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Microcytic
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Type
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Aeitology
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Clinical features
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Investigations
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Management
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Blood loss: GI bleeding (peptic ulcer, diverticulitis), Menorrhagia, hookworm (developing countries)
Poor Diet
Malabsorption
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– Brittle hair + nails
– Atrophic glossitis
– Angular stomatitis
– Koilonychia
– (Rare: post- cricoid webs)
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– Hb ↓, ↓MCV
– RBC microcytic, hypocgromic, anisocytosis, poikilocytosis.
-Serum ferritin ↓
-Serum Iron ↓
– TIBC ↑
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– Treat underlying cause.
– Oral iron – ferrous sulphate (SE = constipation)
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Diseases: infection, colloagen vascular disease, rheumatoid arthritis, malignancy, renal failure, chronic inflammatory disease (crohns), TB, endocarditis.
↓ release of iron from bone marrow to developing erythroblasts, inadequate erythropoietin response to the anaemia, ↓RBC survival.
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Normochromic, normocytic or microcytic anaemia
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– ↓serum iron levels
– ↓ serum iron binding capacity
– ↑or normal serum ferritin.
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– Treat underlying cause
– If due to renal failure then anaemia partly due to erythropoeitin deficiency – thus recombinant erythropoietin is useful.
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Sideroblastic
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– Inherited
or
– Acquired
· 2* to myelodysplasia,
· alcohol,
· lead or isoniazid poisoning,
· idiopathic,
· malignancy,
· anti- TB drugs,
· – malabsorption
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There is iron available but the body is unable to synthesize it into the RBCs’
· Dyserythropoiesis (defective developement of eyrocytes)
· iron loading bone marrow
· haemosiderosis (storage of iron compound – haemosiderin in various places e.g. endocrine, liver, cardiac damage)
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Disorder of haem synthesis:
· refractory anaemia
· hypochromic cells in the peripheral blood
· ring sideroblasts in bone marrow. (erythrocytes with granules of iron in their cytoplasm)
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– Withdraw causative agents
– some response to pyridoxine (Vit B6)
– Maybe transfusion dependent and iron overload is a problem.
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See haemolytic anaemias
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Macrocytic – Macrocytosis – presence of abnormally large red blood cells in the blood
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Type
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Aetiology
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Clinical Features
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Investigations
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Management
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Megaloblastic
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The presence in the bone 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)
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– Usually asymptomatic as 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.
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Blood film:
– 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 to hypothyroidism)
Increased erythropoiesis
– e.g. haemolysis
Abnormal erythropoiesis
– sideroblastic anaemia,
leukaemia, aplasia.
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Vit B12 Deficiency
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Diet: If no animal products are consumed (vegan)
Impared absorption:
– Pernicious anaemia,
– Gastrectomy (no IF from terminal ileum),
– illeal disease/resection, coeliac disease.
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Peripheral neuropathy – dorsal column degen.
(Rarely – dementia) |
– Treat cause NB confirm whether B12 or folate deficient as folate will correct Hb in B12 deficiency but will not treat neuropathy |
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Pernicious anaemia
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Autoimmune condition where 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 blue eyes.
– Associated with other autoimmune conditions:
e.g. Thyroid,
Vitiligo
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General:
– Glossitis
– Angular stomatitis
– Mild jaundice
– weakness + tiredness
– Dysponea
– Mild Splenomegaly
– Fever
Neurological – fits with very low levels of B12 and in
Polyneuropathy – weakness, ataxia, paraplegia
Optic atrophy – dementia, visual disturbances.
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Macrocytic anaemia
– MCV > 110 with hypersegmented neutrophil nuclei
– in severe cases leucopoenia and thrombocytopenia.
– Hb ↓
– WCC + Platelets ↓
– 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.
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– IM Hydroxocobalamin
– x2 weekly for 3 weeks to replenish body stores, 3 monthly for life.
– watch for hypokalaemia when tx begins – oral K+ may be required
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Folate Deficiency
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Poor Intake
– old age
– poverty
– alcohol excess
– anorexia
Sources = green veg, beans, whole grains, some breakfast cereals Malabsorption
– coeliac disease
– tropical sprue
Excess utilization
– pregnancy, lacatation, prematurity
– chronic haemolytic anaemia, malignant and inflammatory diseases,
– dialysis
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Anaemia symptoms
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– Red cell folate ↓
– Serum folate ↓
– jejunal biopsy to look for small bowel disease.
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– Tx of underlying conditon.
– Oral folic acid 5mg daily for 4 months, higher doses if due to malabsorption.
– Prophylactic folic acid is given to pts with chronic haemolysis and pregnant women.
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Normocytic
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Type
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Aeitology
|
Clinical features
|
Investigations
|
Management
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Aplastic anaemia
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Pancytopenia
– deficiency of all cell elements of the blood,
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
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Resulting from deficiency of RBCs, WBCs, Platelets.
– Anaemia
– ↑ likelyhood of infection
– Bleeding
– Bruising
– Bleeding gums
– Mouth infections are common
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FBC – pancytopenia with low/ abscent reticulocytes.
Bone marrow exam –hypocellular marrow with ↑fat spaces.
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Tx Cause:
– Supportive care
– Transfusions of RBC, platelets
– Antibiotic tx.
Poor prognosis:
– peripheral blood neurtophil count < 0.5 x10⁹/L
– peripheral blood platelet count < 20×10⁹/L
– reticulocyte count of <40×10⁹/L
If no recovery:
– Bone marrow transplantation
– Immunosuppressive tx with antilymphocyte gobulin and ciclosporin (where BMT is not possible due to ↑GVHD risk)
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Haemolytic anaemias overview
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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:
– Hereditary spherocytosis
– Hereditary elliptocytosis
Haemoglobin abnormlaities:
– Thalassaemia
– Sickle cell disease
RBC metabolic defects:
– Glucose-6-phosphate dehydrogenase defieciency
-Pyruvate kinase defeicency
Immune:
– Autoimmune haemolytic anaemia
– Haemolytic transfusion reactions
-Drug induced
Non-Immune:
– Paroxysmal noctural haemoglobinuria
– Microangiopathic haemolytic anaemia
– March haemoglobinuria
Other:
– Infections (e.g. malaria)
– Drugs/chemicals
– Hypersplenism
– Trauma
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Jaundice
Hepatospenomegaly
Hx:
– family history
– race
-drugs
-previous anaemia
Is there significant haemolysis:-
Is there increased cell breakdown:-
– bilirubin↑ (unconjugated),
– urinary urobilinogen ↑,
– haptoglobin↓.
Is there increased red cell production:-
e.g. reticulocytosis,
-polychromasia,
-macrocytosis,
-marrow hyperplasia.
Is the haemolysis mainly intra/extra vascular:-
E: → splenic hypertrophy
I: methaemalbuminaemia,
– free plasma haemoglobin,
– haemoglobinuria,
– ↓haptoglobin,
– haemosiderinuria.
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-FBC,
-Reticulocytes,
-Bilirubin,
-LDH,
-Haptoglobin,
-Urinary urobilinogen.
Blood films:polychromasia, macrocytosis, spherocytes, elliptocytes, fragmented cells or sickle cells.
Direct Coombs’ test: identifies RBCs coated with antibody/complement and a positive result ususally indicates an immune cause.
Chromium labelling: for RBC lifespan and the major site of breakdown
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Thalassaemia
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Multiple gene defects → ↓ rate of production of one or more globin chains.
The imbalance of globin chain production leads precipitation of globin chains within red cells or precursors. This → cell damage, death of RBC precursors in the bone marrow and haemolysis.
– α thalassaemia: reduced α chain synthesis
– β thalassaemia: reduced β chain synthesis
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– Symptoms may be mild–severe, depending on how many α/β chain genes have been deleted
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– FBC
– MCV
– Film
– Iron
– HbA2
– HbF
– Hb
– Electrophoresis
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– Transfusion keep Hb >9g/dL
– Iron chelators e.g. desferrioxamine. To protect against cardiac disease & DM.
– ↑ doses of ascorbic acid (vitamin C) also ↑iron output
– Splenectomy , if hypersplenism px.
– Folate supplements
– BMT
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Sickle cell anaemia
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Inheritance of the β-globin 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).
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HbAS – there are usually no symptoms unless the patient is exposed to extreme hypoxia
HbAC – a milder course of HbSS but there is a ↑likelyhood of thromboses occuring.
HbSS – symptoms due to haemolysis and vaso-occlusion. As the sickled cells are fragile and haemolyse and block small vessels.
…continued in large box below….
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– ↓ Hb
– ↑ Reticulocyte count
– Bilirubin may be raised
– Blood film shows sickled erythrocytes
Dx:
Viz electrophoresis showing 80-90% HbSS and absent Hb A.
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– 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
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Haemolysis:
– mild anaemia (usually no symptoms due to hyperdynamic circulation and a lower O2 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
– 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
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