Haematology Flashcards
What are the 4 mechanisms behind iron deficiency anaemia?
- Increased loss of iron
- Malabsorption
- Reduced intake
- Increased utilisation of iron
What Hb levels indicate iron deficiency anaemia in men and non-pregnant women?
Men - <130g/L
Non-pregnant women - <120g/L
What is the most common form of anaemia?
Iron deficiency - globally affects 500 million people
How much iron on average is absorbed daily from the diet?
Only 1mg on average of iron is absorbed daily from the diet so even modest blood loss over time can lead to iron deficiency
Give some conditions that can cause iron deficiency anaemia via an increased loss of iron?
- Menorrhagia
- GI bleeding e.g. ulcers
- Hookworm
- IBD
- Malignancy
What is the biggest risk factor for iron deficiency anaemia due to reduced intake of iron>
Poor diet – Main sources of dietary iron; meat, leafy green vegetables, fortified foods including bread and cereals
Vegans, vegetarians, poor or restricted diets at risk
Where does most iron absorption occur?
Small intestine
Which conditions can result in iron deficiency anaemia due to malabsorption?
- Coeliac disease & IBD – result in reduction in the mucosal surface area available for iron absorption
- Gastrectomy & cystic fibrosis – malabsorption of iron occurs at pre-mucosal level when digestive enzyme activity is disrupted
- Intestinal resection & jejuno-illeal bypass: inadequate absorption in the small intestine
- Lymphoma: causes lymphatic obstruction leads to post-mucosal absorption
- Drugs: Reduce absorption of iron e.g. tetracyclines/quinolones (chelate iron), PPIs (decrease gastric acid necessary for iron absorption)
Why can IBD and coeliac disease predispose to iron deficiency anaemia?
Conditions result in reduction in the mucosal surface area available for iron absorption
Why can CF predispose to iron deficiency anaemia?
malabsorption of iron occurs at pre-mucosal level when digestive enzyme activity is disrupted
Why can PPIs predispose to iron deficiency anaemia?
decrease gastric acid necessary for iron absorption
What 2 patient populations are at risk of iron deficiency anaemia due to increased utilisation of iron?
- Pregnancy
- Growth spurts in children
Describe the MCV in iron deficiency anaemia
Low (microcytic)
Describe the appearance of RBCs in iron deficiency anaemia
Higher % of hypochromic cells (pale cells)
What type of heart failure can iron deficiency anaemia cause?
High-output heart failure
What are 2 other causes of microcytic hypochromic anaemia? (i.e. differentials for iron deficiency anaemia)
- Thalassaemia
- Sideroblastic anaemia
What is thalassaemia?
A genetic defect of Hb production common in certain parts of the world e.g. Mediterranean coast
What is sideroblastic anaemia?
A congenital or acquired inability to integrate iron into haemoglobin
Give some causes of anaemia of chronic disease?
- Inflammatory arthritis
- Cancer
- Kidney disease
- Infections (e.g. TB, HIV)
What symptoms are common in iron deficiency anaemia?
N.B. Iron deficiency anaemia is often asymptomatic or only causes mild symptoms, especially if the anaemia develops gradually in otherwise healthy individuals (able to compensate).
- Lethargy
- Tiredness
- Weakness
- Jaundice
- Heavy periods
- Change in bowel habits
What red flags may be seen in iron deficiency anaemia?
- Dysphagia
- Weight loss
- Dyspepsia
- Abdominal pain
- Rectal bleeding
- Change in bowel habit
Clinical signs potentially seen in iron deficiency anaemia?
- Conjunctival pallor
- Pale mucosal membranes (mouth)
- Angular cheilitis (ulcers/cracking at corners of mouth)
- Atrophic glossitis (painful tongue with loss of papillae)
- Koilonychia (spoon-shaped nails)
- Dry skin and hair
- In severe anaemia:
- Tachycardia
- Murmurs
- Signs of cardiomegaly
- Sins of heart failure e.g. peripheral oedema
results of FBC in iron deficiency anaemia?
- Low Hb - anaemia
- Low MCV (<95fl) - microcytic
- Reduced MCH - hypochromic
- Reduced MCHC
- Increased red cell distribution width (RDW)
What is the MCH?
The mean corpuscular haemoglobin is he average mass of haemoglobin per red blood cell in a sample of blood → diminished in hypochromic anaemias.
What is MCHC?
The mean corpuscular hemoglobin concentration (MCHC) is the average concentration of hemoglobin in your red blood cells.
What does an increased red cell distribution width (RDW) indicate?
indicates variation in size of RBCs
Describe the ferritin levels in iron deficiency anaemia
Low - as iron stores in the body are mobilised to counteract the iron deficiency
Ferritin is an acute phase reactant. What does this mean?
It rises in inflammatory states
Patients who are iron deficient may appear to have normal (or even raised) serum ferritin levels in the context of acute inflammation (infection, autoimmune disease)
Describe the transferrin saturation levels in iron deficiency anaemia
Low - as less iron to saturate the transferrin
Describe the total iron binding capacity (TIBC) in iron deficiency anaemia
Raised total iron-binding capacity (TIBC) → there is increased capacity to bind iron due to reduced levels of iron
In what form is iron best absorbed?
In its ferrous state (Fe2+)
Once absorbed into the bloodstream, what is iron bound by?
Transferrin
What stores iron?
Ferritin
Describe a blood film in iron deficiency anaemia
Hypochromic cells (pale) which differ in size (anisocytosis) and shape (poikilocytosis)
Define anisocytosis
having red blood cells (RBCs) that are unequal in size
Define poikilocytosis
an increase in abnormal red blood cells of any shape
When should B12 and folate levels be checked in anaemia?
- Presenting with normocytic/macrocytic anaemia and low or normal ferritin
- Who have not demonstrated an adequate response to iron treatment
Which antibody is screened for in suspected coeliac disease?
tissue transglutaminase antibody
If a patient has recently travelled to high-risk areas, what test can be done if they present with anaemia?
Stool examination → detect parasites
What are some red flags for GI malignancy in those presenting with iron deficiency anaemia?
- > 60 y/o
- Premenopausal women with bowel symptoms
- Family history of GI cancer
- Persistent anaemia despite treatment
What is the treatment for iron deficiency anaemia?
- Ferrous sulphate (oral or IV)
- Treat underlying cause
Risk of IV ferrous sulphate?
Anaphylaxis
Side effects of oral iron?
- Unreliable, not good compliance
- Side effects: nausea, GI irritation, constipation/diarrhoea
Give 3 major causes of microcytic anaemia
- Iron deficiency anaemia (most common)
- Sideroblastic anaemia
- Alpha and Beta Thalassaemia
Define microcytic anaemia
Microcytic anaemia is defined as the presence of small, often hypochromic, RBCs in a peripheral blood smear and is usually characterised by a low MCV (less than 83 microns)
What are the major causes of macrocytic anaemia?
- B12/folate deficiency
- Haemolysis
- Marrow damage
- Metabolic e.g. thyroid/liver disease
Give 3 major causes of normocytic anaemia
- Anaemia of chronic disease
- Inflammatory
- Acute blood loss
Do we have an excretory mechanism for iron?
No excretion, only 7% is consumed. Therefore, mostly recycled.
How can B12 deficiency lead to anaemia?
B12 is essential for synthesis of RBCs
Where is B12 absorbed?
Terminal ileum
What is required for the absorption of B12 in the terminal ileum?
Intrinsic factor
Which cells produce intrinsic factor?
Gastric parietal cells
Why is a daily intake of folate required?
Not stored well
Where is folate absorbed?
Upper small bowel
Define macrocytosis
Refers to RBCs that are larger than normal
Define macrocytic anaemia
Fall in Hb + large RBCs
Macrocytic anaemia can be divided into what 2 groups?
- Megaloblastic
- Non-megaloblastic
What are megaloblastic types of macrocytic anaemia caused by?
due to B12/folate deficiency → characterised by the failure to synthesise adequate amounts of DNA
What is the most common cause of B12 deficiency in the UK?
Pernicious anaemia
Give some other causes of B12/folate deficiency
- Dietary insufficiency
- Malabsorption:
- Crohn’s disease
- Gastrectomy
- Atrophic gastritis
- Malnutrition (e.g. alcoholism)
Give some causes of non-megaloblastic macrocytic anaemia
- Alcoholism
- Liver disease
- Bone marrow failure
- Myelodysplastic syndromes (MDS)
How does haemolysis lead to macrocytic anaemia?
Causes reticulocytosis - RBCs are large and immature due to compensation
What conditions cause haemolysis?
Malaria
Autoimmune conditions e.g. lupus
Risk factors for B12 deficiency?
- Pernicious anaemia
- Dietary (think vegan/veggie)
- Medications; PPIs
- Gastrectomy
- Elderly age
- Atrophic gastritis
- Small bowel problems; Crohn’s disease, terminal ileum resection
Risk factors for folic acid deficiency?
- Dietary
- Small bowel disease/malabsorption
- Increased usage (pregnancy, haemolysis, inflammatory disorders)
- Drugs: PPI’s & certain anticonvulsants (e.g. Phenytoin) can prevent uptake of folic acid
- Alcohol
- Pregnancy
Complications of macrocytic anaemia?
- Heart failure
- Enlarged heart
- Circulatory problems
Why → when the blood does not have enough Hb, it does not have enough oxygen so the body will try to fix this by increasing heart rate and/or blood pressure
Symptoms of B12 deficiency?
- Jaundice
- Glossitis
- Aphthous ulcers
- Angular cheilitis
- Paraesthesia
- Visual disturbances
- Irritability
- Depression
- Pseudo-dementia (always check B12 in new onset dementia)
Why should you always check B12 in new onset dementia?
Can be a cause
MCV in macrocytic anaemia?
High
Treatment for B12/folate deficiency anaemia?
- IM B12 injections
- Folic acid supplements
- Often need potassium & iron too (B12 can cause potassium to drop)
What foods are rich in B12?
fish, meat and dairy
What is pernicious anaemia?
An autoimmune disorder affecting the gastric mucosa, resulting in vitamin B12 deficiency (pernicious means – causing harm, especially in a gradual or subtle way).
Pathophysiology behind pernicious anaemia?
- Antibodies to intrinsic factor +/- gastric parietal cells
- IF antibodies → bind to IF, blocking the B12 binding side
- Gastric parietal cell antibodies → reduced acid production and atrophic gastritis
- Reduced IF production → reduced B12 absorption
Why can small bowel bacterial overgrowth lead to b12 deficiency?
as bacteria utilise vitamin B12
2 major complications of pernicious anaemia?
- Megaloblastic anaemia → B12 is important in the production of blood cells
- Neuropathy → B12 is important in the myelination of nerves
Why can B12 deficiency lead to neuropathy?
B12 is important in the myelination of nerves
What blood group is at risk of pernicious anaemia?
A
Neurological features of B12 deficiency?
- Peripheral neuropathy – pins and needles, numbness (typically symmetrical and affects the legs more than the arms)
- Neuropsychiatric features – memory loss, poor concentration, confusion, depression, irritability
- Progressive weakness
- Ataxia
- Paraesthesia
MCH in pernicious anaemia?
High (macrocytic)
What is the MCH?
the average amount of Hb in each RBC
Blood film results in pernicious anaemia?
megaloblasts (large) and oval-shaped RBCs
What Abs can be tested in suspected pernicious anaemia?
Anti-intrinsic factor Abs
Management of pernicious anaemia?
Life-long replacement treatment with cobalamin (B12)
What is cobalamin?
vitamin B12
What characterises Hodgkin’s lymphoma?
Reed-Sternberg cells in lymph node biopsy
Risk factors for Hodgkin’s lymphoma?
- Epstein Barr virus
- HIV
- Smoking
- Immunosuppression
Presentation of Hodgkin’s lymphoma?
- Young adults
- Cervical or supraclavicular tender lymphadenopathy
- Alcohol induced pain
- Compression of surrounding structures e.g. SOB, abdominal pain
- B symptoms – fever, night sweats, weight loss)
Which 2 infections can predispose to anaemia of chronic disease?
- HIV
- TB