Haematology - anaemia Flashcards
Name the types of megaloblastic anaemia and define the MCV level required.
Folate deficiency, pernicious anaemia, vitamin B12 deficiency
MCV>96fL
What is functional vitamin B12 deficiency?
Failure of intracellular transport of B12 by transcobalamin-2 can lead to functional B12 deficiency but with apparently normal serum levels. Neurological complications can occur.
What is folate and where is it absorbed?
Vitamin B9
Jejunum
What are the four causes of folate deficiency?
Dietary deficiency
Excessive requirements
Excessive urinary excretion
Antifolate drugs
Name three causes of excessive requirement of folate.
Pregnancy
Malignancy
Chronic inflammatory conditions
Name three anti-folate drugs.
Nitrofurantoin
Sulfasalazine
Methotrexate
What are megaloblasts?
Hypersegmented polymorphs with six or more lobes in the nucleus.
What is found on blood tests and blood films in folate deficiency anaemia?
MCV>96fL
Macrocytosis/megaloblasts
Serum folate<7nmol/L
<340nmol erythrocyte folate
What is the treatment of folic acid deficiency?
5mg folic acid OD for four months
Why is it important to check serum Vitamin B12 in patients with folate deficiency anaemia?
Folic acid may aggravate the neuropathy and precipitate subacute combined degeneration of the spinal cord.
Name three causes of microcytosis.
Pregnancy and the neonatal period
Alcohol excess and liver disease
Severe hypothyroidism
Where is Vitamin B12 absorbed and what does it require?
Terminal ileum
Requires intrinsic factor which is secreted by parietal cells
Give five causes of vitamin B12 deficiency.
Gastric causes e.g. gastrectomy, h.pylori infection
Vegan diet
Crohn’s disease
Long term PPI use
As well as typical symptoms of anaemia, what can Vitamin B12 deficiency present with?
Damage to peripheral nerves and posterior and lateral columns of spinal cord
Paraesthesiae Numbness Cognitive changes Visual disturbances Subacute combined degeneration of the cord
What are the signs of subacute combined degeneration of the cord?
Weakness, paraesthesiae, numbness of legs, arms, trunk –> Bilateral spastic paresis but loss of reflexes –> Decreased pressure, vibration, and touch sense –> Positive Babinski sign
How is Vitamin B12 deficiency diagnosed?
MCV>96fL Macrocytosis/megaloblasts Increased unconjugated bilirubin Vitamin B12 low Raised total homocysteine
What autoantibodies should be screened for in Vitamin B12 deficiency anaemia?
Intrinsic factor antibodies
What does it mean if the MCV is normal but Vitamin B12 is low?
There is a co-existing iron deficiency so there is a dimorphic blood film
What is the treatment of vitamin B12 deficiency anaemia?
Neuro involvement - 1mg Hydroxycobalamin IM 3x week for 2 weeks, then 1mg every 3 months
Neuro involvement - 1mg Hydroxycobalamin IM alternate days until no further improvement, then 1mg every 2 months
What are the indications for referral in B12 deficiency?
Haem - neuro symptoms, pregnancy, uncertain cause
Gastro - malabsorption is suspected.
Give four causes of iron deficiency anaemia.
GI/PV blood loss
Vegetarianism
PPI use
Tropical gut infestation
Give six signs of iron deficiency anaemia?
Pallor Koilonychia Angular cheilitis Atrophic glossitis Tachycardia Flow murmur
What are the laboratory results in iron deficiency anaemia?
Hypochromic (low MCH) microcytic (low MCV) anaemia
Hb<12g/dl
Serum ferritin <12-15mcg
What does serum ferritin correlate with?
Total body iron stores
What is seen on blood film in iron deficiency anaemia?
Anisocytosis (variety in size)
Poikilocytosis (abnormal shapes)
Which patients with iron deficiency should have upper/lower GI investigations?
All males
Postmenopausal females
What is the treatment of iron deficiency anaemia?
PO ferrous sulfate 200mg TD for 3 months
Name three side effects of ferrous sulfate.
Constipation/diarrhoea
Black stools
Nausea
What are three other causes of microcytic anaemia?
Haemoglobinopathies
Sideroblastic anaemia
Anaemia of chronic disease
What tests form part of a haemolytic screen?
Direct Coombs' test Bilirubin Reduced haptoglobin Reticulocytes Spherocytes LDH
By what mechanisms can haemolysis occur?
Intravascular (trauma etc)
Extravascular (removed because defective or Ig attached to surface)
Give six causes of haemolytic anaemia.
Red cell membrane - spherocytosis/elliptocytosis
Haemoglobinopathies - sickle cell/thalassaemia
Enzyme defects - G6PD, pyruvate kinase deficiency
Autoimmune e.g. SLE
Haemolytic disease of the newborn
Malaria
Other than typical anaemia symptoms, name some S+S of haemolytic anaemia.
Gallstones - RUQ pain
Haemoglobinuria
Jaundice
Splenomegaly
What is seen on the FBC in haemolytic anaemia?
Normocytic (Normal MCV) hypochromic (normal MCH) anaemia
Low Hb
Normal platelets, but thrombocytopenia can occur in SLE and CLL
What is the treatment of haemolytic anaemia?
Treat the cause e.g. splenectomy, iron therapy, transfusion therapy, corticosteroids if autoimmune
What are the two types of thalassaemia?
Alpha or beta
What are the subtypes of thalassemia?
Beta thalassemia minor, intermedia, and major
Alpha thalassemia silent, trait, haemoglobin H disease, and major (1, 2, 3, and 4 alpha HbA alleles affected respectively)
What is the prognosis of alpha thalassemia homozygous?
Death in utero: hydrops fetalis
Which type of thalassemia has the more severe symptoms?
Alpha > Beta
What is the gold standard of diagnosis in thalassemia?
Haemoglobin electrophoresis: HbA2>3.5%
What other investigations are required in suspected thalassemia?
Low Hb, low MCH, low MCV (microcytic hypochromic)
Raised serum iron and ferritin
What are the symptoms of thalassemia trait?
Asymptomatic
What are the signs of heterozygous thalassemia?
Anaemia
Splenomegaly
Bone changes (frontal bossing, prominent facial bones, dental malocclusion)
What are the signs of homozygous beta thalassemia?
Severe haemolytic anaemia
Hepatosplenomegaly
What is the management of thalassemia?
Intermedia: transfusion if pregnant/ill
Major: chronic transfusion dependency
What is the pathophysiology of sickle cell disease?
Cells have a reduced deformability and are easily destroyed
There is occlusion of microcirculation and chronic haemolytic anaemia
What are the main types of sickle cell disease?
HbSS/Sickle cell anaemia - homozygous
HbSC/Sickle cell trait - heterozygous (40% HbS)
Sickle beta plus thalassemia
Sickle HbD
What is the inheritance pattern of sickle cell disease and thalassemia?
Autosomal recessive
How does sickle cell trait present?
Usually asymptomatic
Protects against malaria
Occasionally haematuria, decreased ability to concentrate urine, renal papillary necrosis, splenic infarction, exertional rhabdomyolysis
When does sickle cell anaemia present?
Between 3 and 6 months of age when HbF levels are falling
Give five symptoms/presentations of sickle cell anaemia.
Acute splenic sequestration
Acute chest syndrome
Increased susceptibility to encapsulated bacteria such as pneumococcus
Splenomegaly but recurrent splenic infarcts cause autosplenectomy
Anaemia, jaundice, lethargy, growth restriction
How is sickle cell anaemia diagnosed?
Low Hb, high reticulocytes
Blood film shows sickled erythrocytes
Haemoglobin electrophoresis: no HbA, 80% HbSS, 20% HbF
What is the treatment of sickle cell anaemia?
Hydroxycarbamide
Penicillin prophylaxis
Avoid precipitating crises
What is a treatment of major haemorrhage (except surgery)?
Tranexamic acid
IV bolus followed by slow infusion
How long before an operation should the COCP be stopped for?
4 weeks
How is anaemia of chronic disease diagnosed?
Increased ferritin
Decreased total iron binding capacity (TIBC)
Normo/microcytic
In blood transfusions, what is a non-haemolytic febrile transfusion reaction?
Mild fever due to an acute reaction to plasma proteins
If no other symptoms, continue transfusion, treat with paracetamol, and increase observations.
What does phenytoin cause?
Folate deficiency with microcytosis
or just macrocytosis
What is glucose 6-phosphate dehydrogenase deficiency and what are the triggers for symptoms?
X-linked red cell enzymopathy renders RBC vulnerable to oxidative stress and haemolysis under certain conditions (asymptomatic until triggers)
Triggers:
- Fava beans
- Aspirin
- Infection
- Anti-malarials
What are the causes of sickle crises in sickle cell disease?
HbS has an increased affinity for oxygen than adult haemoglobin which results in crises in conditions of infection, cold, stress, and hypoxia.
Why are sickle cell patients at increased risk of infection with encapsulated bacteria?
Autosplenectomy
What are the characteristics of aplastic anaemia?
Pancytopenia and lack of reticulocytes
Hypocellular bone marrow with increased fat spaces
