Haematology Flashcards
1
Q
What is myeloma?
A
Cancer of plasma B lymphocytes.
2
Q
Pathophysiology of myeloma
A
Excess production of monoclonal immunoglobulins known as paraproteins by the plasma cells.
3
Q
Which paraproteins are most commonly produced by myelomas?
A
IgG and IgA.
4
Q
What are the types of light chains that can make up immunoglobulins?
A
Kappa and gamma light chains
5
Q
Clinical presentation of myeloma
A
Hypercalcaemia
Renal impairment - nephrotic syndrome (thirst)
Normocytic normochromic anaemia, neutropaenia/thrombocytopaenia
Back pain due to lytic bone lesions.
Hyperviscosity of blood.
6
Q
What causes hypercalacemia and lytic bone lesions in myeloma?
A
Malignant plasma cells release factors like RANK ligand which stimulate osteoclast activity increasing bone resorption.
7
Q
What causes nephrotic syndrome in myeloma?
A
Increased light chain presence causes deposition in renal tubules causing impairment.
8
Q
Investigation of myeloma
A
FBC - pancytopaenia
U + E - hypercalcaemia
Blood film - rouleaux formation
Serum electrophoresis
CT/MRI/X-ray - lytic bone lesions
Urinalysis - Bens Jones proteins
Bone marrow trephine biopsy - DIAGNOSTIC
9
Q
What would the FBC reveal in myeloma?
A
Low haemoglobin, platelets, neutrophils.
10
Q
What would a blood film reveal in myeloma?
A
Rouleaux formation - linear aggregates of erythrocytes that occur when there are increased plasma protein levels.
11
Q
What would the ESR and creatinine be in myeloma?
A
Both would be high.
12
Q
What is serum electrophoresis?
A
Separates immunoglobulins by mass and charge to identify abnormal bands and immune paresis
13
Q
Usually where is a bone marrow biopsy taken?
A
Iliac crest (anterior or posterior).
14
Q
What can a bone marrow biopsy show with myeloma?
A
Infiltration by plasma cells.
15
Q
What would U + E reveal in myeloma?
A
Hypercalcaemia,
16
Q
What are the clinical stages of myeloma?
A
Monoclonal Gammopathy of Undetermined Significance (MGUS)
Smouldering Myeloma
Symptomatic Myeloma
17
Q
Features of MGUS
A
Paraprotein<30g/dl, <10% plasma cells in the bone marrow, no related organ or tissue impairment (ROTI), no evidence of amyloid or other lymphoproliferative disorder (LPD)
18
Q
Features of smouldering myeloma
A
Paraprotein >30g/l and/or >10% plasma cells in BM, no ROTI (relative organ or tissue impairment)
19
Q
Features of symptomatic myeloma
A
Paraprotein > 30 g/l and/or >10% plasma cells in BM
Evidence of related organ or tissue impairment (ROTI) or amyloid
20
Q
First line management of myeloma
A
Bortezomib + dexamethasone
Chemotherapy + bisphosphonates
21
Q
Management to prevent myeloma bone disease
A
Zoledronic acid
22
Q
Pharmacodynamics of bortezomib
A
Proteasome inhibitor
23
Q
Pharmacodynamics of zoledronic acid
A
Bisphosphonates - prevent osteoclast activity and bone resorption.
24
Q
What long term therapy can be given for myeloma patietns
A
Chemotheraphy, stem cell transplant
25
What can a skull X-ray show in myeloma?
Pepper pot appearance due to bone lesions.
26
What is a lymphoma?
Neoplastic, clonal proliferation of lymphoid cells.
27
What are the 2 classifcations of a lymphoma?
Hodgkin's and non-hodgkin's lymphoma (NHL)
28
What can non-hodgkin's lymphomas be classed into?
Indolent and aggressive NHLs.
29
What cell is most commonly affected by non-hodgkin lymphomas?
B cells
30
What are cells that can be affected by indolent non-hodgkin lymphomas?
B cells, T cells, NK cells.
31
Risk factors for NHLs
Mainly idiopathic
Primary Immunodeficiency e.g. Wiscott-Aldrich Syndrome
Secondary Immunodeficiency e.g. HIV; transplant recipients
Infection e.g. EBV; HTLV-1; h.pylori
Pesticide exposure e.g trichloroethylene
32
What generally defines an indolent NHL?
Neoplasms of non-dividing mature lymphocytes
33
What generally defines an aggressive NHL?
Neoplasms of proliferating lymphocytes.
34
Clinical presentation of non-hodgkin lymphomas
Painless lymphadenopathy
B symptoms - fever, night sweats, weight loss.
Skin itching.
35
Investigation of non-hodgkin lymphomas
Core needle or excision biopsy of lymph node
Bone marrow biopsy
CT/MRI Chest,Abdo,Pelvis or PET-CT for staging.
WHO patient performance status
36
Management of non-hodgkin lymphomas
Active surveillance
Radiotherapy
Chemoimmunotherapy
37
What drug combinations can be used in chemotherapy for non-hodgkin lymphomas?
R-CHVP, R-CVP
R = rituximab
C = cyclophosphamide
H = hydroxydaunorubicin
V= vincristine
P = prednisolone
38
What are some B-cell NHLs?
Mantle cell lymphoma, follicular lymphoma, Burkitt lymphoma, diffuse large B cell lymphoma, marginal zone lymphoma.
39
What are some T-cell NHLs?
Adult T cell lymphoma, Sezary syndrome.
40
What is anaemia?
Abnormally decreased haemogloblin/erythrocytes in the blood.
41
What deficiencies cause decreased erythrocyte production?
Iron deficiency
Folate deficiency
B12 deficiency
42
What can caused increased erythrocyte loss?
Haemolysis
Bleeding
43
What are normal serum haemoglobin levels?
Female: 110-147g/l,
Male:131 – 166g/l
44
What is mean corpuscular volume?
Average erythrocyte volume/size.
45
What is a normal mean corpuscular volume?
80-100 femtoliters.
46
What is microcytic anaemia?
When RBCs MCV<80 fl
47
What is normocytic anaemia?
When 80 < RBC MCV < 100 fl
48
What is macrocytic anaemia?
When RBC MCV > 100 fl
49
Aetiology of microcytic anaemia
Thalassemia
Anaemia of chronic disease
Iron deficiency anaemia
Lead poisoning
Sideroblastic anaemia
(TAILS)
50
Aetiology of normocytic anaemia
Anaemia of chronic disease
CKD
Anaplastic anaemia
Blood loss
Haemolysis
51
Aetiology of macrocytosis (large RBCs not necessarily with anaemia)
B12 deficiency
Folate deficiency
Hypothyroidism
Reticulocytosis
Myeloma
Methotrexate, hydroxyurea
52
What is mean cell haemoglobin (MCH)?
Amount of haemoglobin in each erythrocyte.
53
What does hypochromic mean?
Erythrocytes contain less haemoglobin than normal.
Low MCH
54
How would hypochromic erythrocytes appear?
Pale colour.
55
What does normochromic mean
Erythrocytes contain normal amounts of haemoglobin
Normal MCH
56
What test can be used to indicate the rate of RBC production?
Reticulocyte count
57
General clinical presentation of anaemia
Dyspnoea, fatigue, headaches, palpitations and faintness, tachycardia, pallor.
58
What type of anaemia is iron deficiency anaemia?
Hypochromic, microcytic anaemia.
59
How is iron stored in the body
As ferritin (an iron-protein complex)
60
What protein transports iron around the body?
Transferrin
61
Aetiology of iron deficiency anaemia
Bleeding (GI, menstrual)
Pregnancy (500mg-1000mg transferred to foetus, body stores 4g)
Malabsorption - gastrectomy,
Dietary deficiency - veganism
62
Pathophysiology of iron deficiency anaemia
Iron is needed for haemoglobin synthesis, lack of iron can cause anaemia.
63
Clinical presentation of iron deficiency anaemia
General anaemia symptoms
Brittle nails & hair
Spoon-shaped nails (koilonychia)
Conjunctival pallor
Atrophic glossitis (swollen tongue)
64
Investigation of iron deficiency anaemia
Blood film - microcytic, hypochromic RBCs
Iron studies:
Ferritin levels - low
Serum iron - low
Transferrin levels - high
Transferrin saturation - low
Total iron binding capacity - high
65
What would a blood smear show for iron deficiency anaemia?
Microcytic, hypochromic red cells,
66
Management of iron deficiency anaemia
Treat underlying cause
Oral iron - ferrous sulphate 200mg 1-3x daily
IV iron - dextran if intolerant to oral iron.
After Hb and MCV return to normal, continue supplementation for a further 3 months to replenish stores.
67
How is Vitamin B12 absorbed?
By binding to intrinsic factor secreted by gastric parietal cells.
68
Where in the bowel is vitamin B12 absorbed?
Terminal ileum.
69
What is vitamin B12 needed for in the body?
DNA synthesis and fatty acid synthesis.
Present in sphingolipids of the myelin sheath.
70
Aetiology of vitamin B12 deficiency
Pernicious anaemia (autoimmune gastric atrophy; loss of intrinsic factor production)
Gastrectomy/ ileal resection
Vegan diet
Oral contraceptives
Hypochloridia - stomach acid deficiency (PPIs)
Nitric oxide substance abuse.
71
What are the 2 types of macrocytic anaemia?
Megaloblastic and non-megaloblastic macrocytic anaemia
72
What is megaloblastic macrocytic anaemia?
Presence of erythroblasts with delayed nuclear maturation because of delayed DNA synthesis.
These are megaloblasts, they are large (i.e. high MCV) and have no nuclei
73
What is non-megaloblastic macrocytic anaemia
Macrocytic anaemia with mature (normoblastic) erythrocytes.
74
Aetiology of megaloblastic macrocytic anaemia
Vitamin B12 deficiency
Folate deficiency
Hydroxycarbamide/hydroxyurea usage
75
Aetiology of non-megaloblastic macrocytic anaemia
- Excess alcohol consumption
- Liver disease
- Hypothyroidism
- Haemolysis
Myelodysplasia
76
What is pernicious anaemia?
An autoimmune disorder resulting in the lack of intrinsic factor production and vitamin B12 absorption which causes anaemia.
77
Pathophysiology of pernicious anaemia
Autoimmune gastritis with plasma cell and lymphoid infiltration causes parietal and chief cells to be replaced by mucin-secreting cells.
78
Clinical presentation of pernicious anaemia
Glossitis (swollen tongue)
Pallor
Peripheral parasthesia
Ataxia
Dementia, hallucinations
79
Investigation of pernicious anaemia
FBC - anaemia
Blood film - oval macrocytes, neutrophils with hypersegmented nuclei.
Serum B12 - low
Parietal cell antibodies - present
80
Management of pernicious anaemia
IM hydroxycobalamin
If dietary deficiency, oral B12 tablets.
81
What are some sources of folate?
Green leafy vegetables, nuts, bread, liver.
82
Where is folate absorbed in the bowel?
Proximal jejunum.
83
Aetiology of folate deficiency
Dietary insufficiency
Malabsorption (Crohn’s disease, coeliac disease).
Pregnancy
Haemolysis - increased folate consumption due to compensatory increased erythrocyte production.
84
Clinical presentation of folate deficiency
No neuropathic symptoms unlike B12 deficiency.
General anaemia symptoms:
Dyspnoea, fatigue, headaches, palpitations and faintness, tachycardia, pallor.
85
Investigation of folate deficiency
Serum folic acid levels - low
86
Managmenet of folate deficiency
Folic acid supplements 5mg daily
87
What is the relationship between treating folate deficiency and vitamin B12 deficiency?
Do not replace folate without checking B12.
B12 replacement must be started before folate replacement
Folate replacement can cause increased erythrocyte production = further B12 depletion = neurologic effects.
88
What would be seen on a blood film of a macrocytic megaloblastic anaemia?
Oval macrocytes
Neutrophils with hypersegmented nuclei (>6 lobes)
89
What is sideroblastic anaemia?
Anaemia where there is excess iron but it cannot bind to haemoglobin.
90
Aetiology of sideroblastic anaemia
Deficiency of aminolevulinic acid synthetase (ALAS; rate-limiting enzyme in haem synthesis.
91
Pathophysiology of sideroblastic anaemia
Mutations causes lack of protoporphyrin synthesis which does not allow iron to bind. Iron buildup in mitcochondria occurs.
92
Appearance of sideroblastic anaemia on blood film
Ringed sideroblasts seen in mitochondria stained with Prussian blue.
93
Iron study results of sideroblastic anaemia
Serum iron - raised
Ferritin - raised
Transferrin - raised
TIBC - low
94
What is haemolysis?
The destruction of red blood cells.
95
Aetiology of haemolytic anaemia
RBC membrane defects:
* Hereditary spherocytosis
- Enzyme defects:
* Glucose-6-phosphate dehydrogenase (G6PD) deficiency
- Haemoglobinopathies:
* B Thalassaemia
* A Thalassaemia
* Sickle cell disease
- Autoimmune haemolytic anaemia
96
What is compensated haemolysis?
Increased destruction of RBCs matched by increased synthesis.
97
What is uncompensated haemolysis?
Rate of destruction exceeds rate of synthesis, causing anaemia.
98
Aetiology of hereditary spherocytosis
Defect in structural protein spectrin in RBC cell membrane.
99
Pathophysiology of hereditary spherocytosis
Causes reduced SA:V ratio making the cell sphere shapes.
100
Investigation of hereditary spherocytosis
Direct antiglobulin test - negative
101
What would the direct antiglobulin test result be for autoimmune haemolytic anaemia?
Positive
102
What is the function of glucose-6-phosphate dehydrogenase enzyme?
Produces NADPH in glycolysis which protects red cells from oxidative stress.
103
Investigation of G6PD deficiency
G6PD activity - low
Blood smear - Bite cells and heinz bodies.
104
Investigation of haemolysis
Blood film (spherocytes, polychromasia, red cell fragments?)
Reticulocyte count - high
Serum bilirubin (inc unconjugated) - raised
Urinary urobilinogen - high
Lactate dehydrogenase - high
Haptoglobin - low
105
What is the composition of foetal haemoglobin?
2 alpha and 2 gamma subunits
106
What is the composition of adult haemoglobin?
2 alpha and 2 beta subunits.
107
Mutations in which haemoglobin subunit is incompatible with life?
Alpha subunit
108
Aetiology of sickle cell anaemia
Point mutation in B globin chain
Autosomal recessive
109
Pathphysiology of sickle cell anaemia
Deoxygenated HbS molecules are insoluble and polymerize. The flexibility of the cells is decreased, and they become rigid and take up their characteristic sickle appearance.
Sickled RBCs have shortened survival and obstruction of small vessels leading to infarction.
110
Clinical presentation of sickle cell anaemia
Acute pain crises caused by vessel occlusion.
Acute chest syndrome - dyspnoea, angina
Pulmonary hypertension
111
Pathphysiology of acute chest syndrome in sickle cell anaemia
Lung damage due to any other reason can result in hypoxia.
Causes HbS polymerisation & sickling in pulmonary circulation.
Results in less pulmonary perfusion and further lung damage.
112
Investigation of sickle cell anaemia
CXR: Cardiomegaly compensatory for anaemia
Blood films: Sickling
FBC: Low haemoglobin
GS: Haemoglobin electrophoresis
113
Management of acute sickle cell crisis
Analgesia - paracetamol/NSAIDs
Oxygen
Fluid resuscitation - compensates for sodium loss during crises
Exchange blood transfusion.
114
Management of long term sickle cell anaemia
Regular blood transfusions
Hydroxycarbamide - foetal haemoglobin analogue.
Bone marrow transplant - curative therapy.
Folic acid - haemolysis
115
What is thalassaemia?
Thalassaemia where there is no/reduced Beta chain synthesis
Defective synthesis of globin chains in haemoglobin leading to imbalanced chain production.
116
What are the types of thalassaemia?
Alpha and beta thalassaemia
Further classified based on severity:
Carrier thalassaemia
Non-transfusion dependent (intermediate)
Transfusion dependednt (major)
117
Pathophysiology of thalassaemia
Can cause ineffective erythropoiesis and haemolysis.
Can result in iron overload through lowering hepcidin levels.
118
Clinical presentation of thalassaemia
Systemic: Pallor, fatigue
Cardiac: tachycardia, low blood pressure.
arrhythmias
Jaundice. dark urine, hepatosplenomegaly
119
Investigation of thalassaemia
Hb electrophoresis
Blood film: Hypochromic-microcytic erythrocytes, Decreased MCV
120
Management of thalassaemia
Dietary: Long term folic acid
1st line: Regular transfusions
Iron-chelating agents to prevent iron overload
If major (transfusion-dependent) -
Splenectomy
Bone marrow transplant
121
What is anaemia of chronic disease?
Deficient RBC production due to chronic diseases (e.g. infection, inflammation,
malignancy)
122
Aetiology of anaemia of chronic disease
Chronic inflammatory disease (Crohn's, fibromyalgia, tuberculosos)
123
Pathophysiology of anaemia of chronic disease
Cytokine release causes increased hepcidin secretion by liver.
Prevents GI iron absorption and iron sequestration .
Causes less iron available for erythropoesis.
124
Investigation of anaemia of chronic disease
FBC: anaemia
Raised ESR/CRP
Iron studies:
Decreased serum iron levels
Decreased serum transferrin saturation
Decreased total iron binding capacity
High ferritin to allow for iron retention in cells.
125
Clinical presentation of anaemia of chronic disease
General anaemia symptoms: Pallor, fatigue, tachycardia,
126
Management of anaemia of chronic disease
Treatment of underlying disease.
If unresponsive, consider:
Erythropoetin
Supplemental iron IV
127
What is aplastic anaemia
Aplastic anaemia is defined as pancytopenia with hypocellularity (aplasia) of the bone marrow;
128
Aetiology of aplastic anaemia
Radiation
Viral agents (eg, EBV, HIV, hepatitis viruses)
Fanconi anemia (autosomal recessive DNA
repair defect causing bone marrow failure);
Idiopathic
Drugs (eg, benzene, alkylating agents, antimetabolites)
129
Pathophysiology of aplastic anaemia
Due to a reduction in the number of pluripotent stem cells
Combined with a fault in those remaining or an immune reaction against them
Makes them unable to repopulate the bone marrow.
130
Clinical presentation of aplastic anaemia
Anaemia
Increased susceptibility to infection
Bleeding gums, epistaxis
131
Investigation of aplastic anaemia
Pancytopenia (Low RBC, WBC, platelets)
The virtual absence of reticulocytes.
A hypocellular or aplastic bone marrow with increased fat spaces
132
Management of aplastic anaemia
RBC and platelet transfusion
Bone marrow transplant with immunosuppresive therapy if >40: ANTITHYMOCYTE GLOBULIN (ATG) and
CICLOSPORIN
133
What is autoimmune haemolytic anaemia
Anemia caused by immune destruction of
red blood cells by autoantibodies against
antigens on RBCs surface
134
What are the different types of autoimmune haemolytic anaemia?
Warm AIHA
Cold AIHA
135
What is the main antibody in warm AIHA?
IgG
136
What is the main antibody in cold AIHA?
IgM
137
In which autoimmune haemolytic anaemia is RBC agglutination seen?
Cold AIHA
138
Investigation of autoimune haemolytic anaemia
Direct antiglobulin test - positive
139
What is polycythaemia vera?
A myeloproliferative disorderd causing excess erythrocyte production.
140
Aetiology of polycythaemia vera
JAK2 protein mutation
141
Aetiology of secondary polycythaemia
Exess erythropoetin production
Smoking - causes hypoxia
Renal artery stenosis
142
Clinical presentation of polycythaemia vera
Itching after bathing
Splenomegaly
Erythromelalgia: burning pain, warmth and redness in the hands and feet
Visual field defects due to hyperviscosity
Fatigue
143
Investigation of polycythaemia vera
FBC: high haematocrit/Hb levels
JAK2 mutation screening
Serum erythropoetin: low
144
Management of polycythaemia vera
Venesection - removal of 400-500ml of blood weekly
Low dose aspirin 75 mg daily
Chemotherapy - hydroxyurea
145
What is normal platelet count levels?
100-400 x 10^9/L
146
What is thrombocytosis?
Thrombocytosis is elevated platelet count secondary to another condition/infection.
147
Aetiology of thrombocytosis
Essential (primary) thrombocythaemia
Iron deficiency anaemia
Excess thrombopoetin production
CML
148
Investigation of thrombocytosis
ESR, CRP - raised
Ferritin
Serum iron
Transferrin saturation
149
What is essential thrombocythaemia?
Myeloproliferative disorder characterized by excess platetelet production.
150
Aetiology of essential thrombocythaemia
JAK2 mutation
151
Investigation of essential thrombocythaemia
Platelet count - >450 x 10^9/L
JAK2 mutation test
Trephine bone marrow biopsy - high megakaryocyte number.
152
Clinical presentation of essential thrombocythaemia
Easy bleeding
Bruising
Erythromelalgia
Headaches
Can have splenomegaly
153
Management of essential thrombocythaemia
If <60, aspirin
If >60, platelet count >1500, thrombotic or haemhorragic episode - hydroxycarbamide 500mg + aspirin
Treat cardiovascular risk factors.
Try and keep platelets to 150-400.
154
What is the risk of platelet counts being above 1500?
Platelet >1500 causes quick clearing of von willebrand factor which can cause increased bleeding and result in subarachnoid haemorrhages.
155
What is myelofibrosis?
Myelofibrosis is a debilitating myeloproliferative neoplasm characterized by clonal proliferation of stem cells and abnormal myeloid
cells in the bone marrow, liver, spleen and other organs.
156
What is myelofibrosis?
Myelofibrosis is a debilitating myeloproliferative neoplasm characterized by clonal proliferation of stem cells and abnormal myeloid
cells in the bone marrow, liver, spleen and other organs.
157
Aetiology of myelofibrosis
JAK2 mutation
158
Pathophysiology of myelofibrosis
Increased fibrosis
in the bone marrow is caused by hyperplasia of abnormal megakaryocytes, which release fibroblast-stimulating factors such as
PDGF
159
Clinial presentation of myelofibrosis
Splenomegaly
LUQ pain
Lethargy
Weakness
Weight loss
160
Investigation of myelofibrosis
FBC: Anaemia
Blood film: Leucoerythroblastic cells and tear-drop shape erythrocytes.
Bone marrow trephine biopsy: fibrosis
JAK2 mutation - positive
161
Management of myelofibrosis
Ruxolitinib - JAK2 inhibitor.
Bone marrow transplant
162
What are the main 4 types of leukaemia?
Acute myeloid leukaemia
Chronic myeloid leukaemia
Acute lymphoblastic leukaemia
Chronic lymphocytic leukaemia
163
General aetiology of leukaemia
Ionizing radiation exposure
Benzene exposure
Chemotherapy drugs
164
What is acute myeloid leukaemia?
Neoplastic proliferation of myoblasts in bone marrow.
165
Investigation of acute myeloid leukaemia
FBC: Anaemia, thrombocytopoenia, high circulating WBCs
Blood film: Auer rods + blast cells
Aspirate/trephine bone marrow biopsy
166
Management of acute myeloid leukaemia
Intensive chemotherapy - anthracycline e.g daunorubin
167
Pharmacodynamics of anthracyclines
Damaging malignant cell DNA through DNA intercalation in the malignant cells
168
What is acute lymphoblastic leukaemia?
Neoplastic proliferation of
lymphoblasts in bone marrow
169
What are the types of acute lymphoblastic leukaemia?
T-cell ALL
B-cell ALL (more common)
170
What is the most common cancer affecting children?
Acute lymphoblastic leukaemia
171
Clinical presentation of acute lymphoblastic leukaemia
Acute leukaemia symptoms
Mediastinal mass
Testicular enlargement
172
Investigation of acute lymphoblastic leukaemia
FBC: Pancytopaenia,
Bone marrow biopsy: Raised lymphoblasts (>20%)
Immunophenotyping: Presence of CD10 marker (B-ALL), TdT+ (B+T-ALL)
173
Management of acute lymphoblastic leukaemia
PCVD
Prednisolone
Cyclophosphamide
Vincristine
Daunorubicin
174
What condition is a risk factor for acute lymphoblastic and acute myeloid leukaemia?
Down's Syndrome
175
What are supportive treatments for acute leukaemias?
Antibiotics for neutropaenia
Blood transfusions for anaemia
176
Genetic aetiology of acute lymphoblastic leukaemia
t(12,21) - better prognosis
t(9,22) - philadelphia chromosome, worse prognosis
177
General clinical presentation of acute leukaemia
Anaemia - dyspnoea, pallor, fatigue
Neutropaenia - infection, mouth ulcers
Thrombopaenia - easy bleeding,
High WCC - visual problems
Hepatosplenomegaly
Lymphadenopathy
178
Clinical presentation of acute myeloid leukaemia
General acute leukaemia symptoms
Gum hypertrophy
179
What is chronic myeloid leukaemia?
Neoplasmic proliferation of mature granulocytes.
180
Clinical presentation of chronic myeloid leukaemia
Symptomatic anaemia - dyspnoea(e.g. shortness of breath)
Abdominal discomfort due to splenomegaly
Fever, night sweats, weight loss
Pallor
181
Investigation of chronic myeloid leukaemia
FBC: Anaemia, thrombocytopoenia, raised WBC
Hyperviscosity - high haematocrit because
Blood film: Increased granulocytes
Genetic test for Philadelphia chromosome in BCR ABL gene
182
Management of chronic myeloid leukaemia
Imatinib - tyrosine kinase inhibitor
Chemotherapy
183
Aetiology of chronic myeloid leukaemia
Philadelphia chromosome - t(9,22) Causing BCR-ABL gene fusion
Causes overactivation of tyrosine kinase
184
What is chronic lymphocytic leukaemia?
Neoplastic proliferation
of abnormal B
lymphocytes in bone marrow.
185
What is the most common adult leukaemia?
Chronic lymphocytic leukaemia
186
Clinical presentation of chronic lymphocytic leukaemia
Mainly asymptomatic
General acute leukaemia symptoms.
187
Investigation of chronic lymphocytic leukaemia
FBC: Lymphocytosis, anaemia, raised WBC, thrombocytopoenia
Blood film: Smudge cells - leukocytes that have ruptured.
Hypogammaglobulinaemia (low immunuglobulins)
188
Management of chronic lymphocytic leukaemia
Chemotherapy
Immunotherapy
189
What are some indolent (low grade) non-hodgkin lymphomas?
Marginal zone lymphoma
Lymphoplasmacytic lymphoma
Follicular lymphoma
190
What are some aggressive (high grade) non-hodgkin lymphomas?
Burkitt's lymphoma
Diffuse large B cell lymphoma
Mantle cell lymphoma
191
What infection is associated with Hodkin's lymphomas?
Epstein Barr Virus and glandular fever (infectious mononucleosis)
Autoimmune diseases - SLE,
192
Clinical presentation of Hodgkin's lymphoma
B-symptoms - fevers, night sweats, unexplained weight loss.
Painless, rubbery lymphadenopathy
Lymphadenopathy can be painful after alcohol consumption.
Women can present with cough due to mediastinal lymphadenopathy.
Hepatosplenomegaly
193
Investigation of Hodgkin's lymphoma
CT-PET (chest, abdo, pelvis) for staging
Lymph node biopsy - Reed-Steinberg cells with dual nuclei (owl eyes).
194
What are the 2 types of Hodgkin's lymphoma?
Classic Hodgkin's lymphoma
Nodular lymphocyte-predominant HL
195
What would a lymph node biopsy show for nodular lymphocyte predominant hodgkin's lymphoma?
Presence of popcorn cells (variant of Reed-Steinberg cells) surrounded by B lymphocytes.
196
Management of Hodgkin's lymphoma
ABVD
Adriamycin (Doxorubicin hydrochloride)
Bleomycin sulfate
Vinblastine sulfate
Dacarbazine
197
Which type of lymphoma is more likely to spread extra-nodally?
Non-hodgkin's lymphoma
198
Clinical presentation of acute myeloid leukaemia
Splenomegaly
Swollen gums
199
What is the driving force of arterial thrombosis?
Platelet plug formation
200
What is the driving force for venous thrombosis?
Fibrin
201
Aetiology of arterial thrombosis
Atherosclerotic plaque rupture
Trauma
Hypertension
202
Complications of arterial thrombosis
Stroke/TIA
Myocardial infarction
Peripheral vascular disease
203
Management of arterial thrombosis
Aspirin + other antiplatelets
Heparin: LMWH, enoxaparin, fondaparinux
Thrombolytics: streptokinase, TPA
Reperfusion: Catheter stenting
204
Pharmacodynamics of streptokinase
Promotes conversion of plasminogen to plasmin allowing for fibrin degradation.
205
Aetiology of venous thrombosis
Endothelial cell damage, stasis in blood flow, change in blood constituents (hypercoagubility)
206
What can cause endothelial cell damage to cause venous thrombosis?
Trauma
Chemical injury
Hypertension
207
What can cause stasis in blood flow to cause venous thrombosis?
Immobilisation due to:
Surgery
Fractures (cast)
Long-haul flights
208
What can cause change in blood constituents to cause venous thrombosis?
Oral contraceptive pill
Malignancy
209
Genetic aetiology of change in blood constituents and venous thrombosis
Antithrombin deficiency
Protein C deficiency
Protein S deficiency
210
Acquired aetiology of change in blood constituents and venous thrombosis
Anti-phospholipid syndrome
Lupus anticoagulant
Hyperhomocysteinaemia
211
Clinical presentation of DVT
Pain, swelling, tenderness, redness.
212
Where does DVT usually occur?
Great veins of the legs
213
Investigation of DVT
D-dimer - fibrinogen degradation product.
Doppler ultrasound compression - gold standard.
CT/MRI venogram.
Doppler can miss acute DVT because the thrombus is still fresh so the vein can still be compressed.
214
Examination of DVT
Pitting oedema - indentation remains on swelling after pressing.
215
Management of DVT
LMWH min. 5 days
Oral Warfarin (INR 2-3) for 3-6 months or DOAC/NOAC
Compression stockings
Treat underlying cause
Endovascular/surgical repair
216
Pharmacodynamics of warfarin
Vit. K antagonist so prevents production of Vit.K dependent clotting factors X, IX, VII, III
217
Examples of DOACs/NOACs
Rivaroxaban, apixaban
218
Pharmacodynamics of Rivaroxaban
Direct factor Xa inhbitor, stopping the rest of the clotting cascade from occurring.
219
What score is used to assess the risk of DVT?
Well's score
220
What must be considered when interpreting a D-dimer for DVT?
Sensitive, not specific.
Normal D-dimer excludes diagnosis.
Positive does not confirm diagnosis (can be raised in sepsis, surgery, DIC).
221
When can a doppler ultrasound be inaccurate for DVT?
Doppler can miss acute DVT because the thrombus is still fresh so the vein can still be compressed.
222
Complications of DVT
Pulmonary embolism
Compartment syndrome
223
Clinical presentation of pulmonary embolism
Dyspnoea
Pleuritic chest pain
Hemoptysis
Cough
224
Examination of pulmonary embolism
Pleural rub upon ausculation
Tachypnoea, tachycardia
225
Investigation of pulmonary embolism
ECG sinus tachycardia (Q1S1T3)
ABG: type 1 resp failure
D-dimer: raised, normal excludes diagnosis.
CTPA spiral CT with contrast - gold standard.
226
Management of pulmonary embolism
LMW Heparin s/c od weight adjusted 5/7
Oral warfarin INR 2-3 (2.5) for 6 months
DOAC
Treat underlying cause
227
Contraindications for NOAC/DOAC usage
Prosthetic heart valve insertion
Pregnancy
228
How is warfarin monitored?
Looking at INR (international normalised ratio) which is derived from prothrombin time.
Higher INR means blood takes longer to clot.
Should be between 2-3
229
Modes of administration of anticoagulants
Heparins - IV/subcutaneous
Warfarin - orally
DOACS/NOACs - orally
230
Why are NOACs/DOACs preferred over warfarin?
Less monitoring needed.
Shorter half life so decreased haemhorragic risk.
231
Why does atherosclerosis not occur in veins?
Lack of tunica media (smooth muscle cells)
232
Aetiology of peripheral vascular disease
Smoking
Hypertension
Diabetes
Hypercholesterolaemia
Increasing Age
233
Clinical presentation of acute limb ischaemia
Painful
Pulseless
Paraesthesia - nerves are more sensitive to ischaemia than muscles
Pallor
Perishingly cold
Paralysis - muscles don’t work and limb is unsalvageable.
234
Clinical presentation of critical limb ischaemia
Intermittent claudication
Non-healing ulcers
Pain at rest
Gangrene
235
What test can be used to see if there is limb ischaemia?
Burgers test
Lift foot up and it goes pale, then tell patient to hang it over the bed, reactive hyperaemia causes sudden flushing redness of leg.
236
Medical management of acute limb ischaemia
Risk factor prevention - antiplatelets, statins
Exercise programme
Aspirin + unfractionated heparin.
Naftidrofuryl oxalate - vasodilator
Analgesia - IV opioids
237
Interventional management for critical limb ischaemia
Endovascular stenting
Bypass surgery
238
What is an aneurysm?
Weakening of the blood vessel wall causing a dilation.
239
What is a false aneurysm?
Not the arterial wall that is dilated.
Can be caused by a puncturing of artery due to angiogram for example, localised haemhorrage can look like an aneurysm.
240
What is a mycotic aneurysm?
Aneurysm caused by infection
241
Where is a true aneurysm most commonly formed?
Infra-renal aorta
242
Why can atherosclerosis lead to aneurysms?
Ischaemia of tissue around the plaque causing weakening of arterial wall.
243
Investigation of acute/chronic lower limb ischaemia
Duplex ultrasound
ABPI - ankle brachial pressure index
CT/MR angiography
244
Aetiology of aneurysm/abdominal aortic aneurysms
Smoking
Hypertension
Atherosclerosis
Infection
Ehler Dahnos
Marfans
245
Clinical presentation of abdominal aortic aneurysm rupture
Normally asymptomatic.
If ruptured:
Severe abdominal pain
Hypotension
Tachycardia
Profound anaemia
Sudden collapse/death
246
Investigation of abdominal aortic aneurysm
Duplex abdominal ultrasound
CT/MR angiography
247
Management of abdominal aortic aneurysm
If non-ruptured, lifestyle improvement + statins.
If ruptured, open/endovascular repair.
248
Management of carotid arterial disease
Carotid endarterectomy
Or endovascular stenting.
249
Aetiology of venous disease
Valve dysfunction
Vein obstruction - malignancy, May thurner syndrome.
250
Pathophysiology of venous disease
Can result in venous hypertension.
Can cause vein torsion and oedema.
251
Clinical presentation of venous disease
Varicose veins (tortuous and enlarged sueprficial veins)
Itching
252
Investigation of venous diseae
Duplex ultrasound - gold standard.
253
Management of superficial venous disease
Lifestyle changes
Compression therapy
Sclerotherapy
Endo-venous treatments
Surgical stripping
254
Management of deep venous disease
Lifestyle changes
Compression therapy
Valve insertion
Stenting
255
What can often be seen in imaging at areas of occlusion?
Collateral angiogenesis to bypass the occluded point.
256
Management of hereditary spherocytosis
Splenectomy
257
Investigation of alpha thalassaemia
Haemoglobin electrophoresis
258
What anticoagulant should be given first in an acute case of thrombosis?
Heparin
259
Why should heparin be administerd before warfarin during anticoagulant therapy?
Warfarin initially inhibits synthesis of protein C, S which can cause initial overcoagulation and where heparin is needed to counteract it.
260
What are contraindications/interactions of warfarin?
Vit.K rich foods such as spinach, cranberry juice, grapefruit juice.
261
Aetiology of haemophilia A
Deficiency in clotting factor VIII
262
What is the genetic transmission of hemophilia A?
X-linked recessive
263
Clinical presentation of haemophilia
Haemarthroses (bleeding into joints)
Easy bruising
Excessive bleeding after trauma/surgery
264
Investigation of haemophilia A
Raised APTT
Normal bleeding time, PTT
265
Management of haemophilia A
Desmopressin
IV factor VIII concentrate
Emicizumab (mimics action of factor VIII in CC)
266
Aetiology of haemophilia B
Deficiency in fact IX, X linked recessive
267
Aetiology of haemophilia C
Deficiency in factor XI, autosomal recessive
268
Aetiology of Von WIllebrand Disease
Deficiency in Von Willebrand factor - autosomal dominant
269
Clinical presentation of VWD
Increased occurence of epistaxis, menorrhagia
Mildly increased bleeding after trauma
270
Investigation of VWD
Normal PT
Elevated APTT and bleeding time.
271
Management of VWD
Desmopressin
Factor VIII concentrates with VWF for replacement.
272
Aetiology of disseminated intravascular coagulation
Malignancy
Liver disease
Trauma
Snake bites
Sepsis
273
Pathophysiology of disseminated intravascular coagulation
Widespread clotting factor activation causes
thromboembolic state with excessive
clotting factor consumption.
This can lead to increased bleeding.
274
Clinical presentation of disseminated intravascular coagulation
Shock
Ecchymoses (skin bruising causing discoloration)
275
Investigation of disseminated intravascular coagulation
Raised PT, PTT, Bleeding time
Raised D-dimer
276
What are some complications of chemotherapy?
Immunocompromisation
Tumour lysis syndrome
277
What value is used to monitor heparin?
APTT
278
What are some side effects of chemotherapy?
Hair loss
Immunosupression (pancytopaenia)
Infertility
GI disturbances
Secondary malignancy
