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Oncology, haematology and palliative care > Anaemia > Flashcards

Anaemia Flashcards

1
Q

What is anaemia defined as?

A

Low Hb concentration

Hb <135g/L for men OR <115g/L for women

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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
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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

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4
Q

In what situation may blood transfusion for anaemia be fatal?

A

In heart failure

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5
Q

Which blood value is most important to look at when diagnosing anaemia

A

MCV (mean cell volume)

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6
Q

List some causes of a microcytic anaemia (low MCV)

A 
Iron deficiency 
Thalassemia 
Sideroblastic anaemia (very rare)
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7
Q

What happens to iron in thalassemia?

A

Accumulation so tests show increased iron and ferritin with a low total iron binding capacity

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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
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9
Q

What should you suspect if there is decreased WCC or decreased platelets in normocytic anaemia?

A

Bone marrow failure

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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)
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11
Q

What is reticulocytosis?

A

> 2% of RBCs are reticulocytes or reticulocyte count >100

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12
Q

How may a haemolytic patient present?

A

Mildly jaundice - pre hepatic unconjugated jaundice

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13
Q

When does a patient require a blood transfusion?

A

If Hb<70g/L and acute anaemia

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14
Q

What factors must be considered before giving a blood transfusion?

A

Comorbidities - IHD
Symptoms
Blood group
Religion

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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

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16
Q

What are some signs of worsening overload?

A

Rising JVP

Basal crackles

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17
Q

When would you suspect haemolytic anaemia?

A 
Reticulocytosis 
Mild macrocytosis
Decreased haptoglobin
Increased bilirubin
Increased LDH
Increased urobilinogen
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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

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19
Q

What are some signs of chronic iron deficiency anaemia

A

Koilonychia
Angular cheilosis
Atrophic glossitis
Post-cricoid webs (Plummervison syndrome)

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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

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21
Q

What is ferritin also a marker of

A

Inflammation - infection and malignancy - acute phase protein

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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

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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

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24
Q

What are some side effects of ferrous sulphate?

A

Nausea, abdominal discomfort, diarrhoea, constipation, black stools

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25
Q

What is the main reason iron replacement fails?

A

Patient non-compliance

Consider alternative diagnosis

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26
Q

How should Hb rise in iron deficiency anaemia treated with oral iron replacement?

A

10g/L/week

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27
Q

Describe how anaemia of chronic disease arises

A

Poor use of iron in erythropoiesis
Cytokine induced shortening of RBC survival
Production of and response to erythropoietin reduced

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28
Q

Describe the blood test results for anaemia of chronic disease

A

Normal MCV, low Hb, ferritin normal or increased in mild normocytic/microcytic anaemia

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29
Q

List some causes of anaemia of chronic disease

A 
Malignancy
Infection
Vasculitis
Rheumatoid 
Renal failure
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30
Q

What other investigations should be done for anaemia of chronic disease?

A 
Blood film
B12
Folate
TSH
Haemolysis tests
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31
Q

How is anaemia of chronic disease managed?

A

Treat the underlying cause

Erythropoietin

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32
Q

Give the side effects of erythropoietin

A

Flu like illness
Hypertension
Mild rise in platelet count
Thromboembolism

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33
Q

Which type of anaemia is most likely with an increased red cell distribution width?

A

Mixed anaemia

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34
Q

Which anaemia must be thought of for a microcytic anaemia not responsive to iron

A

Sideroblastic anaemia

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35
Q

What causes sideroblastic anaemia

A

Congenital (rare, x linked)
Idiopathic as a myeloproliferative disorder
Follows chemo and TB medications
Alcohol or lead excess

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36
Q

What is sideroblastic anaemia characterised by?

A

Ineffective erythropoiesis leading to increased iron absorption, iron loading into the marrow +/- haemosiderosis

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37
Q

What is haemosiderosis?

A

endocrine, liver and heart damage due to iron deposition

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38
Q

How is sideroblastic anaemia diagnosed?

A

Increased ferritin

Blood film - hypochromic blood film and sideroblasts in marrow

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39
Q

How is sideroblastic anaemia treated?

A

Remove cause

Pyridoxine +/- repeated transfusions for severe anaemia

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40
Q

What is ferritin?

A

Protein which stores iron

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41
Q

What are howell jolly bodies?

A

DNA nuclear remnants in RBCs, which are normally removed by the spleen

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42
Q

Which conditions are howell jolly bodies seen in?

A 
Post-splenectomy, Hyposplenism (sickle cell, coeliac, IBD, congenital, myeloproliferative disease
Dyserythropoietic states (myelodysplasia and megaloblastic anaemia)
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43
Q

When are reticulocytes seen?

A

Haemolysis
Active haemorrhage
When treatment is given to Iron/B12/folate deficient marrow

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44
Q

What are reticulocytes?

A

Young, larger RBCs containing RNA

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45
Q

What is a rouleaux formation?

A

RBCs stack on top of one enough

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46
Q

Which blood result is increased as a result of rouleaux formation?

A

ESR

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47
Q

When are rouleaux formations seen?

A

Chronic inflammation
Myeloma
Paraproteinemia

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48
Q

What are target cells?

A

Also known as mexican hat cells

RBCs with central staining, ring of pallor and an outer rim of staining

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49
Q

Where are target cells seen?

A

Liver disease
Hyposplenism
Thalassaemia

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50
Q

Give an example of when a macrocytosis is not associated with anaemia

A

Alcohol excess

51
Q

What is a megaloblast?

A

Cell in which nuclear maturation is delayed in comparison with the cytoplasm

52
Q

What causes a megaloblastic macrocytic anaemia?

A

B12 and folate deficiency

Cytotoxic drugs

53
Q

List some causes of non-megaloblastic macrocytosis

A 
Alcohol excess
Hypothyroidism
Reticulocytosis - haemolysis 
Liver disease
Pregnancy
54
Q

What cells are seen on blood film in B12 and folate deficiency

A

Hyper segmented neutrophils

55
Q

What can maternal folate deficiency cause

A

Neural tube defects

56
Q

Where is folate absorbed?

A

Duodenum

Jejunum

57
Q

List some causes of folate deficiency

A

Poor diet
Increased demand - pregnancy, haemolysis, inflammation
Malabsorption - coeliac and tropical sprue
Drugs - antiepileptics (phenytoin and valproate), methotrexate and trimethoprim

58
Q

What is the advised folate dose for pregnant women?

A

400mcg/day from conception till 12 weeks to prevent anaemia and spina bifida

59
Q

How is folate deficiency anaemia treated?

A

5mg/day folic acid PO for 4 months

Assess underlying cause

60
Q

How long do folate stores in the body last?

A

4 months

61
Q

How long do B12 stores in the body last?

A

4 years

62
Q

What is vitamin B12 used for in the body?

A

Synthesis of DNA

63
Q

How is B12 absorbed?

A

Binds to intrinsic factor in the stomach

Absorbed via the terminal ileum

64
Q

List the causes of Vitamin B12 deficiency

A

Dietary - vegans
Malabsorption - lack of intrinsic factor or problems with terminal ileum (Crohns, bacterial overgrowth, resection and tapeworm)
Congenital metabolic error

65
Q

What is pernicious anaemia?

A

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
Q

List the symptoms of B12 deficiency

A

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
Q

Describe subacute combined degeneration of the spinal cord

A

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
Q

What other conditions are associated with pernicious anaemia?

A

Autoimmune - hypothyroidism, DM, vitiligo, addisons, hypoparathyroidism
Carcinoma of the stomach - low upper GI endoscopy threshold

69
Q

What investigations could you do for pernicious anaemia

A

FBC (decreased Hb, Increased MCV), serum B12 (decreased), reticulocytes (decreased), blood film (hyper segmented neutrophils), specific antibodies for IF and Parietal cells

70
Q

Describe how you treat B12 anaemia

A

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
Q

How do you know B12 anaemia is improving?

A

Marked reticulocytosis - increased MCV after 4-5 weeks

72
Q

What is haemolysis?

A

The premature breakdown of RBCs, before their normal lifespan of 120 days

73
Q

Where does haemolysis occur?

A

Intravascular - in the circulation

Extravascular - by macrophages in the liver, spleen and bone marrow

74
Q

How short may the RBC lifecycle be in sickle cell anaemia?

A

5 days

75
Q

What is significant in the history for detecting haemolysis?

A 
FH
Travel
Jaundice
Dark urine
Race
Drugs
Previous anaemia
76
Q

What is significant on clinical examination for detecting haemolysis?

A

Jaundice
Hepatosplenomegaly
Gallstones - pigmented - bilirubin high
Leg ulcers - poor blood flow

77
Q

Give the results of a typical picture of haemolysis

A

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
Q

Describe drug induced haemolysis

A

Formation of RBC autoantibodies from binding to RBC membranes (penicillin) or production of immune complexes (quinine)

79
Q

What is autoimmune haemolytic anaemia

A

Mediated by autoantibodies causing mainly extravascular haemolysis and spherocytosis

80
Q

Give the two classifications of autoimmune haemolytic anaemia

A

Warm

Cold

81
Q

Describe warm autoimmune haemolytic anaemia

A

IgG mediated

Bind at body temp 37

82
Q

How do you treat warm autoimmune haemolytic anaemia

A

Steroids/immunosuppression +/- splenectomy

83
Q

Describe cold autoimmune haemolytic anaemia

A

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
Q

How do you treat cold autoimmune haemolytic anaemia

A

Keep warm

Chlorambucil may help

85
Q

What causes cold autoimmune haemolytic anaemia

A

Infection - mycoplasma or EBV

86
Q

What causes warm autoimmune haemolytic anaemia?

A

Lymphoproliferative disease - CLL, lymphoma
Drugs
Autoimmune disease - SLE

87
Q

What happens in paroxysmal cold haemoglobinuria

A

Caused by donath-landsteiner antibodies sticking to RBCs in the cold, causing self limiting complement mediated haemolysis on rewarming

88
Q

What is paroxysmal cold haemoglobinuria associated with?

A

Syphilis and viral illness

89
Q

Describe isoimmune haemolytic anaemia

A

Acute transfusion reaction, haemolysis of the new-born

90
Q

Which haemolytic anaemias can be considered if DAT is negative?

A

Autoimmune haemolytic anaemia (2%)

Membrane defects - hereditary spherocytosis, hereditary elliptocytosis and hereditary ovalocytosis and stomatocytosis

91
Q

What is microangiopathic haemolytic anaemia

A

Mechanical damage to RBCs in circulation, causing intravascular haemolysis and schistocytes

92
Q

What causes Microangiopathic haemolytic anaemia?

A 
Haemolytic-uraemic syndrome
TTP
DIC
Pre-eclampsia
Eclampsia
Prosthetic heart valves
93
Q

Name the main infection which exacerbates/causes haemolysis

A

Malaria

94
Q

Describe paroxysmal nocturnal haemoglobinuria

A

Rare acquired stem cell disorder with haemolysis especially at nigh, marrow failure and thrombophilia.

95
Q

Describe glucose-6-phosphate dehydrogenase deficiency (X-linked)

A

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
Q

Describe pyruvate kinase deficiency

A

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
Q

Name the 3 membrane defects causing haemolytic anaemia

A 
Hereditary spherocytosis (autosomal dominant)
Hereditary elliptocytosis (autosomal dominant)
Hereditary ovalocytosis and stomatocytosis are rare - refer to haematology
98
Q

Name two haemoglobinopathies which can cause a haemolytic anaemia

A

Sickle cell

Thalassemia

99
Q

What is sickle cell anaemia?

A

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
Q

What are heterozygotes for the sickle cell gene called?

A

Sickle cell trait

101
Q

When might heterozygotes/sickle cell trait experience symptomatic sickling?

A

In hypoxia - unpressurised aircraft or anaesthesia

102
Q

Describe the pathogenesis of sickle cell disease

A

HbS polymerizes when deoxygenated, causing RBCs to deform, producing sickle cells, which are fragile and haemolyse, also block small vessels

103
Q

How do you test for sickle cell anaemia?

A

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
Q

When should you aim for a sickle cell diagnosis and why?

A

At birth from cord

Able to give pneumococcal prophylaxis

105
Q

What are the three types of sickle cell crisis?

A

Vaso-occlusive “painful” crisis
Aplastic crisis
Sequestration crisis

106
Q

What triggers a vaso-occlusive crisis?

A

Cold
Dehydration
Infection
Hypoxia

107
Q

Describe vaso-occlusive crisis

A

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
Q

What causes an aplastic crisis?

A

Parvovirus B19

109
Q

Describe aplastic crisis

A

Sudden reduction in production of RBCs

Usually self limiting but may require transfusion

110
Q

Describe sequestration crisis

A

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
Q

List the complications of sickle cell crisis?

A

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
Q

Describe the management of chronic sickle cell anaemia

A

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
Q

How can sickle cell anaemia be prevented?

A

Parental education - prevents 90% deaths from sequestration crises
Genetic counselling
Prenatal tests

114
Q

Describe the acute management of a sickle cell crisis

A

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
Q

Describe the acute chest syndrome and its management

A

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
Q

What is beta thalassaemia?

A

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
Q

Which chromosome is beta globin found?

A

11

118
Q

What investigations do you do for thalassaemia?

A 
FBC
MCV
Film
Iron studies
HbA2
HbF
Hb electrophoresis
MRI when myocardial siderosis suspected
119
Q

Name the 3 types of beta thalassaemia

A

Beta thalassaemia minor/trait
Beta thalassaemia intermedia
Beta thalassaemia major

120
Q

Describe Beta thalassaemia minior/trait

A

Carrier state and usually asymptomatic
Minor anaemia, well tolerated, may worsen in pregnancy
MCV<75, HbA2 >3.5%, slight increased HbF

121
Q

Describe beta thalassaemia intermedia

A

Intermediate state with moderate anaemia not requiring transfusion
Splenomegaly
Variety of causes

122
Q

Describe beta thalassaemia major

A

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
Q

Describe the treatment for thalassaemia

A

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

Oncology, haematology and palliative care (19 decks)

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