Anaemia Flashcards
1
Q
What is anaemia defined as?
A
Low Hb concentration
Hb <135g/L for men OR <115g/L for women
2
Q
Give the symptoms of anaemia
A
May be due to the cause or due to the anaemia itself Fatigue Dyspnoea Faintness Palpitations Tinnitus Anorexia Headache
3
Q
What are some signs of anaemia
A
May be absent
Pallor - conjunctival pallor although not a reliable sign
Angina if pre-existing coronary artery disease
Hyperdynamic circulation in severe anaemia - ejection systolic murmur heard at the apex and cardiac enlargement
Retinal haemorrhages
Heart failure
4
Q
In what situation may blood transfusion for anaemia be fatal?
A
In heart failure
5
Q
Which blood value is most important to look at when diagnosing anaemia
A
MCV (mean cell volume)
6
Q
List some causes of a microcytic anaemia (low MCV)
A
Iron deficiency Thalassemia Sideroblastic anaemia (very rare)
7
Q
What happens to iron in thalassemia?
A
Accumulation so tests show increased iron and ferritin with a low total iron binding capacity
8
Q
List some causes of normocytic anaemia (normal MCV)
A
Acute blood loss Anaemia of chronic disease Bone marrow failure Hypothyroidism Renal failure Haemolysis Pregnancy
9
Q
What should you suspect if there is decreased WCC or decreased platelets in normocytic anaemia?
A
Bone marrow failure
10
Q
List some causes of macrocytic anaemia (high MCV)
A
B12 or folate deficiency Alcohol excess or liver disease Reticulocytosis Cytotoxic - hydroxycarbamide Myelodysplastic syndromes Marrow infiltration Hypothyroidism Antifolate drugs (phenytoin)
11
Q
What is reticulocytosis?
A
> 2% of RBCs are reticulocytes or reticulocyte count >100
12
Q
How may a haemolytic patient present?
A
Mildly jaundice - pre hepatic unconjugated jaundice
13
Q
When does a patient require a blood transfusion?
A
If Hb<70g/L and acute anaemia
14
Q
What factors must be considered before giving a blood transfusion?
A
Comorbidities - IHD
Symptoms
Blood group
Religion
15
Q
Explain how you treat severe anaemia with heart failure
A
Restore Hb to 60-80g/L
Give blood slowly with 10-40mg furosemide IV/PO with alternate units
16
Q
What are some signs of worsening overload?
A
Rising JVP
Basal crackles
17
Q
When would you suspect haemolytic anaemia?
A
Reticulocytosis Mild macrocytosis Decreased haptoglobin Increased bilirubin Increased LDH Increased urobilinogen
18
Q
What are the causes of iron deficiency anaemia
A
Blood loss - menorrhagia or bleeding (upper and lower GI)
Malabsorption (eg. coeliac) may cause refractory IDA
19
Q
What are some signs of chronic iron deficiency anaemia
A
Koilonychia
Angular cheilosis
Atrophic glossitis
Post-cricoid webs (Plummervison syndrome)
20
Q
Describe the blood test results in iron deficiency anaemia
A
Blood film - microcytic, hypochromic anaemia witgh anisocytosis and poikilocytosis
Decreased MCV, MCH, MCHC, ferritin
Increased transferrin
21
Q
What is ferritin also a marker of
A
Inflammation - infection and malignancy - acute phase protein
22
Q
What should all non menstruating men and women be referred for if they have iron defiency anaemia and a negative coeliac serology?
A
Upper and Lower GI endoscopy
23
Q
How do you treat iron deficiency anaemia?
A
Ferrous sulphate 200mg/8h PO, continue 3 months after Hb has normalised to replenish the stores
24
Q
What are some side effects of ferrous sulphate?
A
Nausea, abdominal discomfort, diarrhoea, constipation, black stools
25
What is the main reason iron replacement fails?
Patient non-compliance
| Consider alternative diagnosis
26
How should Hb rise in iron deficiency anaemia treated with oral iron replacement?
10g/L/week
27
Describe how anaemia of chronic disease arises
Poor use of iron in erythropoiesis
Cytokine induced shortening of RBC survival
Production of and response to erythropoietin reduced
28
Describe the blood test results for anaemia of chronic disease
Normal MCV, low Hb, ferritin normal or increased in mild normocytic/microcytic anaemia
29
List some causes of anaemia of chronic disease
```
Malignancy
Infection
Vasculitis
Rheumatoid
Renal failure
```
30
What other investigations should be done for anaemia of chronic disease?
```
Blood film
B12
Folate
TSH
Haemolysis tests
```
31
How is anaemia of chronic disease managed?
Treat the underlying cause
| Erythropoietin
32
Give the side effects of erythropoietin
Flu like illness
Hypertension
Mild rise in platelet count
Thromboembolism
33
Which type of anaemia is most likely with an increased red cell distribution width?
Mixed anaemia
34
Which anaemia must be thought of for a microcytic anaemia not responsive to iron
Sideroblastic anaemia
35
What causes sideroblastic anaemia
Congenital (rare, x linked)
Idiopathic as a myeloproliferative disorder
Follows chemo and TB medications
Alcohol or lead excess
36
What is sideroblastic anaemia characterised by?
Ineffective erythropoiesis leading to increased iron absorption, iron loading into the marrow +/- haemosiderosis
37
What is haemosiderosis?
endocrine, liver and heart damage due to iron deposition
38
How is sideroblastic anaemia diagnosed?
Increased ferritin
| Blood film - hypochromic blood film and sideroblasts in marrow
39
How is sideroblastic anaemia treated?
Remove cause
| Pyridoxine +/- repeated transfusions for severe anaemia
40
What is ferritin?
Protein which stores iron
41
What are howell jolly bodies?
DNA nuclear remnants in RBCs, which are normally removed by the spleen
42
Which conditions are howell jolly bodies seen in?
```
Post-splenectomy, Hyposplenism (sickle cell, coeliac, IBD, congenital, myeloproliferative disease
Dyserythropoietic states (myelodysplasia and megaloblastic anaemia)
```
43
When are reticulocytes seen?
Haemolysis
Active haemorrhage
When treatment is given to Iron/B12/folate deficient marrow
44
What are reticulocytes?
Young, larger RBCs containing RNA
45
What is a rouleaux formation?
RBCs stack on top of one enough
46
Which blood result is increased as a result of rouleaux formation?
ESR
47
When are rouleaux formations seen?
Chronic inflammation
Myeloma
Paraproteinemia
48
What are target cells?
Also known as mexican hat cells
| RBCs with central staining, ring of pallor and an outer rim of staining
49
Where are target cells seen?
Liver disease
Hyposplenism
Thalassaemia
50
Give an example of when a macrocytosis is not associated with anaemia
Alcohol excess
51
What is a megaloblast?
Cell in which nuclear maturation is delayed in comparison with the cytoplasm
52
What causes a megaloblastic macrocytic anaemia?
B12 and folate deficiency
| Cytotoxic drugs
53
List some causes of non-megaloblastic macrocytosis
```
Alcohol excess
Hypothyroidism
Reticulocytosis - haemolysis
Liver disease
Pregnancy
```
54
What cells are seen on blood film in B12 and folate deficiency
Hyper segmented neutrophils
55
What can maternal folate deficiency cause
Neural tube defects
56
Where is folate absorbed?
Duodenum
| Jejunum
57
List some causes of folate deficiency
Poor diet
Increased demand - pregnancy, haemolysis, inflammation
Malabsorption - coeliac and tropical sprue
Drugs - antiepileptics (phenytoin and valproate), methotrexate and trimethoprim
58
What is the advised folate dose for pregnant women?
400mcg/day from conception till 12 weeks to prevent anaemia and spina bifida
59
How is folate deficiency anaemia treated?
5mg/day folic acid PO for 4 months
| Assess underlying cause
60
How long do folate stores in the body last?
4 months
61
How long do B12 stores in the body last?
4 years
62
What is vitamin B12 used for in the body?
Synthesis of DNA
63
How is B12 absorbed?
Binds to intrinsic factor in the stomach
| Absorbed via the terminal ileum
64
List the causes of Vitamin B12 deficiency
Dietary - vegans
Malabsorption - lack of intrinsic factor or problems with terminal ileum (Crohns, bacterial overgrowth, resection and tapeworm)
Congenital metabolic error
65
What is pernicious anaemia?
Autoimmune condition in which atrophic gastritis leads to a lack of intrinsic factor secretion from parietal cells of the stomach. Dietary B12 remains unbound and cannot be absorbed in terminal ileum
66
List the symptoms of B12 deficiency
Symptoms of anaemia - fatigue, dyspnoea, faintness, palpitations, headache, tinnitus, anorexia
Yellow tinge to skin - combination of pallor (anaemia) and jaundice (haemolysis)
Mouth - Glossitis (beefy, red sore tongue), Angular cheilosis
Neuropsychiatric - irritability, depression, psychosis, dementia, subacute combined degeneration of the spinal cord
67
Describe subacute combined degeneration of the spinal cord
Combination of peripheral sensory neuropathy with both upper (extensor plantars) and lower motor neuron signs (loss of knee and ankle jerk). Pain and temperature still in tact even in severe cases due to spinothalamic tract. This degeneration affects the posterior dorsal column and corticospinal tracts.
68
What other conditions are associated with pernicious anaemia?
Autoimmune - hypothyroidism, DM, vitiligo, addisons, hypoparathyroidism
Carcinoma of the stomach - low upper GI endoscopy threshold
69
What investigations could you do for pernicious anaemia
FBC (decreased Hb, Increased MCV), serum B12 (decreased), reticulocytes (decreased), blood film (hyper segmented neutrophils), specific antibodies for IF and Parietal cells
70
Describe how you treat B12 anaemia
Treat the cause
If malabsorption - give hydroxocobalamin (B12) 1mg IM every 2 weeks and then 1mg IM every 3 months for life
If dietary - Oral after IM course (50-150mcg daily, between meals)
71
How do you know B12 anaemia is improving?
Marked reticulocytosis - increased MCV after 4-5 weeks
72
What is haemolysis?
The premature breakdown of RBCs, before their normal lifespan of 120 days
73
Where does haemolysis occur?
Intravascular - in the circulation
| Extravascular - by macrophages in the liver, spleen and bone marrow
74
How short may the RBC lifecycle be in sickle cell anaemia?
5 days
75
What is significant in the history for detecting haemolysis?
```
FH
Travel
Jaundice
Dark urine
Race
Drugs
Previous anaemia
```
76
What is significant on clinical examination for detecting haemolysis?
Jaundice
Hepatosplenomegaly
Gallstones - pigmented - bilirubin high
Leg ulcers - poor blood flow
77
Give the results of a typical picture of haemolysis
Decreased Hb
Normal or high MCV
Increased bilirubin (unconjugated from haem breakdown - pre-hepatic jaundice)
Increased urinary urobilinogen
Increased serum LDH
Increased reticulocytes
Decreased plasma haptoglobin
Polychromasia and macrocytosis on the blood film
Positive direct antiglobulin test (coombs)
78
Describe drug induced haemolysis
Formation of RBC autoantibodies from binding to RBC membranes (penicillin) or production of immune complexes (quinine)
79
What is autoimmune haemolytic anaemia
Mediated by autoantibodies causing mainly extravascular haemolysis and spherocytosis
80
Give the two classifications of autoimmune haemolytic anaemia
Warm
| Cold
81
Describe warm autoimmune haemolytic anaemia
IgG mediated
| Bind at body temp 37
82
How do you treat warm autoimmune haemolytic anaemia
Steroids/immunosuppression +/- splenectomy
83
Describe cold autoimmune haemolytic anaemia
IgM mediated
Bind at lower temperatures
Activates cell surface complement
Causes a chronic anaemia made worse by the cold, often with raynauds or acrocyanosis
84
How do you treat cold autoimmune haemolytic anaemia
Keep warm
| Chlorambucil may help
85
What causes cold autoimmune haemolytic anaemia
Infection - mycoplasma or EBV
86
What causes warm autoimmune haemolytic anaemia?
Lymphoproliferative disease - CLL, lymphoma
Drugs
Autoimmune disease - SLE
87
What happens in paroxysmal cold haemoglobinuria
Caused by donath-landsteiner antibodies sticking to RBCs in the cold, causing self limiting complement mediated haemolysis on rewarming
88
What is paroxysmal cold haemoglobinuria associated with?
Syphilis and viral illness
89
Describe isoimmune haemolytic anaemia
Acute transfusion reaction, haemolysis of the new-born
90
Which haemolytic anaemias can be considered if DAT is negative?
Autoimmune haemolytic anaemia (2%)
| Membrane defects - hereditary spherocytosis, hereditary elliptocytosis and hereditary ovalocytosis and stomatocytosis
91
What is microangiopathic haemolytic anaemia
Mechanical damage to RBCs in circulation, causing intravascular haemolysis and schistocytes
92
What causes Microangiopathic haemolytic anaemia?
```
Haemolytic-uraemic syndrome
TTP
DIC
Pre-eclampsia
Eclampsia
Prosthetic heart valves
```
93
Name the main infection which exacerbates/causes haemolysis
Malaria
94
Describe paroxysmal nocturnal haemoglobinuria
Rare acquired stem cell disorder with haemolysis especially at nigh, marrow failure and thrombophilia.
95
Describe glucose-6-phosphate dehydrogenase deficiency (X-linked)
X-linked
Affects male mediteranean, africa, middle east
100 million
Most asymptomatic - may gegt oxidative crises due to decreased glutathione production
Precipitated by drugs - sulphonamides, primaquine and aspirin, exposure to broad beans or illness.
In attacks, rapid jaundice and anaemia
Tests - enzyme assay
Treat with transfusion if severe, otherwise avoid precipitants
96
Describe pyruvate kinase deficiency
Autosomal recessive
Decreased ATP decreased RBC survival
Homozygotes presents with neonatal jaundice. Jaundice, haemolysis and splenomegaly if present later
Tests - enzyme assay
Treatment - usually none, splenectomy may help some
97
Name the 3 membrane defects causing haemolytic anaemia
```
Hereditary spherocytosis (autosomal dominant)
Hereditary elliptocytosis (autosomal dominant)
Hereditary ovalocytosis and stomatocytosis are rare - refer to haematology
```
98
Name two haemoglobinopathies which can cause a haemolytic anaemia
Sickle cell
| Thalassemia
99
What is sickle cell anaemia?
Autosomal recessive disorder in which production of abnormal haemoglobin results in vaso-occlusive crises
Arises from an amino acid substitution in the gene encoding the beta chain (glu-val at position 6)
Leads to production of HbS rather than HbA
100
What are heterozygotes for the sickle cell gene called?
Sickle cell trait
101
When might heterozygotes/sickle cell trait experience symptomatic sickling?
In hypoxia - unpressurised aircraft or anaesthesia
102
Describe the pathogenesis of sickle cell disease
HbS polymerizes when deoxygenated, causing RBCs to deform, producing sickle cells, which are fragile and haemolyse, also block small vessels
103
How do you test for sickle cell anaemia?
Haemolysis is variable, may have reticulocytosis
Increased bilirubin
Film - sickle cells and target cells
Sickle solubility test - confirms diagnosis but does not distinguish between HbSS and HbAS types
Hb electrophoresis - confirms the diagnosis and type
104
When should you aim for a sickle cell diagnosis and why?
At birth from cord
| Able to give pneumococcal prophylaxis
105
What are the three types of sickle cell crisis?
Vaso-occlusive "painful" crisis
Aplastic crisis
Sequestration crisis
106
What triggers a vaso-occlusive crisis?
Cold
Dehydration
Infection
Hypoxia
107
Describe vaso-occlusive crisis
Microvascular occlusion, often affects the marrow causing severe pain
Mesenteric ischemia
CNS - stroke, seizures and cognitive effects
Hands and feet are affected if <3yo leading to dactylitis
Avascular necrosis (femoral head)
Leg ulcers
Low flow priapism (venous blood not being able to leave the penis)
108
What causes an aplastic crisis?
Parvovirus B19
109
Describe aplastic crisis
Sudden reduction in production of RBCs
| Usually self limiting but may require transfusion
110
Describe sequestration crisis
Mainly affects children as in adults the spleen becomes atrophic
Pooling of blood in the spleen and sometimes liver
Organomegaly
Severe anaemia
Shock
Urgent transfusion needed
111
List the complications of sickle cell crisis?
Splenic infarction - commonly occurs <2yo, leads to increased susceptibility to infection
Poor growth
Chronic renal failure
Gallstones
Retinal disease
Iron overload
Lung damage - hypoxia causes fibrosis and leads to pulmonary hypertension
112
Describe the management of chronic sickle cell anaemia
Hydroxycarbamide if frequent crises - increases production of fetal Hb
Splenic infarction leads to Hyposplenism and immunocompromise so vaccinations and prophylactic antibiotics
Bone marrow transplant - curative but controversial
113
How can sickle cell anaemia be prevented?
Parental education - prevents 90% deaths from sequestration crises
Genetic counselling
Prenatal tests
114
Describe the acute management of a sickle cell crisis
Give prompt, generous analgesia eg. IV opiate
Cross match blood, FBC and reticulocyte count
Do a septic screen - blood cultures, MSU and CXR
Rehydrate with iVI and keep warm
Give O2 by mask if PaO2 decreases or sats<95%
Consider starting empirical antibiotics early if unwell, temp >38 or chest signs
Inform their haematologist and get help early
Measure PCV, reticulocytes, liver and spleen size daily
Give blood transfusion if Hb or reticulocytes fall sharply (aplastic). Match for RH (C,DE) and kell to prevent alloantibody formation
Exchange transfusion for those who are rapidly worsening
115
Describe the acute chest syndrome and its management
Pulmonary infiltrates (fat embolism from the bone marrow or infection with chlamydia, mycoplasma and viruses) involving complete lung segments, causing pain, fever, tachypnoea, wheeze and cough
```
O2
Analgesia
Empirical antibiotics - cephalosporin and macrolide until cultures known
Blood transfusion
ITU if PaO2 <9.2
```
116
What is beta thalassaemia?
Genetic disease, caused by point mutations in globin genes, of unbalanced Hb synthesis with underproduction/overproduction of one globin chain (beta). Unmatched globin precipitate, damaging RBC membranes, causing their haemolysis which still in the marrow. Common in areas from the Mediterranean and far east
117
Which chromosome is beta globin found?
11
118
What investigations do you do for thalassaemia?
```
FBC
MCV
Film
Iron studies
HbA2
HbF
Hb electrophoresis
MRI when myocardial siderosis suspected
```
119
Name the 3 types of beta thalassaemia
Beta thalassaemia minor/trait
Beta thalassaemia intermedia
Beta thalassaemia major
120
Describe Beta thalassaemia minior/trait
Carrier state and usually asymptomatic
Minor anaemia, well tolerated, may worsen in pregnancy
MCV<75, HbA2 >3.5%, slight increased HbF
121
Describe beta thalassaemia intermedia
Intermediate state with moderate anaemia not requiring transfusion
Splenomegaly
Variety of causes
122
Describe beta thalassaemia major
Significant abnormalities in both beta globin genes and presents in 1st year of life with severe anaemia and failure to thrive
Extra-medullary haematopoiesis (RBCs made outside the marrow) occurs in response to anaemia and causes characteristic bossing of the skull.
Osteopenia
Skull X-ray shows hair on end sign due to increased marrow activity
Lifelong blood transfusions needed with resulting iron overload seen >10 years as endocrine failure, cardiac toxicity and liver disease
Film - hypochromic microcytic cells, target cells, nucleated RBCs
Increased HbF and variable HbA2, HbA absent
123
Describe the treatment for thalassaemia
Promote fitness, healthy diet and folate supplements
Lifelong regular (2-4 weekly) transfusions to keep Hb>90 and suppress extramedullary haematopoiesis
Iron chelators and ascorbic acid to help mitigate iron overload from transfusions
Splenectomy if hypersplenism persists but avoid till >5yo due to increased infection risk
Hormone replacement and endocrine complication treatment
Bone marrow transplant
