GP - Anaemia Flashcards
What is aplastic anaemia?
Characterised by:
- Pancytopenia (reduced RBC, WBC and platelets)
- Hypoplastic bone marrow (few blood cells vs aplastic which is no cells)
Peak incidence = 30-yrs old
What are the features of aplastic aneamia?
Features:
- Normochromic, normocytic anaemia
- Leukopenia (lymphocytes relatively spared)
- Thrombocytopenia
- Can be the presenting features of acute lymphoblastic or myeloid leukaemia
What can cause aplastic anaemia?
- Idiopathic
- Infections: parvovirus, hepatitis
- Congenital: Fanconi anaemia, dyskeratosis congenita (DKC)
- Drugs: cytotoxics, chloramphenicol, sulphonamides, phenytoin, gold
- Toxins: benzene
- Radiation
What are some ‘Red-flag’ questions for suspected anaemia?
- Indigestion or vomiting - upper GI cancer can present with anaemia + these symptoms
- Blood loss anywhere - urine, on wiping front/back passage, in stool, in sperm, vaginal bleeding, haematemesis, haemoptysis
- Diet - diet low in red-meat / vegetarian / vegan can cause iron-deficiency anaemia
- Change in bowels (loose/constipated) - a symptom of bowel cancer can be anaemia
- Medications - NSAIDs can increase risk of peptic ulcer and GI inflammation –> causing anaemia
What are the normal ranges for haemoglobin in men and women?
- Men = 130 - 180 g/L
- Women = 115 - 165 g/L
What are some causes of Microcytic Anaemia?
Causes of Microcytic anaemia (< 80 fL):
- Iron-deficiency anaemia
-
Thalassaemia
- In beta-thalassaemia minor, the microcytosis is disproportionate to the anaemia
- Congenital sideroblastic anaemia
-
Anaemia of chronic disease
- more commonly a normocytic, normochromic picture
- Lead poisoning
What are the main categories of anaemia?
- Microcytic = < 80 fL
- Normocytic = 80-100 fL
- Macrocytic = > 100 fL
New onset microcytic anaemia in a pt > 60-yrs requires investigation for what?
2WW referral to invetigate for colorectal cancer
What are some causes of normocytic anaemia?
-
Anaemia of chronic disease
- Can be microcytic but more commonly normocytic
- Chronic kidney disease (CKD) - deficiency of erythropoietin
- Aplastic anaemia (pancytopenia)
- Haemolytic anaemia (↑ reticulocytes)
-
Acute blood loss
- Hb doesn’t drop immediately in blood loss as the concentration of Hb doesn’t actually fall
- Sickle Cell anemia
What are some causes of macrocytic anaemia?
Megaloblastic bone marrow:
- Vitamin B12 deficiency
- Folate deficiency
Normoblastic bone marrow:
- alcohol
- liver disease
- hypothyroidism
- reticulocytosis (increased immature RBCs)
- myelodysplasia (cancers in which immature blood cells don’t mature)
- pregnancy
- drugs: cytotoxics
What is Megaloblastic anaemia?
Anaemia (of macrocytic classification) which results from inhibition of DNA synthesis during RBC production
- DNA synthesis impairment –> cell cycle can’t progress from G2 growth stage to mitosis –> results in continued cell growth without division (macrocytosis)
- Often due vitamin deficiency:
- Vitamin B-12 deficiency
- Folate deficiency
What are some causes of hereditary haemolytic anaemia?
RBC membrane defects:
- hereditary spherocytosis
- hereditary elliptocytosis
Metabolism defect:
- G6PD deficiency
Haemoglobin defects:
- Sickle cell anaemia
- Thalassaemia
What are some causes of Acquired haemolytic anaemia?
Immune causes:
- Autoimmune - warm / cold antibody type
- Alloimmune - tranfusion reaction, haemolytic disease of newborn
- Drugs - methyldopa, penicillin
Non-immune causes:
-
Microangiopathic haemolytic anaemia (MAHA) - TTP / HUS, DIC, malignancy, pre-eclampsia
- Microangiopathy - refers to microvascular disease
- Prosthetic cardiac valves
- Paroxysmal nocturnal haemoglobinuria (PNH)
- Malaria
- Drugs - Dapsone (Abx often used for; leprosy, dermatitis herpetiformis, pneumocystis jirovecii pneumonia)
What is Fanconi anaemia?
Autosomal recessive - impaired response to DNA damage
Features:
- aplastic anaemia
- increased risk of acute myeloid leukaemia
- ~80% develop bone marrow failure by 20-yrs
- skeletal abnormalities e.g. short stature
- skin hyperpigmentation e.g. cafe au lait spots
What is pernicious anamia?
Pernicious anaemia is a type of B-12 deficiency anaemia, resulting from an autoimmune condition against gastric parietal cells or intrinsic factor → ↓ B-12 absorption
Epidemiology:
- F > M
- Commoner in middle age - old age
- Increased risk of gastric carcinoma
Associated with other autoimmune conditions:
- Thyroid disease
- Addisons
- RA
- Vitiligo
What are the features of pernicious anaemia?
General:
- Lethargy & weakness
- SoB
- Paraesthesia
- Glossitis (inflammed tongue)
- Mild jaundice
- Diarrhoea
- Premature grey hair
- Fever (low-grade)
- Neurological: mild cognitive impairment, ataxia, muscle weakness
- Signs: retinal haemorrhages, mild splenomegaly, retrobulbar neuritis (posterior optic nerve inflammation)
What are the causes of B12 deficiency?
- Poor intake
- Vegan diet
- Malabsorption of B12
- Pernicious anaemia (most common!)
- Gastrectomy (no or reduced intrinsic factor from gastric mucosa)
- Terminal ileum disease (Crohn’s) / Resection
- Coeliac disease
- Losses
- Cancer
What are the causes of folate deficiency?
- Poor Intake:
- old age
- poverty
- alcohol excess (though beer is a good source!)
- anorexia
- Malabsorption:
- coeliac disease (more common to experience folate than B12 deficiency)
- tropical sprue (tropical malabsorption disease with inflammation of lining of small intestine)
- Excess utilization:
- pregnancy, lacatation, prematurity
- chronic haemolytic anaemia, malignant and inflammatory diseases
- dialysis
- Drugs:
- Methotrexate
- Anticonvulsants
What are the causes of iron deficiency anaemia?
Poor dietary iron intake:
- Diet low in red meat or low in dark greens if vegetarian / vegan
Malabsorption:
- Coeliac disease
- Colorectal cancer
- Bowel ressection
- IBD
Excessive blood loss:
- Menorrhagia (most common cause of iron-deficiency in pre-menopausal women)
-
GI bleed:
- peptic ulcer
- mallory weiss tear
- oesophageal varices
- diverticulitis
- colorectal cancer
- haemorrhoidal bleeding
- Parasitic (hookworm, Africa)
- Haematuria
- Medication (blood thinners)
- Pregnancy (↑ demands)
How do you treat iron deficiency anaemia?
Treat underlying cause!!
Oral ferrous sulfate:
- Continue take iron medication for 3-months after iron-deficiency has been corrected (normal Hb) to replenish iron stores
- Side-effects:
- nausea
- abdo pain
- constipation
- diarrhoea
- dark stools
What are the signs of iron deficiency anaemia?
- Brittle hair + nails
- Atrophic glossitis (bald/smooth tongue, tender, due to atrophy of lingual papillae)
- Angular stomatitis
- Koilonychia
How is B12 deficient anaemia managed?
If no neurological involvement:
- 1 mg of IM hydroxocobalamin (B12) 3 times per week for 2-weeks –> then once every 3-months
If pt is also deficient in folic acid:
- Treat B12 deficiency 1st!! –> this is to avoid precipitating subacute combined degeneration of the spinal cord (Lichtheim’s disease) - which can be caused by B12 deficiency
What are the counselling points of iron replacement therapy?
- Black poo!
- If you experience side-effects –> can be reduced by changing preparation
- SEs: nausea, abdo pain, diarrhoea, constipation
- Avoid taking with food (reduces absorption) unless it is causing nausea
- Avoid taking with:
- tea
- coffee
- milk
- eggs
- But can take with OJ (acid helps absorption)
- Will take a few months before benefit is felt
When should iron replacement be used with caution/ not be given?
- May exacerbate symptoms of;
- IBD
- diverticular disease
- intestinal strictures
- Can reduce absorption of;
- Levothyroxine
- Bisphosphonates
- Stop 7 days before colonoscopy (black sticky stools makes hard to visualise)
What is Coomb’s test?
aka direct antiglobulin test
Coombs’ Test:
Direct Coombs’ test (direct antiglobulin test):
- Tests a sample of red blood cells, and identifies RBCs coated with antibody/complement
-
Positive result (agglutination) = ususally indicates an immune cause of anaemia e.g.
- Autoimmune haemolytic anaemia (AIHA) - cold / warm subtypes
- Alloimmune - tranfusion reaction, haemolytic disease of newborn
- Drug induced haemolysis - methyldopa, penicillin
Indirect Coombs’ test:
- Test is done on a sample of blood serum
- Detect antibodies in the serum that could bind to certain red blood cells, leading to problems if blood mixing occurs (e.g. pregnancy)
- Uses:
- Pre-transfusion testing e.g. blood types / cross-matching
- Pre-natal antibody screen (IgG antibodies that can cross placenta)
What is Autoimmune haemolytic anaemia (AIHA)?
Autoimmune heamolytic anaemia (AIHA) is characterised by a positive direct antiglobulin test (i.e. Direct Coombs’ test positive)
- Cause = often idiopathic - can be secondary to lymphoproliferative disorder, infection or drugs
- AIHA divided into 2 types - depending on the temp the antibodies best cause haemolysis:
- Warm
- Cold
What are the features of Warm AIHA?
Warm AIHA:
- Antibody (usually IgG antibody) causes haemolysis best at body temp
- Haemolysis tends to occur in extravascular sites e.g. spleen
- Management:
- Steroids
- Immunosuppression
- Splenectomy
- Causes:
- autoimmune disease e.g. SLE
- neoplasia e.g. lymphoma, CLL
- drugs e.g. methyldopa
What is hereditary spherocytosis?
Hereditary spherocytosis = cause of inherited haemolytic anaemia - due to RBC membrane defect (bi-concave disc shape replaced with sphere-shape)
- Is the most common form of inherited haemolytic anaemia in the US and northern Europe
- Autosomal dominant
- RBC survival reduced (destroyed be spleen) –> haemolytic anaemia
Features:
- Failure to thrive
- Pallor
- Neonatal jaundice
- Splenomegaly
- Gallstones
- Aplastic crisis (precipitated by parvovirus infection) - body doesn’t make enough RBCs to replace those lost to haemolysis (reticulocytopenia)
- Variable degree of haemolysis
- MCHC elevated (mean corpuscular haemoglobin)
Treatment:
- Folic acid replacement
- Splenectomy
Diagnosis:
- British journal of haematology recommend diagnosis if following picture:
- FHx of hereditary spherocytosis
- Typical clinical features
- Spherocytes on blood film
- Raised MCHC
- Increased reticulocytes
- If unsure –> EMA binding tests for specific binding
What are the features of Cold AIHA?
Cold AIHA:
- Antibody (usually IgM antibody) causes haemolysis best at ~ 4 degrees C
- Haemolysis is mediated by complement
- Commonly occurs at intravascular sites
- Features:
- May have Raynaud’s symptoms
- May have acrocyanosis (persistent, painless, symmetric cyanosis of the hands + feet or face) - due to vasospasm of small vessels in response to cold
- Management:
- Pts respond less well to steroids
- Causes:
- neoplasia e.g. lymphoma
- infections e.g. mycoplasma,
What are the main signs of anaemia?
- Fatigue / weakness
- Pale or yellowish skin
- Irregular heartbeats
- SoB – worse if underlying respiratory or cardiac disease
- Dizziness or light-headedness
- Chest pain – worse if underlying arterial disease
- Cold hands and feet
- Headache
