Anaemia Flashcards
Anaemia definition in men
Hb <135g/L (13.5g/dL)
Anaemia definition in women
Hb <115g/L (11.5g/dL)
3 causes of anaemia
Reduced production of RBCs
Increased loss of RBCs (haemolytic anaemias)
Increased plasma volume (pregnancy)
Microcytic anaemias
IDA
Anaemia of chronic disease
Sideroblastic anaemia
Thalassaemia
Normocytic anaemias
Acute blood loss Anaemia of chronic disease Bone marrow failure Renal failure Hypothyroidism Haemolysis Pregnancy
Macrocytic anaemias
Fetus (pregnancy) Antifolates (e.g. phenytoin) Hypothyroidism Reticulocytosis (release of larger immature cells e.g. haemolysis) B12/folate deficiency Cirrhosis (EtOH excess/liver disease) Myelodysplastic syndromes
Symptoms of anaemia
Tiredness, shortness of breath, palpitations, headache, tinnitus, anorexia
Signs of anaemia
Pallor, in severe hyperdynamic circulation (tachycardia + flow murmurs (ejection-systolic loudest over apex), heart failure)
Koilonychia Brittle hair and nails Atrophic glossitis Angular cheilosis Post-cricoid webs (Plummer-Vinson syndrome) =?
IDA
IDA blood film
Microcytic, hypochromic
Anisocytosis (varying size)
Poikilocytosis (varying shape)
Pencil cells
Clinically considered cause of IDA
Bleeding until proven otherwise, menorrhagia in young women
5 classifications of IDA
Blood loss Increased utilisation Decreased intake Decreased absorption Intravascular haemolysis
Blood loss-related causes of IDA
Gastrointestinal loss of blood
- peptic ulcers/gastritis
- polypa/colorectal cancer (>50)
- menorrhagia (W <50)
- Meckel’s diverticulum (children)
- hookworm infestation (developing countries)
Increased utilisation-related causes of IDA
Pregnancy/lactation
Growth - infants/children
Decreased intake-related causes of IDA
Prematurity - loss of iron each day foetus isn’t in utero
Infants/children/elderly - suboptimal diet
Decreased absorption-related causes of IDA
Coeliac disease - absence of villi in duodenum
Post-gastric surgery - rapid transit so less acid to aid iron absorption
Intravascular haemolysis-related causes of IDA
Microangiopathic Haemolytic anaemia
PNH (paroxysmal nocturnal haemoglobinuria)
Investigations for IDA
Identify cause
If no obvious cause then OGD + colonoscopy, urine dip, coeliac Ix
IDA treatment
Treat the cause
Oral iron (ferrous sulphate)
IV iron if severe + symptomatic
If septic then blood transfusion instead of iron (fuels infection)
Anaemia of chronic disease causes
Chronic infection (e.g. TB, osteomyelitis)
Vasculitis
Rheumatoid arthritis
Malignancy etc (long-standing illness)
Mechanism of cause for anaemia of chronic disease
Cytokine-driven inhibition of RBC production
1 - Inflammatory markers reduce EPO receptor production (and thus EPO synthesis) by kidneys
2 - Iron metabolism dysregulated, IL6/LPS stimulate production of hepcidin by liver decreasing iron absorption by inhibiting transferrin and causing iron accumulation in macrophages
OR renal failure (EPO deficiency)
Ferritin (intracellular protein indicating iron store) status in ACD
Raised due to iron storage in macrophages
Aetiology of sideroblastic anaemia
Ineffective erythropoiesis - iron loading (accumulation of iron in body) causing haemosiderosis (endocrine, liver, cardiac damage due to iron deposition)
Diagnostic feature for sideroblastic anaemia
Ring sideroblasts seen in marrow
Ring sideroblast description
Erythroid precursors with iron deposited in mitochondria in a ring around nucleus
Sideroblastic anaemia causes
Myelodysplastic disorders Post-chemo Irradiation !!Alcohol excess Lead excess Anti-TB drugs Myeloproliferative disease
Sideroblastic anaemia treatment + drug
Remove cause
Pyroxidine (vit B6 to promote RBC production)
Plasma iron study categories (3)
Serum iron
TIBC (total iron binding capacity)
Ferritin
Iron study results - Dx?
Serum iron - lowered
TIBC - raised
Ferritin - lowered
IDA
Plasma iron study results - Dx?
Serum iron - lowered
TIBC - lowered
Ferritin - raised
Anaemia of chronic disease
Iron study results - Dx?
Serum iron - raised
TIBC - lowered
Ferritin - raised
Chronic haemolytic anaemia
Iron study results - Dx?
Serum iron - raised
TIBC - lowered or normal
Ferritin - raised
Haemochromatosis
Iron study results - Dx?
Serum iron - raised
TIBC - raised
Ferritin - normal
Pregnancy
Sideroblastic anaemia iron study results
Serum iron - raised
TIBC - normal
Ferritin - raised
Transferrin saturation calculation + iron deficiency threshold
serum iron/TIBC
<20% = Fe deficiency
Adjustment to iron study necessary if patient in inflammatory state (e.g. infection/malignancy)
Ferritin is raised so check CRP with each ferritin sent and transferrin saturation will be more useful
Investigations for pancytopenia
B12/folate/iron
Abdo exam to assess spleen (myelofibrosis = splenomegaly)
Reticulocyte count (aplastic anaemia or bone marrow failure syndromes if low)
Blood film (hairy cell leukaemia, dysplasia = myelodysplasia, blasts = acute leukaemia)
Myeloma screen
Parvovirus (can cause this in immunosuppressed)
Some medications may cause this
Bone marrow biopsy
Macrocytic anaemia types (3)
Megaloblastic
Non-megaloblastic
Other haematological disease
Megaloblastic macrocytic anaemia causes
B12 deficiency
Folate deficiency
Cytotoxic drugs
Non-megaloblastic macrocytic anaemia causes
Alcohol excess (commonest cause of macrocytosis without anaemia as well) Reticulocytosis Liver disease Hypothyroidism Pregnancy
Other haematological diseases that cause macrocytic anaemia (neither megaloblastic/non-megaloblastic)
Myelodysplasia
Myeloma
Myeloproliferative disorders
Aplastic anaemia
Megaloblastic macrocytic anaemia blood film description
Hypersegmented polymorphs Leucopenia Macrocytosis Anaemia Thrombocytopenia with megaloblasts
Main sources of vitamin B12
Meat and dairy
Large body stores
Causes of vitamin B12 deficiency
Dietary
Malabsorption
Causes of vitamin B12 malabsorption
Stomach - lack of intrinsic factor produced by gastric parietal cells - pernicious anaemia or post-gastrectomy
Terminal ileum - ileal resection, Crohn’s, bacterial overgrowth, tropical sprue, tapeworms
Clinical features of B12 deficiency
Mouth - glossitis, angular cheilosis (swelling, fissuring of lips)
Psych - irritability, depression, psychosis, dementia
Neuro - parasthesiae, peripheral neuropathy (loss of vibration/proprioception, absent ankle reflex, spastic paraperesis, subacute combined degeneration of spinal cord)
Pernicious anaemia aetiology and physiological consequences
Autoimmune atrophic gastritis - achlorydia and lack of gastric intrinsic factor
COMMONEST cause of macrocytic anaemia in Western countries (>40yrs)
!!TESTS for pernicious anaemia
!!Parietal cell antibodies (90%)
!!Intrinsic factor antibodies (50%)
Schilling test (outdated)
Treatment for vit B12 deficiency
Replenish stores with !!IM hydroxycobalamin
Main sources of folate
DIET - green veg, nuts, yeast & liver, synthesised by gut bacteria (low body stores, can’t produce de novo)
Causes of folate deficiency
Poor diet
Increased demand - pregnancy or increased cell turnover (haemolysis, malignancy, inflammatory disease, renal dialysis)
Malabsorption - coeliac, tropical sprue
Drugs - alcohol, anti-epileptics (phenytoin), methotrexate, trimethoprim
Treatment for folate deficiency
Oral folic acid (don’t give if cause of anaemia is unknown as may exacerbate)
Definition of haemolytic anaemias
Breakdown of RBCs before their normal life span of around 120 days
Features present in all haemolytic anaemias
Raised bilirubin (unconjugated) Raised urobilinogen Raised LDH (lactate dehydrogenase) Reticulocytosis (raised MCV and polychromasia)
May have pigmented gallstones
Features present in intravascular haemolytic anaemias
Raised free plasma Hb
Lowered haptoglobin (binds free Hb)
Haemoglobinuria (dark red urine)
Methaemalbuminaemia (haem + albumin in blood)
Main feature of extravascular haemolytic anaemias
Splenomegaly
Issues patients in erythroid hyperplasia state are susceptible to
Parvovirus B19 (aplastic crisis)
Iron overload
Osteoporosis
Expected outcome of reticulocyte count if patient is acutely anaemic
High reticulocyte count - bone marrow responding appropriately to produce more RBCs
Classifications of causes of haemolytic anaemias
Inherited
- membrane defect
- enzyme defect
- haemoglobinopathies
Acquired
- immune
- non-immune
Inherited causes of haemolytic anaemias
Membrane defect - hereditary spherocytosis/elliptocytosis
Enzyme defect - G6PD deficiency, pyruvate kinase deficiency
Haemoglobinopathies - sickle cell disease, thalassaemias
Acquired causes of haemolytic anaemias
Immune - autoimmune (warm or cold), alloimmune (haemolytic reactions to transfusions)
Non-immune - mechanical (e.g. metal valves, trauma), PNH, MAHA, infections (e.g. malaria), drugs
Hereditary spherocytosis + elliptocytosis inheritance pattern
Autosomal dominant
Aetiology of hereditary spherocytosis and susceptibilities
Spectrin or ankyrin deficiency (membrane proteins)
Susceptible to parvovirus B19 and gallstones
Site of haemolysis in hereditary spherocytosis + clinical sign
Extravascular
Splenomegaly
Diagnosis method for hereditary spherocytosis
Spherocytes on blood film
Increased osmotic fragility (lysis in hypotonic solution)
Negative DAT/Coombs test (not autoimmune Ab mediated)
Flow cytometry
Treatment of hereditary spherocytosis
Splenectomy
Folic acid
Only form of hereditary elliptocytosis that ISN’T autosomal dominant
Hereditary pyropoikilocytosis (overly sensitive to heat) - autosomal recessive
Severity range of outcomes for hereditary elliptocytosis
Hydrops foetalis to asymptomatic
Hereditary elliptocytosis appearance on blood film
RBCs are elliptical in shape
South East Asian Ovalocytosis inheritance pattern + clinical relevance
Recessive - heterozygous +/- malaria protection
Inheritance pattern for commonest RBC enzyme defect (G6PD def)
X-linked
Prevalent areas of G6PD def
Malarial endemicity (i.e. Africa, mediterranean, middle eastern populations)
G6PD def attack clinical features + blood film description
Rapid anaemia + jaundice + dark urine Bite cells (RBCs with small semicircular part cut out, like a bite) + !!Heinz bodies (blue deposits, oxidised Hb)
Causes of G6PD def attacks
Oxidants (G6PD usually helps RBCs make glutathione = antioxidant)
- drugs (2-3 days after starting)
- broad beans
- acute stressors
- moth balls
- acute infection
Diagnosis method for G6PD def
Classical signs of anaemia on basic Ix
G6PD def spot test - NON-FLUORESCENT as no NADPH
Enzyme assay 2-3 months after crisis - young RBCs may have sufficient enzyme so appear normal
Treatment for G6PD def
Supportive + folic acid, avoid precipitants
Blood transfusion if severe attack
Genetic screening can be useful
Inheritance pattern for pyruvate kinase def
Autosomal recessive
Clinical features of pyruvate kinase def
Severe neonatal jaundice
Splenomegaly
Haemolytic anaemia
Management of pyruvate kinase def
Most don’t require treatment but can do blood transfusion or splenectomy
