Haematology - Anaemia Flashcards
Which investigations would you do for microcytic anaemia?
Peripheral Blood Smear + Iron Studies
Which investigations would you do for macrocytic anaemia?
Peripheral Blood Smear + LFTs + TFTs
Which investigations would you do for normocytic anaemia?
Peripheral Blood Smear + Direct Antiglobulin Test + CRP + ESR
What are three causes of anaemia?
- Reduced production of RBCs
- Increased loss of RBCs (haemolytic anaemias)
- Increased plasma volume/dilution (pregnancy)
What are some symptoms of anaemia?
- Fatigue
- Dyspnoea
- Faintness
- Palpitations
- Headache
- Tinnitus
- Anorexia
What are some signs of anaemia?
- Pallor
In severe anaemia (Hb <80g/L):
- Tachycardia
- Flow murmurs (ejection-systolic loudest over apex)
- Heart Failure
What is a high MCV?
> 100fL
Decreased production of RBCs
What is a low MCV?
<80fL
Normal number of RBCs (most of the time), but not much to go in them
Define anaemia
A condition in which the number of RBCs or the haemoglobin in them is lower than normal.
What are some causes of a microcytic anaemia?
FAST:
F - (Fe) Iron-deficiency anaemia
A - Anaemia of chronic disease
S - Sideroblastic anaemia
T - Thalassaemia (may not be anaemic if mild)
What are some causes of normocytic anaemia?
All Hoes Fuck Prostitutes:
All - Anaemia of chronic disease
Hoes - Haemorrhage, Hypothyroidism, Haemolysis
Fuck - Failure (renal + bone marrow)
Prostitutes: Pregnancy
What are some causes of macrocytic anaemia:
FAT RBC
F - Foetus (pregnancy)
A - Antifolates (e.g. phenytoin)
T - Thyroid (hypothyroidism)
R - Reticulocytosis (release of larger immature cells e.g. with haemolysis)
B - B12/folate deficiency
C - Cirrhosis (alcohol excess or liver disease)
What are some signs of IDA?
Koilonychia
Atrophic Glossitis
Angular Cheilosis
Post-cricoid webs (PLUMMER-VINSON SYNDROME)
Brittle hair + nails
What are signs of IDA on a blood film?
Microcytic
Hypochromic
Ansiocytes
Poikilocytosis
PENCIL CELLS
How does IDA present with on iron studies?
Decreased Iron
Decreased Ferritin
Increased Transferrin
Decreased Transferrin Saturation
Increased TIBC
What is the commonest cause of IDA?
Bleeding (commonest cause)
Menorrhagia in young women
Name four causes of IDA
Blood loss = Gi loss (e.g. peptic ulcers, Meckel’s diverticulum, menorrhagia etc.)
Increased utilisation = pregnancy/lactation or growth in children
Decreased uptake = prematurity/suboptimal diet
Decreased absorption = coeliac/post-gastric surgery (decreased acid which helps Fe absorption)
Intravascular haemolysis = MAHA/PNH (chronic loss of Fe in urine)
What investigations would youo do for IDA?
IF no obvious cause = OGD + colonoscopy, urine dip, ceolia investigations
What is the treatment of IDA?
- Treat Cause
- Oral Iron
- IV Iron (e.g. Ferrinject/Monofer - anaphylaxis risk)
- Blood transfusion in SEPSIS (iron will not absorb well)
What are some side effcts of oral iron supplements?
Nausea
Abdominal discomfort
Diarrhoea/constipation
Black stools
What are the indications for IV iron?
Poor oral absorption
Failure of oral iron trial
Need for rapid rise (e.g. imminent major surgery)
What is Anaemia of Chronic Disease?
Cytokine driven inhibition of red cell production
EXCEPT in renal failure: it’s due to erythropoeitin (EPO) deficiency which is made by the kidney
What are the causes of ACD?
- Chronic infection (e.g. TB/osteomyelitis)
- Vasculitis (inflammation)
- Rheumatoid arthritis
- Malignancy
What would iron studies show for ACD?
Normal Iron
Increased Ferritin
Decreased Transferrin
Decreased TIBC
Why is Ferritin high in ACD?
Iron is sequestered in macrophage to depreive invasding bacteria of iron
What causes reduced EPO synthesis by the kidneys in renal failure-causing ACD?
Inflammatory markers (e.g. IFNs, TNF, IL1) reduce receptor production and therefore synthesis
Why is iron metabolism dysregualted in ACD?
IL6 and LPS stimulate liver to make hepcidin, which decreases iron absorption from the gut (by inhibiting transferrin) and causes iron accumulation in macrophages
How would you manage ACD?
Treat underlying cause
What are the iron studies of sideroblastic anaemia?
Increased Iron
Increased Ferritin
Decreased Transferin
Decreased TIBC
What would be seen on the blood film of sideroblastic anaemia?
Basophilic stippling
How is sideroblastic anaemia diagnosed?
Ring sideroblasts seen in marrow
What are ring sideroblasts?
Erythroid precursors with iron deposited in mitochrondria in a ring around the nucleus
What are some causes of sideroblastic anaemia?
Congenital or acquired
Myelodysplastic disorders
Post-chemo
Irradiation
ALCOHOL EXCESS
lead excess
Anti-TB drugs
Myeloproliferative disease
?Lead poisoning
What is the management of sideroblastic anaemia?
- Remove cause
- ?Pyridoxine (vitamin B6 promotes RBC production)
- ?Giving EPO
- Transfusions
What is sideroblastic anaemia?
Congenital or acquired anaemias of INEFFECTIVE ERYTHROPOEISIS leading to iron loading, causing haemosiderosis.
What is Transferrin saturation?
Serum Iron / TIBC
IF <20% = IDA
What are the Iron studies for chronic haemolysis?
Increased Iron
Decreased TIBC
Increased Ferritin
What are the iron studies for haemachromatosis?
Increased Iron
Low/Normal TIBC
Increased Ferritin
What are the iron studies for pregnancy?
Increased Iron
Increased TIBC
Normal Ferritin
What is ferritin?
An acute phase protein that increases with inflammation.
What investigations would you do for pancytopenia?
- B12/Folate/Iron
- Abdo exam (Splenomegaly = ?myelofibrosis)
- Reticulocyte count (if low = bone marrow problem)
- Blood Film for abnormal cells (?acute leukaemia) + dysplasia (?myelodysplasia)
- Myeloma screen
- Blood PCR for Parvovirus
- ?check medications
- Bone marrow UNLESS clear cause found from other tests
What are the megaloblastic causes of macrocytosis
- B12 deficiency
- Folate deficiency
- Cytotoxic drugs
What are the non-megaloblastic causes of macrocytosis
- Alcohol
- Reticulocytosis
- Liver disease
- Hypothyroidism
- Pregnancy
What is the most common cause of macrocytosis without anaemia?
Alcohol
What are other haematological diseases causing macrocytosis?
- Myelodysplasia
- Myeloma
- Myeloproliferative disorder
- Aplastic anaemia
What are features of a megaloblastic blood film?
- Hypersegmented polymorphs
- Leucopenia
- Macrocytosis
- Anaemia
- Thrombocyopenia with megaloblasts
What are megaloblasts?
Red cell precursors with an immature nucleus and mature cytoplasm
What vitamin is required for nucelus maturation in megaloblasts?
B12 + Folate
What investigations would you do to assess for macrocytic anaemia?
- Peripheral blood smear
- LFTs
- TFTs
Where does Vitamin B12 come from?
Meat + dairy products
What are some causes of B12 deficiency?
- Diet (e.g. vegans)
- Malabsorption (e.g. pernicious anaemia, post-gastrectomy, ileal resection, crohn’s disease, bacterial overgrowth, tropical sprue + tapeworms)
What glycoprotein is required for the absorption of B12, where is it produced and where is B12 absorbed?
- Intrinsic Factor
- Produced by gastric parietal cells
- B12 absorbed in terminal ileum
What are the clinical features of B12 deficiency?
- Mouth: Glossitis, angular cheilosis
- Neuropsychiatric: Irritability, depression, psychosis, dementia
- Neurological: Paraesthesiae, peripheral neuropathy
Which carboxylic acid is elevated in B12 deficiency?
Serum Methylmalonic Acid (MMA)
What is the most common cause of macrocytic anaemia in Western countries?
Pernicious anaemia
(Usually >40yrs)
What is pernicious anaemia?
A type of B12 anaemia
- Autoimmune atroophic gastritis leading to achlorhydria and lack of gastric intrinsic factor
Achlorhydria = condition where stomach does not produce hydrochloric acid
What are specific tests for pernicious anaemia?
- Parietal cell antibodies (90%)
- Intrinsic factor antibodies (50%)
- Schilling test (outdated - positive if B12 deficiency secondary to pernicious anaemia)
What is the treatment of B12 deficiency?
- Replenish stores with IM hydroxocobalamin (B12) - 6 injections over 2 weeks
- Test for anti-parietla cell/ anti-intrinsic factor Abs as IF autoimmune cause then need 3-monthly injections
What are some sources of folate?
DIET
- Green vegetables
- Nuts
- Yeast
- Liver
What are some causes of folate deficiency?
- Poor diet
- Increased demand (e.g. pregnancy)
OR increased cell turnover (e.g. haemolysis, malignancy, inflammatory disease and renal dialysis) - Malabsorption (e.g. coeliac disease, tropical sprue)
- Drugs (e.g. alcohol, anti-epileptics, phenytoin, methotrexate, trimethoprim)
How does phenytoin cause folate deficiency?
It inhibits folate absorption
What is the management of folate deficiency?
- Oral folic acid
- Ensure B12 checked + replaced before folic acid as it may exacerbate neuropathy of B12 deficiency