Anaemia Flashcards
Anaemia associated with decreased production =
Low reticulocyte count
Hypoproliferative anaemia (reduced amount of erythropoiesis)
Maturation defect (erythropoiesis is active but ineffective)
Failure to produce Hb (a cytoplasmic defect)
Failure of cell division (a nuclear defect)
Anaemia associated with increased loss/destruction =
High reticulocyte count
Bleeding
Haemolysis
Mean cell volume is low (microcytic) =
Haemoglobin cause
Mean cell volume is high (macrocytic) =
Problems with cell division i.e. maturation
Causes of microcytic anaemias
TAILS
Thalassaemia
Anaemia of chronic disease
Iron deficiency
Lead poisoning
Sideroblastic anaemias (congenital)
What does circulating iron bind to ?
Transferrin
(transports iron from donor tissues [macrophages, intestinal cells and hepatocytes] to tissues expressing transferrin receptors - especially erythroid marrow)
How to measure iron supply
% saturation of transferrin with iron
- reduced in iron deficiency
- reduced in anaemia of chronic disease
- increased in genetic haemochromatosis
Why is serum ferritin measured ?
Indirect measure of storage iron
Low ferritin = low iron
How iron is stored:
Iron supplement given to children ?
Sodium feredetate (sytron) - liquid prep with lower elemental iron concentration
Low Hb, low RBC, high MCV
What happens as normoblasts (red cell precursors) develop?
- Accumulate Hb
- Reduce in cell and nuclear size as the nucleus matures
- Stop dividing and lose nucleus (Hb content triggers this)
What happens in megaloblastic anaemia?
Larger precursor cells with an immature nucleus
They accumulate Hb - but there is a smaller number of macrocytes - therefore ANAEMIA
Causes of megaloblastic anaemia ?
B12 deficiency
Folate deficiency
Drugs
Rare inherited abnormalities
What causes pernicious anaemia ?
Autoimmune condition with resulting destruction of gastric parietal cells
- results in intrinsic factor deficiency with B12 malabsorption and deficiency
B12/Folate deficiency symptoms
Symptoms/signs of anaemia
weight loss, diarrhoea, infertility
Sore tongue, jaundice
Developmental problems
+ B12 only: Neurological problems
Pernicious anaemia treatment
Vitamin B12 (hydroxycobalamin) injections for life
Causes of non-megaloblastic anaemia
- Alcohol
- Liver disease
- Hypothyroidism
- Marrow failure: Myelodysplasia, Myeloma, Aplastic anaemia
Why are people with pernicious anaemia mildly jaundiced ?
- Red cells die prematurely in the marrow
- Haemoglobin and lactate dehydrogenase (LDH) are released from dead red cells
- Haemoglobin converted to bilirubin
- High reticulocyte count
- Increased unconjugated serum bilirubin
- Increased urinary urobilinogen
- Splenomegaly
Haemolysis
Microcytic anaemia differential diagnosis
TAILS
Thalassaemia
Anaemia of chronic disease
Iron defiency
Lead poisoning
Sideroblastic anaemia
Physiology of EPO
Kidneys detect reduced O2
EPO secreted into blood
EPO stimulates erythropoiesis by bone marrow
Additional circulating erythrocytes improve O2 carrying
Role of hepcidin
Regulates ferroportin (the iron exporter)
Binds to ferroportin - breaks down ferroportin - therefore iron can’t be exported from iron storage
Where is hepcidin synthesised?
Primarily hepatocytes (liver)
Ferritin levels in anaemia of chronic disease ?
Normal or increased
Ferritin levels in iron deficiency ?
Low
Excess alcohol = micro/macrocytosis?
Mild macrocytosis
MCV > 120fl = (usually)
B12 or Folate deficiency
Hypersegmented neutrophils + oval macrocytes on blood film =
Megaloblastic
Dysplastic neutrophils on blood film =
Myelodysplasia
Uniform macrocytosis on blood film =
Alcohol
Malabsorption of iron is primarily in ______
Jejunum
Iron deficiency over 50 y.o. - what investigations must be done ?
GI investigations for malignancy even with negative FOBs (foetal occult blood tests)
Macrocytic anaemia causes =
FAT RBC
Foetus
Alcohol
Thyroid
Reticulocytosis - acute blood loss OR haemolysis
B12 + Folate deficiencies
Cirrhosis/chronic liver disease
Explain why TAILS conditions cause reduced MCV
T = Globin (imbalanced ratio of globin chains, Unbound globin chains precipitate, leading to the destruction of erythroid precursors)
A = depends
I = iron
L = inhibits ferrochelatase (used in haem synthesis)
S = inhibits mitochondrial proteins which regulate protoporphyrin (and therefore haem) synthesis
When is IV iron prescribed?
When rapid iron replacement is needed e.g. 3rd trimester of pregnancy, before surgery
Malabsorption
Reticulocytosis could be due to either…
- Acute blood loss
or - Haemolysis
Blood film for B12/Folate deficiency =
Macroovalocytes + hypersegmented neutrophils in megaloblastic anaemia
Why does reticulocytosis cause increased MCV?
Reticulocytes are immature and therefore larger
So this is a “pseudomacrocytosis” as the RBCs haven’t actually increased MCV
Reticulocytosis appearance on blood film
Polychromasia !!
What do the red arrows indicate?
Spherocytes
- indicate haemolysis
- indicated by raised MCHC (mean corpuscular haemoglobin concentration)
Spherocytes are…
Red blood cells with no central pallor due to membrane damage
seen in haemolysis
LFT which shows liver synthesis levels ?
Albumin
LFT which shows haemoglobin breakdown (haemolysis)
Bilirubins
What does raised lactate dehydrogenase indicate?
Non-specific cell damage/necrosis
What does reduced haptoglobulin indicate?
Haemolytic anaemia
(protein which binds to free haemoglobin released from lysed red cells)
When to suspect haemolytic anaemia?
Reticulocytosis (high ret count, anaemia with polychromasia) = either haemolysis or acute blood loss
Chronic blood loss = microcytosis, iron deficiency, no reticulocytosis
Spherocytes - cells with no central pallor due to membrane damage in haemolysis
Other name for DAT (Direct Antibody Test)
Coombs test
Management of autoimmune haemolysis =
Steroids + folic acid
