Haematology Flashcards
1
Q
What is the term and range for low neutrophils?
A
Neutropenia
< 2 x 10^9 / L
2
Q
What can cause neutropenia?
A
Myeloma
Lymphoma
3
Q
What is the term and range for high neutrophils?
A
Neutrophilia
> 7.5 x 10^9 / L
4
Q
What can cause neutrophilia?
A
Acute bacterial infection
5
Q
What is the term and range for low lymphocytes?
A
Lymphocytopenia
< 1.3 x 10^9 / L
6
Q
What is the term and range for high lymphocytes?
A
Lymphocytosis
> 3.5 x 10^9 / L
7
Q
What can cause lymphocytosis?
A
Chronic bacterial infection
8
Q
What is the term and range for high platelets?
A
Thrombocytosis
> 400 x 10^9 / L
9
Q
What is the term and range for low platelets?
A
Thrombocytopenia
< 150 x 10^9 / L
10
Q
What leukocyte is elevated in parasitic infection?
A
Eosinophils
11
Q
Why might monocytes be elevated?
A
Myelodysplastic syndromes
12
Q
What 4 measurements are included in an iron study?
A
Serum Fe - Level of circulating blood bound to transferrin
Transferrin - The main Fe transport protein
Total iron binding capacity (TIBC) - Blood’s ability to attach to iron
Ferritin - Storage form of iron
13
Q
Which iron study measurement is the best test for iron deficiency anaemia?
A
Ferritin
14
Q
Why might TIBC be increased?
A
Iron deficiency
15
Q
Why might TIBC be decreased?
A
Haemochromatosis
16
Q
Which measurements are included in a clotting screen?
A
Prothrombin time (PT) / International Normalised Ratio (INR)
Activated Partial Thromboplastin Time (APTT)
17
Q
How is INR calculated?
A
Patient PT / Reference PT
18
Q
When is INR used instead of PT?
A
INR is used to monitor patients who are being treated with blood-thinning medication (such as Warfarin)
19
Q
Prothrombin Time measures the coagulation speed through which pathway? Which factors are involved in this pathway?
A
External pathway
Factors 3 and 7
20
Q
Activated Partial Thromboplastin Time measures the coagulation speed through which pathway? Which factors are involved in this pathway?
A
Internal pathway
12, 11, 9 and 8
21
Q
What is normal PT?
A
10 - 13.5s
22
Q
What is normal INR for a normal patient? What about if the patient is on Warfarin?
A
0.8 - 1.2
Warfarin: 2 - 3
23
Q
What is normal APTT? What about if the patient is on heparin?
A
35 - 45s
Heparin: 60 - 80s
24
Q
Why might INR be raised?
A
Anticoagulation
Liver disease
Vitamin K deficiency
Disseminated intravascular coagulation (DIC)
25
Why might APTT be raised?
Haemophilia A (F8)
Haemophilia B (F9)
Von Willebrand Factor disease
In these conditions, PT will be normal and APTT will be prolonged
26
What do bleeding time and thrombin time measure?
How long it takes for fibrinogen to be converted to fibrin
27
What is normal thrombin time?
12 - 14s
28
Which factors are involved in the common pathway?
10, 5, 2 and 1
29
Prothrombin is the name for which factor? Which pathway is it a part of?
2
Common pathway
30
Fibrinogen is the name for which factor? Which pathway is it a part of?
1
Common
31
Define anaemia
Haemoglobin < 120g/L (in females) or < 130g/L (in males)
32
When should blood transfusion be considered for anaemia?
If Hb < 70g/L
OR Hb < 80g/L with cardiac comorbidity
33
What are the 3 types of anaemia? How are they classified?
Microcytic: MCV < 80
Normocytic: MCV 80-95
Macrocytic: MCV > 95
34
List some causes of Microcytic anaemia. Which is the most common worldwide??
Fe deficiency (MOST COMMON)
Thalassemia
Chronic disease
Sideroblastic anaemia
35
What are the 2 types of Normocytic anaemia? How are they different
Haemolytic and non-haemolytic
Haemolytic: High rate of RBC death BUT good bone marrow response - high reticuloytes
Non-haemolytic: Failing bone marrow - low reticulocytes
36
List some causes of haemolytic anaemia
Sickle cell
G6DPH deficiency
Autoimmune haemolytic anaemia
Hereditary spherocytosis
37
List some causes of non-haemolytic anaemia
Aplastic syndrome
Chronic disease (eg. CKD)
Myelopathic process
Pregnancy
38
What are the 2 types of macrocytic anaemia? How are they different?
Megaloblastic - Affect DNA synthesis
Non Megaloblastic - Don’t affect DNA synthesis
39
List 2 causes of Megaloblastic anaemia
B12 deficiency
Folate deficiency
40
List 2 causes of non Megaloblastic anaemia
Alcohol
HypOthyroidism
NAFLD
41
List the general symptoms of anaemia
FATIGUE
PALLOR
CHEST PAIN
Exertional dyspnoea
Tachycardia
Hypotension
Palpitations
42
Define iron deficiency anaemia
A non inherited iron deficiency, impairing Hb synthesis
43
Which type of anaemia is most common worldwide?
Iron deficiency anaemia
44
What are the causes of iron deficiency anaemia for infants, children and adults?
Infants: Malnutrition, prolonged breastfeeding
Children: Malnutrition, malabsorption (eg. IBD, coeliac)
Adults: Malnutrition, malabsorption, menorrhagia, hookworm
45
What is the most common cause of iron deficiency anaemia worldwide? How does it cause anaemia?
Hookworm
Causes GI bleeding
46
In which age group is iron deficiency anaemia a cause for concern? Why?
The elderly (60+)
Iron def anaemia is rare in the elderly, and is a red flag for colon cancer
47
What action should be taken if an elderly person has iron deficiency anaemia?
Urgent endoscopy should be ordered
48
What are the symptoms of iron deficiency anaemia?
The same as general anaemia
Fatigue
Pallor
Chest pain
Exertional dyspnoea
Tachycardia
Hypotension
Palpitations
49
List 3 signs of iron deficiency anaemia
Kalonchya (spoon shaped nails)
Angular stomatitis (ulceration at mouth corners)
Atrophic glossitis (enlarged tongue)
50
List the investigations for iron deficiency anaemia and what they show
FBC = Microcytic anaemia
Blood film = Hypochromic RBCs, target cells + Howell Jolly bodies
Iron studies = Decreased serum Fe, ferritin and transferrin saturation. Increased TIBC
Endoscopy if 60+
51
Describe the appearance of target cells
Bullseye pattern
52
What eponymous finding is seen on a blood film in iron deficiency anaemia?
Howell Jolly bodies
53
What is the first line Tx for Fe deficiency anaemia? (Apart from treating any underlying cause)
Oral iron supplements (ferrous sulphate)
54
List some side effects of oral Fe supplements. What can be given instead?
GI upset, diarrhoea/constipation, black stool
Ferrous gluconate can be given if ferrous sulphate is poorly tolerated
55
Describe the pathology of iron deficiency anaemia
Iron is usually absorbed and circulates in blood bound to transferrin
It is then either stored as ferritin or incorporated into Hb
Less iron means reduced Hb synthesis causing Microcytic anaemia
56
How is Thalassemia inherited?
Autosomal recessive
57
Define Thalassemia
Autosomal recessive haemoglobinopathy
58
Where is Thalassemia most prevalent? Why?
In areas where malaria is prevalent (Mediterranean, SE Asia and Pacific)
Thalassemia is protective against Plasmodium falciparum malaria - similar to Sickle Cell
59
What are the 2 types of Thalassemia? What are the differences?
Alpha and beta Thalassemia
Alpha - DELETION of up to 4 of the 4 alpha globin genes on chromosome 16
Beta (more common!!) - MUTATION of one or both beta globin genes on chromosome 11
60
What are the symptoms of beta Thalassemia major (ie homozygous genotype)?
General anaemia symptoms
Failure to thrive
Hepatosplenomegaly
RUQ (gallstones are a common presenting feature)
Chipmunk face (enlarged forehead and cheekbones)
61
What causes “Chipmunk face” in beta Thalassemia?
Fewer RBC means extramedullary haematopoiesis is needed (RBC are produced at forehead and cheekbones instead so these sites are enlarged)
62
When do beta Thalassemia symptoms present? Why?
In the 1st year of life. Symptoms aren’t present at birth because foetal Hb (HbF) is made up of 2 alpha and 2 gamma chains (no beta), so HbF is unaffected
HbF production stops and HbA production begins over the first 2 years of life.
63
What will a FBC and blood film show in Thalassemia?
FBC: Hypochromic RBCs
Blood film: Microcytic anaemia, target cells, increased reticulocytes
64
What investigation is diagnostic for Thalassemia? Which other condition is this investigation diagnostic for?
Hb electrophoresis (shows the proportion of different types of haemoglobin)
Also diagnostic for sickle cell anaemia
65
Why are reticulocytes raised in Thalassemia?
Thalassemia is essentially a haemolytic anaemia (despite not being normocytic)
66
What are reticulocytes?
Immature red blood cells
67
What X ray finding might be seen in Thalassemia?
Hair on end sign due to increased bone marrow activity
68
What are the 4 phenotypes of alpha Thalassemia?
1 deletion: Normal phenotype (carrier)
2 deletions: Alpha Thalassemia trait
3 deletions: Alpha Thalassemia minor (marked anaemia)
4 deletions: Alpha Thalassemia major (HYDROPS FETALIS aka heart failure in utero)
69
What is the 1st line treatment for Thalassemia? What needs to be given alongside and why?
Regular blood transfusion
Iron chelation (desferoxamine) needs to be given alongside prevent iron overload
70
Name the drug used in iron chelation therapy
Desferoxamine
71
List the side effects of iron chelation therapy
Deafness and cataracts
72
What is the definitive treatment for thalassemia? Why is it not always used?
Bone marrow stem cell transplant
It's risky
73
List all the treatment options for thalassemia
1st line - Blood transfusion with iron chelation therapy (desferoxamine)
Splenectomy
Folate supplements (for haemolytic anaemia)
Ascorbic acid (vitamin C)
Bone marrow stem cell transplant
74
When should you wait until to perform a splenectomy? Why?
After 6 years old
The spleen has a role in defending against encapsulated bacteria
75
What is desferoxamine? When is it used?
Iron chelation therapy
Used to prevent Fe overload from blood transfusion (to treat thalassemia) or haemochromatosis
76
Define sideroblastic anaemia
Defective Hb synthesis within mitochondria due to ALA synthase deficiency
77
How is sideroblastic anaemia often inherited?
X-linked inheritance
78
Sideroblastic anaemia is caused by the deficiency of which enzyme?
ALA synthase
79
What investigations are done for sideroblastic anaemia? What would they show?
FBC + blood film -Microcytic anaemia with ringed sideroblasts and basophilic stippling
Iron studies - Increased serum Fe, transferrin and ferritin. Decreased TIBC
80
Define sickle cell anaemia
Haemoglobinopathy affecting beta globin chains
81
How is sickle cell anaemia inherited?
Autosomal recessive
82
Where is sickle cell anaemia most common? Why?
Africa. Being a carrier is portective against Plasmodium falciparum malaria
83
Describe the pathology of sickle cell anaemia
GAG mutates to GTG on the 6th codon of beta globin causing glutamic acid to be replaced by valine. This causes irreversible RBC sickling. The RBCs are more fragile and have lower surface area so are less efficient, at risk of sequestration and die quicker.
84
Which types of haemolysis are seen in sickle cell?
Intravascular and extravascular
85
What is the difference between intravascular and extravascular haemolysis?
Intravascular - in blood vessels, marked by increased haptoglobin
Extravascular - Outside vessels at the spleen
86
What are the symptoms of sickle cell?
General anaemia symptoms and jaundice
87
Name 3 complications of sickle cell anaemia
Splenic sequestration - Can cause autosplenectomy
Vaso-occlusive crises - Sickle cells polymerise and get trapped in long bone bone vessels
Acute chest crises - Pulmonary vessel occlusion causes respiratory distress (medical emergency!!)
88
Which infection is common in sickle cell? Why is it idfferent in sickle cell?
Oestomyelitis
Normally caused by Staph aureus, but in sickle cell patients is due to Salmonella
89
How does Salmonella appear on XLD agar?
Red colonies with black centres
90
Which investigation is diagnostic for sickle cell anaemia? What other condition is this also diagnostic for?
Hb electrophoresis showing 90% HbS
Thalassemia
91
How are newborns screened for sickle cell?
Guthrie heel prick test
92
What does an FBC and blood film show in sickle cell anaemia?
Normocytic normochromic anaemia with increased reticulocytes
Sickle red blood cells
Howell Jolly bodies
93
What emponymous finding is seen in sickle cell anaemia? Which other condition is it seen it?
Howell Jolly bodies
Iron deficiency anaemia
94
What is the treatment for acute complicated sickle cell atacks?
IV fluid
Analgesia (NSAIDs)
Oxygen
Antibiotics if infection
95
What is the long term treatment for sickle cell anaemia?
Avoid precipitants
Drugs (hydroxycarbaminde and folic acid supplements)
Transfusion and iron chelation
Last resort: BM stem cell transplant
96
What is the last resort treatment for sickle cell anaemia?
BM stem cell transplant
97
List some precipitants of sickle cell attacks
Cold, infection, dehydration, hypoxia (acidosis)
98
What is hydroxycarbamide used for?
To prevent sickling of red blood cells in sickle cell anaemia
99
How is G6PDH deficiency inherited?
X-linked recessive inheritance
100
Define G6PDH deficiency
X-linked excessive enzymopathy causing halved lifespan and RBC degradation (aka haemolysis)
101
What does G6PDH do?
Protects against oxidative damage to red blood cells
102
Describe the pathology of G6PDH deficiency
G6PDH is involved in slutathione synthesis
Glutathione protects against reactive oxidation species such as H2O2
103
What are the symptoms of G6PDH deficiency?
Mostly asymptomatic unless haemolysis is precipitated
104
What can precipitate acute haemolysis in G6PDH deficiency?
Major cause: Napthelene (pesticide) in moth balls
Nitrofurantoin
Aspirin
Fava beans
105
What are the symptoms of acute haemolysis in G6PDH deficiency?
Rapid anaemia and jaundice (intravascular haemolysis)
106
What are the investigations for suspected G6PDH deficiency?
FBC + blood film
Serum G6PDH levels
107
What does a FBC + blood film show in G6PDH deficiency?
Between attacks: Normal
During attacks: Normocytic normochromic anaemia with raised reticulocytes, Heinz bodies and bite cells
108
What is the treatment for G6PDH deficiency?
Avoid precipitants
Blood transfusions when attacks get worse
109
What protein is deficient in hereditary spherocytosis?
Spectrin
110
How is hereditary spherocytosis inherited?
Autosomal dominant
111
Where is hereditary spherocytosis more common?
Northern Europe and America
112
How are RBCs different in hereditary spherocytosis?
Spherical and rigid
113
Which kind of haemolysis is seen in hereditary spherocytosis
Extravascular
114
Define hereditary spherocytosis
Autosomal dominant deficiency in spectrin causing increased splenic recycling (extravascular haemolysis)
115
What are the symptoms of hereditary spherocytosis
Anaemia
Neonatal jaundice
Splenomegaly
Gall stones (in 50%)
116
What would a FBC and blood film show in hereditary spherocytosis?
Normocytic normochromic anaemia with increased reticulocytes and spherocytes
117
Which condition also shows spherocytes on a blood film? How can you differentiate these two conditions?
Autoimmune haemolytic anaemia
Direct Coombs test (looks for Abs attached to RBCs). AHA is positive, HS is negative
118
What is the treatment for hereditary spherocytosis? When should you wait until and why?
Splenectomy (plus folate supplements and transfusions)
After 6 years old. Spleen plays a role in defending against encapsulated bacteria
119
What is the treatment for neonatal jaundice? Why is it important to treat?
Phototherapy
KERNICTERUS if untreated (bilirubin accumulates in basal ganglia causing CNS dysfunction and death)
120
Define kernicterus and name 2 conditions it is a complication of
CNS damage caused by the accumulation of unconjugated bilirubin in the brain and nerve tissues
Crigler Najjar syndrome and hereditary spherocytosis
121
What are the 2 subtypes of autoimmune haemolytic anaemia? Which is ore common?
Warm and cold. Warm is more common
122
Describe the pathology of autoimmune haemolytic anaemia
Anti-RBC autoantibodies bind to RBCs and cause increased intravascular and extravascular haemolysis
123
What is the diagnostic investigation for autoimmune haemolytic anaemia?
Postiive Direct Coombs test
124
What precipitates haemolysis in autoimmune haemolytic anaemia?
Temperature change
125
Define aplastic anaemia
Pancytopenia caused by failing bone marrow (no longer produces haematopoietic stem cells)
126
List 3 causes of aplstic anaemia
Mostly idiopathic acquired
Could be infection (EBV, parovirus B19)
Congenital
127
What would a FBC show in aplastic anaemia?
Normocytic anaemia with decreased reticulocytes
128
What would a bone marrow biopsy show in aplastic anaemia?
Hypocellularity
129
What is a complication of aplastic anaemia? What is the prophylactic treatment?
Increased infection risk due to neutropenia
Broad spectrum ABx and bone marrow transplant
130
What causes anaemia of chornic disease?
Reduced erythropoietin causes reduced bone marrow stimulation for erythropoiesis
131
What would a FBC show in anaemia of chronic disease?
Normocytic normochromic anaemia with reduced reticulocytes
132
Define myelopathic process and state what kind of anaemia it causes
Bone marrow is replaced with something else eg. malignancy
Normocytic non-haemolytic anaemia
133
Pernicious anaemia is the deficiency of what vitamin?
B12
134
What are some risk factors for pernicious anaemia?
Older patient
Vegan diet
135
List some causes of B12 deficiency
Pernicious anaemia
Malnutrition
Pregnancy
Crohn's (affects iluem)
Gastrectomy
136
Define pernicious anaemia
B12 deficiency caused by autoantibody mediated immune destruction of parietal cells in the fundus and body of the stomach
137
Describe the pathophysiology of pernicious anaemia
Anti parietal antibodies destroy parietal cells in the stomach. Less intrinsic factor is produced so fewer B12-IF complexes are formed and less B12 is absorbed.
138
What are symptoms of pernicious anaemia?
General anaemia
Lemon yellow skin
Angular stomatitis
Glossitis
Neurological symptoms (eg. symmetrical parasthesia, muscle weakness, altered mental status)
139
Why does low B12 cause neurological symptoms?
Low B12 causes demyelination
140
What is a haematinimic and give examples? What are the symptoms of haematinimic deficiency?
Nutrients needed for haematopoiesis
B12, folate, iron
Angular stomatitis and glossitis
141
What would a FBC and blood film show in pernicious anaemia?
Macrocytic anaemia
Megaloblasts (hypersegmented nucleated neutrophils with 6+ lobes)
142
What is a megaloblast? Which conditions are they seen in?
Hypersegmented nucleated neutrophils with 6+ lobes. Less mature DNA has more lobes, since DNA becomes more tightly wound into histones as it matures. (Bigger therefore MEGA)
B12 deficiency and folate deficiency
143
What is the treatment for Thalassemia?
1st line - Regular blood transfusions + Iron chelation (to prevent iron overload from the transfusions) in the form of desferoxamine
Splenectomy (after 6 years old)
Folate supplements
Ascorbic acid (vitamin C)
Definitive treatment is bone marrow stem cell transplant
144
List the investigations for B12 deficiency and what they show
FBC + Blood film: Macrocytic anaemia, megaloblasts
Low serum B12
Anti IF antibodies (very specific to pernicious anaemia so DIAGNOSTIC but not present in all patients)
Anti parietal antibodies
145
What is the treatment for pernicious anaemia?
Dietary advice (salmon, eggs)
B12 supplements (oral hydroxycoalbumin)
146
What is hydroxycoalbumin ?
Oral B12 supplement used to treat pernicious anaemia
147
What are 2 complications of pernicious anaemia?
Neurological disorders
CVD
148
List the causes of folate deficiency anaemia?
Trimethoprim (antibiotic) and methotrexate (DMARD)!!
Malnutrition
Malabsorption
Pregnancy
Alcohol
149
Why do trimethoprim and methotrexate cause folate deficiency?
They are dihydrofolate reductase inhibitors
150
Where is folate found in the diet?
Animal protein and leafy greens
151
What are symptoms of folate deficiency?
General anaemia
Angular stomatitis
Glossitis
152
What symptoms are found in B12 deficiency but NOT folate deficiency?
Lemon yellow skin
Neurological symptoms
153
List the investigations for folate deficiency and what they show
FBC + blood film: Macrocytic anaemia and megaloblasts (DDx - B12 def)
Low serum folate
May have concomitant B12 deficiency
154
What is the treatment for folate deficiency?
Dietary advice (leafy greens, brown rice)
Folate supplements (not before B12 supplements!!)
155
If a patient has folate deficiency with concomitant B12 deficiency, which should be supplemented first? Why?
B12 should be replaced first
Giving folate first further depletes B12 by activating the complex DNA synthesis pathway (risk of neurological symptoms)
156
Which patients should be given prophylactic folate supplements? How much?
Pregnant patients
400mg for first 12 weeks
157
What is a complication of folate deficiency?
CVD
158
What does dihydrofolate reductase do?
Catalyses the reduction of dihydrofolate to tetrahydrofolate. THF is needed for the action of folate-dependent enzymes
159
List 3 causes of non Megaloblastic macrocytic anaemia
Alcohol - Toxic to RBCs and depletes folate (+ vit B1)
Hypothyroidism - Multifactorial, interferes with erythropoietin
Liver disease - Decompensated cirrhosis (hep B associated, +/- HCC) is strongly linked to macrocytic anaemia (short term predictor or mortality)
160
What are the 4 type of leukaemia? Which cells does each type affect?
Acute myeloblastic leukaemia - Immature myeloblasts
Chronic myeloblastic leukaemia - Mature myelocytes (eg. Neutrophil, eosinophil, basophil)
Acute lymphocytic leukaemia - Immature lymphocytes
Chronic lymphocytic leukaemia - Mature lymphocytes (eg. T cells, B cells)
161
List some differences between chronic and acute leukaemias
Acute tends to affect younger patients, chronic tends to affect older patients
Acute is generally symptomatic, chronic is generally asymptomatic
Cytopenias are more likely in acute than chronic (bone marrow has less time to adapt)
Cytopenias can still appear in chronic leukaemia when significantly progressed
162
Define leukaemia
Neoplastic production of the WBC line (myeloblasts and lymphoblasts) in bone marrow, causing reduced production of other haematopoietic cells leading to pancytopenia
163
Which kind of cancer causes pancytopenia? What are the complications?
Leukaemia
Neutropenia - Increased infection risk
Anaemia - Decreased Hb
Thrombocytopenia - Increased bleeding risk
164
What are the general symptoms of leukaemia?
Bone pain
Bleeding (thrombocytopenia)
Infection (neutropenia)
Anaemia symptoms
TATT
165
Which cells proliferate in acute myeloblastic leukaemia?
Immature myeloblasts
166
Which mutation causes AML?
t(15:17)
167
Which types of leukaemia are associated with Down’s and radiation?
AML and ALL
ALL is 30x higher with Down’s syndrome
168
What is the prognosis for AML?
Rapidly progresses if not treated ASAP
3 year survival is only 20%
169
What are the symptoms of AML?
General leukaemia symptoms
Gum infiltration
Hepatosplenomegaly
170
List the investigations for AML and what they show
FBC + blood film: Pancytopenia. Myeloperoxidase +ve and Auer roads
BM biopsy: >=20% myeloid blasts
171
What are auer rods?
Myeloperoxidase cytoplasmic aggregates in neutrophils
172
What is the 1st line treatment for AML?
Chemo and ATRA (all trans-retinoid acid)
ATRA is used in subtype of AML called acute promyelocytic leukaemia
173
What is the last resort treatment for AML?
Bone marrow transplant
174
List the treatments for AML
1st line - Chemo and ATRA
Prophylactic antibiotics (neutropenia)
Transfusion for anaemia
Allopurinol if doing chemo
Last resort - BM transplant
175
Why should allopurinol be given when doing chemo for AML?
To prevent tumour lysis syndrome
Chemo releases uric acid from cells, which can accumulate in kidneys
176
What is a common complication of acute myeloblastic leukaemia? Which subtype of AML is known to cause this?
Disseminated intravascular coagulation
Acute promyelocytic leukemia
177
What cell proliferates in chronic myeloid leukaemia?
Mature myelocytes (neutrophils, eosinophils, basophils)
178
What mutation causes CML?
t(9:22) on the Philadelphia chromosome
BCR-ABL gene fusion causes tyrosine kinase to be irreversibly switched on, causing increased cell proliferation
179
What are the symptoms of CML?
General leukaemia
Massive hepatosplenomegaly
180
List 2 conditions that can cause massive hepatosplenomegaly
Chronic myeloid leukaemia
Malaria
181
List the investigations for CML and what they show
FBC + blood count: Pancytopenia BUT granulocytosis (too many neutrophils, basophils and eosinophils). Blood blast cell % (shows severity)
BM biopsy: Raised granulocytes
Gold standard: Philadelphia chromosome genetic test
182
How is CML severity determined?
Blood blast cell % on FBC
< 10: Chronic (best)
10 - 19: Accelerated
>20: Blast crisis (worst)
183
What is the gold standard investigation for CML?
Philadelphia chromosome genetic test
184
What is the treatment for CML?
Chemo and Imantinib
Consider allopurinol (to prevent tumour lysis syndrome)
185
What is imantinib?
Tyrosine kinase inhibitor used to treat CML
186
What can CML progress to if untreated or diagnosed late? Why is this bad?
Acute myeloblastic leukaemia
Poorer prognosis
Indicated by >20% blast cells on BM biopsy
187
What is the prognosis for CML?
Decent (if no progression)
188
What cell proliferates in acute lymphoblastic leukaemia?
Immature lymphoblasts - mostly B cell lineage
189
What mutation causes ALL?
t(12:21)
190
What is the prognosis for ALL?
Good
191
What is the most common childhood malignancy?
ALL
75% cases over 6 yrs old
192
What are the symptoms of ALL?
General leukaemia (except 6yr old with Down’s syndrome)
Hepatosplenomegaly
193
List the investigations for ALL and what they show
FBC: Pancytopenia
Blood film: Increased lymphoblasts
Bone marrow biopsy: Over 20% lymphoblasts (DIAGNOSTIC)
Immunefluorescence: Terminal deoxynucleotidyl transferase positive lymphoblasts (GOLD STANDARD)
194
What is the treatment for ALL?
Chemo
Consider allopurinol
195
What cell proliferates in chronic lymphocytic leukemia?
Lymphocytes (mostly B cells)
196
Which leukaemia is the most common overall? Which is the most common in childhood?
CLL is most common overall
ALL is most common in children
197
Which age group is CLL most common in?
Later life (70+)
198
What is the prognosis for CLL?
Ok - 75% 5 year survival
199
What are the symptoms for CLL?
General anaemia symptoms
Lymphadenopathy (non-tender)
Hepatosplenomegaly
200
List the investigations for CLL and what they show
FBC: Pancytopenia BUT lymphocytosis
Blood film: SMUDGE CELLS
Immunoglobulins: Hypogammaglobulinemia
201
Why does CLL cause hypogammaglobulinemia?
B cells proliferate BUT they don’t differentiate into plasma cells (which produce IgG)
202
Smudge cells on a blood film are indicative of which condition?
Chronic lymphocytic leukaemia
203
What is the treatment for CLL?
Chemo
Palliative care (if old)
Consider allopurinol
IV IgG for hypogammaglobulinemia
204
What is a complication of CLL?
RICHTER TRANSFORMATION
B cells massively accumulate in lymph nodes causing massive lymphadenopathy and transformation from CLL to aggressive lymphoma
205
Richter transformation is a complication of which condition?
Chronic lymphocytic leukaemia
206
What are the 2 types of lymphoma? How can they be told apart on a blood film?
Hodgkin’s and non-Hodgkin’s
Hodgkin’s has REED STERNBERG cells (owl-eye nuclei)
207
What are the general symptoms of lymphoma?
B SYMPTOMS
Fever
Night sweats
Unintentional weight loss
(Lymphadenopathy)
208
What is the distribution of age of Hodgkin’s lymphoma patients?
Bimodal: Teens and elderly
209
What virus is Hodgkin’s lymphoma associated with?
Epstein Barre Virus (aka “glandular fever”)
210
What are the symptoms of Hodgkin’s lymphoma?
B symptoms + painless rubbery lymphadenopathy (especially after drinking alcohol)
211
List the investigations for Hodgkin’s lymphoma and what they show
Lymph node biopsy: Reed Sternberg cells (DIAGNOSTIC)
Raised lactate dehydrogenase
Low Hb
Raised ESR
CT/MRI chest/abdo/pelvis for staging (Ann Arbour staging)
212
How is lymphoma staged?
Ann Arbour staging
1) Single lymph node
2) >= 2 lymph nodes on same diaphragm side
3) Lymph nodes on both diaphragm sides
4) Extranodal organ spread
A = No “B” symptoms
B = B symptoms present
213
What is the treatment for Hodgkin’s lymphoma?
ABVD chemotherapy - Adriamycin (doxorubicin), Bleomycin, Vinblastine, Dacarbazine
214
What are the side effects of ABVD chemo?
Alopecia, N+V, Myelosuppression and bone marrow failure, infection
215
What are patients who have had recent / high dose chemo (or on carbimazide) at risk of?
Febrile neutropenia
216
What are the symptoms of febrile neutropenia?
Fever
Tachycardia
Sweats
Rigors
Tachypnoea
217
What is the treatment for febrile neutropenia?
Immediate broad spectrum antibiotics (eg. Amoxicillin, fluoroquinolone)
218
What subtype of Hodgkin’s lymphoma does popcorn cells on lymph node biopsy indicate?
Nodular lymphocyte predominant Hodgkin’s
219
What are the subtypes of non-Hodgkin’s lymphoma? Which is most common?
Follicular - low grade
Diffuse large B cell - high grade (MOST COMMON)
Burkitt’s - Very high grade
220
Which subtype of non-Hodgkin’s lymphoma is linked to EBV?
Burkitt’s lymphoma. Often causes massive jaw lymphadenopathy in children
221
What are the symptoms of non Hodgkin’s lymphoma?
Varied since many subtypes
B symptoms
Painless rubbery lymphadenopathy NOT affected by alcohol
222
List the investigations for Non-Hodgkin’s lymphoma and what they show
Lymph node biopsy: No RS/popcorn cells (DIAGNOSTIC). Confirms NHL subtype (eg. Burkitt’s = “starry sky” biopsy)
CT/MRI chest/abdo/pelvis for staging
223
What is the treatment for Non-Hodgkin’s lymphoma?
R-CHOP chemotherapy - Rituximab,cyclophosphamide, Hydroxydoxorubicin, Vincristine (Oncovin is brand name), Prednisolone
224
How does Rituximab work?
Monoclonal antibody which targets CD20 on Bcell
225
List some differences between Hodgkin’s and Non-Hodgkin’s lymphoma
NHL has subtypes (follicular, B cell, Burkitt’s), HL does not
HL presents with painless lymphadenopathy which is painful with alcohol, NHL is unaffected
HL is treated with ABVD chemo, NHL is treated with R-CHOP chemo
226
Define multiple myeloma
Neoplastic monoclonal proliferation of a plasma cell
227
Describe the pathophysiology of multiple myeloma
Typically excess production of one immunoglobulin (“monoclonal paraprotein”)
55% IgG, 20% IgA
228
What might a typical MM patient look like?
70 years old, Afro-Caribbean
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What are the symptoms of MM? (There’s an acronym)
Old CRAB
Old - 70+
HyperCalcaemia
Renal failure
Anaemia
Bone lesion
230
What causes hypercalcaemia in MM?
Increased osteoclast bone resorption
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What are the symptoms of Hypercalcaemia (theres a phrase)
Bones (weak bones)
Stones (kidney stones)
Abdo moans
Psychedelic groans
232
What causes renal failure in MM?
Hypercalcaemia causes calcium oxalate renal stones
Immunoglobulin light chain kappa deposition is nephrotoxic - Bence Jones protein in urine!
233
What causes anaemia in MM?
Bone marrow failure
234
What causes bone lesions in MM?
Bone marrow failure (which is painful - new onset back pain in elderly)
235
List the investigations for MM and what they show
FBC + blood film = Normocytic normochromic anaemia and raised ESR. ROULEAUX FORMATION (abnormal aggregation of RBCs together) - pathognomic!!
Urine dipstick = Bence jones proteins
U+E = Renal failure. Consider X-RAY KUB for kidney stones
Bone profile: Hypocalcaemia and raised ALP
Serum electrolytes = Ig paraprotein “M spike”, hypergammaglobulinemia for that specific IgG
X-RAY = Pepper pot skull (Osteolytic lesions = punch out holes)
DIAGNOSTIC: BM biopsy —> More than 10% plasma cells
236
What investigation is diagnostic for Multiple myeloma?
BM biopsy: More than 10% plasma cells
237
Name the precursor to multiple myeloma. How does it differ from MM?
Mammyloid gammopathy of undetermined significance
BM biopsy: Under 10% plasma cells
No/little paraprotein spike
ASYMPTOMATIC
238
Why do NICE recommended a full body MRI when investigating MM?
To identify bone marrow infiltration
239
What is the treatment for MM?
Chemotherapy
Bisphosphonates (eg. Alendronate) to protect bones
Dialysis (for renal failure)
Consider BM stem cell transplant
240
Define polycythaemia
Erythrocytosis of any cause
241
What is a primary cause of polycythaemia?
Polycythaemia Vera
JAK2V617 mutation
242
What are secondary causes of polycythaemia?
Hypoxia
More erythropoietin (eg. Renal cell carcinoma)
Dehydration (eg. Alcohol)
243
What causes polycythaemia Vera?
JAK2V617 mutation
244
List the symptoms of polycythaemia vera?
ITCHING AFTER A BATH
BURNING IN FINGERS AND TOES (Erythromelalgia)
Reddish plethoric complexion (facial swelling and puffiness, purplish face like in Cushings)
Blurred vision / headache
HEPATOSPLENOMEGALY
Nonspecific features of HYPERVISCOSITY
245
List the investigations for polycythaemia vera and what they show
FBC = High WCC, platelets and high RBCs
Increased Hb
Genetic test for JAK2V617 mutation
246
What is the aim to polycythaemia vera treatment?
Maintain normal blood count (not curative)
247
What is the 1st line treatment for polycythaemia vera?
Regular venesection + aspirin (anti platelet)
248
What treatment for polycythaemia could be considered after the 1st line?
Chemotherapy - Hydroxycarbamide aka hydroxyurea (only in high risk patients)
