Anaemia Flashcards
What is the definition of anaemia?
Decreased haemoglobin in the blood such that there is inadequate oxygen delivery to tissues
Hb <135g/L in men
Hb <115g/L in women
What are the symptoms of anaemia?
Asymptomatic: a slowly falling haemoglobin allows for haemodynamic compensation
Non specific: fatigue, weakness, headaches
Cardiovascular: dyspnoea on exertion, angina, intermittent claudication, palpitations
What are the signs if anaemia?
Pallor
Tachycardia
Systolic flow murmur
Cardiac failure
What are the specific signs for certain types of anaemia?
Koilonychia: spoon shaped nails in IDA
Jaundice: haemolytic anaemia
Leg ulcers: often seen in sickle cell disease
Bone marrow expansion: leading to abnormal facial structure or pathological fractures, in thalassemia (rare)
When is transfusion indicated?
Generally not indicated unless there’s an acute bleed and the patient is not symptomatic
Beware of associated heart failure
Should be given slowly alongside furosemide
What does MCV and MCH stand for?
MCV: size of each red blood cell
MCH: amount of haemoglobin in each red blood cell
What causes a low MCV (<80fL, microcytic anaemia)?
Iron deficiency anaemia (IDA): blood loss until proven otherwise
Thalassemia
Lead poisoning
Sideroblastic anaemia (rare)
What causes a normal MCV (normocytic anaemia)?
Acute blood loss Anaemia of chronic disease Renal anaemia Haemolytic anaemias (can be macrocytic due to reticulocytes) Marrow failure Pregnancy Connective tissue diseases Diamorphic blood film (combined microcytic/macrocytic processes)
What causes a high MCV (>96fL microcytic anaemia)?
B12 deficiency (pernicious anaemia/Crohn's) Folate deficiency (coeliac disease) Alcohol excess (or severe liver disease) Myelodysplastic syndromes Severe hypothyroidism (myoxedema can be normocytic)
What should you find on examination in microcytic anaemia?
Koilonychia
Angular stomatitis
Brittle nails/hair
What are further tests that should be done for microcytic anaemia?
Iron studies: serum iron, serum ferritin, total iron binding capacity, serum soluble transferrin receptors
Blood film: microcytic anaemia, generally also hypochromic (pale on the blood film, representing low MCH)
Film may show sideroblasts/signs of thalassemia
What is iron deficiency anaemia (IDA)?
Most common cause of anaemia
Iron is much more readily taken up in the gut as ferrous iron (Fe2+) which is far less abundant than th insoluble ferric (Fe3+)
IDA develops when there is an inadequate iron for haemoglobin synthesis
There is a ‘latent iron deficiency’ period, where normal Hb is maintained despite the iron deficiency
What are the causes of IDA?
Blood loss: hookworm the most common cause worldwide, UK due to heavy menstruation or GI bleeds
Decreased absorption: Coeliacs, patients on antacids (less ferric to ferrous iron conversion) or post gastrectomy
Increased demand: in growth/pregnancy
Inadequate intake: premature infants/prolonged breast fed infants most at risk
How is IDA diagnosed?
Blood film: microcytic, hypochromic cells with poikilocytosis (shape variation) and anisocytosis (size variation)
Serum iron: decreased
Total iron binding capacity: increased
Serum ferritin: decreased
Represent amount of stored iron
Soluble transferrin receptor: increased (most specific test)
What are the test results of anaemia of chronic disease?
Serum iron will be decreased
TIBC will also be decreased and STR will be normal
Ferritin will be raised
What is ferritin?
This represents increased stored iron, but it is an acute phase reactant and is raised in infection or malignancy
If ferritin is low-normal in the presence of raised inflammatory markers then this can be a false negative and may suggest IDA
What are further investigations which should be carried out in anaemia?
If there is a good history of menorrhagia start oral iron, and do coeliac serology
Ask about number of sanitary items used, clots
In all other patients without an obvious cause of bleeding, check coeliac serology then refer all patients for GI investigation
OGD and colonoscopy
Stool microscopy is also advised of recent foreign travel
What other tests should be carried out in macrocytic anaemia?
Blood film: Hypersegmented neutrophils in B12/folate deficiency, may reveal other clues (target cells in liver)
LFTs/TFTs: thyroid/hepatic cause, raised bilirubin in B12/folate deficiency
Serum B12/folate levels: serum folate reflects recent intake, so many labs do red cell folate
What should you do if B12 is low?
Anti-parietal cell Ab, anti-IF Ab
Schilling test: distinguishes between pernicious anaemia and small bowel disease (radiolabelled B12 given with, and then without IF, amount of labelled B12 excreted in urine then detected)
What does a bone marrow biopsy show?
Megaloblasts suggest B12/folate deficiency, also seen in myelodysplasia
Deoxyuridine suppression test: can be used to differentiate B12/folate deficiency in vitro after bone marrow biopsy
How do B12 and folate deficiency lead to megaloblastic anaemia?
B12 acts as a co-enzyme for the conversion of folate (B9) to activated folate
Activated folate is required for DNA synthesis and thus there is a deficiency in either B12 or folate, DNA synthesis malfunctions
In this case the DNA fails to stop erythrocyte development, leading to very large cells, which are eventually trapped and destroyed in the reticule-endothelial system
How is B12 excreted?
Liver contains a very large store of B12 and it’s excreted in the bile but around 70% of this is normally absorbed
Where does B12 bind?
Free vitamin B12 binds to R proteins in the upper GI tract, but these complexes are degraded by pancreatic proteases
Intrinsic factor is secreted by the gastric parietal cells and binds free B12 with far less affinity than R proteins, but the IF-B12 complex is highly resistant to protease degradation
Receptors for the IF-B12 complex are present on the brush border of the terminal ileum, where B12 is absorbed
How is B12 ingested?
IF is general necessary for B12 ingestion, even in its absence around 2% can still be ingested
High dose PO supplementation can be enough to treat pernicious anaemia
Even in total malabsorption, body stores will last for 3 years
