Microcytic

Type Aeitology Clinical features Investigations Management

Iron Blood loss: GI bleeding (peptic - Brittle hair + nails - Hb , MCV - Treat underlying cause.
Deficiency ulcer,diverticulitis, Bowel Ca), - Atrophic glossitis - RBC microcytic, hypocgromic, - If over 60 requires 2WW referral for
Menorrhagia, hookworm - Angular stomatitis anisocytosis, poikilocytosis. suspected lower GI Ca
(developing countries) - Koilonychia -Serum ferritin
Poor Diet - (Rare: post- cricoid webs) -Serum Iron - Oral iron ferrous sulphate (SE
Malabsorption - TIBC =constipation)

Anaemia of Diseases: infection,
chronic colloagen vascular
disease disease, rheumatoid
arthritis, malignancy, renal
failure, chronic inflammatory
disease (crohns), TB,
endocarditis.
Normochromic, normocytic or
microcyticanaemia
- serum iron levels
- serum iron binding capacity
- or normal serum ferritin.
- Treat underlying cause
- If due to renal failure
thenanaemia partly due to
erythropoeitin deficiency thus
recombinant erythropoietin is useful.

release of iron from bone

marrow to developing
erythroblasts, inadequate
erythropoietin response to
the anaemia, RBC survival.
Sideroblastic - Inherited There is iron available but Disorder of haem synthesis: - Withdraw causative agents
or the body is unable to refractoryanaemia - some response to pyridoxine (Vit
- Acquired synthesize it into the RBCs hypochromic cells in the peripheral B6)
2* to myelodysplasia, blood - Maybe transfusion dependent and
alcohol, Dyserythropoiesis (defective ring sideroblasts in bone marrow. iron overload is a problem.
lead or isoniazid poisoning, developement of eyrocytes) (erythrocytes with granules of iron in
idiopathic, iron loading bone marrow their cytoplasm)
malignancy, haemosiderosis (storage of
anti- TB drugs, iron compound - haemosiderin in
- malabsorption various places e.g.
endocrine, liver, cardiac
damage)
Thalassemia See haemolytic anaemias

Macrocytic - Macrocytosis - presence of abnormally large red blood cells in the blood
Type Aetiology Clinical Features Investigations Management
Megaloblastic The presence in the bone - Usually asymptomatic as Blood film:
 marrow of developing RBCs with
delayed nuclear maturation
relative to that of the cytoplasm.
- defective DNA synthesis,
- WC (leukopenia)- may be
hyper-segmented,
- platelets
(thrombocytopenia)
Causes:
- B12/ Folate deficiency
- Drugs (hydroxycarbamide/
hydroxyurea)
Vit B12 Diet: If no animal products are
Deficiency consumed (vegan)
Impared absorption:
- Pernicious anaemia,
- Gastrectomy (no IF from
terminal ileum),
- illeal disease/resection, coeliac
disease.
Pernicious an Autoimmune condition where
aemia there is atrophy of the gastric
mucosa, with failure of Intrinsic
Factor (and acid production)
B12 absorption.
- usually older people,
- common in women, fair hair
the fall in the levels of Hb in
response to the falling levels of
B12/ folate occur over a long
period of time therefore allowing
the body to adjust.
Peripheral neuropathy - dorsal
column degen.
(Rarely - dementia)
General:
- Glossitis
- Angular stomatitis
- Mild jaundice
- weakness + tiredness
- Dysponea
- Diarrhoea
- Premature grey hair
- hypersegmented polymorphs (B12 ),
target cells (liver disease).
- ESR
- Malignancy
- LFTs
- T4
- Serum B12 and serum folate/ red cell
folate.
Bone marrow biopsy if above
unsignificant:-
Megaloblastic
B12/folate deficiency, cytoxic drugs
Normoblastic marrow
liver damage, myoxedema (coarsening
of skin due tohypothyroidism)
Increased erythropoiesis
e.g. haemolysis
Abnormal erythropoiesis
sideroblastic anaemia,
leukaemia, aplasia.
- Treat cause
- IM B12 injections
NB confirm whether B12 or folate
deficient as folate will correct Hb in
B12 deficiency but will not treat
neuropathy
Macrocytic anaemia - IM Hydroxocobalamin
- MCV > 110 with hypersegmented
neutrophil nuclei - x2 weekly for 3 weeks to replenish
- in severe cases leucopoenia and body stores, 3 monthly for life.
thrombocytopenia.
- watch forhypokalaemiawhen tx
- Hb begins oral K+ may be required
- WCC + Platelets
 blue eyes. - MildSplenomegaly
- Fever
- Associated with other
autoimmune conditions: Neurological - fits with very
e.g. Thyroid, low levels of B12 and in
Vitiligo
Addisons. Polyneuropathy weakness,
ataxia, paraplegia
Optic atrophy dementia,
visual disturbances.
- Serum B12 < 50ng
- Red cell folate
- Serum autoantibodies. Parietal cell
antibodies 90% , IF antibodies 50%.
- Serum Bilirubin (
breakdown of haemoglobin, due to
ineffective erythropoiesis in the Bone
marrow)
- Schilling test
(to differenciate PA from small bowel
malabsorption)

- Bone marrow exam

-Hypercellular BM with megaloblastic
changes.
Folate Poor Intake Anaemiasymptoms - Red cell folate - Tx of underlying conditon.
Deficiency - old age - Serum folate
- poverty - jejunal biopsy to look for small bowel - Oral folic acid 5mg daily for 4
- alcohol excess disease. months, higher doses if due to
- anorexia malabsorption.
Sources = green veg, beans,
whole grains, some breakfast - Prophylactic folic acid is given to
cereals pts with chronic haemolysis
Malabsorption andpregnant women.
- coeliac disease
- tropical sprue
Excess utilization
- pregnancy, lacatation,
prematurity
- chronic haemolytic anaemia,
malignant and inflammatory
diseases,
- dialysis
Normocytic
Type Aeitology Clinical features Investigations Management
Aplastic anae Pancytopenia Resulting from deficiency of FBC pancytopenia with low/ abscent Tx Cause:
mia deficiency of all cell elements RBCs, WBCs, Platelets. reticulocytes. - Supportive care
of the blood, - Transfusions of RBC, platelets
 Aplasia
hypocellularity of the bone
marrow
- Congenital
- Idiopathic acquired (50%)
Chemicals e.g benzenes
Drugs e.g. cytotoxics,
chemotherapy, chloramphenicol,
gold, insecticides, ionising
radiation
- Infections e.g.
viral hepatitis,HIV
Haemolytic There is increased
destruction of red cells and a
reduction of circulating
lifespan to which the bone
marrow is unable to
compensate for the
increased loss.
This may be:
extravascular (within
reticuloendothelial system) they
are removed from the circulation
as they are defective
or
intravascular (within blood
vessels)e.g. due to trauma,
complement fixation or other
extrinisic factors.
Causes:
RBC membrane defect:
- Anaemia Bone marrow exam - - Antibiotic tx.
- likelyhood of infection hypocellular marrow with fat spaces.
- Bleeding Poor prognosis:
- Bruising - peripheral blood neurtophil count
- Bleeding gums < 0.5 x10/L
- Epistaxis - peripheral blood platelet count <
- Mouth infections are common 20x10/L
- reticulocyte count of <40x10/L
If no recovery:
- Bone marrow transplantation
-Immunosuppressive
tx withantilymphocyte gobulin
and ciclosporin (where BMT is not
possible due to GVHD risk)
Jaundice -FBC,
Hepatospenomegaly -Reticulocytes,
-Bilirubin,
Hx: -LDH,
- family history -Haptoglobin,
- race -Urinary urobilinogen.
-haematuria
-drugs Blood films:polychromasia,
-previous anaemia macrocytosis, spherocytes, elliptocytes,
fragmented cells or sickle cells.
Is there significant
haemolysis:- Direct Coombs test:identifies RBCs
coated with antibody/complement and a
Is there increased cell positive result ususally indicates an
breakdown:- immune cause.
- bilirubin (unconjugated),
- urinary urobilinogen , Chromium labelling: for RBC lifespan
- haptoglobin. and the major site of breakdown
Is there increased red cell
production:-
e.g. reticulocytosis,
-polychromasia,
-macrocytosis,
-marrow hyperplasia.
 - Hereditary spherocytosis Is the haemolysis mainly
- Hereditary elliptocytosis intra/extra vascular:-
Haemoglobin abnormlaities: E: splenic hypertrophy
- Thalassaemia
- Sickle cell disease I: methaemalbuminaemia,
RBC metabolic defects: - free plasma haemoglobin,
- Glucose-6-phosphate - haemoglobinuria,
dehydrogenase defieciency - haptoglobin,
-Pyruvate kinase defeicency - haemosiderinuria.
Immune:
- Autoimmune
haemolytic anaemia
- Haemolytic transfusion
reactions
-Drug induced
Non-Immune:
- Paroxysmal noctural
haemoglobinuria
- Microangiopathic
haemolyticanaemia
- March haemoglobinuria
Other:
- Infections (e.g. malaria)
- Drugs/chemicals
- Hypersplenism
- Trauma
Thalassaemia Multiple gene defects - Symptoms may be mild - FBC - Transfusion keep Hb >9g/dL
rate of production of one or severe, depending on how - MCV
more globin chains. many / chain genes have - Film - Iron chelators e.g.
The imbalance of globin chain been deleted - Iron desferrioxamine. To protect against
production leads precipitation of - HbA2 cardiac disease & DM.
globin chains within red cells or - HbF
precursors. This cell damage, - Hb - doses of ascorbic acid also
death of RBC precursors in the - Electrophoresis iron output
bone marrow and haemolysis.
- Splenectomy , if hypersplenism
- thalassaemia: reduced px.
chain synthesis
- thalassaemia: reduced - Folate supplements
chain synthesis

Sickle Inheritance of the -globin
cell anaemia gene.
May have:
sickle cell anaemia HbSS
sickle cell trait HbAS
HbSC one S haemoglobin and
one C haemoglobin group, (the C
group causes the red blood cells
to develop).
HbAS - there are usually no
symptoms unless the patient is
exposed to extreme hypoxia
HbAC a milder course of
HbSSbut there is alikelyhood
of thrombosesoccuring.
HbSS symptoms due to
haemolysis and vaso-
occlusion. As the sickled cells
are fragile and haemolyse and
block small vessels.
- Hb
- Reticulocyte count
- Bilirubin may be raised
- Blood film shows sickled
erythrocytes
Dx:
Viz electrophoresis showing 80-90%
HbSS and absent Hb A.
- BMT
- Folic acid in patients with severe
haemolysis
- pneumococal vaccine
to infection risk, daily oral
penecillin
- Exchange transfusions to
frequency of crises
- Hydroxycarbamide(hydroxyurea)
raises the conc of fetal Hb
- possible BMT

continued in large box

below.
Haemolysis:
- mild anaemia (usually no symptoms due to hyperdynamic circulation and a lower O 2 affinity of HbS than normal Hb).
- jaundice
- painful swelling of hands and feet
- recurrent sickle cell crises
- recurrent haemolysis formation of pigment gallstones

Vaso-occlusion:
A vascular necrosis of BM results in the bone marrow pain crisis, may be precipiated by hypoxia, dehydration or infection
- usually affects ribs, spine, pelvis in adults
- hands and feet (dactylitis) in children
- may require addmission to hospital for analgesia

Other complications:-
- Splenic atrophy
resulting in infection risk with Pneumococcus, Salmonella species and Haemophilus
- Cerebral infection
causing fits and hamiplegia
- Retinal ischaemia,
may precipitate proliferative sickle retinopathy and visual loss.
Other:-
- renal papaillary necrosis
- chronic renal failure
- leg ulcers
- acute chest syndrome (commonest cause of death in adults with sickle cell )
- fever
- cough
- dysponea
- pulmonary infarcts on the CXR
Caused by infection, fat emboli from necrotic bone marrow or pulmonary infarction due to sequestration of sickle cells