Anaemia Flashcards
What are the reference ranges for anaemia?
Hb:
Men: <135 g/L
Women: < 115g/L
(Note: there is a growing argument that women should be labelled anaemic based on male
reference ranges, as a lot of women with Hb 115-135 will actually have iron deficiency)
What are the three main mechanisms which result in anaemia?
Reduced RBC production
Loss of RBCs (haemolytic anaemias)
Increased plasma volume (pregnancy)
What are the signs in severe anaemia (Hb < 80g/L)?
Hyperdynamic circulation
e.g. tachycardia, flow murmurs (ejection-systolic over apex)
Can lead to heart failure
What does a high MCV mean in anaemia?
Often decreased production of RBCs
What does a low MCV mean in anaemia?
Often a normal number of RBCs but not enough haemoglobin to go in them
List the causes of a microcytic anaemia:
(FAST)
F: Iron-deficiency
A: anaemia of chronic disease
S: Sideroblastic anaemia
T: Thalassaemia
List the causes of a normocytic anaemia:
Acute bleed
Anaemia of chronic disease
Bone marrow failure
Renal failure
Hypothyroidism
Haemolysis
Pregnancy
List the causes of a macrocytic anaemia:
(FATRBC)
F: Foetus
A: Antifolates (e.g. phenytoin, methotrexate)
T: Hypothyroidism
R: Reticulocytosis
B: B12 or folate deficiency
C: Cirrhosis
+ Myelodysplastic syndromes
What is Reticulocytosis?
Release of larger immature cells e.g. in haemolysis
What are the signs of iron deficiency anaemia?
Koilonychia, atrophic glossitis, angular cheilosis, post-cricoid webs (Plummer-Vinson syndrome), brittle hair and nails.
What would you see on a blood film with Iron deficiency anaemia?
Microcytic, hypochromic, anisocytosis (varying size), poikilocytosis (shape) pencil cells.
What are the 5 main underlying mechanisms of iron deficiency anaemia?
Blood loss
Increased utilisation
Decreased Fe intake
Decreased absorption
Intravascular haemolysis
List common causes of IDA through blood loss:
Meckel’s diverticulum (older children)
Peptic ulcers / Gastritis (chronic NSAID use) Polyps/colorectal Ca (most common cause in adults >50yrs)
Menorrhagia (women <50 yrs)
Hookworm infestation (developing countries)
When might increased utilisation of RBCs cause IDA?
In pregnancy/lactation
Growth in infants/children
When might problems with absorption cause IDA?
Coeliac (absence in villous surface in duodenum)
Post-gastric surgery
(rapid transit / reduced acid which aids Fe absorption)
What causes of intravascular haemolysis cause IDA and how?
Microangiopathic haemolytic anaemia
Paroxysmal nocturnal haemoglobinuria
Loss of Hb in urine results in Fe deficiency
What investigations should be carried out for a pt with IDA with no obvious cause?
OGD + Colonoscopy
Urine Dip
Coeliac screen
What are the indications for IV Iron replacement?
Poor oral absorption
Failure of oral trial
Need for rapid rise
Note: Fe does not absorb well in sepsis and fuels bacteria
What are some common causes of Anaemia of chronic disease?
Chronic inflammation (e.g. TB, osteomyelitis)
Vasculitis
Rheumatoid arthritis
Malignancy
(Renal failure)
Explain the aetiology of anaemia of chronic disease:
Cytokine driven inhibition of RBC production
Inflammatory markers like IFNs, TNF and IL1 reduce EPO receptor production (and thus EPO synthesis) by kidneys
Iron metabolism is dysregulated. IL6 and LPS stimulate the liver to make hepcidin, which decreases iron absorption from gut (by inhibiting transferrin) and also causes iron accumulation in macrophages.
What happens to Ferritin in anaemia of chronic disease?
High (unless coinciding IDA)
(Ferritin is intracellular protein iron store)
Fe is sequestered in macrophages to deprive bacteria
What causes anaemia in renal failure?
Failing kidneys fail to produce enough erythropoietin - less RBC production stimulated
Treat any iron deficiency before giving epo
Describe ring sideroblasts
Erythroid precursors containing deposits of non-heme iron in mitochondria forming a ring-like distribution around the nucleus. The iron-formed ring covers at least one-third of the nucleus rim
How is sideroblastic anaemia diagnosed?
Ring sideroblasts are seen in bone marrow
Is sideroblastic anaemia micro or macrocytic?
Sideroblastic anemia is known to cause microcytic and macrocytic anemia depending on what type of mutation led to it.
What causes sideroblastic anaemia?
Ineffective erythropoiesis resulting from abnormal utilisation of Fe during erythropoiesis
What Iron levels would you expect in sideroblastic anaemia?
Normal to high iron levels (unlike IDA)
What causes sideroblastic anaemia?
Hereditary
Acquired:
Myelodysplastic disorders
Post-chemo
Irradiation
Alcohol excess
Lead excess
TB Tx
Myeloproliferative disease
What is the treatment for sideroblastic anaemia?
Treat cause
Pyridoxine (B6) may promote RBC production
Consider EPO
May require chronic transfusion with chelation
Plasma Iron Studies: what would Iron, TIBC, Ferritin be in IDA?
Iron: ↓
TIBC: ↑
Ferritin: ↓
Plasma Iron Studies: what would Iron, TIBC, Ferritin be in Anaemia of chronic disease?
Iron: ↓
TIBC: ↓
Ferritin: ↑
Plasma Iron Studies: what would Iron, TIBC, Ferritin be in Chronic haemolysis?
Iron: ↑
TIBC: ↓
Ferritin: ↑
Plasma Iron Studies: what would Iron, TIBC, Ferritin be in Haemochromatosis?
Iron: ↑
TIBC: ↓ (or N)
Ferritin: ↑
Plasma Iron Studies: what would Iron, TIBC, Ferritin be in Pregnancy?
Iron: ↑
TIBC: ↑
Ferritin: N
Plasma Iron Studies: what would Iron, TIBC, Ferritin be in Sideroblastic anaemia?
Iron: ↑
TIBC: N
Ferritin: ↑
What is Ferritin?
An acute phase protein
The total body stores of iron
Remember to check CRP when checking Ferritin
What is TIBC?
Total Iron Binding Capacity
Blood capacity to bind iron with transferrin
What is Serum Iron?
Amount of circulating iron bound to transferrin
What is transferrin saturation?
Ratio of serum iron / TIBC
If <20% indicates Fe deficiency
What are the three types of Macrocytosis?
Megaloblastic
Non-megaloblastic
Other haematological disease (e.g. myelodysplasia, myeloma, MPDs, Aplastic anaemia)
What causes Megaloblastic macrocytic anaemias?
B12 / Folate deficiency
Cytotoxic droogs
What causes a non-megaloblastic macrocytic anaemia?
Alcohol (most common macrocytosis w/o anaemia)
Reticulocytosis (e.g. haemolysis)
Liver disease
Hypothyroid
Pregnancy
What are megaloblasts?
Red cell precursors with an immature nucleus and mature cytoplasm
What is the typical appearance of a megaloblastic blood film?
Hypersegmented polymorphs, leucopenia, macrocytosis, anaemia, thrombocytopenia with megaloblasts.
What causes B12 deficiency?
Dietary (vegans)
Malabsorption:
Stomach: Pernicious anaemia
Terminal ileum: Crohn’s, resection, bacterial overgrowth, tropical sprue, tapeworms
What are the clinical features of B12 deficiency?
Glossitis, angular cheilitis
Paraesthesia, peripheral neuropathy
Irritability, depression, psychosis, dementia
What is the dietary source of B12?
Meat and dairy
What is pernicious anaemia?
Autoimmune atrophic gastritis - Achlorhydria and lack of gastric intrinsic factor
What is the test for pernicious anaemia?
Parietal cell antibodies (90%)
Intrinsic factor antibodies (50%)
What is the treatment for Pernicious anaemia?
IM Hydroxycobalamin
Replenish stores with 6 injections over 2 weeks
Then 3-monthly
What is the dietary source of folate?
Green vegetables
Nuts
Yeast
Liver
(low body stores, cannot produce de novo)
What causes folate deficiency?
Poor diet
Increased demand: Pregnancy or increased cell turnover (haemolysis, malignancy, inflammatory disease)
Malabsorbtion: coeliac disease, tropical sprue
Drugs: EtOH, methotrexate, trimethoprim, phenytoin
What is the treatment for folate deficiency?
Check B12 and replace first to avoid exacerbating neuropathy
Oral folic acid
