- Anaemia with MCV < 80
- Causes
- "microcytic cells are STIC thin"
- Sideroblastic anaemia
- Thalassaemias
- Iron deficiency anaemia
- Chronic disease
- Erythroblast
- large
- Divides until becomes small RBCs
- So microcytic anaemia due to an "extra division"
- Problem is decreased Hb production
- So making this "extra division" means you increase the Hb concentration by decreasing the volume
- Hb
- = Haem + Globin
- = (Fe+ protoporphyrin) + (globin)
- So
- Too low Fe leads to too little haem, Hb and thus small cells
- e.g. sucked into macrophages in anaemia of chronic disease
- e.g. not enough in diet or chronic loss
- Too low protoporhyrin
- Too low globin protein
Iron deficiency anaemia
- Most common anaemia
- Dev world - Fe most common deficiency
- From diet
- Haem in meat
- Non haem in veg
- Absorbed in duodenum, jejunum
- "Iron (II) absorbed in two places "
- Only absorbed in Fe2+ form (Iron(II) gets into the body)
- Enterocyte exports into blood out of ferroportin channel
- Transferrin binds in blood, delivers to liver + bone marrow macrophages for storage
- RBCs have sTfRs = soluble transferrin receptors - "iron stuffers"
- Store bound to ferritin intracellularly
- Binding prevents fento reaction ROS
- Ix
- Serum Fe
- TIBC - Total Iron Binding Capacity
- Transferrin % Saturation
- 20-50% normal adults, >16% normal kids
- Serum Ferritin
- Causes
- Dietary
- Infants - breast feeding
- Children - poor diet, drinking cows milk as major component of diet, not enough for growth
- Adults
- peptic ulcer disease - most common cause in middle aged men
- menorrhagia
- pregnancy
- Elderly
- Colon polyps
- Colon carcinoma
- Hookworm in developing world
- Ancylostoma duodenale - ME, NAfrica, India
- Necator americanus - Americas, SubSahara, SEAsia
- Malnutrition
- Malabsorption
- Coeliac - destroys duodenal vili
- Gastrectomy
- Cut out part stomach so less acid
- So can't reduce Fe3+ to Fe2+/prevent oxn of Fe2+ to allow efficient absorption
- Blood loss - colon Ca etc
- Stages
- ONE Deplete existing stores
- so serum ferritin dec
- & inc TIBC as less iron around and liver inc TIBC as recognises that need to try and grab as much iron as possible
- (ie if ferritin goes down, TIBC goes up)
- TWO Deplete what Fe is in serum
- dec serum iron
- Transferrin % Sat dec
- THREE Normocytic anaemia - less iron so make less cells
- FOUR Microcytic, hypochromic anaemia - far too little Fe so make less cells and the cells that are made have less Hb
- PresentsIx
- Anaemia
- Koilonychia
- Pica
- eat dirt etc
- psych drive to get Fe2+ from any "source" possible

- Microcytic
- Hypochromic
- Inc RDW - red cell distribution width - basically make RBC syn shit so lots of diff shapes
- Dec serum ferritinInc TIBC - more made by liver to grab what can
- Best measure
- Less than 15 microgram /L suggestive of deficiency
- But acts as acute phase reactant so well increase if there's coinciding inflammation! Eg infection - body sequesters as much iron as possible so not available for bacteria
- So check CRP, ESR when interpreting
- If ferritin not low but sTfR is, likely deficiency and inflammation - eg infection
- Dec serum iron
- Dec transferrin saturation
- Inc serum sTfRs - RBCs grab what can
- Not routine
- May end up using other tests plus inflammatory markers and a trial of iron supplements
- Inc FEP
- Free Erythrocyte Protoporhyrin
- Because less haem to bind to protoporhyrin to make Hb
- Bone marrow biopsy
- Little or no iron on marrow when deficient
Rx
- Underlying cause
- Ferrous sulfate
Plummer-Vinson Syndrome
- Iron deficiency anaemia with oesophageal web
- Atrophic glossitisAnaemia
- Dysphagia
Anaemia of chronic disease
- NB may be found at normocytic stage - ie has same stages as iron deficiency
- as slow and chronic, may take long time to reach the microcytic stage
- AssocMost common type in hospitalised pts
- Chronic inflammation
- Cancer
- RhA
- etc
- Cause - inc acute phase reactants
- Causes a microcytic anaemia as dec Fe available for RBC synth
- Hepcidin - sequesters storage into storage sites
- Meant to prevent bugs getting Fe
- Stops macrophage to erythroid precursor Fe transfer
- Suppresses EPO synth
- Ix
- Inc ferritin
- Because hepcidin (an acute phase reactant) has made Fe go into cell storage
- So behaves as if an acute phase reactant so will be Inc due to the inflammatory state
Dec TIBC
- Because liver cells stuffed with iron so thinks plenty around, so makes less TIBC as don't feel the need to grab what's there
- Dec serum iron
- Dec transferrin saturation
- Inc FEP - as less haem made
- Rx
- Underlying cause
- Exogenous EPO in a few pts esp Ca pts
Sideroblastic anaemia
- Due to defective protoporhyrin synth
- So make less Hb
- So microcytic
- How protoporhyrin is made:
- 8 rxns!
- Some in cytoplasm, some in mitochondria in erythroblasts
- First step
- SuccinylCoA converted into AminoLevulinic Acid (via ALASynthase)
- ALAS is RDS in protoporhyrin production
- use Vit B6 as cofactor
- ALA converted to Porphobilinogen by ALADehydrogenase
- then bunch of other rxns
- Final rxn attaches protoporhyrin IX to Fe to make haem
- by ferrochelatase
- in mitochondria
- Problem:
- Not making enough protoporhyrin, so less haem
- And iron transfer from cytoplasm into microchondria
- Gets trapped
- Builds up in mitochondria
- As these are around nucleus, get a "ring" of mitochondria filled with Fe around nucleus
- So characteristic erythroblast cell = ring sideroblast on bone marrow biopsy
- Prussian Blue Stain - makes iron blue

- Types
- Congenital
- Most common: defect in ALAS - rds
- Acquired
- EtOH+++
- Pb poisnoning
- Denatures enzymes inc ALAD and ferrochelatase
- Vit B6 deficiency
- Certain haematological malignancies with mitochondrial iron homoeostasis problems - somatic mut in SF3B1
- Ix
- "iron overloaded state"
- Death of overloaded sideroblastic erythroblasts (fenton rxns etc cause death)
- Some Fe taken up by macrophages - store xs
- Some spills into blood, so see in serum
- So watch out - very same iron lab findings in haemochromatosis!
- Inc ferritin
- Dec TIBC
- Inc serum iron
- Inc transferrin saturation
- Pappenheimer bodies (also in haemolytic anaemia and post splenectomy)
Thalassaemia
- Dec synthesis of α or β globin chains
- So dec Hb
- So microcytic
- (NB synth is the problem; cf in sickle cell where you can make them but they are shit)
- Mostly inherited mutations
- Carriers protected against Plasmodium falciparum
- NB normal Hb
- HbF = α2γ2
- HbA = α2β2
- HbA2 = α2ẟ2
- So α in all Hb, β only in HbA
- Types - dec prod of α or β chains
- α-thalassaemia
- Most due to gene deletion
- 4 alleles of gene
- 1 allele deleted = aSx
- 2 " " = mild anaemia, slight inc RBC count - may be aSx clinically
- either both on same Chr = cis deletion - worse!
- assoc with inc risk of severe offspring thalassaemia
- as pass on 2 deleted muts if pass this Chr on to child
- More common in Asians - may be cause of higher rate of spontaneous abortion in Asia
- or on oppposite Chr = trans deletion
- 3 " " = Severe anaemia
- after birth, β chains form tetramers (instead of dimers) = HbH
- HbH mostly seen in SEAsia, Middle East, Med
- these damage the cell membrane
- also too high O2 affinity
- HbH seen on electophoresis
- Target cells with Heinz bodies (precipitated HbH)

- microcytic hypochromic anaemia
- Hepatosplenomegaly
- May also get Hb Barts (see below)
- hydrops foetalis
- γ chains form tetramers = Hb Barts - damage RBCs
- precipitates in RBC
- has excessive O2 affinity - none delivered to tissues
- See Hb Barts on electrophoresis
- β-thalassaemia
- 2 β genes on each copy of Chr 11
- Mutation lead to (cf α which were deletions)
- zero β production = β° ("null") - note may be a deletion or mut
- dec = β+
- most muts in promoter preceding the gene
- get poikilocytosis - abnormal RBCs > 10% of film
- get a "bleb" in centre where pallor normally is
- so get some Hb building up in the middle
- so get an additional red bit in middle
- happens due to
- decreased cytoplasm or
- inc membrane surface area
- makes cell "flabby"
- anisocytosis
- elliptocytosis
- Hypochromic anemia
- schistocyte
- wide spectrum of disease
- Minor
- Mildest
- β/β+
- Some target cells
- Mostly aSx
- Inc RBC count
- Microcytic hypochromic
- Hb electrophoresis
- Slight dec HbA
- Inc HbA2 - 5% instead of 2.5%
- Inc HbF - 2% instead of 1%
- Major = Cooley's anaemia
- β°/β°
- Most severe
- Mediteraneans
- Presents as severe anaemis in a few motnhs after birth
- Survive antenatally as HbF = α2γ2
- α chains make tetramers
- precipitate, damage RBC
- Get ineffective erythropoiesis - precipitates and damages as making cell
- Spleen recognises that cell is fekked so extravascular haemolysis
- So severe anaemia
- get massive erythroid hyperplasia
- Expansion of haematopoesis into marrow of skull, facial bones
- (see these two signs in sickle cell too)
- "crew cut appearance" on X ray

- Extramedullary haematopoiesis with hepatosplenomegally
- Risk aplastic crisis if infected with Parvovirus B19
- infects erythroid precursors and shuts it down
- normal people - not really an issue as have major reserve
- usually self limiting to a week or so
- in these pts, no reserve so fekked
- Chronic transfusions needed
- But secondary haemochromatosis risk
- Blood smear
- microcytic hypochromic anaemia
- target cells
- nucleated red blood cells - due to extramedullary haematopoiesis
- they "escape" spleen/liver before fully denucleated
- "as not made in the proper location so bit crap"
- Electophoresis
- Little or no HbA
- Inc HbA2, HbF
- Basophilic stippling
- Rx
- Minor
- not really needed
- Poss transfusions if problems in pregnancy
- Inc risk of gallstones - may need cholecystecomy
- Major
- Transfusions - haemochromatosis risk, transfusion reaction risk!Splenectomy - reduces transfusions neded as inc t1/2 of RBCs
- Iron chelation to dec haemochromatosis risk
- BM Transplant
- Induce increased HbF