Anaemia [COMPLETE] Flashcards
1
Q
Structure of RBCs
A
no nucleus
biconcave shape
2
Q
What makes RBCs good at transporting oxygen?
A
Biconcave shape
Haemoglobin
3
Q
How long do RBCs last?
A
120 days
4
Q
How can you tell if RBCs are immature?
A
Visible reticulocytes (immature RBC with nucleus)
5
Q
How can you tell if RBCs are lysing too quickly?
A
Patient has jaundice - Bilirubin is a byproduct of RBC breakdown
6
Q
What percentage of the blood are RBCs?
A
40-45%
7
Q
How do RBCs work to transport oxygen to tissue?
A
- RBCs travel to lung to pick up oxygen
- Oxygen binds to haemoglobin to form oxyhemoglobin
-Circulated to tissue
-Oxygen is liberated from haemoglobin to give deoxyhaemoglobin
-RBCs travel back to lung
8
Q
What is the production of RBCs called?
A
Erythropoiesis
9
Q
Describe the process of erythropoiesis?
A
Stem cells produced in bone marrow –> common myeloid progenitor cell –> erythroblasts –> reticulocyte (immature RBC which enter bloodstream to mature) –> erythrocyte
10
Q
What hormone is required to stimulate erythropoiesis?
A
Erythropoietin (EPO)
11
Q
Where is EPO synthesised?
A
In the kidney in response to an increased oxygen demand (hypoxia)
12
Q
What are some other things needed for erythropoiesis? (THREE THINGS)
A
Iron
Folate (VIT B9) - needed for DNA synthesis and production of cells
Vitamin B12 - Removes CH3 from THF (tetrahydrofolate) so folate can be used
13
Q
A
14
Q
Define anemia.
A
Less RBCs that normal OR reduced Hb in each red blood cell leading to less oxygen carried in bloodstream
15
Q
What is optimal haemoglobin concentration dependent on?
A
- Age
- Sex
- Elevation (altitude)
- Pregnancy
16
Q
Why is there a higher prevalence of anaemia in pregnant women?
A
Blood volume expands to accommodate for mother and baby + higher oxygen need BUT more RBCs are not being made –> DILUTIONAL ANAEMIA.
17
Q
What is considered a reduction of haemoglobin in males and females?
A
Males - less than 13g/dL
Females - less than 12g/dL (lower due to menstruation)
18
Q
What are the causes of anaemia (TWO broad)
A
Increased Hb loss
Decreased Hb production
19
Q
What may lead to an increase in Hb loss?
A
Haemmorhage ( internal or external bleeding, trauma, injury, aneuryms, weakness in arterial wall, bleeding disorders)
Chronic low volume loss
Excessive haemolysis (infections, meds, cancer, autoimmune disorders, overactive spleen
20
Q
What may lead to an decrease in Hb synthesis ?
A
Reduced proliferation of precursors:
Iron deficiency
Anaemia of chronic disease
Anaemia of renal failure
Aplastic anaemia
Infiltration of bone marrow
Defective maturation of precursors
Folate deficiency
Vit B12 deficiency
Iron deficiency
Disorder of globin synthesis (thalassaemias) or iron metabolism
21
Q
Symptoms of anaemia.
A
Fatigue
Low energy
Increased HR
Shortness of breath
Headache
Dizziness
Chest pain
22
Q
Symptoms of severe anaemia.
A
Fainting
Chest pain/angina
Heart attack
23
Q
Anaemia classification by disease (FIVE).
A
- Aplastic and hypoplastic (bone marrow failure)
- Nutritional (iron/B12/folate deficiency)
- Common haemolytic (sickle cell/thalassaemias)
- Autoimmune haemolytic anaemia
- Anaemias of chronic disease (chronic renal failures)
24
Q
What is MCV?
A
Mean corpuscular volume - size of red blood cells
25
Anaemia classification by size and colour of RBCs (THREE).
1. MICROCYTIC
2. MEGALOBLASTIC
3. HAEMOLYTIC
26
What are some causes of microcytic anaemias?
Iron deficiency
Chronic disease
Sideroblastic anaemias (RARE)
27
What are some causes of megaloblastic anaemias?
Folate deficiency
Vitamin B12 deficiency
28
What are some causes of haemolytic anaemias?
Autoimmune
Sickle cell
Thalassaemia
G6PD deficiency
29
What do blood tests used to indicate anaemia look at? (SEVEN)
FBC is done.
Hb
RBC count
MCV
Haematocrit
Also Iron, folate and Vit b12
30
What is the normal MCV?
80-100fL (fentolitres)
31
What is haematocrit?
The proportion of RBCs in the blood
32
What are some causes of iron deficiency anaemia? (THREE)
Inadequate iron absorption (diet, malabsorption from gut)
Increased loss (chronic blood loss - menstruation, Gi tract such as ulcers or cancers or IBD)
Increased requirement (Pregnancy, other physiological demands)
33
Complications of anaemia. (not pregnant - FOUR)
- cognitive/behavioural impairment in children
- impaired muscular performance
- heart failure (severe cases
- lowered immunity and higher risk of morbidity from infection
34
Complications of anaemia. (PREGNANCY - THREE)
- Increased morbidity for mum and baby
- Preterm delivery (BEFORE 37 WEEKS)
- Post partum fatigue, altered cognition, PPD
35
Signs (8) and symptoms (3) when assessing for anaemia?
Symptoms: fatigue, dyspnoea, headache
Signs: Pallor , atrophic glossitis (smooth tongue), dry skin. dry hair, alopecia. angular cheilitis/stomatitis, nail changes, pica
36
How is iron deficiency anaemia assessed? (FOUR)
FBC (low Hb, low MCV)
Ferritin (iron stores less than 30mcg/L)
Reduced mean cell Hb (hypochromia -loss of colour)
Exclusion of underlying cause (GI bleeds, cancer, ulcers)
37
Why is ferritin and not serum iron tested?
Ferritin is an iron complex that shows the amount of iron incorporated into RBCs.
Serum iron only shows Fe2+ and has diurnal variations.
38
When should a patient being assessed for iron deficiency anaemia be referred? (EIGHT)
- GI symptoms that could suggest bleed or malignancy
- FIT (faecal immunochemical test) with Hb of least 10mcg/g of stool
- Men and post menopausal women with iron deficiency anaemia (unless overt non-GI bleed)
- Pregnant women with severe symptoms or severe anaemia (Hb < 70g/L) or advanced gestation (34 weeks)
- Coeliac serology +ve
- Profound anaemia with heart failure signs
- No response or not tolerating oral iron treatment
- Initial response to treatment but anaemia recurs with no underlying cause
39
What does of iron is needed to treat iron deficiency anaemia?
65mg elemental iron once daily on empty stomach
40
Doses of iron formulations?
Ferrous sulphate, ferrous fumarate: 1 tablet OD
Ferrous gluconate: 2 tablets OD
41
What can be done if daily oral iron is not tolerated?
Alternate daily dosing
42
How long should a patient continue to take oral iron supplements for?
3-4 months after defiency is corrected
43
How much of a rise in Hb should be seen after 4 weeks of iron supplements?
20g/L in daily dosing
10g/L in alternate day dosing
44
What counselling should a patient given when supplying oral iron supplements? (5)
- Time for symptoms to improve
- Side effects
- If not tolerated - can reduce to alternate days
- Taking on empty stomach vs taking with food to alleviate GI side effects
- Dietary changes : adding iron rich foods
45
What are some side effects of oral iron? (5)
- Constipation
- Diarrhoea
- Epigastric pain
- Nausea
- Dark stools (how to differentiate from bloody stools)
46
What can affect iron absorption? (2)
Taking with food especially whole grain, tea/coffee, dairy
Taking with medications such as antacids, tetracyclines and bisphosphonates
47
What may enhance the absorption of iron?
Vitamin C - take with orange juice
48
What are some examples of iron rich foods? (6)
- Spinach
- Red meats
- Fish
- Apricots
- Prunes
- Raisins
49
Why are modified release preparations of oral iron not reccomended?
poor absorption
50
How should patients taking oral iron supplementation be monitored?
- FBC after 3-4 weeks to look at initial Hb response (Refer if response inadequate)
- Recheck Hb after 2-4 months
- Monitor FBC every 3 months for 1 year and again 1 year later.
51
What may a lack of response to oral iron treatment with 3 weeks indicate? (5)
- Non compliance
- Continued blood loss with inadequate replacement
- Malabsorption
- Incorrect diagnosis
- Complicating factors
52
What is the ongoing prophylactic dose for iron deficiency anaemia?
200mg ferrous sulphate OD
53
Who might benefit from an ongoing prophylactic dose of oral iron? (6)
- Recurring anaemia where further investigation is not appropriate or needed (e.g. elderly)
- Diet unlikely to meet requirements e.g. plant based
- Malabsorption (e.g. coeliac)
- Menorrhagia (heavy periods)
- Pregnant women
- Haemodialysis patients
54
When may parenteral iron be used?
- Oral therapy unsuccessful
- Continuing blood loss
- Continuing malabsorption
- REGULARLY in patients with CKD on dialysis
55
Does parenteral iron produce a faster response to oral iron?
NO - as new RBCs still take time to form
56
What are the types of parenteral iron? (4)
Iron dextran (cosmofer)
Iron sucrose (venofer)
Ferric carboxymaltase (Ferinject)
Ferric derisomaltase
57
How is a dose of parenteral iron calculated?
- Body weight
-Iron need by looking at Hb deficit
58
What should happen when patients taking oral iron are given parenteral iron?
HOLD oral iron for FIVE days.
59
What are the risks associated with parenteral iron? (3)
- Iron overload
- Serious hypersensitivity reactions/anaphylaxis
- Symptomatic hypophosphataemia causing osteomalacia and fractures (FERRIC CARBOXYMALTASE FERINJECT ONLY)
60
How should a serious hypersensitvity to parenteral iron be managed (5 TREATMENTS)
IV CHLORPHENAMINE
IV HYDROCORTISONE
IV PARACETAMOL
OXYGEN
FLUIDS
61
How should the risk of anaphylaxis with parenteral iron be managed?-
- Appropriately trained staff
- Resuscitation facilities
- Closely monitor patients during and 30 mins after administration
- Check patient for known allergies, immune or inflammatory conditions, history of severe asthma/eczema (HIGHER RISK so only use if benefits outweigh risks)
62
What is anaemia of chronic disease associated with?
Anaemia due to inflammatory conditions such as ulcerative colitis, Crohn's disease, systemic lupus erythematosus, rheumatoid arthritis and cancer
63
What happens in anaemias of chronic disease?
There is an impaired response to EPO and inflammatory cytokines which reduce the amount of circulating iron - iron stores may still be normal
64
Serum test results in anaemias of chronic disease. (4)
Serum iron - LOW
Serum ferritin - NORMAL/HIGH
Serum transferrin - NORMAL/HIGH
Total iron binding capacity - LOW
65
Describe RBCs in anaemias of chronic disease.
May be normocytic or microcytic
66
How is iron metabolised in the body?
after ingestion most of it is excreted without being absorbed
stomach - ferric 3+ to ferrous 2+ conversion
Fe 2+ can be absorbed into bloodstream and stored as ferritin
Transferrin makes iron available to be used in the body from ferritin stores
67
Where is transferrin synthesised?
Liver
68
What are the risk factors for anaemias of chronic disease? (6)
Autoimmune disorders
malignancy
acute/chronic infection
critical illness
major trauma
chronic disease
69
How are anaemias of chronic disease treated?
By treating the underlying cause
70
Can anaemias of chronic disease be treated with iron?
NO - Except in CKD patients where IV iron is given with EPO
71
Why does anaemia occur in CKD?
damage to kidney leads to EPO deficiency which causes reduced erythropoiesis.
CKD patients can also have infection or inflammation
72
Haemoglobin levels in patients with anaemia of renal disease?
less than 10g/dL
73
How should anaemia of renal disease be treated?
Erythropoietic stimulating agents such as Epoetin usually given subcutaneously once a week to those who would benefit usually given in severe CKD.
Dose may be dependent on dialysis
74
When should ESAs not be initiated?
If the person has absolute iron deficiency - manage iron deficiency first using IV iron - serum ferritin should not exceed 800mcg/L to avoid iron overload.
75
Should adjuvant supplements like vitamin C, folic acid or carnitine be prescribed in anaemia of CKD.
No
76
Target Hb ranges for people with anaemia of CKD.
Tailor to the person
77
What is sideroblastic anaemia?
A rare, hereditary anaemia where iron is not utilised correctly during erythropoiesis causing the production of ring sideroblasts in the bone marrow - erythroblasts with iron granules surrounding the nucleus.
78
What are a patients iron levels in sideroblastic anaemia?
normal to high
79
Describe the RBCs in sideroblastic anaemia?
Hypochromic - lack colour due to low Hb
Microcytic
80
How may sideroblastic anaemia be acquired?
Impaired haem synthesis due to myeloproliferative disorders or secondary ingestion of drugs
81
What disorders may be associated with sideroblastic anaemias? (4)
Myeloid leukaemia
Myeloma
Myelodysplastic disorders
Collagen diseases
82
What drugs and toxins may be associated with sideroblastic anaemias? (8)
Alcohol
Isoniazid
Chloramphenicol
Penicillamine
Pyrazinamide
Cycloserine
Progesterone
Drugs that cause copper deficiency
83
How is sideroblastic anaemia treated?
Stop any drugs that are known to cause it
X-linked sideroblastic anaemia - trial pyridoxine 50-200mg daily (vit B6 coenzyme) - slow response and blood transfusion may be needed if severe
Idiopathic sideroblastic anaemia - high dose pyridoxine (100-400mg daily)
DO NOT buy OTC iron, vitamins such as ascorbic acid and pyridoxine
84
What are megaloblastic anaemias caused by? (2 broad)
Folate or vitamin B12 deficiency.
85
What size are the RBCs in megaloblastic anaemias?
macrocytic : MCV > 100fL
86
Why do megaloblastic anaemias occur?
defective DNA synthesis causes abnormalities in the maturation of HSCs in the bone marrow
87
What is pernicious anaemia?
A type of megaloblastic anaemia where an autoimmune disease causes atrophy of the gastric mucosa --> less parietal cells --> less secretion of intrinsic factor needed for Vit B12 secretion
Associated with vitiligo and thyroid disease
88
What is the role of folate (folic acid) and vitamin B12 in DNA synthesis.
Needed as cofactors in the synthesis of DNA components (purine and pyrimidine synthesis)
89
medication What are some causes of megaloblastic anaemia? (3 kinda 4)
Medication that modulate purine metabolism - azathioprine, allopurinol, mycophenolate mofetil
Medications that interfere with pyrimidine synthesis - hydroxyurea, trimethoprim
METHOTREXATE INTERFERES WITH BOTH
Medications which affect folate or B12 absorption
90
What would blood tests in megaloblastic anaemias show? (7)
LOW Hb
HIGH MCV
HIGH bilirubin - defective cells broken down more quickly
Low B12 and/or folate
May consider:
Serum autoimmune antibodies (parietal cells and IF in pernicious anaemia)
Bone marrow examination
LFT and TFT to identify underlying cause
91
What are the main clinical features of megaloblastic anaemias? (8)
Glossitis
Angular stomatitis
Altered bowel habit
Anorexia
Mild jaundice
Insidious onset - slow and levels already quite low by the time there are symptoms
Sterility (cannot conceive)
Skin pigmentation
Also regular anaemia symptoms : dyspnoea, headache, lethargy
92
Which clinical features separates folate and B12 deficiency? (2)
B12 deficiency is associated with severe peripheral neuropathy which is bilateral (occurs in both legs but sometimes arms)
also FEVER
93
What are some neurological complications of B12 deficiency? (7)
- Loss of cutaneous sensation
- Loss of mental and physical drive
- Muscle weakness
- Optic neuropathy
- Psychiatric disturbances
- Symmetrical neuropathy
- Urinary or faecal incontinence
94
What level is considered folate deficient?
less than 3mcg/L
95
What are some causes for folate deficiency? (6)
Dietary deficiencies
Alcoholism
GI disorders such as Coeliac disease
Pregnancy - preferential delivery to foetus
Haematological disorders
Medications
96
What dose of folic acid should pregnant women take and why?
400mcg or 5mg (high risk patients) for FIRST 12 WEEKS
risk of neural tube defects in foetus
97
What drugs can cause malabsorption of folate? (5 - PBSCO)
Phenytoin
Barbiturates
Sulfasalazine
Colestyramine
Oral contraceptives
98
What drugs can cause impaired metabolism of folate? (2 important ones)
METHOTREXATE
Pyrimethamine
Triameterene
Pentamidine
TRIMETHOPRIM
99
How is folate deficiency managed? (4)
- Advise on improving dietary intake
- Check for coeliac disease
- Treat with folic acid 5mg daily
- Check B12 levels
100
What are some foods rich in folate? (6)
Beans
Legumes
Citrus
Dark green leafy vegetables
Shellfish
Poultry
101
Why should patients with low folate have their Vitamin B12 levels checked?
Folic acid improves wellbeing but can mask symptoms of low B12 which can lead to neurological disease developing.
If B12 is also low it should replaced first or alongside folic acid
102
What level is considered Vitamin B12 deficient?
less than 200ng/L
103
How is B12 absorbed?
It binds to intrinsic factor to form the IF-B12 complex which binds to surface receptors in the ileum so B12 can be absorbed.
104
What is the most common cause of severe B12 deficiency?
Pernicious anaemia
105
What are some other causes of B12 deficiency (NOT pernicious anaemia)? (5)
Drugs
Gastric (gastrectomy, congenital IF deficiency)
Inherited
Intestinal (malabsorption, ileal resection, crohn's, parasites)
Nutritional (malnutrition, vegan diet (B12 found in meat)
106
How much vitamin B12 is needed daily?
1-3 mcg , stores last 2-5 years so slow onset
107
What are some drugs that can cause a decreased absorption of Vitamin B12?
Cycloserine
Isoniazid
Metformin
Amosalicylic acid
Colchicine
Neomycin
H2 antagonists
PPIs
108
What drug can destroy Vitamin B12?
Nitrous oxide (anaesthesia)
109
How is Vitamin B12 deficiency managed?
INTRAMUSCULAR hydroxocobalamin
ORAL cyanocobalamin
110
What should patients with a known cobalt allergy be advised before taking hydroxocobalamin or cyanocobalamin?
Risk of adverse skin reactions up to 72 hours after dose.
Assess risk vs benefit if person develops a reaction
111
How should Vitamin B12 deficiency be managed in patients with neurological symptoms?
- Urgent specialist advice should be sought
- IM hydroxocobalamin 1mg on alternate days until there is no more improvement in symptoms then 1mg every 2 months
112
How should Vitamin B12 deficiency due to medicine be managed in patients without neurological symptoms?
- Give IM or PO B12 while taking medicine or see if an alternative medication can be given
113
How should B12 deficiency due to dietary causes be managed?
- Rule out other causes and explore person's diet
- improve dietary intake : eggs. meat, dairy, salmon, cod, or foods fortified with B12
- Consider ORAL cyanocobalamin 50-150mg OD between two meals or 1mg OD in pregnancy/breastfeeding
114
How should B12 deficiency due to dietary causes be managed in patients with adherence issues?
Initally IM hydroxocobalamin 1mg 3 times a WEEK for 2 WEEKs
115
What is the maintenance dose for Vitamin B12 ?
PO Cyanocobalamin 50-150mcg OD
IM Hydroxocobalamin 1mg twice a year
Treatment can be stopped when B12 is corrected and diet has improved but may be lifelong for vegan diet
116
What is haemolytic anaemia?
Reduced lifespan of erythrocytes
RBCs are lysing quicker than they are being produced
Can be caused by genetic and acquired disorders
117
How will RBCs look in haemolytic anaemias?
Normochromic and normocytic but bursting
118
What are some symptoms of haemolytic anaemias?
Malaise
Fever
Abdominal pain
Dark urine
Jaundice
119
What is sickle cell anaemia?
Deformed RBCs sickle cell shape so reduced surface area and less able to pick up oxygen and flow around the bloodstream leading to anaemia
120
What can cause sickle cell anaemia symptoms to get worse?
Infection with parvovirus (slapped cheek syndrome)
121
What are the symptoms of sickle cell anaemia?
sudden drop in RBCs leading to headache, rapid heartbeat, dizziness, fainting
122
Do patients with sickle cell anaemia have symptoms all the time?
No but they can come on very suddenly
123
How is sickle cell anaemia treated?
Blood transfusion
124
What can also cause anaemia in young children with sickle cell?
swelling of the spleen
will require blood transfusion
125
What else can sickle cell anaemia cause?
Sickle cell crises
Frequent infection
126
What is a sickle cell crisis?
Blockage of blood vessels due to sickle shape of cells.
Leads to extreme pain lasting days or weeks
Commonly in limbs or back but can affect any part of the body
Frequency can vary - once a week or less than once a year
Requires hospitalisation - IV fluids, IV opioids, treating any concurrent infections
127
What are some complications of sickle cell crises?
Skin ulceration
Renal failure
Increased susceptibility of infection - due to spleen being damaged
128
How is sickle cell anaemia managed?
Folic acid --> increased haemolysis leads to an increase in erythropoiesis so more demand for folate
Severe cases: Blood transfusions or hydroxycarbamide
Chelation therapy
Prophylactic antibiotics
129
Why are patients on regular transfusions for sickle cell anaemia given chelation therapy?
Chelation therapy such as deferasirox or desferoxamine prevents iron overload by forming a complex with iron so less of it is absorbed.
130
What is G6PD deficiency?
A recessive hereditary disease - lack of G6PD enzyme which protects RBCs from haemolysis and premature destruction so person is more susceptible to acute haemolytic anaemia when they have an infection, when they take certain drugs or when eating fava beans
131
Who is at risk of G6PD deficiency?
Individuals from Africa, Mediterranean and Middle East
More common in men
132
How are drugs that can cause acute haemolytic anaemia in G6PD deficiency classed?
Definite risk vs possible risk
- patient variability for each drug
- risk is dose related
133
What are some drugs with a definite risk in G6PD deficiency?
Dapsone da
Fluoroquinolones
Quinolones
Nitrofurantoin
Primaquine
Rasburicase (hyperuricaemia following chemo)
Sulfonamides (including co-trimoxazole)
134
What are some drugs with a possible risk in G6PD deficiency?
Aspirin (up to 1g daily is acceptable in most patients)
Chloroquine (acceptable if being used in malaria)
Menadione (Vit K3)
Quinine (acceptable for acute malaria)
Sulfonylureas (-ide diabetes drugs)
135
What is thalassaemia?
An inherited autoimmune disorder where a person produces little to no haemoglobin so oxygen can't be carried around the body leading to anaemia symptoms.
136
What is the most severe type of thalassaemia?
Beta thalassaemia - can cause serious organ damage and life threatening complications
137
How is thalassaemia managed?
regular blood transfusions - patient will also need chelation therapy to avoid iron overload
138
What is the only cure for thalassaemia?
Stem cell/bone marrow transplant
