Anaemia (CH) Flashcards
Define anaemia.
Anaemia is a Hb level two standard deviations below the mean for the age and sex of the patient
A decrease in the [Hb] in circulating blood
What are the general blood results for anaemia?
Reduced RBC, reduced Hct, reduced PCV (packed cell volume)
What can be used to distinguish the mechanism of anaemia?
Reticulocyte count
- increased = haemolytic anaemia, recent blood loss, recent treatment with iron, B12/folate
- decreased = reduced output of RBC from bone marrow
What are the causes of anaemia? (4 types + examples of each)
- reduced production of RBC by bone marrow
- iron deficiency anaemia
- anaemia of chronic disease
- megaloblastic anaemia (B12 deficiency)
- blood loss from body (normocytic)
- reduced survival of RBC in circulation
- hereditary spherocytosis
- autoimmune haemolytic anaemia
- G6PD deficiency
- increased pooling of RBC in enlarged spleen (sickle cell anaemia)
What are the general symptoms of anaemia? (5)
- tiredness
- lethargy
- malaise
- dyspnoea
- pallor
What are some general investigations for anaemia?
- FBC - low Hb
- iron studies - IDA
- blood film - reticulocytes, abnormalities
- electrophoresis - haemoglobinopathies
- DAT/Coomb’s Test
- LFTs, bilirubin - haemolytic anaemia
What are the three types of anaemia?
- microcytic
- normocytic
- macrocytic
Define microcytic anaemia.
- insufficient Hb production
- MCV < 80 fL
What are the types of causes of microcytic anaemia?
- defective haem synthesis
- iron deficiency anaemia
- anaemia of chronic disease (may also be normocytic)
- defective globin synthesis
- thalassaemia
- sideroblastic anaemia
- lead poisoning
- anaemia of chronic disease
How does microcytic anaemia present?
- brittle hair and nails
- pallor
- koilonychia (spoon-shaped nails in IDA)
- glossitis
- angular stomatitis (red patches in corner of mouth in IDA)
- signs of thalassaemia
- ankle swelling
- palpitations
- tachycardia
- post-cricoid webs
- exacerbation of ischaemic conditions
What investigations are done for microcytic anaemia?
- FBC - MCV<80, reticulocytes
- blood film - microcytes, increased area of central pallor, hypochromic, basophilic stippling
- iron studies
- CRP, ESR - elevated in ACD
- serum lead - elevated in lead poisoning
- Hb electrophoresis - thalassaemia, SCA
Iron studies - what would be suggestive of iron deficiency anaemia?
- low iron and ferritin
- raised transferrin
- increased TIBC (total iron binding capacity)
Iron studies - what would be suggestive of anaemia of chronic disease?
- low/normal iron and ferritin
- low transferrin
- low TIBC
- increased hepcidin
Iron studies - what would be suggestive of sideroblastic anaemia?
- high iron
- high ferritin
- high transferrin saturation
Iron studies - what would be suggestive of thalassaemia?
Mentzer index (MCV/RBC) <13
What is the difference in blood count results between iron deficiency anaemia vs anaemia of chronic disease?
- MCV: low vs low/normal
- ferritin: low vs high
- transferrin: high vs low/normal
- transferrin saturation: low vs normal
- ESR: may be high (due to low Hct) vs high
What are the causes of iron deficiency anaemia?
- increased blood loss
- hookworm
- menstrual
- GI (aspirin/NSAIDs, cancers, ulcers, coeliac, gastrectomy, H.pylori, angiodysplasia)
- insufficient intake
- dietary
- malabsorption - coeliac, gastritis
- increased requirement
- pregnancy
- infancy
What investigations are done for iron deficiency anaemia?
- FBC
- iron studies (high transferrin/TIBC, low serum iron/ferritin)
- blood film (poikilocytosis, anisocytosis, microcytosis hypochromia)
- if >40yrs OR post-menopausal women OR male with unexplained IDA: upper GI endoscopy, colonoscopy
- if Hb<10 - refer within two weeks
How do we manage iron deficiency anaemia?
- iron supplements
- oral ferrous sulfate/fumarate/gluconate, continue for 3 months after IDA correction to allow stores to replenish
- if oral iron not tolerated, IV iron
- iron-rich diet (dark leafy veg, meat, iron-fortified bread)
- address underlying causes (e.g. treat menorrhagia, stop NSAIDs)
What are some causes of anaemia of chronic disease?
- no unrelated cause except for a different unrelated pathology (hepcidin production increased in inflammation –> reduced iron supply by blocking absorption from gut/release of storage iron)
- infections: TB and HIV
- autoimmune disorders (inflammatory): RA, SLE, Crohn’s/UC, CKD
- cancer, lymphomas/leukaemia
What investigations are done for anaemia of chronic disease?
FBC - increased ferritin, low/normal transferrin
What is the pathophysiology of anaemia of chronic disease?
- involvement of pro-inflammatory cytokines
- IL1, TNF-a, IL6
- all decreased EPO production
- increase hepcidin production = decreased release of storage iron
How do we manage anaemia of chronic disease?
Treat the underlying cause
What is sideroblastic anaemia?
Inability to form haem in mitochondria –> deposits of iron in mitochondria form a ring around nucleus called a ring sideroblast
What is a congenital cause of sideroblastic anaemia?
Delta-aminolevilinate synthase-2 deficiency
What are the acquired causes of sideroblastic anaemia?
MALA
- myelodysplasia
- alcohol
- lead
- anti-TB medications
What is seen on a blood film of sideroblastic anaemia? (3)
- basophilic stippling of RBCs
- dimorphic blood film
- hypochromic microcytes
- (bone marrow film: Prussian blue staining shows ring sideroblasts)
How do we manage sideroblastic anaemia?
- supportive
- if secondary - treat the cause
- pyridoxine
- iron chelation if not treatment
Define normocytic anaemia.
- decreased blood volume or erythropoiesis
- MCV 80-100 fL
What are some causes of normocytic anaemia?
- aplastic
- bleeding (haemorrhage/trauma, BM failure or infiltration)
- chronic disease (early stages)
- CKD
- destruction - haemolysis
- endocrine disorders (hypothyroidism, hypoadrenalism)
- splenic sequestration (hypersplenism, liver cirrhosis)
- vitamin B2/B6 deficiency
- uncompensated increase in plasma volume (pregnancy, fluid overload)
What investigations are done for normocytic anaemia?
- FBC - normal MCV, low Hb
- check Hx for haemorrhage
- if WCC or platelets low - suspect marrow failure
How can we classify normocytic anaemia by reticulocyte count?
- <2% (hypoproliferative) - leukaemias, aplastic anaemia, pure red cell aplasia, other marrow failure syndromes
- > 2% (hyperproliferative) - haemorrhage, haemolytic anaemias
What will ferritin be in normocytic anaemia?
Normal/high
What is aplastic anaemia?
Pancytopenia and hypoplastic bone marrow caused by diminished haematopoietic precursors –> normocytic anaemia
What are some causes of aplastic anaemia?
- acquired anaemia (at 30y)
- autoimmune
- congenital
- Fanconi anaemia (AR) = increased risk of AML
- dyskeratosis congenita
- drugs (cytotoxics, chloramphenicol, sulphonamides, phenytoin, gold)
- toxins (benzene)
- infections (Parovirus, hepatitis)
- paroxysmal nocturnal haemoglobinuria or myelodysplasia
How does aplastic anaemia present?
- thrombocytopenia
- easy bruising
- bleeding gums
- epistaxis
- leukopenia - infections
How do we investigate aplastic anaemia?
- FBC - leukopenia with lymphocytes spared, thrombocytopenia
- bone marrow biopsy
How can we manage aplastic anaemia?
- haematopoietic stem cell (bone marrow) transplant
- immunosuppressive therapy
- androgens e.g. oxymetholone
Define macrocytic anaemia.
- defective DNA synthesis or repair
- MCV > 100 fL
What are the causes of macrocytic anaemia?
FAT RBC
- foetus
- alcohol excess
- thyroid disorders
- reticulocytosis
- B12/folate deficiency (megaloblastic)
- cirrhosis
Also:
- drugs interfering with DNA synthesis - tyrosine kinase inhibitors
- haemolytic anaemia
- myelodysplasia, multiple myeloma, pregnancy
- aplastic anaemia
How does pernicious anaemia (macrocytic anaemia) present?
- jaundice
- glossitis
- angular stomatitis
- weight loss
How does B12 deficiency (macrocytic anaemia) present?
- peripheral neuropathy
- ataxia
- SACD
- optic atrophy
- dementia
- positive Babinksi’s
- absent ankle reflex
- increased knee reflex
What investigations do we do for macrocytic anaemia?
- FBC - MCV>100fL, low Hb, pancytopenia in megaloblastic anaemia
- LFTs - high BR in ineffective erythropoiesis or haemolysis
- ESR
- TFT
- B12/folate
- homocysteine and methylmalonic acid levels
- anti-parietal cell and anti-IF antibodies
- protein electrophoresis (dense band in myeloma)
- blood film - large erythrocytes, megaloblasts, hypersegmented neutrophil nuclei, target cells (liver disease)
- Schilling test (pernicious anaemia) - B12 absorbed with IF
What is seen in a blood film of macrocytic anaemia?
- large erythrocytes
- megaloblasts
- hypersegmented neutrophil nuclei
- target cells (liver disease)
What investigation is done for pernicious anaemia?
Schilling test - B12 absorbed with IF
How can we treat pernicious anaemia?
IM hydroxycobalamin
How can we treat anaemia caused by B12 deficiency?
Dietary supplements - PO cyanocobalamin
How can we treat anaemia caused by folate deficiency?
Folic acid (B12 must be corrected first) - oral folic acid 5mg daily for 4 months
What is a complication of pernicious anaemia?
Gastric cancer
What is a complication of folate deficiency?
Neural tube defects
What blood result may suggest macrocytic anaemia due to alcohol use?
Isolated GGT raise
What are some inherited causes of haemolytic anaemia?
- membrane integrity defects - hereditary spherocytosis/elliptocytosis
- haemoglobinopathies - sickle cell anaemia, thalassaemia
- defect in glycolytic pathway - pyruvate kinase deficiency
- defect in pentose shunt pathway - G6PD deficiency
What are some acquired causes of haemolytic anaemia?
- *autoimmune haemolytic anaemia** - antibodies attach = intravascular + extravascular haemolysis
- isoimmune (transfusion, haemolytic disease of the newborn)
- drugs (penicillin, quinine)
- trauma (microangiopathic haemolytic anaemia, haemolytic uraemic syndrome, DIC, malignant hypertension
- infection - sepsis, malaria
- paroxysmal nocturnal haemoglobinuria
- snake venom, alloimmune (blood transfusion)
What can precipitate haemolysis?
Drugs, infections or consumption of broad beans –> hypotension, tachycardia, petechiae, ecchymosis, altered conscious state
What are some risk factors for haemolytic anaemia?
- African-American
- X-linked recessive (G6PD deficiency) = men more likely
- Fx of hereditary spherocytosis (autosomal dominant)
How does haemolytic anaemia present?
- jaundice
- hepatosplenomegaly
- leg ulcers (poor flow)
- haematuria
- dark urine
What investigations is diagnostic for haemolytic anaemia?
DAT test AKA Coomb’s test
What are the blood results of someone with haemolytic anaemia?
- increased: unconjugated bilirubin, LDH, reticulocytes
- deranged LFTs
- reduced haptoglobins
What does a blood film of haemolytic anaemia show?
- reticulocytosis
- leucoerythroblastic (macrocytosis, polychromasia)
- Heinz bodies (oxidised Hb in G6PD deficiency), bite cells, blister cells (G6PD)
- spherocytes (hereditary spherocytosis)
What investigation is done for hereditary spherocytosis?
Eosin-5-malemide (EMA) for binding
What investigations are done for membrane abnormalities in haemolytic anaemia?
Osmotic fragility test or Spectrin mutation analysis
What investigations are done for paroxysmal nocturnal haemoglobinuria?
- Ham’s test - lysis of erythrocytes in acidified serum
- flow cytometry
How do we manage hereditary spherocytosis?
Folic acid, splenectomy
How do we manage G6PD deficiency?
Patients should avoid oxidant drugs, should not eat broad beans (fava beans), avoid naphthalene and be aware that haemolysis can result from infection
What is the aetiology of autoimmune haemolytic anaemia?
Mostly idiopathic, can be secondary to a lymphoproliferative disorder, infection or drugs
What are the two types of autoimmune haemolytic anaemia?
- warm AIHA (more common
- cold AIHA
Describe warm autoimmune haemolytic anaemia and how to manage it.
- IgG causes haemolysis in extravascular sites (spleen)
- caused by autoimmune disease (SLE), neoplasia (lymphoma, CML), drugs (methyldopa)
- management: treat underlying disorder, steroids +/- rituximab (1st line)
Describe cold autoimmune haemolytic anaemia.
- IgM causes haemolysis mediated by complement in intravascular sites
- caused by neoplasia (lymphoma), infections (mycoplasma, EBV)
- Raynaud’s, acrocyanosis
- less responsive to steroids
What is haemolytic uraemic syndrome?
- uraemia, thrombocytopenia, microangiopathic haemolytic anaemia
- two forms: diarrhoea-associated, and no diarrhoea prodrome
- overlap with thrombotic thrombocytopenia purpura: additional features of fever, fluctuating CNS signs
- E.coli with bloody diarrhoea in children under 5
How is haemolytic anaemia treated?
Steroids (prednisolone) +/- rituximab
How is anaemia treated if severe?
Blood transfusion with RBCs
