Haematology 3 (Anaemia + Polycythaemia) Flashcards
What is anaemia?
Anaemia = reduction in amount of hb in a given volume of blood - below what would be expect of a healthy subject
I.e hb is reduced
- rbc and hct usually also reduced
- usually due to reduction in hb
- but sometimes due to increase in volume of plasma (this type of anemia doesn’t persist in healthy individuals - excreted)
What is the mechanism of anaemia ?
- reduced rbc / hb production in bone marrow
- loss of blood from the body
- reduced survival of rbc in circulation
- pooling of rbc in enlarged spleen
- note: mechanism = e.g reduced synthesis of hb
Cause = e.g condition causing reduced synthesis of haem or globin
What are the classification if anaemia based on cell size?
- Microcytic (HYPOchromic)
- Normocytic (NORMOchromic)
- Macrocytic (NORMOchromic)
What are the common causes of microcytic anaemia ?
Common causes of microcytic anaemia
a) defect in haem synthesis
- iron deficiency
- anaemia of chronic disease
b) defect in globin synthesis (thalassaemia)
- defect in alpha chain synthesis (alpha thalassaemia)
- defect in beta chain synthesis (beta thalassaemia)
What is macrocytic anaemia?
And what is the most common cause of macrocytic anaemia?
Macrocytic anaemia = average cell size is increased
- usually results from abnormal haemopoiesis (rbc precursors continue to synthesise hb + other cellular proteins but fails to divide normally —> so rbc end up being much larger than normal)
Cause:
1. megaloblastic erythropoiesis (delay in maturation of nucleus while cytoplasm continues to mature + the cell continues to grow)
- premature release of cells from the bone –> raises the mean cell volume
What is a feature of a megaloblast?
What is an alternative mechanism of macrocytosis?
Megaloblast :
- larger than normal
- shows nuclei-cytoplasmic dissociation
- nuclear development is not matching cytoplasmic development
Macrocytosis alternative mechanisms:
- premature release of cells from the bone marrow
(Reticulocytes -young rbc are 20% larger than mature rbc so increase in proportion = increase in MCV)
State various causes of macrocytosis
- lack of vit b12 or folic acid
- use of drugs interfering with dna synthesis
- liver disease and ethanol toxicity
- recent major blood loss (reticulocytes increased)
- haemolytic anaemia (reticulocytes increased)
What is the mechanism behind normocytic normochromic anaemia ?
- recent blood loss
- failure of production of rbc
- pooling of rbc in the spleen
What are the causes of normocytic normochromic anaemia ?
- peptic ulcer
- oesophageal varies
- trauma
- failure of production of rbc
(e. g early stages of iron deficiency , renal failure, bone marrow failure, bone marrow infiltration) - hypersplenism e.g portal cirrhosis
What is haemolytic anaemia ?
Haemolytic anaemia = anaemia resulting from shortened survival of rbc in the circulation
How might haemolysis occur?
Haemolysis can result from:
a) intrinsic abnormality of rbc
b) extrinsic factors acting on normal rbc
How is haemolytic anaemia classified?
a) intravascular haemolysis
- occurs if there is very acute damage to the rbc
b) extravscular haemolysis
- occurs when defective rbc are removed by the spleen
(Often haemolysis = partly both intra+extravascular)
When would you suspect haemolytic anaemia?
- unexplained anaemia which is normochromic and usually either normocytic / macrocytic
- evidence of morphologically abnormal rbc
- evidence of increase rbc breakdown
- evidence of increased bone marrow activity
What is hereditary spherocytosis ?
Hereditary spherocytosis:
- haemolytic anaemia or chronic compensates haemolysis due to inherited intrinsic defect of rbc memb
- when they enter circulation, the cells lose memb in the spleen and becomes spherocytic
What are the features of hereditary spherocytosis ?
And what is the consequence of it?
Features:
- cells are larger + rounder
- increased MCHC
- rbc becomes less flexible (they are removed prematurely in the spleen - extravascular haemolysis )
Consequence:
- bone marrow responds to haemolysis by increasing rbc output —> leads to polychromasia + reticulocytosis
- haemolysis leads to increased bilirubin production (jaundice + gallstones)
- spherocytes can move through gaps so you get early removal of these cells in the spleen
What is the only effective treatment for hereditary spherocytosis?
Splenectomy
Good diet / folic acid tablet may also help
- patients with haemolysis = quickly becomes folate deficient
Why is glucose-6-phosphate dehydrogenase deficiency important?
G6PD:
- important enzyme involved in pentose phosphate pathway
- G6PD = only source of reduced glutathione rbc
- essential for protection of rbc from oxidant damage
What happens if a patient has glucose - 6 - phosphate dehydrogenase deficiency?
What happens to the appearance of cells?
- they are at risk if haemolytic anaemia in states of oxidative stress
- causes intermittent, severe intravascular haemolysis following infection or exposure to an exogenous oxidant.
- episodes of intravascular hemolysis
Appearance:
- associated with presence of irregularly contracted cells
- hb is denatured (forms Heinz bodies)
How does acute haemolytic anaemia occur?
Acute haemolytic anaemia occurs due to:
- production of antibodies against red cell antigens
- immunoglobulin bound to rbc memb = recognised by splenic macrophages
- which removes parts of the cell memb —> spherocytosis
What is the consequence / effects of autoimmune haemolytic anaemia?
- Anaemia
- spherocytosis
Effects:
- due to spherocytosis =
- cell rigidity + recognition of antibody and complement on red cell surface by splenic macrophages —> removal of cells from circulation (by spleen)
How would you diagnose autoimmune haemolytic anaemia?
- find spherocytes + increased reticulocyte count
- detect immunoglobulin on rbc surface
- detect antibodies to rbc antigens / or other antibodies in the plasma
How would you treat autoimmune haemolytic anaemia?
- corticosteroids + other immunosuppressive agents
- splenectomy for severe cases
what happens in megaloblastic erythropoiesis?
(delay in maturation of nucleus while cytoplasm continues to mature + the cell continues to grow)
common causes of macrocytic anaemia
- lack of vit b12 / folic acid
- use of drugs interfering with DNA synthesis
- liver disease + ethanol toxicity
- recent major blood loss (increase in reticulocytes)
- hemolytic anaemia
