Haem Flashcards
1
Q
Signs / Symptoms Anaemia
A
Fatigue
Dyspnoea
Faintness
Palpitations
Headache
Tinnitus
Anorexia
Pallor
Hyperdynamic circulation e.g. tachycardia, flow mumurs, cardiac enlargement
2
Q
Big consequences of anaemia
A
↓O2 Transport
Tissue hypoxia
Compensatory changes - (↑tissue perfusion, ↑O2 transfer to tissue, ↑RBC production)
3
Q
Pathological consequences of anaemia
A
Myocardial fatty change
Fatty change in liver
Aggravate angina
Skin and nail atrophic changes
CNS cell death (cortex and basal ganglia)
4
Q
State causes of macrocytic anaemia
A
B12/Folate def
+ HLARD
Hypothyroidism
Liver disease
Alcohol
Reticulocytes - haemolysis
Drugs - Azathioprine
5
Q
State causes of normocytic anaemia
A
- Acute blood loss!
- Anaemia of Chronic disease
- BM failure
- Renal failure
- Hypothyroidism
- Haemolysis
- Pregnancy
6
Q
Is haemolytic anaemia microcytic or macrocytic?
A
Neither - bc it can be normocytic or macrocytic
7
Q
Define anaemia
State values
A
Low haemoglobin conc
< 135 g/L for men
< 115g/L for women
8
Q
Investigations for anaemia
A
FBC + film
Reticulocyte count
U&Es, LFTs, TSH
Iron def - ferritin, iron studies, look for cause
Chronic disease - clinical Ix, lab investigation, renal failure?
B12 def - IF antibodies, schilling test, coeliac ab
9
Q
Define FBC
What does one consist of?
A
Basic blood test that gives info on blood constituents
RBC vol
WBC vol (all types)
Platelet vol
Haemoglobin conc
Mean corpuscular volume (MCV)
10
Q
Why is the GS Ix for IDA limited?
A
Because ferritin is an acute phase protein
11
Q
What does reticulocyte count show?
A
How quickly new RBCs are being formed
12
Q
What are reticulocytes?
A
Immature RBCs
13
Q
What does a low reticulocyte count show?
Give an example of a cause
A
Something is preventing new RBCs from being produced
e.g. Haemantinic deficiency
14
Q
What does a high reticulocyte show?
Give an example of a cause
A
RBCs are being lost or destroyed & ↑Reticulocyte as a compensatory mechanism
e.g. Bleeding or Haemolytic anaemia
15
Q
What is ferritin?
A
Major iron storage protein of the body
16
Q
What can ferritin be used to measure?
A
Used to indirectly measure iron levels in body
17
Q
When and why can ferritin be falsely raised?
A
In inflammation and malignancy
Because it is an acute phase protein
18
Q
What does a thick blood film permit?
A
Examination of a large amount of blood for presence of parasites (NOT identification of species)
19
Q
What does a thin blood film permit?
A
Observation of RBC morphology, inclusions and intracellular/extracellular parasites
20
Q
What does each haemoglobin molecule consist of?
A
2 alpha and beta chains
21
Q
State the value ranges for micro, normo and macrocytic anaemia
A
MCV < 80 = Microcytic
MCV 80 - 100 = Normocytic
MCV > 100 = Macrocytic
UNITS - femtolitres 2
22
Q
Where is iron absorbed?
A
Duodenum
23
Q
Pathophysiology of Iron-Def anaemia
A
↓Iron available for haem synthesis
∴ ↓ Haemoglobin
∴ ↓ Effective RBCs
∴ Anaemia
24
Q
Causes IDA
A
Low iron diet
Blood loss - menorrhagia, GI bleeding, Hookworm
Malabsorption - coeliac disease
Pregnancy
Breastfeeding
25
Signs/Symptoms more specific to IDA
Brittle hair and nails
Atrophic glossitis
Angular stomatitis
Koilonychia
26
DDx IDA
Anaemia of chronic disease
Thalassaemia
27
Ix IDA
FBC & Blood film - **hypochromic microcytic RBCs**
Also, anisocytosis and poikilocytosis
Serum ferritin - low
↑ Total iron binding capacity
**↓Reticulocyte count**
Endoscopy/Colonoscopy - to see if upper/lower GI bleed
28
Tx IDA
Treat cause!
Ferrous sulphate - oral iron
Ferrous fumarate
Continue for 3 months until Hb is normal
29
If a patient is responding to iron treatment, what should you find?
An increase in reticulocyte count
then gradual increase in Hb until normal
30
S/E of ferrous sulphate / fumarate
Black stool (melaena) ! (DDx for upper Gi bleed)
Constipation
Diarrhoea
Nausea
GI upset
Epigastric abdo pain
31
Microcytic Anaemia Causes
**TAILS**
**T**halassaemia
**A**naemia of Chronic Disease
**I**ron def
**L**ead poisoning
**S**ideroblastic anaemia
32
What is Plummer Vinson Syndrome?
TRIAD OF :
1. Dysphagia
2. Iron def
3. Oesophageal webs
33
What is Thalassaemia?
Inherited disease
↓ Rate of production or NO production
of one or more globin chains (α or β̞)
in red cell precursors OR mature RBCs
∴ in red cell precursors = ineffective erythropoiesis
& in mature RBCs = haemolysis
∴ **↓Production and ↑premature destruction of RBCs**
34
Where is Thalassaemia most common?
Mediterranean
Middle East
Asia
35
How is Thalassaemia inherited?
Autosomal recessive
36
Types of Thalassaemia
α-Thalassaemia
β̞-Thalassaemia
37
What globin chains are found in the majority of adult haemoglobin?
2x alpha globin chains
2x beta globin chains
38
Where the gene for alpha-globin chains found?
On both chromosome 16s
39
Cause Alpha Thalassaemia
Gene deletions
40
How does alpha Thalassaemia present with **1 gene deletion**?
(-a/aa)
Usually normal blood picute
Asymptomatic
41
How does alpha Thalassaemia present with **2 gene deletions**?
(--/aa)
Asymptomatic with possible mild microcytic anaemia
Carrier for alpha thalassaemia
42
How does alpha Thalassaemia present with **3 gene deletions**?
(--/-a)
Common in parts of Asia!
↓↓ Reduction of alpha chain synthesis ∴ HbH disease
Severe haemolytic anaemia & features of haemolysis = splenomegaly, jaundice, leg ulcers
Sometimes transfusion dependent
43
How does alpha Thalassaemia present with **4 gene deletions**?
(--/--)
NO a-chain synthesis
Only Hb Barts present - not compatible w life bc cannot carry oxygen
Death in utero
Infants stillborn - pale, oedematous with huge livers and spleen
44
What chains does Hb Barts have?
4x gamma chains
Not compatible with life!
45
What is an evolutionary advantage of carriers of alpha thalassaemia?
Protected from falciparum malaria
46
Cause of B Thalassaemia?
Point mutation causing - transcription, RNA splicing and translation mutations
∴ Unstable and unusable B chains
47
Pathophysiology B Thalassaemia
Genetic defects
∴ little/no normal B chain production
∴ **XS a chain production**
∴ a-chains combine with whatever is available - B, gamma or delta chains
∴ ↑ Production of HbA2 and HbF
∴ Result in ineffective erythropoiesis and haemolysis
48
What chains does HbA contain?
2 alpha
2 beta
49
What chains does HbA2 contain?
2 alpha
2 delta
50
What chains does HbF contain?
2 alpha
2 gamma
51
Where are B-globin genes found?
Chromosome 11
52
What mutations occur in B-Thalassaemia?
Point mutations ?
53
Describe how B-Thalassaemia **minor** presents
Asymptomatic
Carrier state
Mild micro and hypochromic anaemia
Iron stores and ferritin normal
54
Describe how B-Thalassaemia **intermedia** presents
Moderate anaemia - Patients don't require transfusion
Splenomegaly, bone abnormalities, recurrent leg ulcers & gallstones
55
Describe how B-Thalassaemia **major** presents
Presents in 1st year of life - Cooley's anaemia (severe) - with :
Failure to thrive
Recurrent infections
Listless (lacks energy)
Crying
Pale
Bony abnormalities (bc hypertrophy of ineffective BM) e.g. skull bossing, thalassaemic faces w enlarged maxilla + prominent frontal and parietal bones, hair on end sign on skull XR
Hepatosplenomegaly (bc haemolysis)
Will require lifelong transfusion if develop to adulthood
56
Ix B-Thalassaemia
Blood film - microcytic hypochromic anaemia
Target cells visible!
Increased reticulocytes and nucleated RBCs in periph circulation
**GS!! Hb electropheresis!** - shows ↑ HbF and absent/low HbA
Skull XR - hair on end sign, enlarged maxilla
57
Tx B-Thalassaemia
Blood transfusions regularly (~2-4x per week)
HbA has time to replenish
Long term folic acid supplements
Histocompatible marrow transplant could cure!!
**nB** - risk of iron overload!!
∴ give iron chelation (SC desderrioxamine, oral deferiprone) to decrease iron loading
& Ascorbic acid to ↑urinary excretion of iron
--
Things to consider : bone health, endo supplements, psych support
58
Why is there a risk of iron overload with blood transfusions?
Repeat transfusions = deposition of iron in major organs
e.g. *liver, spleen (cirrhosis and fibrosis)
pancreas, heart and endocrine glands (DM, HF, premature death)
59
What should be monitored in a patient with B-Thalassaemia?
Why?
Ferritin
Cardiac & liver MRI
Endo testing - gonadal function, DM screening, growth and puberty
--
bc blood transfusions can lead to complications in major organs
60
What is sideroblastic anaemia?
BM produces ringed sideroblasts instead of healthy RBCs
61
Causes Sideroblastic anaemia
Congenital - rare, X-linked
Chemotherapy
Anti-TB drugs
XS alcohol
62
Ix Sideroblastic anaemia
Increased ferritin
Blood film - hypochromic RBCs
**GS!!** - Sideroblasts in BM
63
Tx Sideroblastic anaemia
Remove cause
Pyridoxine
Repeated transfusions for severe anaemia
(& ∴ iron chelation and ascorbic acid)
64
3 Main Causes Normocytic anaemia
1. Acute blood loss
2. Combined haematinic def e.g. iron and B12 def - balances out micro and macro
3. Anaemia of chronic disease
65
Causes Anaemia of Chronic disease
*Crohn's
*RA
TB
SLE
Malignancy
CKD
66
Ix Anaemia of Chronic disease
FBC and blood film - normocytic/microcytic and hypochromic
Low serum iron
Low total iron binding capacity (TIBC)
↑ or normal serum ferritin
67
Tx Anaemia of Chronic disease
Treat underlying cause
Recombinant erythropoietin
68
What 2 groups can macrocytic anaemia be divided into?
Megaloblastic
Non-Megaloblastic
69
What is a megaloblast?
When does one form? Why?
Cell where nuclear maturation is delayed but cytoplasm is not
∴ Lots of cytoplasm, tiny nucleus
Forms with B12 and folate deficiency
Bc both are required for DNA synthesis
70
What is a non-megaloblast?
When does one form?
Not a megaloblast
XS alcohol, reticulocytosis, liver disease, hypothyroidism
71
Other than causes for megaloblastic and non-megaloblastic, what are some causes for macrocytic anaemia?
Myelodysplasia
Myeloma
Myeloproliferative disorderes
Aplastic anaemia
72
What is folate found in?
Green vegetables, nuts, yeast and liver
73
What is folate synthesised by?
Gut bacteria
74
What is folate essential for?
DNA synthesis
75
Where is folate absorbed?
Jejunum
76
What does maternal folate deficiency cause?
Foetal neural tube defects
77
Causes of Folate Deficiency
Poor diet e.g. poverty, alcoholics, elderly
↑ Demand e.g. pregnancy or ↑cell turnover
Malabsorption e.g. coeliac disease, Crohn's
Alcohol
Drugs - anti-epileptics, methotrexate
78
Ix Folate Deficiency
Blood film - anisocytosis and poikilocytosis w/ large oval macrocytes
Serum & red cell folate assay
79
Tx Folate Def
Assess for underlying cause (poor diet, malabsorption etc)
Folic acid (5mg/day PO for 4 months)
80
Prophylaxis for folate deficiency if pregnant
What does it prevent?
400mcg/day are given until 12 weeks
Helps prevent spina bifida
81
What is pernicious anaemia?
Autoimmune condition
Parietal cells are attacked
∴ atrophic gastritis AND ↓IF production
∴ **↓ B12** absorbed by iluem
82
Causes B12 Def
Diet - vegans
Pernicious Anaemia
Atrophic Gastritis
Malabsorption - Crohn's, coeliac etc
Gastrectomy
Congenital metabolic errors
Basically anything that affects IF production by parietal cells in stomach
OR
anything that affects absorption in ileum
83
Where is B12 absorbed?
Terminal ileum
Bound to intrinsic factor (IF)
84
What produces B12?
Parietal cells
85
Signs / Symptoms Pernicious anaemia
Normal anaemia ones
+
Jaundice - XS breakdown of Hb
**Neurological Sx** - Polyneuropathy
Tongue Sx
Lemon yellow tinge
86
What is polyneuropathy caused by?
(Specifically relating to pernicious anaemia)
Symmetrical damage to peripheral nerves and posterior + lateral columns of spinal cord
87
How can you differentiate between B12 and folate deficiency?
Folate def does not have neuropathy but B12 does!
88
B12 and folate deficiency anaemias are what type of anaemia?
Megaloblastic macrocytic
89
Why are B12 and folate deficiency anaemia megaloblastic?
B12 and folate help with DNA synthesis
∴ deficiency = less DNA synthesis
∴ little nucleus + lots of cytoplasm
90
Ix Pernicious anaemia
FBC - ↓ Hb, ↑ MCV obvs
If severe, ↓WBC + platelets
Blood film - macrocytic RBCs
Megaloblasts in BM
Maybe ↓ Reticulocytes - production impaired
↓ Serum B12
**MORE SPECIFIC TESTS :**
Autoantibody screen for IF and parietal cells (present in 50% and 90% of cases respectively)
91
Tx Pernicious anaemia
Vitamin B12 (hydroxocobalamin) IM injections
**NOT EVER FOLIC ACID !!** - will cause fulminant neuro deficits
92
Comps Pernicious anaemia
HF
Angina
Neuropathy
93
A carrier of sickle cell disease (heterozygous) is protected from?
Falciparum malaria!
94
What is sickle cell disease?
Autosomal recessive normocytic haemolytic disease
95
Where is sickle cell disease more common?
In Afro-Caribbean ethnicities
96
Pathophysiology Sickle Cell disease
B globin gene mutation (glutamic -> valine)
∴ HbS variant is formed
When ↓O2, Hb variant polymerises and forms rod-like aggregates
∴ RBC becomes sickle-shaped + rigid
97
What triggers RBCs to turn sickle-shaped in sickle cell anaemia?
"Stress" e.g.
Cold
Infection
Dehydration
Hypoxia
Acidosis
Causes microvascular occlusion
98
Signs / Symptoms Sickle Cell disease
Can be Asx
Anaemia symptoms
Acute pain in hands + feet (dactylitis)
Jaundice (breakdown of Hb)
99
Ix Sickle cell anaemia
FBC - Normocytic normochromic with *↑reticulocyte count*
Blood film - sickled erythrocytes
Howell-Jolly bodies
**Hb electrophoresis**
If 90% of Hb = HbS, then diagnostic!
--
NEONATAL SCREENING
100
Tx Sickle Cell disease
ACUTE ATTACKS :
IV fluid + Analgesia + O2
LONG TERM :
Avoid precipitants
Hydroxycarbamide + Folic acid supps
Transfusion (+ Iron chelation + Ascorbic acid)
101
What is the most common cause of death in adults with Sickle cell disease?
Pulmonary HTN
Chronic lung disease
102
Comps Sickle cell disease
Splenic sequestration - autosplenectomy !
Vaso-occlusive crisis
Osteomyelitis (In sickle cell patients, caused by salmonella!!!)
ACUTE CHEST CRISIS = pulmonary vessel vaso-occlusion!! can cause resp distress!!! EMERGENCY!!!
103
Type of haemolysis in Sickle Cell Anaemia
BOTH - Intravascular (inside vessels) && Extravascular (inside spleen)
104
How is spherocytosis inherited?
Autosomal dominant
105
Pathophysiology spherocytosis
↓ Spectrin
∴ ↑ RBC membrane permeability to Na+
∴ RBCs become rigid and spherical
∴ Spleen believes RBCs are damaged are they are prematurely destroyed
= _Extravascular_ haemolysis
106
Signs / Symptoms Spherocytosis
General anaemia
NEONATAL JAUNDICE
Splenomegaly
Gallstones!
107
Ix Spherocytosis
FBC & reticulocyte count - ↑↑Reticulocytes!
Blood film - shows spherocytes
Osmotic fragility tests - RBCs fragile in hypotonic solution
Coombs' test! (Direct anti-globulin test) = NEG !!
Rules out autoimmune haemolytic anaemia! (spherocytes are often seen in AHA)
108
What is the most common cause of spherocytosis or elliptocytosis ?
↓ Spectrin
109
What is spectrin?
RBC structural membrane protein
110
What is the structural difference between spherocytosis and elliptocytosis?
Spherocytosis - vertical deformity
Elliptocytosis - horizontal deformity
111
Signs / Symptoms Elliptocytosis
Same as spherocytosis i think
112
Tx Spherocytosis
Splenectomy!
Wait until 6 years old at least - otherwise very high sepsis risk!
113
Tx Neonatal Jaundice
Phototherapy
114
Comps of untreated Neonatal jaundice
Kernicterus!
Where bilirubin accumulates in basal ganglia
∴ CNS dysfunction and death!!
115
Ix Autoimmune Haemolytic Anaemia
Direct Coomb's test +VE
116
How is Glucose-6-phosphate dehydrogenase deficiency inherited?
X-linked recessive
117
Pathophysiology of G6PD deficiency
G6PD essential in hexose monophosphate shunt - maintains glutathione in reduced state
Glutathione protects RBC from oxidative crisis
∴ without G6PD, RBCs will undergo oxidative crisis!
118
What type of individuals does G6PD deficiency mostly affect?
Mediterranean
Africa
Middle/Far East
119
What does G6PD deficiency protect against?
Falciparum malaria
120
Signs / Symptoms G6PD Def
Asymptomatic until exposed to oxidative stressor !!
--
Neonatal jaundice
Chronic haemolytic anaemia
--
Acute haemolysis - Rapid anaemia, Jaundice (dark urine)
Back pain
121
What can G6PD def be caused by?
Ingestion of fava beans !!!
Henna
Illness
& common drugs - quinine, sulphonamides, quinolones and nitrofurantoin
122
Ix G6PD Def
FBC - anaemia, raised reticulocytes
Blood film - **Bite and blister cells**, Heinz bodies!!
Confirmed with enzyme assay!
123
Tx G6PD Deficiency
Avoid precipitants e.g. Henna
Transfuse if severe
124
When should you assume malaria until proven otherwise?
FEVER + EXOTIC TRAVEL
125
3 stages of Malaria
Exo-erythrocytic
Endo-erythrocytic
Hypnozoite stage
126
Causes Malaria
Parasites from plasmodium family
Plasmodia falciparum - MC !!!
P. Ovale & P. Vivax - latent!!
P. Malariea
127
How is Malaria transmitted?
Infected female Anopheles mosquito
OR contaminated needle OR transfusion
128
Describe the stages of transmission of malaria
1. Mosquito bites human host, spreads plasmodium sporozoites into blood stream
2. Travels to liver
Maturation occurs, forms schizonts
3. After few days, infected hepatocytes rupture
Releases merozoites into blood
Merozoites taken up by erythrocytes
4. They develop further inside erythrocytes, then rupture (contributes to anaemia) and release pyogens (causes fever)
5. If RBCs are infected w/ P. Falciparum, they adhere to endothelium in small vessels
∴ vascular occlusion
∴ severe organ damage (esp in gut, kidney, liver, brain)
If RBCs are infected w/ P. Ovale or P. Virax, remain latent in liver as hypnozoites
These are the reason for any relapses that occur
129
DDx Malaria
Dengue
Typhoid
Hepatitis
Meningitis
Encephalitis
Viral haemorrhagic fever
130
What does a thick and thin blood film show with malaria?
Thick - v sensitive but low res, shows IF parasite is there
Thin - shows type of parasite
131
What is neutropenic sepsis?
Temp > 38
AND absolute neutrophil count > 1x10^9
132
How do you treat neutropenic sepsis?
ABX IMMEDIATELY
133
How do you treat acute sickle cell crisis?
i.e. Painful crisis
Pain relief
IV fluid
134
How do you treat Chest crisis?
IV fluid
Abx
Closely monitor
135
How do you treat spinal cord compression?
Steroid e.g. high dose dexamethasone and MRI
136
What is tumour lysis syndrome?
When chemo is given, cancer cells are broken down and contents are released (e.g. hyperkalaemia, nucleic acid)
Produce crystals and get deposited in kidneys
Causes damage and loss of function
137
How do you prevent tumour lysis syndrome?
Allopurinol
138
How do you treat tumour lysis syndrome?
ALLOPURINOL
IV fluids
Correct electrolytes
139
What is DVT?
Blood clot in a deep vein in body, usually leg
140
Causes DVT
Usually after long periods of immobilisation!!
--
Surgery
Immobilisation! - bed rest
Long haul flights
-
Factor V Leiden
Anti-thrombin def
-
Anti-phospholipid syndrome
Lupus anticoagulant
141
RF DVT
Same as for PE
Age
Obesity
Pregnancy, OC Pill, HRT
Varicose veins
Long haul travelling often
Plasminogen def
Thrombophilia - predisposition towards caucasians
142
Signs / Symptoms DVT
Usually vague
Pain, Swelling (Calf)
Warmth
Redness
Ankle oedema
143
Ix DVT
**D-dimer** - normally excludes diagnosis!
BUT positive doesn't confirm diagnosis
**Doppler US**
Compression US - tests proximal veins
Find popliteal vein, if CANNOT be squashed = DVT!!!!!!!!
Venogram - for calf
FBC - incl. platelets
--
If low Well's score, do D dimer as initial
If high Well's score, go straight to Doppler US
144
What things can produce a positive D-dimer?
Surgery
Pregnancy
Infection
Cancer
145
DDx DVT
Cellulitis
146
What is the main aim of treatment for DVT?
To prevent PE
147
Tx DVT
LMW heparin
e.g. SC enoxaparin
Warfarin - PO, target INR = 2-3
DOACs e.g. apixaban
148
Why are DOACs now preferred to warfarin?
Don't need to be monitored!
149
Mechanism for Warfarin
Antagonises vit K dependent clotting factors -> 10, 9, 7, 2
(1972)
150
Prevention DVT
Compression stockings
Early mobilisation
Leg elevation
151
Comps DVT
PE
Post-thrombotic syndrome
Recurrence of thrombosis
152
Which is more common - ITP or TTP?
ITP
153
RF Acute Myeloid Leukaemia
Age
Down's syndrome
Chemo
Irradiation
154
Define Leukaemia
WBC's lose ability to differentiate but maintain ability to replicate
155
What age group is AML usually found in?
Elderly (65 - 75 years avg)
but really might not be
156
Signs / Symptoms AML
Cancer B symptoms
Fatigue - anaemia
Easier bleeding & bruising - thrombocytopenia
Infection - leukopenia
Bone pain - ↑Cell production ∴ BM expansion
Fever
**GUM SWELLING**
Hepatosplenomegaly
157
What are Cancer B symptoms?
Unexplained weight loss
Night sweats
Anorexia
Fatigue
Haemoptysis
158
Name a subtype of AML
What can occur in this subtype?
Acute promyelocytic Leukaemia
DIC
159
~ Cause AML
t (15;17)
160
Ix AML
FBC + Blood film - pancytopenia
Myeloperoxidase +ve
**AUER RODS**
**GS!!** - BM BIOPSY ≥ 20% myeloid blasts
161
Tx AML
Chemo - to induce remission
+ Allopurinol - to prevent tumour lysis syndrome
Supportive - blood/platelets/Abx
IV fluids
BM transplant + steroids - maintain remission
--
Subtype of AML = Acute promyelocytic leukaemia
Tx = All-Trans-Retinoic-Acid !!
162
In AML, how would you give IV Abx/fluids?
Describe and Why do we do this?
Hickman line!
Permanent cannula into main vessel, tunnelled under SC fat
∴ harder for infection!!
163
Describe progression of AML
Rapid progression unless treatment asap!
164
What is tumour lysis syndrome?
Chemo releases uric acid from cells!
Can accumulate in the kidneys!
165
What age group does ALL affect?
Describe the prognosis
Children :( below 6 years
But good prognosis!! :)
166
Cause ALL
t (12;21)
167
What is ALL?
Proliferation of immature lympho
168
Most common childhood malignancy?
ALL
169
RF ALL
Down's syndrome
Radiation
Neurofibromatosis
170
Signs / Symptoms ALL
Cancer B symptoms - more common than AML
Fatigue - anaemia
Easier bleeding & bruising - thrombocytopenia
Infection - leukopenia
Bone pain - ↑Cell production ∴ BM expansion
Fever
**Hepatosplenomegaly**
**Swollen testicles**
Lymphadenopthy
171
Ix ALL
FBC - pancytopenia
Blood film - ↑Lymphoblasts
Immunofluorescence - TdT +ve lymphoblasts
(terminal deoxynucleotidyl transferase)
**GS!!** BM BIOPSY ≥ 20% lymphoblasts
172
Tx ALL
Chemo
+ Allopurinol
Usually good prognosis! :)
173
Which is the most common leukaemia?
CLL
174
What age group does CLL tend to affect?
70+
175
RF CLL
FHx of ALL and CLL
Caucasian
Male
176
What _might_ be a trigger for CLL?
Pneumonia
177
What is CLL?
Chronic Lymphocytic Leukaemia
Accumulation of mature B cells that have escaped apoptosis
178
CLL Pathophysiology
Too many mature B cells that have escaped apoptosis
∴ too many premature cells which accumulate in BM
∴ crowding out
∴ Cytopenia
179
Signs / Symptoms CLL
Symptomatic patient assoc with later stage of cancer !
Usually incidentally found on FBC etc
--
General anaemia Sx
Lymphadenopathy (non-tender)
Hepatosplenomegaly
Infection - low IgG
180
Ix CLL
FBC - pancytopenia (but not lymphocytes), anaemia
Blood film - **SMUDGE CELLS**
Immunophenotyping - HYPOGAMMAGLOBULINAEMIA
(B cells don't differentiate into plasma cells! ∴ no Ig!)
181
Progression CLL
**Rules of 3s!**
1/3 never progress
1/3 progress slowly
1/3 progress actively
Might tranform into aggressive lymphoma - **RICHTER'S SYNDROME**
182
Comps CLL
RICHTER'S TRANSFORMATION
B cells massively accumulates in lymph nodes - Huge lymphadenopathy !
Becomes aggressive lymphoma!
183
How can Hepatosplenomegaly present?
Abdo fullness
184
Tx CLL
If late stages - chemo + allopurinol
IV Ig - hypogammaglobulinaemia
Palliative if old
185
Cause + Pathophysiology CML
t (9;22)
PHILADELPHIA CHROMOSOME
BCR-ABL gene fusion - causing tyrosine kinase irreversibly switched on!
∴Granulocytes prolif!
∴ XS premature cells
∴ Accumulate in BM
∴ Crowding out
∴ CYTOPENIA etc
186
Signs / Symptoms CML
Cancer B symptoms
Fatigue - anaemia
Easier bleeding & bruising - thrombocytopenia
Infection - leukopenia
Bone pain - ↑Cell production ∴ BM expansion
Fever
**MASSIVE Hepatosplenomegaly**
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Ix CML
FBC - pancytopenia (but granulocytosis)!
**Blood blast cell %** - severity (WHO)
≥ 10 - Chronic (BEST)
10-19 Accelerated
20 ≤ Blast crisis!! (WORST)
**BM Biopsy** = ↑ Granulocytes
Taken from iliac crests
PHILADELPHIA CHROMOSOME genetic test! - Fluorescent in situ hybridisation (_FISH_)
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Tx CML
Chemo + Allopurinol
Imantinib - TK inhibitor
Only if Philadelphia chromosome POS
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Comps CML
Risk of progression to AML if untreated/late Dx!!
190
What is the Staging used for Lymphoma?
Ann-Arbor
For HL + NHL
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What is Lymphoma?
Malignant proliferation of lymphocytes which accumulate mostly in lymph nodes
Can be in blood, BM, liver + spleen too!
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Types of Lymphoma
Hodgkin's Lymphoma
Non-Hodgkin's Lymphoma
Burkitt's Lymphoma
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What age group do you expect to see Hodgkin's Lympma?
BIMODAL - Teens and elderly!
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What is Hodgkin's Lymphoma assoc with?
Epstein Barr Virus
195
Signs / Symptoms Hodgkin's Lymphoma
B symptoms
Painless, rubbery, non-tender lymphadenopathy - often cervical LN
Lymph pain caused by alcohol !!!
Cachexia
Hepatosplenomegaly
Some young women present w cough (bc mediastinal lymphadenopathy) - Kinda rare tho!
Also can be SVC obstruction
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How are Hodgkin's Lymphoma and Non-Hodgkin's Lymphoma divided?
Histologically
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Ix Hodgkin's Lymphoma
**GS!!!!** LN BIOPSY
**REED-STERNBERG CELLS** = diagnostic!!!!
↑Lactate dehydrogenase
↓Hb
↑ESR
STAGING - CT/MRI Chest/Abdo/Pelvis
--
(NB: Nodular Lymphocyte Predominant Hodgkin's lymphoma produces _Popcorn cells_ - variant of RS cells)
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Describe Ann-Abor Staging
STAGE 1 - LN in one region
STAGE 2 - 2 or more LN regions but same side of diaphragm
STAGE 3 - Affects LN both sides of diaphragm
STAGE 4 - Widespread disease outside LN in bone, liver, lung etc
A - Absence of B symptoms
B - B symptoms
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Tx Hodgkin's Lymphoma
**ABVD**
**A**driamycin
**B**leomycin
**V**incristine
**D**acarbazine
Stage 1-2a - shorter course, then radiotherapy
Stage 2b-4b - longer course
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S/E Of Chemo
Alopecia
N+V
Myelosuppression
BM failure
INFECTION
Infertility
TUMOUR LYSIS SYNDROME
201
Describe Reed-Sternberg cells
"Owl eye" nuclei cells
202
Bigboi comp of Chemo
Signs / Symptoms
Tx
Febrile Neutropenia! - huge risk if recent/high dose chemo
Fever (38+), Tachycardia, sweats, rigors, tachypnoea
IV Beta lactam - Piperacillin + Tazobactem !!!
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Name some differences between HL + NHL
**HL :**
Reed-Sternberg cells
Skin excoriations(?)
Neutrophillia
**NHL :**
NO Reed-Sternberg cells (usually)
Skin rashes e.g. mycosis fungoides
Neutropenia
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Comp of Bleomycin
Lung damage
205
Types of Non-Hodgkin's Lymphoma
Low grade - Follicular
High grade - Diffuse B ** - MC (80%)
VV High grade - Burkitt's
206
Signs / Symptoms NHL
More varied bc more subtypes
--
B Symptoms
Painless, rubbery, non-tender Lymphadenopathy
NOT AFFECTED BY ALCOHOL
Extranodal involvement MC than HL :
GI - bowel obstruction
BM - fatigue, easy bruising
Spinal cord - loss of sensation
Skin involvement - mycosis fungoides
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RF Hodgkin's Lymphoma
EBV
Affected sibling
SLE
Obese
Post-transplant
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Ix Non-Hodgkin's Lymphoma
**GS!!!!** LN BIOPSY
No Reed-Sternberg/Popcorn cells
Burkitt's - "starry sky" biopsy
STAGING - CT/MRI chest/abdo/pelvis
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Tx Non-Hodgkin's Lymphoma
**R-CHOP**
**R**ituximab
**C**yclophosphamide
**H**ydroxydanorubicin
**O**ncovin (brand name) - Vincristine
**P**rednisolone
210
MOA Rituximab
Targets CD20 on B cells
211
Describe Low grade NHL
Slow growing
Usually advanced at presentation
Incurable
Median survival = 9-11 years
212
Describe High grade NHL
Usually has nodal presentation
1/3 have extranodal involvement
213
Why does ↑Lactose dehydrogenase reflect worse prognosis in malignancies usually?
Bc sign of increased cell turnover
∴ cell proliferation ! :/
214
215
Alongside the normal lymphoma signs/symptoms, how might Burkitt's Lymphoma present?
Jaw lymphadenopathy in children
216
Pathophysiology Multiple Myeloma
Neoplastic _monoclonal_ proliferation of plasma cells
∴ XS production of one type of Ig - monoclonal paraprotein (usually IgA or IgG)
217
Signs / Symptoms Multiple Myeloma
**Old CRAB**
**Old** - 75+
**C**a2+ ↑↑ - Bones, Stones, Abdo moans, Psychedelic groans
**R**enal failure - nephrotic + Ig light chains deposit in kidney - BJ proteins !!
**A**naemia (BM failure)
**B**one lesions - new onset back pain in elderly
218
What chromosome abnormalities are assoc with Multiple Myeloma?
T (11;14) - MC
13q - poorer prognosis & Tx resistance
219
RF Mutiple Myeloma
Afro-Caribbean
Elderly
HIV
220
Ix Multiple Myeloma
FBC - normocytic normochromic anaemia, ↑ESR
**ROULEAUX FORMATION**
Urine dipstick - **BENCE JONES PROTEINS**
U&E - Renal failure, consider XR KUB (stones)
Bone profile - Hypocalcaemia + ↑ALP
Serum electrophoresis - IgX spike! Hypergammaglobuliaemia for IgX
XR - **Skull - Pepper pot**
Osteolytic lesion in long bones - "Punched out holes"
**BM BIOPSY** ≥ 10% plasma cells
221
What is a Rouleaux Formation?
Abnormal aggregation of RBCs
222
Tx Multiple Myeloma
Chemo
Bisphosphonates e.g. alendronate
Dialysis
Analgesia
Treat infections w Broad spec Abx
Consider BM stem cell transplant!
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DDx Multiple Myeloma
How to differentiate
**MGUS** - Monoclonal Gammopathy of Undetermined Significant
PRECURSOR, not actual myeloma
< 10% BM plasma cells
No/Little paraprotein spike
ASx
224
Quick!!!!
Malaria Presentation?
Fever!!!! + Travel to malarial area
225
Signs / Symptoms Malaria
FEVER + EXOTIC TRAVEL
Headache
Malaise
Myalgia
Diarrhoea
Cough
BLACKWATER FEVER !!!!
HEPATOSPLENOMEGALY
ANAEMIA
Delayed diagnosis - jaundice, confusion, seizures
226
Ix Malaria
Immediate blood testing - Mandatory in UK
Detailed travel history
**Microscopy of thick AND thin blood smear w/ Giemsa stain**
If 1st comes back neg, serial blood films should be done at 12-24 hrs and then 24 hrs after
Rapid diagnostic test detection of parasite antigen
227
Tx Malaria
Quinine + Doxycycline
If severe, IV artesunate
Primaquine for latent
228
Polycythaemia vera assoc gene?
**JAK-2**
229
What is polycythaemia vera?
Abnormal increase of circulating RBCs
230
Pathophysiology Polycythaemia Vera
Clonal prolif of myeloid stem cells in BM
cells can still differentiate
∴ XS RBCs
231
Cause Polycythaemia Vera
Somatic mutation in single haematopoietic stem cell
232
Signs / Symptoms Polycythaemia Vera
Can be ASx
Vague - headache, dizziness, tinnitus, visual disturbance
Characteristic !!! :
ITCHING AFTER HOT BATH
Erthromelalgia
Burning sensation in fingers and toes
233
Comps of Polycythaemia Vera
Gout
Splenomegaly
Can progress to AML !!!
234
Ix Polycythaemia Vera
FBC - ↑↑RBC, ↑Hb, ↑PCV
↑Haematocrit !!!
JAK-2 TESTING
**BM - hypercellularity**
235
Tx Polycythaemia Vera
Aim : Keep haematocrit < 0.45
so thrombosis doesnt happen!
If low risk (i.e. Young) - venesection
If > 60 and high risk - HYDROXYCARBAMIDE
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What is ITP?
Immune Thrombocytic Purpura
Autoimmune platelet destruction!!! - IgG !
237
Types of ITP and who they affect
T1 - Children, 2-6 years, post viral infection. Acute, Severe.
T2 - Adult women! W/ malignancy, HIV + Other autoimmunes. Chronic, Mild.
238
Signs / Symptoms ITP
PURPURIC RASH
otherwise, systemically well!
239
Tx ITP
1st Line - Prednisolone
+ IV Ig - to decrease splenic platelet destruction!!
2nd Line - Splenectomy
240
What is TTP?
Thrombotic Thrombocytic Purpura
ADAMTS13 DEFICIENCY
241
What does ADAMTS13 do?
Hence Pathophysiology of TTP
VWF cleaving enzyme
∴ When deficienct, remain as Multimers + aggregate at endothelial injury sites !!!
242
RF TTP
Adult Females
Malignancy
HIV
Autoimmune conditions
243
Signs / Symptoms TTP
PURPURIC RASH
Menorrhagia
AKI !!!
Fever
Haemolytic anaemia
Schistocytes!
244
Ix TTP
Thrombocytopenia
Fragmented RBCs - Schistocytes!
Haemolytic anaemia
**↓ ADAMTS13**
245
Tx TTP
1 - Plasmapharesis
2 - Prednisolone + Rituximab
246
Tx Haemophilia A
Desmopressin
+ IV Factor 8
247
Tx Haemophilia B
Factor 9
248
Signs / Symptoms Haemophilia
Joint and soft tissue bleeds
249
Signs / Symptoms Thrombocytopenia
Petechial rash
Mucosal bleeding
Easy bruising
250
Generall, when are eosinophils elevated?
Parasitic infection
251
Generally, when are monocytes elevated?
Myelodysplastic syndromes
252
Generally, when is there neutrophila?
Acute bacteria infection
253
PT/INR is a measurement of:
Coag speed through EXTRINSIC PATHWAY
10-13.5 seconds
254
Normal INR?
On Warfarin?
0.8-1.2
On warfarin = 2-3 !
255
Why might INR be ↑ ?
Anti-coags
Liver disease
Vit K def
DIC !
256
What does APTT measure?
Coag speed through INTRINSIC PATHWAY
257
Pathophysiology vWF
vWF is normally responsible for platelet plug
∴ when not functional, easier bleeding and bruising
258
APTT time?
On Heparin?
35-45 seconds
60-80 on heparin
259
Ix vWF disease
Normal PT
↑ APTT
Normal F8/9
↓ vWF obvs !!
260
What might APTT be affected by?
Haemophilia A
Haemophila B
VWF disease
^ all of these = PT normal + Prolonged APTT !!
261
Tx vWF
No cure
Desmopressin -
262
What does Thrombin Time and Bleeding time measure?
Conversion of fibrinogen to fibrin
263
MOA Desmopressin for vWF disease
Releases vWF from Weibel–Palade bodies
264
Cause vWF disease
Auto-dom mutation of vWF gene on chromosome 12
265
What is DIC?
Massive activation of coag cascade
266
Triggers of DIC
Trauma
Sepsis - Meningococcal meningitis!
Malignancy
267
Ix DIC
↓ Fibrinogen
↓ Platelets
↑ D-Dimer
268
Tx DIC
Replace clotting factors
Cyroprecipitate - replace fibrinogen
Platelet transfusion
RBC transfusion if bleeding
269
Ix Haemophilia
Normal PT
↑ APTT
& then obvs ↓ factor 8 (A) or ↓ factor 9 (B)
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