haem Flashcards

1
Q

What are the criteria smouldering myeloma?

A

paraprotein >30g/l
>10% plasma cells in BM
no related organ or tissue impairment

doesn’t require treatment, monitoring needed

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1
Q

What is MGUS?

A

monoclonal gammopathy of unknown significance
a premalignant condition that makes paraprotein

increases risk of myeloma and lymphoma

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2
Q

What can come before multiple myeloma?

A

MGUS
Smouldering myeloma

all plasma cell dyscrasias

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3
Q

Do you treat MGUS and smouldering myeloma?

A

Not yet
Just monitor

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4
Q

What is the risk of MGUS and smouldering myeloma progressing to multiple myeloma?

A

MGUS: 1%
SM: 20% in first year, then 5%

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5
Q

What is the criteria for MGUS?

A

Paraprotein <30 g/L.
Monoclonal plasma cells in bone marrow <10%.
Absence of myeloma-related organ or tissue impairment

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6
Q

What investigations would be carried out for multiple myeloma?

A

FBC (anaemia or leukopenia in myeloma)
Calcium (raised in myeloma)
ESR (increased in myeloma)
Plasma viscosity (increased in myeloma)
U&E (for renal impairment)
Serum protein electrophoresis (to detect paraprotein)
Serum-free light-chain assay (to detect abnormally abundant light chains)
Urine protein electrophoresis (to detect the Bence-Jones protein)

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7
Q

What are the main presentations in multiple myeloma?

A

C – Calcium (elevated)
R – Renal failure
A – Anaemia
B – Bone lesions and bone pain

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8
Q

What are the symptoms of multiple myeloma?

A

Persistent bone pain and pathological fractures
Unexplained fatigue and weight loss
Fever of unknown origin
Hypercalcaemia
Anaemia
Renal impairment
Dizziness, confusion, blurred vision, headaches, epistaxis, cerebrovascular event

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9
Q

What is myeloma?

A

a type of cancer affecting the plasma cells (differentiated B lymphocytes) in the bone marrow.
Leads to accumulation of malignant plasma cells

proliferation disorder of plasma cells

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10
Q

What is multiple myeloma?

A

myeloma affecting multiple bone marrows in the body

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11
Q

What are some differentials for multiple myeloma?

A

MGUS
Amyloid light-chain (AL) amyloidosis.
Solitary plasmacytoma.
B-cell non-Hodgkin’s lymphoma
Chronic lymphocytic leukaemia

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12
Q

Examples of triplet drug combos for initial therapy in multiple myeloma

A
  • VTD: Bortezomib, thalidomide, and dexamethasone
  • KRD: carfilzomib, lenalidomide and dexamethasone
  • RVD: lenalidomide, bortezomib and dexamethasone
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13
Q

What does allogeneic stem cell transplant mean?

A

stem cells from a healthy donor

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14
Q

What are autologous stem cells?

A

derived from the patient

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15
Q

Treatment for healthy patients, patients younger than 65-70, with multiple myeloma

A

Induction drug therapy
Stem cell transplant

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16
Q

Possible complications of multiple myeloma

A

Infection
Bone pain and fractures
Renal failure
Anaemia
Hypercalcaemia
Peripheral neuropathy
Hyperviscosity syndrome
Venous thromboembolism

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17
Q

What is lymphoma?

A

malignancies of the lymphoid system
disease may arise at any site where lymphoid tissue is present

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18
Q

What is anaemia?

A

haemoglobin <130 g/Lin men aged ≥15 years
<120 g/L in non-pregnant women aged ≥15 years
<110 g/L (11 g/dL) in pregnant women

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19
Q

What can cause a decreased production of RBCs?

A

Iron, folate and B12 deficiencies
Bone marrow failure

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20
Q

What can cause RBC loss?

A

Bleeding
Haemolysis

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21
Q

What is the most common cause of anaemia worldwide?

A

Iron deficiency

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22
Q

What is the aetiology of iron def anaemia?

A

Inadequate iron intake
Impaired iron absorption
Blood loss
Increased need (e.g. growth in children)

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23
Q

What helps to absorb B12?

A

Intrinsic factor
B12 must bind to IF to be absorbed in terminal ileum

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24
How much iron do men and postmenopausal women lose daily?
1mg
25
How much iron do menstruating women lose daily?
2mg
26
Key presentations of iron deficiency anaemia
fatigue dyspnoea on exertion pica restless legs syndrome nail changes
27
What are the symptoms of iron deficiency anaemia?
Fatigue. Shortness of breath on exertion. Palpitations. Sore tongue and taste disturbance. Mouth ulcers Changes in the hair/hair loss. Pale skin and conjuctiva Pruritus. Headache. Tinnitus. Angina, which can occur if there is pre-existing CHD
28
What type of anaemia does iron deficiency cause?
microcytic hypochromic anaemia characterised by small and pale red blood cells on blood film.
29
What would the MCV value be in ID anaemia?
less than 80 fL
30
What investigations would you do for ID anaemia?
FBC (Hb and MCV) Serum iron (low) Total iron binding capacity (high, means more space for iron to be bound) Transferrin saturation (low) Ferritin (low)
31
What are some risk factors for ID anaemia?
pregnancy vegetarian and vegan diet menorrhagia hookworm infestation (via blood loss) chronic kidney disease coeliac disease gastrectomy/achlorhydria (low gastric acid so harder for iron to be absorbed) NSAID use (causes gastric ulcers)
32
Differentials for ID anaemia
Thalassaemia sideroblastic anaemia Anaemia of chronic disease Lead poisoning
33
What's the initial treatment for ID anaemia?
daily oral iron replacement therapy
34
Side effects of iron supplements for IDA
Constipation Black stools Diarrhoea Heartburn Nausea Abdominal/epigastric pain
35
Treatment for patients who can't tolerate oral iron in IDA
IV iron therapy
36
How do you monitor ID anaemia?
Retest Hb within 4 weeks of starting treatment FBC within 2-4 months if responsive to treatment
37
What are some complications of ID anaemia?
Cognitive and behavioural impairment Impaired muscular performance High output heart failure in severe anaemia Preterm delivery (risk if anaemia in first 2 trimesters)
38
What is microcytic anaemia?
anaemia with an MCV of less than 80
39
Why does microcytic anaemia occur?
As there is a lack of haemoglobin, an extra division of RBCs occurs to maintain adequate Hb concentration This results in smaller and paler (hypochromic) RBCs
40
What is the most common cause of microcytic anaemia?
Iron deficiency anaemia
41
What is the mean corpuscular volume?
average size and volume of a red blood cell used in classifying anaemia
42
Which anaemias are microcytic?
Iron def Sideroblastic Thalassaemia Anaemia of chronic disease
43
Which anaemias are normocytic?
anaemia of chronic disease/inflammation haemorrhagic haemolytic leukaemias/ other cancers myeloproliferative
44
What is the MCV for microcytic anaemias?
less than 80fl
45
What is the MCV for normocytic anaemias?
80-95fL
46
What is the MCV for macrocytic anaemia?
above 95 fl
47
Which deficiencies are megaloblastic?
B12 Folate
48
In macrocytic anaemias, what is the difference between megaloblastic and non-megaloblastic?
Megaloblastic has a problem in DNA synthesis and repair, non-meg doesn't
49
Which anaemias are non-megaloblastic?
chronic alcohol use liver disease hypothyroidism MDS haemolysis and haemorrhage
50
What are non-specific symptoms of anaemia?
Pallor Fatigue and weakness Dyspnea Headaches Dizziness
51
What is the difference in the time taken to develop B12 and folate deficiency?
B12 deficiency takes years Folate deficiency can happen much faster, e.g. weeks
52
What type of anaemia is B12 deficiency?
Macrocytic megaloblastic
53
What is the aetiology of B12 deficiency?
- Pernicious anaemia - Insufficient dietary B12 - Medications that reduce B12 absorption (e.g. PPIs, metformin, anticonvulsants) - Malabsorption in GI tract: e.g. Crohn’s, coeliac
54
What medications can lead to B12 deficiency?
PPIs H2 receptor antagonists Metformin Anti-convulsants
55
What are the risk factors for B12 deficiency?
- Age >65 years - history of gastric surgery (gastrectomy, or bypass for obesity) - vegan and vegetarian diet - Chronic GI illnesses (e.g., Crohn's disease or coeliac disease - Use of known causative medications (proton-pump inhibitors, H2 receptor antagonists, metformin, anticonvulsants) - Pregnancy
56
What are some differential diagnoses for B12 deficiency?
Folate deficiency Pernicious anaemia MDS Peripheral/ diabetic neuropathies Crohn’s, coeliac MS Hypothyroidism Alcoholic liver disease
57
What are the key presentations in B12 deficiency?
Paraesthesia Cognitive changes Visual disturbance Numbness | neurological symptoms differntiate it from folate deficiency
58
What is haemolytic anaemia?
Reduction in red cell lifespan due to increased red blood cell destruction
59
Symptoms of B12 deficiency
Fatigue and muscle weakness Neurological symptoms (paraesthesia, numbness) Oral ulcers Vision disturbances Psychological symptoms Pallor
60
Why is B12 needed and what does deficiency mean in this case?
Required for DNA synthesis and fatty acid synthesis Co-factor for methylmalonyl-Co-A, methionine synthesis (important in neural function) and DNA synthesis rapid sphingolipid turnover in myelin sheath means deficiency can cause neurological symptoms
61
What is a low serum b12 level?
<200 picograms/mL
62
What investigations would you order for b12 deficiency and what would they show?
FBC: MCV high, haematocrit low peripheral blood smear: megalocytes, hypersegmented polymorphonucleated cells serum vitamin B12: <200 picograms/mL reticulocyte count: low
63
Initial management for b12 deficiency
IM hydroxocobalamin 3 times weekly for two weeks (or alternate days until there is no further improvement in neurological symptoms)
64
Management for b12 deficiency
IM hydroxycobalamin injections 3x a week for 2 weeks Follow up injections of 1mg every 2-3 months
65
Complications of B12 deficiency
Neurological deficits Haematological deficits Psychological conditions and cognitive impairment If during pregnancy: low birth weight and preterm delivery
66
Difference between b12 and folate deficiency
B12 takes years and has neurological symptoms Folate takes weeks and has no neuro symptoms
67
What is folate (B9) deficiency?
megaloblastic anaemia, with absence of neurological signs.
68
What foods is folate present in?
Green leafy vegetables, legumes, folic acid in fortified cereal-grain products
69
Who does folate deficiency most commonly affect?
Young children Older adults Pregnant women
70
What is the aetiology of folate deficiency?
Inadequate dietary intake Malabsorption Increased requirement (pregnancy, growth) Increased loss of folate: chronic dialysis Medications: anticonvulsants (e.g. phenytoin), sulfasalazine, methotrexate
71
What medications can cause folate deficiency?
anticonvulsants (e.g. phenytoin) sulfasalazine methotrexate
72
How does folate deficiency affect cells?
Folate deficiency impairs DNA synthesis and repair, which holds back cell division and leads to apoptosis of haematopoietic cells in the marrow. The loss of erythropoietic cells causes anaemia | folate is needed for nitrogen base synthesis
73
What happens to cells in megaloblastic anaemia?
Megaloblastic anaemia results from impaired DNA synthesis, preventing the cells from dividing normally. Rather than dividing, they grow into large, abnormal cells
74
What are the risk factors for folate deficiency?
low dietary folate intake age >65 years alcohol-use disorder pregnancy or lactation premature infant intestinal malabsorption disorders use of certain medications infantile exclusive intake of goats' milk (no folate) congenital defects in folate absorption and metabolism
75
Symptoms of folate deficiency
loss of appetite and weight loss fatigue shortness of breath dizziness pallor dyspnea tachycardia
76
What would be seen on a peripheral blood smear in folate and b12 deficiency?
Macrocytic anaemia and hypersegmented neutrophils
77
What investigations would you order for folate deficiency?
Serum folate (low) and serum b12 (normal) Peripheral blood smear (Macrocytic anaemia and hypersegmented neutrophils) FBC (low Hb, elevated MCV) reticulocyte count (low)
78
Why is it important to test patients for both b12 and folate deficiency?
Underlying B12 deficiency should be ruled out before implementing therapy with folic acid, because folic acid may mask neurological complications of untreated vitamin B12 deficiency
79
What does a reticulocyte count show?
indicates red blood cell production
80
Differential diagnoses for folate deficiency
B12 deficiency Alcoholic liver disease Thiamine-responsive megaloblastic anaemia Hypothyroidism Drug-induced macrocytosis MDS
81
How would you manage folate deficiency?
Once B12 deficiency ruled out: Oral folic acid replacement
82
How can you prevent folate deficiency in pregnancy?
Folic acid supplementation
83
What are some possible complications of folate deficiency?
Foetal neural tube deficits Haematological deficits Progression of neuropathy from masked B12 deficiency
84
How long do folate stores in the body last?
4 months
85
What lab results would you get for anaemia of chronic disease?
Low transferrin sats High ferritin levels Normal/low TIBC Low serum iron Microcytic or normal
86
What happens in sideroblastic anaemia?
Abnormality in haem synthesis pathway Iron stores normal
87
What would be seen on a peripheral blood smear for sideroblastic anaemia?
basophilic stippling pappenheimer bodies
88
What can cause sideroblastic anaemia?
Congenital (X-linked) Exposure to lead Medications, e.g. isoniazid for TB
89
Where are the genes for alpha globin found?
Chromosome 16
90
What is alpha-thalassaemia?
a group of disorders of Hb synthesis, caused by mutations or deletions in at least one of the four alpha-globin gene leading to variably impaired alpha-globin chain production, with accumulation of beta-globin chains | symptom severity depends on number of genes affected
91
What are the different alpha-thalassaemias?
1 affected alpha globin gene: silent carrier 2 affected: alpha thalassaemia trait 3 affected: HbH disease 4 affected: Alpha T major, Hb Bart hydrops fetalis syndrome
92
How does hypoxia occur in alpha thalassaemia?
HbH and Hb Bart's have a high affinity for oxygen so don't release it to tissues The hypoxia causes an increase in RBC production and therefore bone marrow, liver and spleen enlargement
93
Pathophysiology of alpha thalassaemia
accumulation of excess unmatched beta-globin chains, which aggregate, causing oxidant and mechanical damage to the affected red cells and leading to their premature destruction
94
What would be seen on a peripheral blood smear in alpha thalassaemia?
Microcytosis, hypochromia, target cells
95
What investigations would be done for alpha-thalassaemia and what do they show?
Hb: normal to low MCV: low MCH: low RBC count: increased Serum iron and ferritin: normal/ elevated
96
Differentials for alpha-thalassaemia
Iron deficiency anaemia Beta-thalassaemia Anaemia of chronic disease Lead poisoning Sideroblastic anaemias (SA) B12 deficiency anaemia and Folate deficiency Other haemolytic anaemias
97
How would HbH disease present?
Anaemic very low MCV and MCH splenomegaly variable bone changes.
98
How does alpha-thalassaemia trait (2 genes affected) present?
mild anaemia and low red blood cell (RBC) indices
99
How would severe thalassaemia present?
Hepatosplenomegaly Bony deformities (frontal bossing, prominent facial bones, and dental malocclusion) Marked pallor Jaundice. Exercise intolerance, cardiac flow murmur or HF secondary to severe anaemia
100
Do silent carriers or alpha-thalassaemia trait require treatment and monitoring?
No Should not be treated with iron therapy unless iron deficiency is proved ## Footnote HbH should be monitored for complications
101
What is the outlook for alpha-thalassaemia major?
Without intervention, the fetus is subject to severe hypoxia, leading to hydrops fetalis and the associated morbidity and mortality Infant can survive into childhood if mother receives intrauterine transfusions, then child has lifelong transfusions
102
What is beta thalassaemia?
Beta-thalassaemia is an inherited blood disorder caused by mutations of the beta-globin gene that results in ineffective erythropoiesis
103
Where is the beta-globin gene located?
Chromosome 11
104
What is HbA?
Adult haemoglobin 2 alpha 2 beta chains
105
What is HbF?
Foetal haemoglobin
106
Why does Beta-thalassaemia major not present until the first 3-6months of life?
HbF still present until this point HbF can also use up some of the free alpha chains
107
What is the pathophysiology of beta-thalassaemia? | (haemolysis and hypoxia)
Free alpha chains accumulate within RBCs, damaging RBC membrane. Causes haemolysis in bone marrow or RBC to be destroyed by macrophages in spleen. Haemolysis causes Hb to spill into plasma, Haem is recycled into iron and unconjugated bilirubin = jaundice and secondary haemochromatosis Haemolysis leads to hypoxia as fewer RBCs. Hypoxia signals BM, liver and spleen to increase RBC production, causing BM containing bones (in skull and face), liver and spleen to all enlarge
108
What is the pathophysiology behind Hb Bart's Hydrops Fetalis?
gamma chains form tetramers in absence of alpha chains Hb Bart's has very high affinity for oxygen. Tissues get no oxygen leading to high output cardiac failure, splenomegaly and oedema across body. Incompatible with life
109
What are the different types of beta-thalassaemia?
1 mutated beta globin gene: B-T minor (B+) or (B0), asymptomatic 2 mutated beta globin genes code for reduced synthesis (B++): B-T intermedia 2 mutations where no beta globin is produced (B00): B-T major
110
Classification of B-T minor (BT trait)
Slightly anaemic low MCV and MCH clinically asymptomatic.
111
Classification of B-T intermedia
-/βo or β+/β+) high HbF, variable. Anaemic very low MCV and MCH splenomegaly variable bone changes variable transfusion dependency
112
Classification of B-T major
(genotype -o/-o) HbF >90% (untransfused) Severe haemolytic anaemia very low MCV and MCH hepatosplenomegaly chronic transfusion dependency
113
What would a peripheral blood smear show for beta-thalassaemia?
microcytic red cells tear drops microspherocytes target cells some fragments large number of nucleated red cells
114
What investigations would you do for beta-thalassaemia?
- Peripheral blood smear: microcytic red cells, tear drops, target cells - FBC: microcytic anaemia, all blood counts may be lower with increasing splenomegaly - LFTs in intermedia and major: elevated total and unconjugated bilirubin - Reticulocyte count: elevated
115
Differentials for beta-thalassaemia
Congenital dyserythropoietic anaemia (CDA) Pyruvate kinase (PK) deficiency Mild iron deficiency anaemia Alpha-gene mutations Haemolytic anaemia Anaemia of chronic disease
116
How would you manage thalassaemia?
Mild and asymptomatic don’t tend to require treatment. Avoid unnecessary iron supplementation to avoid iron overload In very severe cases, consider RBC transfusion
117
Complications of thalassaemia
Iron overload Growth delays (alpha) Gallstones Splenomegaly Leg ulcers MSK complications (beta) Gout (beta) Transfusion related complications
118
Prognosis for beta-thalassaemia
Beta-thalassaemia trait: normal Beta-thalassaemia intermedia: cosmetic changes, variable iron overload B-t major: fatal within a few years if untreated, transfusions can greatly increase quality of life and expectancy
119
What is the pathophysiology of multiple myeloma?
Uncontrolled replication of plasma cells and secretion of antibodies This produces diffuse bone marrow infiltration causing bone destruction and bone marrow failure. There is also overproduction of a monoclonal antibody ('paraprotein') by the malignant plasma cells, detectable in serum and/or urine
120
What is the normal physiology of B cell differentiation?
B cells originate in bone marrow from haematopoietic stem cells Migrate to lymphoid tissues Activated by CD4 T cells and develop into plasma cells in the bone marrow Plasma cells produce large quantities of antibodies
121
Why does hypercalcaemia develop in multiple myeloma?
Increase cytokine secretion (RANK-L) causes increased osteoclast activity More calcium is released
122
Why does anaemia occur in multiple myeloma?
The cancerous plasma cells invade the bone marrow (bone marrow infiltration) Suppression of the other blood cell lines, leading to anaemia (low haemoglobin), leukopenia (low white blood cells) and thrombocytopenia (low platelets). Anaemia in myeloma is normocytic (normal size) and normochromic (normal colour)
123
What are the 4 types of leukaemia?
**Acute myeloid leukaemia** (rapidly progressing cancer of the myeloid cell line) **Acute lymphoblastic leukaemia** (rapidly progressing cancer of the lymphoid cell line) **Chronic myeloid leukaemia** (slowly progressing cancer of the myeloid cell line) **Chronic lymphocytic leukaemia** (slowly progressing cancer of the lymphoid cell line)
124
Pathophysiology of leukaemia
A genetic mutation in one of the precursor cells in the bone marrow leads to excessive production of a single type of abnormal white blood cell. The excessive production of a single type of cell can suppress the other cell lines, causing the underproduction of different cell types. This can result in pancytopenia
125
Who does AML tend to affect?
more common in older adults (65+) slightly more common in men
126
What is acute myeloid leukaemia?
haematological malignancy caused by clonal expansion of myeloid blasts in the bone marrow
127
What is the pathophysiology of AML?
genetic abnormalities in haematopoietic precursor cells result in the accumulation of myeloid blasts unable to differentiate into mature neutrophils, RBCs or platelets. This can lead to bone marrow failure (manifest as anaemia, neutropenia, and/or thrombocytopenia)
128
Risk factors for AML
Exposure to radiation, benzene, or alkylating agents Chromosomal rearrangements such as t(15;17)(q22;q12) Chromosomal abnormalities: Down syndrome Age over 65 Inherited genetic conditions: Bloom's syndrome Myelodysplastic syndromes
129
Signs and symptoms of AML
Pallor Petechiae Fatigue Loss of appetite + Weight loss Fever/ infection Dizziness Palpitations Dyspnoea Bruising and mucosal bleeding: due to thrombocytopaenia Pain and tenderness in the bones Hepatosplenomegaly Lymphadenopathy (enlarged lymph nodes)
130
What are the most common sites of infiltration in AML?
liver, spleen and gums
131
What would an FBC show in AML?
Anaemia, neutropenia, and/or thrombocytopenia WBC may be elevated
132
What would be seen on a peripheral blood smear for AML?
Blast cells presence of Auer rods
133
What is the diagnositc test for AML?
Bone marrow aspiration: ≥20% myeloblasts
134
What investigations should be done for AML and what would they show?
FBC: anaemia, neutropenia, and/or thrombocytopenia, WBC may be elevated despite neutropenia Clotting screen: DIC Peripheral blood smear: presence of Auer rods Bone marrow aspiration: ≥20% myeloblasts Lactate dehydrogenase
135
Differential diagnoses for AML
ALL Biphenotypic leukaemia MDS Aplastic anaemia Myelofibrosis (different blood film) B12 deficiency
136
Management of AML
multi-agent, dose-intense chemotherapy
137
Complications of AML
Pancytopenia Leukostasis Tumour lysis syndrome Neutropenia
138
Poor prognostic factors for AML
> 60 years > 20% blasts after first course of chemo cytogenetics: deletions of chromosome 5 or 7
139
What is acute lymphoblastic leukaemia?
a malignant clonal disease that develops when a lymphoid progenitor cell becomes genetically altered and undergoes uncontrolled proliferation | majority affect B cells but can also affect T
140
Who does ALL normally affect?
Can occur at any age but most common in children Peak incidence ages 1-4 | most common childhood malignancy
141
Risk factors for ALL
Children less than 5 years of age Family history of ALL history of malignancy treatment with chemotherapy exposure to radiation smoking folate metabolism polymorphisms
142
What factors can contribute to the development of ALL?
- Genetic - Genetic disorders: Down, Klinefelter, Bloom - Environmental: including radiation exposure and smoking - Viral infections - History of malignancy - Treatment with chemotherapy - Poor maternal diet
143
What are the chromosomal abnormalities for ALL?
- **t(12;21)** is the most common cytogenetic abnormality in children. - In adults, the Philadelphia chromosome is the most common cytogenetic abnormality and describes the translocation **t(9;22)**
144
What does a blood film for ID anaemia show?
microcytic, hypochromic RBCs variation in shape and size
145
When does anaemia of chronic disease occur?
in chronic inflammatory diseases, e.g. Crohn's, SLE, RA
146
Why does anaemia of chronic disease happen?
decreased release of iron from bone marrow to developing erythroblasts inadequate erythropoietin response to anaemia decreased RBC survival
147
What is the diagnostic feature of sideroblastic anaemia?
Ring sideroblasts
148
What investigation findings would you expect for ID anaemia?
Serum iron: low TIBC: elevated serum ferritin: low FBC: low Hb, low MCV Transferrin saturation: decreased
149
What is total iron binding capacity?
indirect measure of the amount of iron that transferrin will bind
150
What are haemolytic anaemias?
Caused by increased destruction of red cells
151
What can cause haemolytic anaemia?
Hereditary: sickle cell, thalassaemia, hereditary spherocytosis Malaria Metabolic: G6PDH deficiency Autoimmune
152
What is sickle cell anaemia caused by?
An autosomal-recessive single gene defect in the beta chain of haemoglobin Results in production of sickle cell haemoglobin (HbS)
153
What is sickle cell trait?
Heterozygous HbAS ## Footnote Homozygous is HbSS and anaemia
154
What can sickling cause?
- Shortened RBC survival - Impaired passage of cells through microcirculation (leading to obstruction and infarction)
155
What is the mutation in sickle cell?
single base of adenine to thymine Causes a subsitition of valine replacing glutamic acid
156
In sickle cell, what can precipitate a vaso-occlusive episode?
acidosis dehydration cold temperatures extreme exercise + stress hypoxia infections
157
How do cells sickle?
Deoxygenated HbS molecules are insoluble and polymerize. Flexibility decreases and cells sickle. Irreversible, dehydrated and dense, can’t revert shape by oxygenating These cells are also prone to haemolysis, contributing to anaemia
158
Where is sickle cell anaemia most prevelant?
sub-saharan africa + western africa endemic malaria areas, as protective
159
When can symptoms of sickle cell begin?
3-6 months of age when HbF levels start to fall
160
Symptoms of sickle cell anaemia
Pallor Jaundice Lethargy Dactylitis Persistent pain in skeleton, chest and abdo
161
What is the most common sickle cell crisis?
vaso-occlusive
162
What is vaso-occlusive crisis in sickle cell and how does it present?
- caused by the sickle-shaped RBCs clogging capillaries, causing distal ischaemia. - It typically presents with pain and swelling in the hands or feet but can affect the chest, back, or other body areas. - can be associated with fever
163
What is acute chest syndrome in sickle cell?
- vessels supplying the lungs become clogged with RBCs - presents with fever, shortness of breath, chest pain, cough and hypoxia - triggered by vaso-occlusive crisis, fat embolism or infection | CXR shows pulmonary infiltrates
164
What is splenic sequestration? | sickle cell
An acute painful enlargement of the spleen produced by vaso-occlusion There is pooling of RBCs and can have hypovolaemia Can lead to splenic infarction
165
What are non-haemolytic normocytic anaemias?
CKD Aplastic anaemia
166
What is bone marrow aplasia? | sickle cell
Temporary absence of the creation of new RBCs in bone marrow Most commonly after parovirus B19 infection No reticulocytes in peripheral blood because of failure of erythropoiesis in marrow Can lead to aplastic anaemia
166
What is aplastic anaemia?
occurs when your bone marrow doesn't make enough red and white blood cells, and platelets
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In sickle cell anaemia, which crisis is usually precipiated by a parovirus B19 infection?
Bone marrow aplasia
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In sickle cell, which crisis is characterised by pulmonary infiltrate on a CXR?
Acute chest syndrome
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How is sickle cell screened for?
Heel-prick in newborns Carrier screening in parents
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What do Howell-Jolly bodies on a blood film indicate?
Splenic dysfunction
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What is seen on a peripheral blood smear for sickle cell?
Sickle shaped cells Howell-Jolly bodies Nucelated RBCs
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What is seen on a blood smear for HbSC disease?
Oat cells Target cells
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What investigation is used to confirm sickle cell and what does it show?
Haemoglobin electrophoresis no HbA, 80-95% HbS and 2-20% HbF
174
What investigations would you do for sickle cell?
- FBC and reticulocyte count: normocytic anaemia, elevated reticulocytes (except in aplasia) - Peripheral blood smear: Sickle-shaped cells, Howell-Jolly bodies, presence of nucleated RBCs - Haemoglobin electrophoresis: confirms diagnosis no HbA, 80-95% HbS and 2-20% HbF - Haemoglobin solubility: ≥10% to 15% HbS
175
What are the differentials of sickle cell disease?
Gout Connective tissue disorders Osteomyelitis Septic arthritis ID anaemia Avascular necrosis
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What is the management for sickle cell?
Avoid precipitating factors Hydroxycarbamide Blood transfusions Pain relief
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How does hydroxycarbamide work for management of sickle cell?
Stimulating the production of fetal haemoglobin (HbF) Reduces the frequency of vaso-occlusive crises, improves anaemia and decreases frequency of painful episodes
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Long term problems in sickel cell
- Decreased growth - Bone issues as common site of vaso-occlusive episodes (avascular necrosis of hip and shoulder) - Infections - Leg ulcers - Cardiac problems: MI from thrombosis, iron overload - Neuro complications: TIAs, infarction, haemorrhage - Priapism: painful erection - Hepatomegaly and liver dysfunction
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What are the 5 types of malaria?
Plasmodium falciparum (the most common and severe form) Plasmodium vivax Plasmodium ovale Plasmodium malariae Plasmodium knowlesi
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What is malaria?
a parasitic infection caused by protozoa of the genus Plasmodium
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What is the most life-threatening form of malaria?
Plasmodium falciparum
182
What should be a key point to suspect malaria?
fever with a travel history
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What is the life cycle in malaria?
- Mosquito bites infected individual and ingests gametocyte - Gametocytes reproduce inside mosquito and produce sporozoites - Sporozoites in salivary gland of mosquito - Mosquito bites new person and injects sporozoites into patient - Infection reaches patients liver and matures into schizont - Schizont in liver ruptures and enters blood stream as immature trophozoite which becomes a schizont (cyclic) - This rupture cycle can cause cyclical fever and haemolytic anaemia
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What is complicated malaria?
Infection complicated by severe organ dysfunction e.g. cerebral malaria, ARDS, renal failure, sepsis, anaemia
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What are some complications of anaemia?
Cerebral malaria Shock ARDS Renal failure Bleeding
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How can malaria cause renal failure?
Can be caused by vascular occlusion, dehydration and hypotension, haemolysis and haemoglobinuria
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What makes p.falciparum malaria more severe?
* Causes RBCs to adhere to endothelium and each other – causing obstruction in circulation * Vascular occlusion can cause cerebral malaria (drowsiness, seizures, coma), ARDS, renal failure
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What issue can p.ovale and vivax cause in malaria and how do you treat them?
P.ovale and vivax can form hypnozoites in the liver and stay dormant for years, causing relapse. Treated with oral antimalarials, primiquine to eliminate
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How is malaria transmitted?
bite of infected **female Anopheles mosquito**
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What are the risk factors for malaria?
travel to endemic area inadequate/ absent chemoprophylaxis insecticide-treated bed net not used in endemic area
191
What are the risk factors for developing a severe disease with malaria?
- Pregnancy - Under 5 years - Older age - Immunocompromised - Low host immunity
192
What tests should be run for malaria
Blood films: parasites can be seen FBC, U&Es
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Symptoms of malaria
FEVER Chills Headache Myalgia Diarrhoea
194
How is complicated malaria treated?
IV artesunate
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How is uncomplicated malaria treated?
Oral antimalarials, e.g. Artemether with lumefantrine
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How is malaria prevented? | nothing works 100%
Chemoprophylaxis for travellers Using mosquito nets and sprays
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Example of a variation of AML
Acute promyelocytic leukaemia
198
What does the mutation in ALL cause?
- precursors lose ability to differentiate - Uncontrolled blast cell division, taking up space and nutrition This causes cytopaenias like anaemia, thrombocytopenia, and leukopenia.
199
What can happen to some of the uncontrolled blast cells in ALL?
Enter into blood and migrate to other organs, e.g. liver and spleen pre-t cells in T cell ALL can migrate to thymus and lymph node causing these to enlarge
200
Symptoms of ALL
Fever Bone pain Abdominal fullness (from hepatosplenomegaly) Lethargy Infection Headache (CNS involvement)
201
Signs of ALL
lymphadenopathy hepatosplenomegaly pallor, ecchymoses, or petechia testicular enlargement CN palsies
202
What would be seen on a blood film for ALL?
Coarse chromatin Lymphoblasts Glycogen granules in cytoplasm
203
What investigations would be carried out for ALL?
**FBC**: anaemia, leukocytosis, neutropenia, thrombocytopenia **Peripheral blood smear** **Bone marrow aspiration and trephine biopsy**: ≥ 20% lymphoblasts is diagnostic **Cytogenic analysis **to detect chromosomal abnormalities **Immunophenotyping**
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What are the different types of ALL?
common ALL (75%), CD10 present, pre-B phenotype T-cell ALL (20%) B-cell ALL (5%)
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What are some differentials for ALL?
AML ITP Other cancers Aplastic anaemia
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What is the general management for ALL?
multi-agent dose-intense chemotherapy regimens in three treatment phases: induction, consolidation, and maintenance Allogeneic SCT (from a matched donor) is recommended for patients with high-risk disease
207
What are some complications of ALL?
Pancytopenia Infection Tumour lysis syndrome Neutropenia
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What are the poor prognostic factors for ALL?
- Age less than 1 year or older than 10 - WBC >30 × 10⁹/L on presentation - failure to achieve a complete remission within 4 weeks of treatment - cytogenetic abnormalities, e.g. t(9;22) - Presence of extramedullary disease, e.g. CNS involvement
209
What is tumour lysis syndrome?
an oncological emergency caused by the rapid breakdown of cancer cells and the subsequent release of large amounts of intracellular content into the bloodstream | complication of chemo
210
What does tumour lysis syndrome result in?
High uric acid High potassium (hyperkalaemia) High phosphate Low calcium (as a result of high phosphate)
211
What is chronic myeloid leukaemia?
involves the proliferation of partially mature myeloid cells, in particular granulocytes, within the bone marrow and blood
212
What is the pathophysiology of CML? | genetics
CML is associated with the Philadelphia chromosome 22. Translocation of chromosomes 9 and 22: t(9;22). BCR from 22 is fused to ABL from 9, forming a BCR-ABL 1 proteins. BCR::ABL1 is a constitutively active tyrosine kinase causing myeloid cells to continue dividing and become malignant
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How can CML progress to AML?
As the CML cells divide quicker than they should, there’s a high chance that further genetic mutations can happen CML might progress and accelerate into a more serious acute leukaemia which is called a blast crisis Can include the formation of a trisomy on chromosome number 8, or the doubling of the Philadelphia chromosome (22)
214
What age group does CML tend to affect?
Elderly 65+
215
What is the 3 phases of CML?
- Chronic phase - Accelerated phase - Blast phase
216
What is the chronic phase of CML?
often asymptomatic, patients are diagnosed after an incidental finding of a raised white cell count. can last several years before progressing
217
What is the blast phase of CML?
follows the accelerated phase and involves an even higher proportion (over 20%) of blast cells in the blood. Has severe symptoms and pancytopenia and is often fatal
218
What is the acceleratead phase of CML?
occurs when the abnormal blast cells take up a high proportion (10-20%) of the bone marrow and blood cells. Patients are more symptomatic and develop anaemia, thrombocytopenia and immunodeficiency
219
What are the risk factors for CML?
age 65 to 74 years (STRONG) ionising radiation exposure male sex
220
Symptoms of CML
SOB Bleeding Weight loss Fever and sweating
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Signs of CML
Pallor Hepatosplenomegaly Anaemia
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What investigations should be carried out for CML?
FBC: elevated WBC count, anaemia Complete metabolic profile Peripheral blood smear: an increase in all stages of maturing granulocytes Bone marrow biopsy: myeloblast infiltration in the bone marrow Cytogenetic studies: Ph+ t(9,22)
223
What is the management for chronic phase CML?
tyrosine-kinase inhibitors, e.g. imatinib (a first gen) second gen TKIs can be used if imatinib not suitable
224
What is the management for the blast phase of CML?
TKI therapy combined with induction chemotherapy + stem cell transplant
225
Differentials of CML
Ph+ ALL Chronic myelomonocytic leukaemia
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What is the most common form of leukaemia in adults?
CLL
227
What is chronic lymphocytic leukaemia?
An indolent lymphoproliferative disorder in which monoclonal B lymphocytes (>5 x 10⁹/L ) are predominantly found in peripheral blood
228
Epidemiology of CLL
Most common adult leukaemia median age at diagnosis is 70 years more common in men than women
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Whats the difference between acute and chronic leukaemias?
Cells partially mature in chronic Cells don't mature in acute
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How does CLL impact the lymph system?
CLL cells can infiltrate the lymphatic system and haematopoietic organs such as liver, spleen, and bone marrow. Can present with lymphadenopathy, hepatosplenomegaly, and bone marrow suppression. Recurrent infections can occur because CLL cells are immunologically dysfunctional.
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Pathophysiology of CLL
The B cells interfere with receptors and tyrosine kinases. This causes them to only partially mature and die slower than they divide, causing a build up. Premature cells also express proteins in their surface, such as CD5, CD23 CLL cells can then infiltrate the immune system
232
How can CLL cause autoimmune haemolytic anaemia?
CLL cells may also be involved in initiating autoantibody production by normal B cells leading to autoimmune reactions such as autoimmune haemolytic anaemia
233
Signs of CLL
Lymphadenopathy Splenomegaly Hepatomegaly
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Symptoms of CLL
Fatigue SOB Easier bleeding Infections
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What does a blood film show for CLL?
Smudge cells
236
What investigations should be done for CLL?
WBC: elevated Blood film: smudge cells (aka smear cells) Immunophenotype: CD5, CD19, CD20, CD23 FBC (Hb and platelets): anaemia and thrombocytopenia
237
Differential of CLL
Leukemic phase of lymphoma
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Which gene mutations in CLL are associated with a much poorer prognosis and rapid disease?
TP53 NOTCH1 del 17p and 11q
239
Treatment example for CLL
Immunotherapy with anti-CD20 monoclonal antibodies (e.g., rituximab, ofatumumab, obinutuzumab) improves survival and remission rates, particularly when combined with chemotherapy
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What targeted therapies can be used in CLL?
Tyrosine kinase (BTK) inhibitors (e.g., ibrutinib) anti-CD20 Monoclonal antibodies (e.g., rituximab, which targets B-cells)
241
What are some complications of CLL?
tumour lysis syndrome (TLS) hypogammaglobulinaemia autoimmune haemolytic anaemia immune thrombocytopenic purpura second malignancies
242
What is Hodgkin's Lymphoma?
a malignant proliferation of lymphocytes (mature B cells) characterised by the presence of the Reed-Sternberg cell
243
The prescence of which cell characterises Hodgkin's lymphoma?
Reed-sternberg cells
244
Epidemiology of Hodgkin's lymphoma
Peak incidence 20-34 years Bimodal distribution: incidence peaks around age 20-30 then later again above age 55
245
Which form of Hodgkin'a lymphoma has the worst prognosis?
Lymphocyte depleted
246
What are the different classifications of hodgkin's lymphoma?
Classic: nodular sclerosing (70%), mixed cellularity (20%), lymphocyte rich (5%), lymphocyte depleted (rare) Nodular lymphocyte-predominant
247
What is nodular lymphocyte predominant HL characterised by?
Popcorn cells
248
What is the basic pathology of Hodgkin's lymphoma?
B cell malignancy THe cells don't express antibodies and divide uncontrollably Spread to nearby lympho nodes
249
What is the most common presentation of Hodgkin's lymphoma?
persistent cervical and/or supraclavicular lymphadenopathy in a young adult
250
What are the risk factors for hodgkin's lymphoma?
age 20-34 years and >55 years history of Epstein-Barr virus (EBV) infection family history of Hodgkin's lymphoma young adult in higher socio-economic class (weak)
251
What test is needed to diagnose hodgkin's lymphoma and what would it show?
excisional lymph node biopsy Reed-sternberg cells
252
What investigations are done for Hodgkin's lymphoma?
Lymph node biopsy (diagnostic) FBC: low Hb and platelets comprehensive metabolic panel erythrocyte sedimentation rate (ESR) CXR PET/CT
253
What are the 3 B symptoms that occur in lymphoma?
Fever Night sweats Weight loss ## Footnote occur in 30% of patients with HL, usually with advanced disease or other risk factors
254
What staging is used for hodgkin's lymphoma?
Ann-Arbor (More recently replaced by Lugano)
255
What is stage 1 HL?
Involvement of a single lymph node region or lymphoid structure
256
What is stage 2 HL?
involvement of 2 or more lymph node regions on the same side of the diaphragm; localized contiguous involvement of only one extranodal organ/site on same side of the diaphragm
257
What is stage 3 HL?
involvement of lymph node regions on both sides of the diaphragm, may be accompanied by the involvement of the spleen or one extranodal organ site
258
What is stage 4 HL?
diffuse or disseminated involvement of one or more extranodal organs or tissues, with or without associated lymph node involvement
259
What is the treatment for HL?
Chemotherapy and radiotherapy
260
What are the differentials for HL?
Non-Hodgkin's lymphoma (NHL) Lymphadenopathy from other malignancies Infectious mononucleosis Reactive lymph nodes
261
What is early favourable/unfavourable HL?
Early favourable: stage I to stage II without risk factors Early unfavourable: stage I to stage II with risk factors
262
What is advanced HL?
stage III to stage IV, with or without risk factors
263
Why are low grade lymphoma considered incurable?
They often can't be treated by chemo as it acts on the cell cycle, and these cells are slow growing/ not in cell cycle
264
Examples of some NHLs
Diffuse large B-cell lymphoma (DLBCL) Follicular lymphoma Mantle cell lymphoma
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How does diffuse large B cell lymphoma present?
a rapidly growing painless mass in older patients
266
What are non-hodgkin lymphomas?
NHLs are a heterogeneous group of malignancies of the lymphoid system
267
Who does NHL tend to affect?
Uncommon before age of 50, median age at diagnosis 68 Higher chance if first-degree relative has NHL
268
Which viruses are associated with NHLs?
HIV and E-BV with Burkitt's lymphoma Hep C with DLBCL
269
Risk factors for NHL
age >50 years male sex some previous viral infections: HIV, Epstein-Barr, H.Pylori, Hep C, HTLV-1 autoimmune conditions: e.g. Sjogren, coeliac
270
What test is helpful for diagnosing T cell lymphomas?
Skin biopsy
271
What investigations are run for NHL?
Lymph node biopsy FBC with differential PET/CT lactate dehydrogenase (LDH) Skin biopsy – t cell Blood smear
272
Differentials for NHL
ALL Infection Hodgkin lymphoma Sarcoidosis
273
What are the management options for NHLs?
Watchful waiting Chemotherapy Monoclonal antibodies (e.g., rituximab, which targets B cells) Radiotherapy Stem cell transplantation
274
What are the worst prognostic factors for NHL?
- B symptoms (fever, weight loss, night sweats) - Lymphadenopathy - Organomegaly - Extranodal involvement - Poor Eastern Cooperative Oncology Group (ECOG) performance status.
275
What is the official name for glandular fever?
Infectious mononucleosis
276
What virus causes glandular fever?
Epstein Barr virus in 80-90% of cases ## Footnote rare but can also be caused by human herpes 6 or CMV
277
Which age group is most commonly affected by glandular fever?
15-24
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Where in the body is Epstein Barr virus found?
Saliva
279
How can EBV infection be spread?
kissing sharing cups sharing toothbrushes other equipment that transmits saliva
280
Symptoms of glandular fever
fever sore throat enlarged tonsils malaise rash fatigue splenomegaly lymphadenopathy
281
What antibodies would be detected for EBV infection?
VCA-IgM VCA-IgG EA EBV EBNA
282
What investigations should be run for glandular fever?
FBC: lymphocytosis heterophile antibodies Epstein-Barr virus (EBV)-specific antibodies LFTs
283
What is the management for glandular fever?
No specific treatment Just supportive therapy: good hydration, pain relief, rest
284
Differentials for glandular fever
Group A strep pharyngitis Hepatitis A Acute HIV infection Adenovirus Human herpes virus-6 Cytomegalovirus (CMV) infection Flu
285
3 examples of myeloproliferative disorders
Primary myelofibrosis Polycythaemia vera Essential thrombocythaemia ## Footnote also CML, but these 3 can transition to each other
286
What is polycythaemia?
an increase in haemoglobin or haematocrit | erythrocytosis
287
What is polycythaemia vera?
a chronic myeloproliferative neoplasm. Characterised by haematopoietic stem cell-derived clonal myeloproliferation that results in erythrocytosis + thrombocytosis, leukocytosis, and splenomegaly
288
What happens in myelofibrosis?
proliferation of a single cell line leads to bone marrow fibrosis, where bone marrow is replaced by scar tissue
289
What would a blood film for myelofibrosis show?
Teardrop-shaped red blood cells Anisocytosis (varying sizes of red blood cells) Blasts (immature red and white cells
290
Who does polycythaemia vera affect?
Affects middle-aged or older Median age at diagnosis is 65 years
291
What mutation almost always causes polycythaemia vera?
JAK2 V617F mutation
292
What can PCV progress to?
spent phase with anaemia, thrombocytopenia and leukopenia (myelofibrosis)
293
What is the pathophysiology of PCV?
Mutation of JAK2 gene always active and cells can divide in absence of erythropoietin leads to rapid proliferation and subsequent death scar tissue forms can progress to spent phase and myelofibrosis
294
What are the risk facators for PCV?
age >60 years Budd-Chiari syndrome (BCS) affected family member Janus kinase 2 (JAK2) mutations (JAK2 V617F, JAK2 exon 12)
295
Symptoms of PCV
headache generalised weakness/fatigue pruritus (itching) night sweats and bone pain erythromelalgia splenomegaly plethora/ruddy cyanosis blurred vision
296
What would the haematocrit and Hb show in PCV?
>49% in men, >48% in women haematocrit elevated Hb
297
What investigations should be done for PCV?
Haematocrit: >49% in men, >48% in women Haemoglobin: elevated Serum ferritin: low or normal FBC: wbc and platelets elevated LFTs JAK2 gene mutation screen
298
What are the differentials of PCV?
Secondary polycythaemia Essential thrombocythaemia (ET) Primary myelofibrosis CML Polycythaemia owing to elevated erythropoietin level Polycythaemia owing to anabolic steroid or testosterone use Congenital polycythaemia
299
What is a common complication of polycythaemia and thrombocythaemia?
thrombosis leading to MI, stroke or VTE
300
What is the management of PCV?
Low risk of thrombosis: Phlebotomy and low-dose aspirin High risk of thrombosis: cytoreductive therapy (hydroxycarbamide) along with low-dose aspirin (and phlebotomy if required)
301
What is used in the management of myelofibrosis?
Ruxolitinib (JAK2 inhibitor)
302
What are some complications of PCV?
Thrombosis Post-PV myelofibrosis Transformation to acute leukaemia Haemorrhage
303
What is the most common inherited bleeding disorder?
Von Willebrand disease
304
What is type 1 VWD?
partial quantitative deficiency of VWF most common autosomal dominant
305
What is type 2 VWD?
qualitative abnormality of VWF usually inherited as autosomal dominant
306
What is type 3 VWD?
almost complete deficiency of VWF rarest but most severe form autosomal recessive
307
What is von Willebrand disease?
Caused by a deficiency or abnormality of VWF The most common inherited bleeding disorder
308
Why does VWD lead to a deficiency of factor VIII?
VWF protects factor VIII from premature degradation so an absence in VWF leads to a deficiency of factor VIII
309
What is the dual haemostatic defect in VWD?
Decrease in VWF and Factor VIII
310
What is the pathology of VWD?
Mutation on VWF gene on chromosome 12 causes a decrease in working VWF There isn't enough working VWF for platelet adhesion and binding to factor VIII
311
Where is VWF synthesised and stored?
Endothelial cells and megakaryocytes
312
What stimulates the release of VWF?
Histamine and thrombin
313
What causes VWD?
Mutation in VWF gene on chromosome 12 very rarely can be acquired
314
If VWD affects men and women equally, why are women more often diagnosed?
prominent symptom of menorrhagia
315
Symptoms of VWD
Bleeding from minor wounds Easy and excessive bruising Menorrhagia Epistaxis GI bleeding
316
How would VWD typically present?
a history of unusually easy, prolonged or heavy bleeding
317
What investigations would be run for VWD?
- Platelets count: usually normal except in type IIB - PT: tests the extrinsic and common pathway and so is normal - APTT: tests the intrinsic and common pathways, usually prolonged - Measurement of vWF antigen - FBC: usually normal
318
What are the differentials for VWD?
Mild haemophilia A Inherited platelet function disorder
319
What are the management options for VWD?
Desmopressin (stimulates the release of vWF from endothelial cells) TXA Von Willebrand factor infusion (not type 1, more severe) Factor VIII plus von Willebrand factor infusion (not type 1, more severe) | not required daily, more prohylactic or during bleeding
320
What causes haemophilia A?
lack of factor VIII
321
What causes haemophilia B?
lack of factor IX
322
What type of inheritance pattern is haemophilia?
X-linked recessive
323
What is the pathophysiology of haemophilia?
Factors VIII and IX are part of intrinsic clotting pathway. In haemophilia, there is delayed clot formation due to reduced thrombin generation. Leads to the formation of an unstable clot that is easily dislodged, causing excessive bleeding
324
What are the risk factors for haemophilia?
Family history of haemophilia (congenital haemophilia) male sex (congenital haemophilia) age >60 years (acquired haemophilia) autoimmune disorders (acquired)
325
What are the key presentations of haemophilia?
history of recurrent or severe bleeding bleeding into muscles
326
What are the symptoms of haemophilia?
bleeding into muscles (hallmark) prolonged bleeding following heel prick in neonates mucocutaneous bleeding excessive bruising/haematoma fatigue menorrhagia and bleeding following surgical procedures or childbirth (female carriers) extensive cutaneous purpura (acquired haemophilia)
327
Differentials for haemophilia
Von Willebrand disease (VWD) Platelet dysfunction Deficiency of other coagulation factors Ehlers-Danlos syndrome Child abuse
328
What investigations should be done for haemophilia?
APTT: prolonged PT: normal FBC: normal, possible low Hb plasma factor VIII and IX assay
329
Management for haemophilia
infusion of factor VIII or IX concentrate can also include: TXA, desmopressin, pain meds
330
Complications of haemophilia
Compartment syndrome Severe bleeding Joint or muscular damage
331
What are 2 important hallmarks of DIC?
continuous generation of intravascular fibrin consumption/depletion of procoagulants and platelets
332
What is disseminated intravascular coagulation?
an acquired syndrome characterised by activation of coagulation pathways, resulting in formation of intravascular thrombi and depletion of platelets and coagulation factors ## Footnote underlying disease statae must be present
333
What is the pathophysiology of DIC?
In severe disease states, such as sepsis, malignancy and trauma, more procoagulants are released forming more clots. This can cause ischaemia, necrosis and organ damage. But it also depletes supplies of clotting factors and release fibrin degradation products into circulation, interfering more with clot formation ## Footnote Paradoxical, thrombosis and bleeding
334
What can cause DIC?
- Sepsis - Major trauma/ burns - Severe organ failure
335
Symptoms of DIC
336
What are the risk factors for DIC?
major trauma/burn/organ destruction sepsis/severe infection severe obstetric disorders solid tumours and haematological malignancies severe toxic or immunological reactions
337
What are the main points of DIC?
Requires underlying disease state Thrombosis and bleeding
338
Investigations for DIC
Platelet count: shows thrombocytopenia Prothrombin time: often prolonged Fibrinogen: low levels D-dimer/fibrin degradation products: elevated
339
What is thrombocytopenia?
a low circulating platelet count
340
What can cause reduced platelet production?
Certain viral infections (e.g., Epstein-Barr virus, cytomegalovirus and HIV) B12 deficiency Folic acid deficiency Liver failure Leukaemia MDS Chemotherapy
341
What can cause increase platelet destruction?
Medications (e.g., sodium valproate and methotrexate) Alcohol Immune thrombocytopenic purpura (ITP) Thrombotic thrombocytopenic purpura (TTP) Heparin-induced thrombocytopenia (HIT)
342
What is immune thrombocytopenic purpura?
antibodies are created against platelets. An immune response against platelets leads to their destruction and a low platelet count (thrombocytopenia)
343
What is thrombotic thrombycytopenic purpura?
tiny thrombi develop throughout the small vessels, using up platelets microangiopathy
344
What can TTP cause?
Thrombocytopenia Purpura Tissue ischaemia and end-organ damage
345
What is heparin induced thrombocytopenia?
involves the development of antibodies against platelets in response to heparin Heparin-induced antibodies target a protein on platelets called platelet factor 4
346
What are the symptoms of thrombocytopenia?
Nosebleeds Bleeding gums Heavy periods Easy bruising Haematuria (blood in the urine) Rectal bleeding
347
Top differentials of abnormal or prolonged bleeding
Thrombocytopenia Von Willebrand disease Haemophilia A and haemophilia B Disseminated intravascular coagulation
348
What are the risk factors for developing ITP?
women of childbearing age males and females <10 or >65 years old
349
Signs of ITP
Purpura Bleeding
350
What investigations should be done for ITP?
FBC Peripheral blood smear
351
What is the management of ITP?
Asymptomatic can just be monitored A corticosteroid (pred), IVIG, and anti-D immunoglobulin are considered first-line treatments in adults with platelets below 30 × 10⁹/L
352
What is thrombocytosis?
High platelet count
353
What causes TTP?
Unusually large VWF due to a reduction in ADAMTS-13
354
What are the risk factors for TTP?
black ethnicity female gender obesity pregnancy (near term or post-partum period) cancer therapies
355
Symptoms of TTP
Neurological symptoms Digestive issues Fever Bleeding, purpura
356
What investigations would you do for TTP?
FBC and platelet count Shows reduced platelets
357
Management options for TTP
plasma exchange steroids rituximab
358
What is the prothrombin time test?
adding tissue factor and calcium to plasma and establishing length of time to clot measures factors 7, 10, 5 prothrombin and fibrinogen (the extrinsic pathway) | can also be expressed as INR (international normalized ratio)
359
What does the activated partial thromboplastin time (APTT) measure?
Measures factors 12, 11, 9, 8, 10 and 5, prothrombin and fibrinogen (intrinsic pathway)
360
what is lymphopenia?
a reduction in the number of lymphocytes in circulating blood
361
What is lymphocytosis?
Increase in the number of lymphocytes
362
What is neutropenia?
abnormally low level of neutrophils in the blood
363
What is neutrophilia?
transient increase in the number of leukocytes in the blood
364