Hb)
Compensation by bone marrow (Increased Retics)
Level of Hb – balance between red cell production and destruction
Haemolytic anaemia can be of what two forms?
Haemolysis can be extravascular or intravascular (or bit of both!)
Intravascular haemolysis is always pathological and not normal - Bursting in the blood vessels
what are the causes of haemalytic anaemia?
Congenital: eg.
- Hereditary spherocytosis (HS)
- Enzyme deficiency (G6PD deficiency)
- Haemoglobinopathy (HbSS)
Acquired:
- Auto-immune haemolytic anaemia (Extravascular)
- Mechanical eg.artificial valve (Intravascular)
- Severe infection/DIC (Intravascular)
- PET/HUS/TTP (Intravascular)
aquired causes of haemolytic anaemia can either be immune or non-immune - which of this is mainly extravascular and which is mainly intravascular?
immune = mainly extravascular
non-immune = mainly intravascular
what is the Direct Antiglobulin Test?
Detects antibody or complement on red cell membrane
Reagent contains either anti-human IgG or anti-complement
Reagent binds to Ab (or complement) on red cell surface and causes agglutination in vitro
Implies immune basis for haemolysis
If patient has antibodies against red blood cells (either own or transfused ones) then if they have antibodies on surface of red cells and the lab adds an antibody antibody and causes red cells to clump and it tells you that there is an antibody on the surface of red cells
if the DAGT (direct antiglobulin test) is positive, what does this mean?
Positive = antibodies or complement there
(so if reticulocyte count is increased this can be due to haemolysis, haemolytic anaemia can be congenital and aquired. Aquired haemolytic anaemia can be immune related (extravascular) or it can be non-immune related (intravascular) and to determine if its immune related or not you do the DAGT)
in haemolytic anaemia, what are the different kinds of immune haemolysis?
Warm Auto-antibody – bind to the patients cells at body temperature and causes haemolysis
Some antibodies only bind when the body is cold – these are rarer and often cause less of a problem
Alloantibody – antibodies against transfused cells
explain what is happening here
Spleen removes the antibody and at same time nips part of the RC membrane and this results in the cells sphereing and you can see this on the blood film
Cold antibodies are often IgM
Warm antibodies cause haemolysis at room temperature
what do red blood cells look line in Intravascular haemolysis? e.g. in a valve
Red cell fragments - “schistocytes”
(Schistocytes are fragmented red blood cells that can take on different shapes)
haemolytic anaemia:
how do you work out if the patient is haemolysing?
FBC, reticulocyte count, blood film
Serum bilirubin (direct/indirect), LDH
Serum haptoglobin (will be low if someone is haemolysing)
in haemolytic anaemia how do you work out the mechanism?
History and examination
Blood film
Direct Antiglobulin Test (Coombs’ test – tells you if immune or not)
Urine for haemosiderin/urobilinogen(free haemoglobin in circulation)
what is the management of haemolytic anaemia?
Support marrow function - Folic acid
Correct cause:
- Immunosuppression if autoimmune - Steroids, Treat trigger eg.CLL, Lymphoma
- Remove site of red cell destruction - Splenectomy
- Treat sepsis, leaky prosthetic valve, malignancy etc. if intravascular
Consider transfusion
to test for macrocytic anaemia you do B12/folate assay or Blood film/Bone marrow
what can this reveal?
B12/Folate Deficiency causes what?
Anaemia
Neurological symptoms (subacute combined degeneration of the cord in B12 deficiency)
what are the causes of B12 deficiency?
Pernicious anaemia
Gastric/ileal disease
what are the causes of folate deficiency?
Dietary
Increased requirements (haemolysis)
GI pathology (eg.coeliac disease)
Body has B12 stores that ast for 6 months to a year so often a _______ process
chronic
how is vitamin B12 absorbed?
Dietary B12 binds to intrinsic factor, secreted by gastric parietal cells
B12-IF complex attaches to specific IF receptors in distal ileum
Vitamin B12 bound by transcobalamin II in portal circulation for transport to marrow and other tissues
what is Pernicious Anaemia?
Commonest cause of B12 deficiency in western populations
Autoimmune disease
Antibodies against:
- intrinsic factor (diagnostic)
- gastric parietal cells (less specific)
Malabsorption of dietary B12
Symptoms/signs take 1-2 years to develop (As stores of B12 in the body take a long time to run out)
what is the treatment of megaloblastic anaemia?
Replace vitamin
B12 deficiency - B12 intramuscular injection, Loading dose then 3 monthly maintenance
Folate deficiency - Oral folate replacement, Ensure B12 normal if neuropathic symptoms
(Can precipitate worsening of neuropathic symptoms if you give folate and they have abnormal B12)
what are some other causes of macrocytosis?
Alcohol (common cause)
Drugs - Methotrexate, Antiretrovirals, hydroxycarbamide
Disordered liver function
Hypothyroidism
Myelodysplasia
Summay:
Anaemia -Morphological approach
