Haematology Flashcards
1
Q
What is the lifespan of a red blood cell?
A
120 days
2
Q
What is meant by the reticulocyte count?
A
Count of immature RBC’s in the bone marrow. Low reticulocyte count indicates RBC production is an issue.
3
Q
Why is Hb high in a dehydrated patient?
A
Reduction in plasma volume leads to a falsely high Hb.
4
Q
What is meant by hypochromic?
A
Pale red blood cells.
5
Q
What is meant by microcytic?
A
Low mean corpuscular volume.
6
Q
What is meant by normocytic?
A
Normal mean corpuscular volume.
7
Q
What is meant by macrocytic?
A
High mean corpuscular volume.
8
Q
What causes microcytic anaemia?
A
- iron deficiency
- thalassaemia
- anaemia of chronic disease
- sideroblastic anaemia (bone marrow cannot produce normal RBCs despite normal iron)
9
Q
What is meant by megaloblastic anaemia?
A
Large immature red blood cells.
10
Q
What causes megaloblastic anaemia?
A
Vitamin B12 or folate deficiency.
11
Q
What are some causes of normoblastic macrocytic anaemia?
A
- alcohol
- increased reticulocytes due to haemolysis / haemorrhage
- liver disease
- hypothyroidism
- certain drug therapies
12
Q
What are some causes of normocytic anaemia?
A
- acute blood loss
- anaemia of chronic disease
- CKD
- autoimmune rheumatic disease
- marrow infiltration / fibrosis
- endocrine disease
- haemolytic anaemia
13
Q
What are some compensatory changes that occur in response to anaemia?
A
- increased tissue perfusion
- increased O2 transfer to tissues
- increased RBC production
14
Q
What are some pathological consequences of anaemia?
A
- myocardial fatty change
- fatty change in liver
- aggravates angina and claudication
- skin and nail atrophic changes
- CNS cell death
15
Q
What are some symptoms of anaemia?
A
- fatigue
- headaches
- faintness
- dyspnoea
- angina
- anorexia
- intermittent claudication
- palpitations
16
Q
What are some signs of anaemia?
A
- pallor
- tachycardia
- systolic flow murmur
- cardiac failure
17
Q
How are iron ions absorbed?
A
- actively transported into duodenal intestinal epithelial cells by haem transporter HCP1
18
Q
How are iron ions stored?
A
- some is incorporated into ferritin (intracellular iron store)
- remainder stored as haemosiderin (found in macrophages in the bone marrow, liver and spleen)
19
Q
What happens to iron ions that are not stored?
A
- released into the blood bound to transferrin and transported to the bone marrow
- majority of iron is incorporated into haemoglobin
20
Q
What is meant by poikilocytosis?
A
An increase in RBCs of abnormal shape.
21
Q
What is meant by anisocytosis?
A
Variation in RBC size.
22
Q
How is vitamin B12 absorbed?
A
Binds to intrinsic factor and is then absorbed in the terminal ileum.
23
Q
Where is intrinsic factor produced?
A
Parietal cells of the stomach.
24
Q
Why can mild jaundice occur in pernicious anaemia?
A
Due to the increased haemolysis as the body attempts to get rid of macrocytic RBCs.
25
What size RBC are found in haemolytic anaemia?
- normocytic
| - macrocytic (due to there being large young RBCs as a result of excessive destruction of old RBCs)
26
Where can haemolysis occur?
- circulation
- reticuloendothelial system (macrophages in the liver and spleen)
- bone marrow
27
What happens when haemolysis occurs in the circulation?
- liberated haemoglobin initially binds to haptoglobin but these quickly become saturated
- excess free haemoglobin is filtered by the glomerulus and excreted in urine
- small amounts of Hb are reabsorbed into renal tubular cells where it is broken down and deposited in the cells as haemosiderin
28
What is meant by compensated haemolytic disease?
- red cell loss is contained within the bone marrow’s capacity to increase output
- bone marrow expands the volume of active marrow and undergoes erythroid hyperplasia
29
Why might haemolytic anaemia be macrocytic?
Macrocytic reticulocytes are released prematurely from bone marrow.
30
What are the main causes of haemolytic anaemia?
- hereditary spherocytosis
- G6PD deficiency
- beta / alpha thalassaemia
- sickle cell disease
- autoimmune haemolytic anaemia
31
What are some features of haemolytic anaemia?
- high serum unconjugated bilirubin
- high urinary urobilinogen
- high faecal stercobilinogen
- splenomegaly
- bone marrow expansion
- reticulocytosis
32
How is Hodgkins lymphoma histologically different from non-Hodgkin’s lymphoma?
Presence of Reed-Sternberg cells in Hodgkin’s lymphoma.
33
Findings of Auer rods indicates?
Acute myeloid leukaemia.
34
Risk factors for DVT?
- pregnancy
- recent surgery
- recent leg fracture
- recent history of cancer
- immobility
- HRT / oestrogen-containing contraception
35
Most common cause of malaria?
Plasmodium falciparum
36
Gold standard treatment for thrombotic thrombocytopenic purpura?
Plasma exchange
37
What is the Well’s score?
DVT / PE risk scoring.
38
What staging system is used for HL and NHL?
Ann Arbor
39
What are B symptoms?
- fever
- night sweats
- weight loss of > 10% of body weight over 6 months.
40
Examples of LMWH?
- dalteparin
| - enoxaparin
41
Mechanism of action of fondaparinux?
Factor Xa inhibitor.
42
Mechanism of action of dalteparin / enoxaparin?
- binds to and potentiates antithrombin III
| - this forms a complex that irreversibly inactives factor Xa and inhibits thrombin (IIa)
43
Examples of DOACs?
- dabigatran
- rivaroxaban
- apixaban
44
Mechanism of action of dabigatran?
Thrombin inhibitor.
45
Mechanism of action of rivaroxaban / apixaban?
Factor Xa inhibitor.
46
What is the protein target of rituximab?
CD20
47
First line treatment for severe / complicated malaria?
IV artesunate
48
What is the most common form of anaemia?
Iron-deficiency anaemia.
49
What are the four categories of causes of IDA?
- inadequate dietary intake
- impaired iron absorption
- increased iron loss
- increased iron requirement
50
Examples of causes of impaired iron absorption?
- achlorhydria
- gastric surgery
- coeliac disease
- H. pylori infection
51
Examples of causes of increased iron loss?
- GI bleeding (haemorrhoids, peptic ulcer disease, IBD)
| - menorrhagia
52
Examples of causes of increased iron requirement?
- young children
- pregnancy
- lactation
53
Where does iron absorption mostly occur?
Duodenum and proximal jejunum.
54
Iron transport molecule?
Transferrin
55
Iron storage molecule(s)?
Ferritin and haemosiderin.
56
What is hepcidin?
Hormone that decreases intestinal iron absorption and prevents iron recycling.
57
What causes increased hepcidin transcription?
Systemic inflammatory / infectious states.
58
Appearance of RBCs in IDA?
Hypochromic and microcytic.
59
Symptoms of IDA? (8)
- dyspnoea (on exertion)
- fatigue
- headache
- cognitive dysfunction / impaired concentration
- syncope
- irritability
- palpitations
- angina
60
Signs of IDA? (6)
- pallor (& conjunctival pallor)
- atrophic glossitis
- dry skin
- dry / damaged hair
- angular stomatitis
- nail changes (longitudinal ridges, koilonychia)
61
What is atrophic glossitis?
Loss of filiform papillae on the dorsal surface of the tongue.
62
What is angular stomatitis?
Ulceration at the corners of the mouth.
63
What is kolionychia?
Spoon shaped nails.
64
What is seen on a peripheral blood smear in IDA?
- hypochromic & microcytic cells
- anisopoikilocytosis - size and shape variation
- pencil cells
65
What happens to total iron binding capacity in IDA?
Increases
66
Investigations for IDA? (6)
- FBC
- folate and B12
- peripheral blood smear
- blood cultures
- endoscopy
- coeliac serology
67
Oral iron supplement examples?
- ferrous sulphate
- ferrous fumarate
- ferrous gluconate
68
Adverse effects of oral iron?
- constipation / diarrhoea
- epigastric pain
- nausea
69
When would you give a blood transfusion for IDA?
Cardiovascular compromise - dyspnoea at rest, chest pain, lightheadedness.
70
Summary of IDA management?
- oral (or parenteral) iron supplementation
| - blood transfusion if indicated by cardiovascular compromise
71
Most frequent cause of megaloblastic anaemia?
B12 / folate deficiency.
72
What is meant by megaloblastic anaemia?
Macrocytic anaemia, where the cells are immature due to defective DNA synthesis.
73
Most common cause of B12 deficiency?
Pernicious anaemia
74
Causes of B12 deficiency?
- pernicious anaemia
- gastrectomy
- congenital IF deficiency
- malabsorption (IBD, coeliac disease, etc)
- malnutrition
- drugs (PPIs, H2 receptor antagonists)
75
Which drugs can cause folate deficiency?
- methotrexate
- trimethoprim
- sulfasalazine
76
Causes of folate deficiency?
- drugs
- increased folate requirements (malignancy, pregnancy & lactation)
- malabsorption
- malnutrition
77
How is B12 absorbed?
- B12 is released from food by gastric acid
- free B12 binds to intrinsic factor
- the IF-B12 complex is absorbed in the terminal ileum
78
Which cells secrete intrinsic factor?
Parietal cells
79
Symptoms of B12 deficiency?
neurological problems - muscle weakness, loss of cutaneous sensation, pyschiatric disturbances
80
Signs and symptoms of B12 / folate deficiency anaemia?
- same as IDA (dyspnoea, headache, lethargy, palpitations, angular stomatitis, atrophic glossitis, etc)
- PLUS neurological problems (B12 deficiency)
81
Management of B12 deficiency?
- IM hydroxocobalamin
| - dietary advice
82
What is cobalamin?
vitamin B12
83
Management of folate deficiency?
CHECK FOR B12 DEFICIENCY - folic acid treatment may mask B12 deficiency and allow progression to neurological disease development.
Oral folic acid (5mg daily) and dietary advice.
84
Neonatal complications of folate deficiency?
- neural tube defects
| - prematurity
85
What is sickle cell anaemia?
Autosomal recessive condition causing sickle shaped RBCs.
86
Why does sickle cell anaemia result in haemolysis?
Sickle cells are fragile and easily destroyed, resulting in haemolytic anaemia.
87
HbS is the result of?
A single gene defect in the beta chain of haemoglobin.
88
What is meant by sickle cell trait?
A person has one copy of the sickle cell gene. They are usually asymptomatic.
89
What is the single gene mutation in sickle cell anaemia?
Valine replaces glutamic acid at the 6th amino acid of the beta globin chain.
90
When is fetal Hb replaced by adult Hb?
Around 6-12 months of age.
91
What causes the sickle shape of RBCs?
HbS polymerises with the RBC, forming long stiff fibres which result in the sickle shape.
92
What triggers polymerisation of HbS?
Hypoxia & acidosis.
93
What are some precipitating factors for vaso-occlusive episodes in sickle cell anaemia?
- acidosis
- dehydration
- cold temperatures
- stress
- infection
- extreme exercise
94
What are some clinical manifestations of sickle cell anaemia?
- vaso-occlusive crises
- dactylitis
- acute chest syndrome
- bone pain
- failure to thrive
- jaundice
- pallor, tachycardia and lethargy
95
What is meant by acute chest syndrome?
Caused by sickling of RBCs within the pulmonary vasculature. Presents like pneumonia (chest pain, fever, tachycardia, dyspnoea, etc).
96
Triggers for acute chest syndrome?
- thrombosis
- infection
- atelectasis
97
What causes bone pain in sickle cell anaemia?
Infarction and avascular necrosis due to vaso-occlusive crisis.
98
What is meant by splenic sequestration?
Life-threatening complication of sickle cell anaemia in children. Sickle cells obstruct a draining vein, causing RBCs to become trapped in the spleen.
99
What are some complications of sickle cell anaemia? (6)
- stroke
- avascular necrosis
- priapism
- chronic kidney disease
- acute chest syndrome
- increased susceptibility to infection
100
What is priapism?
Persistent and painful erection.
101
How is sickle cell anaemia screened for?
- newborn heel prick test
| - genetic testing during pregnancy (in at-risk patients)
102
Investigations for sickle cell anaemia complications?
X-rays of long bones - infarction / avascular necrosis.
| CXR - acute chest syndrome shows pulmonary infiltrate.
103
Summary of sickle cell disease management?
- avoid triggers
- genetic counselling
- pain management
- hydroxycarbamide stimulates HbF production
- blood transfusion / bone marrow transplant
- prevention and management of infections & complications
104
What is meant by haemolytic anaemia?
Anaemia secondary to the reduced survival of RBCs (lifespan < 100 days).
105
Examples of inherited haemolytic anaemias?
- metabolic abnormalities (G6PD deficiency)
- Hb abnormalities (sickle cell anaemia, thalassemia)
- membrane abnormalities (hereditary spherocytosis)
106
Examples of acquired haemolytic anaemias?
- autoimmune
- mechanical trauma
- infections (malaria)
- hypersplenism
107
Inheritance pattern of hereditary spherocytosis?
autosomal dominant
108
How does hereditary spherocytosis result in haemolysis?
- mutations lead to defects in the RBC membrane and cytoskeleton instability
- the resulting spherocytes are fragile and selectively removed by the spleen for destruction
109
Inheritance pattern of glucose-6-phosphate dehydrogenase deficiency?
X linked recessive
110
How does G6PD deficiency result in haemolysis?
- G6PD is important for NADPH generation
| - NADPH helps scavenge oxidative metabolites that would cause damage to the RBC
111
Symptoms & signs of haemolytic anaemia?
- fatigue
- dyspnoea
- paraesthesia
- atrophic glossitis
- pallor
- splenomegaly
- jaundice
- dark urine
112
Investigations for haemolytic anaemia? (5)
- FBC
- blood film
- LFTs
- DAT test
- Hb electrophoresis
113
What FBC findings are present in haemolytic anaemia?
- normocytic anaemia
| - increased reticulocyte count
114
Haptoglobin levels in haemolytic anaemia?
- may be elevated as it is an acute phase reactant
| - may be decreased due to removal of Hb-haptoglobin complexes once haptoglobin has mopped up free Hb
115
What is the DAT test?
- direct antiglobulin test
- also known as the Coombs test
- detects antibodies on the surface of RBCs
- to investigate an autoimmune cause of haemolysis
116
What is meant by pernicious anaemia?
Autoimmune condition affecting the parietal cells of the stomach, resulting in B12 deficiency anaemia due to intrinsic factor deficiency.
117
What is the pathophysiology of pernicious anaemia?
Autoantibodies form against parietal cells / intrinsic factor.
This leads to a lack of intrinsic factor, preventing B12 absorption.
118
Investigations for pernicious anaemia?
- B12 deficiency anaemia investigations
- intrinsic factor antibody
- parietal cell antibody
119
Management of pernicious anaemia?
IM hydroxycobalamin
120
What is meant by anaemia of chronic disease?
Syndrome in which anaemia is the result of an inflammation-mediated reduction in RBC production and survival.
121
What size and colour RBCs are found in anaemia of chronic disease?
Normocytic normochromic / microcytic hypochromic.
122
Causes of anaemia of chronic disease?
- infection
- neoplasm
- autoimmune disease
- trauma
- major surgery
123
Pathophysiology of anaemia of chronic disease?
- underlying condition causes the release of pro-inflammatory cytokines
- triggers upregulation of hepcidin
- serum iron levels fall, resulting in decreased erythropoiesis
- survival of circulating RBCs may be decreased due to damage by free radicals generated by cytokines, or increased erythrophagocytosis
124
What is the function of hepcidin?
Negative regulator of free iron:
- causes iron trapping in macrophages
- decreases iron absorption from the GI tract
- causes splenic sequestration of iron
- causes impaired bone marrow responsiveness to EPO
125
How is anaemia of chronic disease managed?
- treat underlying disease
- iron supplementation in patients with iron deficiency
- RBC transfusion in severe anaemia
- erythropoiesis-stimulating agents may be used if tranfusion is unsuitable
126
What is meant by deep vein thrombosis?
Formation of a thrombus that develops in one of the deep veins, characteristically occurring within the lower limb.
127
What is meant by distal DVT?
Below the popliteal trifurcation.
128
Distal DVT prognosis?
Likely to resolve spontaneously without symptoms.
129
What is meant by proximal DVT?
Above the popliteal trifurcation - may affect the popliteal, femoral, or iliac veins.
130
Proximal DVT prognosis?
50% of symptomatic patients develop PE within 3 months.
131
Provoked vs unprovoked DVT?
Provoked - DVT occurs within 3 months of exposure to transient / persistent risk factors.
Unprovoked - no readily identifiable risk factor for DVT.
132
Intrinsic risk factors for DVT?
- Hx of DVT
- cancer
- obesity
- thrombophilia
- varicose veins
- smoking
- older age
- male sex
133
Transient risk factors for DVT?
- hospitalisation
- recent major surgery / trauma
- immobility
- oestrogen-containing hormone therapy
- long-distance sedentary travel
- dehydration
- infection
- pregnancy (& up to 6 weeks post partum)
134
Components of Virchow's triad?
- venous stasis
- hypercoagulable state
- endothelial injury
135
Symptoms and signs of DVT? (5)
- unilateral leg swelling (calf asymmetry)
- pain / tenderness in leg
- erythema
- warmth
- venous distention
136
What is the Wells score?
Scoring system used to assess risk of DVT / PE.
137
Investigations if Wells score is 1 or less?
- D-dimer
| - ultrasound proximal leg veins if D-dimer positive
138
Investigations if Wells score is 2 or more?
- ultrasound proximal leg veins within 4 hours
| - if delay is expected: request d-dimer, give anticoagulation, arrange ultrasound within 24 hours
139
Sensitivity and specificity of D-dimer?
High sensitivity - negative result excludes DVT.
| Low specificity - cannot be used to make a positive diagnosis of DVT.
140
Gold standard investigation for DVT?
Ultrasound of proximal leg veins.
141
Management of DVT?
Anticoagulation:
- first-line DOAC (apixaban / rivaroxaban)
- LMWH is an alternative (dalteparin / enoxaparin)
Continue anticoagulation for at least 3 months.
142
How many cases of PE are preceded by DVT?
80%
143
Complications of DVT?
- PE
| - post-thrombotic syndrome
144
What is post-thrombotic syndrome?
- chronic swelling, pain, and skin changes due to venous stasis secondary to venous hypertension
- may lead to ulcers and gangrene
145
What is acute myeloid leukaemia?
Haematological malignancy caused by clonal expansion of myeloid blasts in the bone marrow, peripheral blood, and extramedullary tissues.
146
Which age group is most commonly affected by AML?
Much more common in the over 60s
147
What is myelodysplastic syndrome?
Heterogeneous group of blood disorders affecting haematopoiesis. Increases risk of developing AML.
148
Risk factors for AML? (5)
- increasing age
- myelodysplastic syndrome
- congenital disorders (Down's syndrome)
- radiation exposure
- previous chemotherapy
149
How does AML cause disease?
- uncontrolled proliferation of myeloid progenitor cells
- abnormal cells accumulate in the bone marrow, resulting in reduced production of normal cell lines
- spread and proliferation in other tissues
150
Signs and symptoms of AML?
- anaemia
- neutropenia (recurrent infections)
- thrombocytopenia
- lymphadenopathy
- hepatosplenomegaly
- bone pain
- violaceous skin deposits
- leucostasis
151
What is meant by leucostasis?
White cell plugs within the microvasculature. Presents with symptoms such as: altered mental state, headache, breathlessness, visual changes.
152
Gold standard investigation for AML?
Bone marrow aspirate and biopsy - shows a myeloid blast count of > 20%.
153
What is shown on a peripheral blood smear in AML?
Auer rods (azurophilic structures).
154
How is AML managed?
- cytoreduction with hydroxycarbamide
- tumour lysis syndrome prophylaxis
- chemotherapy
- allogenic stem cell transplant (generally after failure of other treatments)
155
What does tumour lysis syndrome prophylaxis involve?
- good hydration
- monitor electrolytes
- allopurinol to control hyperuricaemia
156
Tumour lysis syndrome definition?
Metabolic and electrolyte abnormalities occurring after the initiation of cancer treatment, due to the rapid breakdown of a large number of cancer cells. The subsequent release of large amounts of intracellular content overwhelms normal homeostatic mechanisms.
157
What is acute lymphoblastic leukaemia?
Haematological malignancy caused by acute proliferation of abnormal lymphoid progenitor cells.
158
Which age group does ALL most commonly affect?
75% of cases occur in children under 6.
Most common cancer in children.
Also affects older adults (>45).
159
Risk factors for ALL?
- young children / > 45 years
- radiation exposure
- genetic disorders (Down's syndrome)
- previous chemotherapy
- family history
160
Pathophysiology of ALL?
- uncontrolled proliferation and clonal expansion of a genetically altered lymphoid progenitor cell
- bone marrow / extramedullary infiltration
161
Signs and symptoms of ALL?
- lymphadenopathy
- hepatosplenomegaly
- anaemia / neutropenia / thrombocytopenia
- bone pain
- weight loss
162
Investigations for ALL?
- bone marrow aspirate (shows leukaemic lymphoblasts > 20%)
- peripheral blood film (shows leukaemic lymphoblasts)
- FBC
163
Management of ALL?
- chemotherapy (induction, consolidation and maintenance) using a combination of drugs that may include a corticosteroid
- allogenic stem cell transplant in patients at high risk of relapse following chemotherapy
164
What is chronic myeloid leukaemia?
Haematological malignancy characterised by abnormal clonal expansion of cells of the myeloid lineage.
165
Which age group does CML affect?
Older adults in their 50s and 60s.
166
What is the genetic cause of CML?
Philadelphia chromosome - formed by a reciprocal translocation between chromosome 9 and 22. Results in formation of the BCR-ABL1 fusion gene.
167
What does the BCR-ABL1 gene encode?
A constitutively activated tyrosine kinase.
168
Pathophysiology of CML?
Clonal expansion of abnormal myeloid cells leads to the replacement of normal myeloid tissues.
169
Signs and symptoms of CML?
- anaemia
- fatigue, weight loss, night sweats
- splenomegaly / hepatomegaly
- lymphadenopathy
- bone pain
170
Investigations for CML? (5)
- FBC (elevated WCC, anaemia)
- peripheral blood smear (immature and mature myeloid cells)
- bone marrow aspirate / biopsy
- cytogenetics for Ph chromosome
- FISH to confirm BCR-ABL1 fusion
171
Platelet count in CML?
Thrombocytosis or thrombocytopenia may be present. Thrombocytopenia occurs during blast crisis (or due to treatment).
172
What are the disease phases of CML?
- chronic
- accelerated
- blast crisis
173
Characteristics of chronic phase CML?
Non-specific clinical features such as weight loss, night sweats and fatigue.
174
Characteristics of accelerated phase CML?
Symptoms become more apparent and severe. 15-29% blasts in blood or bone marrow.
175
Characteristics of blast crisis?
Resembles acute leukaemia with rapid expansion of blasts. > 30% blasts in blood or bone marrow. Extramedullary blast proliferation.
176
Management of CML?
- tyrosine kinase inhibitors (e.g. imatinib)
- cytoreduction (if WCC very high) and tumour lysis syndrome prophylaxis
- allogenic stem cell transplant (when initial options have failed)
177
What is chronic lymphocytic leukaemia?
Haematological malignancy characterised by abnormal clonal expansion of mature B lymphocytes.
178
Which age group does CLL most commonly affect?
Older adults - average age at diagnosis is 72.
179
What is monoclonal B cell lymphocytosis?
A pre-malignant disorder in which a clone of B lymphocytes forms as a result of genetic alterations.
180
What is the pathophysiology of CLL?
Accumulation of abnormal B cells results in cytopenias and extra-medullary manifestations.
181
Signs and symptoms of CLL?
- weight loss, night sweats, lethargy, fever
- lymphadenopathy
- hepatomegaly / splenomegaly
- autoimmune haemolytic anaemia
- immune thrombocytopenia
- hypogammaglobulinaemia (recurrent infections)
182
Investigations for CLL? (5)
- FBC (lymphocytosis and normocytic anaemia)
- serum immunoglobulins
- haemolysis screen
- blood film (lymphocytosis, 'smear cell' artefacts due to damaged lymphocytes)
- bone marrow aspiration / trephine biopsy
183
How is CLL staged?
Binet or Rai staging systems.
184
Binet staging for CLL?
Stage A - less than 3 lymphoid sites.
Stage B - 3 or more lymphoid sites.
Stage C - presence of anaemia or thrombocytopenia.
185
Rai staging for CLL?
Stage 0 - lymphocytosis.
Stage I-II - lymphocytosis, lymphadenopathy, and organomegaly.
Stage III-IV - lymphocytosis and anaemia / thrombocytopenia (with or without lymphadenopathy / organomegaly).
186
Management of CLL?
- watchful waiting for early disease
- pharmacotherapy may involve chemotherapy, corticosteroids, tyrosine kinase inhibitors, rituximab
- allogenic stem cell transplant
- IVIG for hypogammaglobulinaemia
187
What is meant by the Richter transformation?
Development of an aggressive lymphoma from CLL.
188
What are some complications of CLL?
- Richter transformation
- Hodgkin lymphoma
- multiple myeloma
189
What is Hodgkin lymphoma?
Haematological malignancy arising from mature B cells, characterised by the presence of Reed-Sternberg cells.
190
Lymphoma vs leukaemia?
Lymphomas are solid tumours made up of blood cells. Leukaemias occur when there are malignant blood cells in the bloodstream and bone marrow.
191
Which is more common, HL or NHL?
Non-Hodgkin's lymphoma.
192
Cause of Hodgkin's lymphoma?
Unclear, likely multifactorial.
| May have an infectious aetiology.
193
What are Reed Sternberg cells?
Large, multinucleated cells (look 'owl like').
194
What are Hodgkin cells?
Mononuclear variant of Reed Sternberg cells.
195
Typical presentation of Hodgkin's lymphoma?
Gradual lymphadenopathy, malaise, and fatigue.
196
Signs and symptoms of Hodgkin's lymphoma?
- lymphadenopathy (commonly in the neck)
- B symptoms (fever, night sweats, weight loss)
- malaise and fatigue
- hepatosplenomegaly
- dyspnoea and cough (mediastinal mass)
197
Investigations for Hodgkin's lymphoma?
- exisional biopsy and immunophenotyping
- PET CT (for staging)
- CXR to assess mediastinal involvement
- FBC, U&Es, LFTs, etc
198
Staging of Hodgkin's lymphoma?
Lugano system (modified Ann Arbor system)
199
Stage I Hodgkin lymphoma?
Single lymph node region or single extranodal site.
200
Stage II Hodgkin lymphoma?
Two or more lymph node regions on the same side of the diaphragm.
OR stage I/II nodal involvement with limited contiguous extranodal involvement.
201
Stage III Hodgkin lymphoma?
Nodal involvement on both sides of the diaphragm.
202
Stage IV Hodgkin lymphoma?
Dissemination to non-contiguous extra-lymphatic site(s).
203
What is meant by bulky disease in Hodgkin lymphoma?
Mass > 10cm
204
Summary of Hodgkin lymphoma management?
- chemotherapy (radiotherapy may be an adjunct)
| - patients must receive irradiated blood if tranfusion is necessary for any reason
205
Common chemotherapy regimen for Hodgkin's lymphoma?
ABVD:
- doxorubicin (A)
- bleomycin (B)
- vinblastine (V)
- dacarbazine (D)
206
How does doxorubicin work?
Inhibits topoisomerase II, leading to inhibition of DNA and RNA synthesis.
207
Side effects of doxorubicin?
Cardiomyopathy, myelosuppression, skin reactions.
208
How does bleomycin work?
Inhibits DNA synthesis.
209
Side effects of bleomycin?
Pulmonary fibrosis.
210
How does vinblastine work?
Inhibits microtubule formation by binding to tubulin.
211
Side effects of vinblastine?
Peripheral neuropathy and bladder atony.
212
How does dacarbazine work?
Causes methylation of guanine.
213
Side effects of dacarbazine?
Bone marrow suppression and hepatic necrosis.
214
What investigations should be performed prior to starting (ABVD) chemotherapy?
- echocardiogram
| - pulmonary function tests
215
What is the difference between HL and NHL?
Reed Sternberg cells are not seen in NHL.
216
What are the two main types of NHL?
B cell lymphoma (~85%) and T cell lymphoma (~15%).
217
What is the most common form of NHL?
Diffuse large B cell lymphoma.
218
How aggressive is DLBCL?
Aggressive
219
What is the second most common form of NHL?
Follicular lymphoma.
220
How aggressive is follicular lymphoma?
Indolent
221
6 examples of B cell NHL?
- diffuse large B cell lymphoma
- follicular lymphoma
- Burkitt lymphoma
- mantle cell lymphoma
- MALToma
- lymphoplasmacytic lymphoma
222
How aggressive is Burkitt lymphoma?
Highly aggressive.
223
Which age group is most commonly affected by Burkitt lymphoma?
Children
224
How aggressive is mantle cell lymphoma?
Aggressive
225
What is MALToma, and how aggressive is it?
Indolent lymphoma of mucosa-associated lymphoid tissue.
226
How aggressive is lymphoplasmacytic lymphoma?
Indolent
227
What does lymphoplasmacytic lymphoma cause?
Waldenstrom macroglobulinaemia.
228
2 examples of T cell lymphoma?
- adult T-cell lymphoma (leukaemia)
| - mycosis fungoides
229
What is mycosis fungoides?
Cutaneous T cell lymphoma.
230
What are some risk factors for NHL?
- viral / bacterial infection (EBV, H. pylori, human T-lymphotropic virus)
- autoimmune disorders
- inherited and acquired immunodeficiency
231
Which NHL is EBV associated with?
Burkitt's lymphoma (in endemic areas).
232
Which virus is adult T-cell lymphoma associated with?
Human T-lymphotropic virus.
233
Which NHL is H. pylori associated with?
MALToma
234
What is the difference between HL and NHL in terms of tissue involvement?
In HL there is usually nodal involvement only.
| In NHL there may be nodal or extra-nodal involvement.
235
What is meant by extra-nodal involvement?
Involvement of tissues that are not lymph nodes (e.g. skin, GI tract).
236
How does NHL develop (in terms of pathophysiology)?
- multi-step accumulation of genetic mutations results in expansion of a monoclonal population of malignant B / T lymphocytes
- lymphoma can arise during different stages of lymphocyte development (e.g. monoclonal population of abnormal immature B cells may develop, or the lymphoma may consist of mature antigen-activated B cells)
237
Typical signs and symptoms of NHL?
- painless lymphadenopathy
- fever
- night sweats
- weight loss
238
Signs of GI tract involvement in NHL?
Bowel obstruction.
239
Signs of bone marrow involvement in NHL?
- anaemia
- thrombocytopenia
- neutropenia
240
Signs of spinal cord involvement in NHL?
Loss of sensation (usually in the legs).
241
Typical presentation of Burkitt's lymphoma (endemic regions)?
- rapidly enlarging tumour in the jaw of a child
- enlarged neck lymph nodes
- abdominal masses
242
Typical presentation of sporadic Burkitt's lymphoma?
Abdominal symptoms such as bowel obstruction. Ileo-caecal valve is often affected.
243
What are some complications of NHL?
- superior vena cava obstruction (if mediastinal involvement)
- bowel obstruction
- spinal cord compression
244
What is the gold standard diagnostic investigation for NHL?
Excisional biopsy of affected lymph nodes / tissue.
245
What is the gold standard staging investigation for NHL?
PET CT
246
What other investigations (aside from gold standard) might be performed for NHL?
- bone marrow aspirate and biopsy
- FBC, U&Es, LFTs
- LDH
- CXR
247
How is NHL staged?
Lugano staging system (modified version of the Ann Arbor staging system).
248
What is meant by stage I NHL?
Involvement of one node (or a single group of adjacent nodes).
OR a single extra-nodal lesion without nodal involvement.
249
What is meant by stage II NHL?
Two or more nodal groups involved on the same side of the diaphragm.
OR nodal involvement is stage I or II, with limited contiguous extra-nodal involvement.
250
What is meant by stage III NHL?
Nodes on both sides of the diaphragm are involved.
| OR nodes above the diaphragm with spleen involvement.
251
What is meant by stage IV NHL?
Disease with additional non-contiguous extra-lymphatic involvement.
252
Summary of NHL management?
- chemoimmunotherapy
- radiotherapy
- autologous haematopoeitic stem cell transplant (for recurrent disease)
- tumour lysis syndrome prophylaxis
253
What is a common chemoimmunotherapy regimen for NHL?
R-CHOP
- rituximab
- cyclophosphamide
- doxorubicin
- vincristine
- prednisolone
254
Side effects of rituximab?
- infusion reactions
- hep B reactivation
- mucocutaneous reactions
- progressive multifocal leucoencephalopathy
255
Mechanism of action for cyclophosphamide?
- alkylating agent
| - inhibits DNA synthesis through cross-linking of DNA
256
Side effects of cyclophosphamide?
- secondary malignancies
- bone marrow suppression
- infertility
257
Which grade of tumour tends to be more chemosensitive (NHL)?
High grade, aggressive tumours are very chemosensitive.
258
What is multiple myeloma?
Haematological malignancy characterised by clonal proliferation of abnormal plasma cells in the bone marrow. Typically associated with a monoclonal component in the serum / urine (paraprotein). Associated with extra-medullary manifestations.
259
What are some typical extra-medullary manifestations of multiple myeloma?
- osteolytic bone disease
- anaemia
- renal failure
260
What is meant by MGUS?
Monoclonal gammopathy of undetermined significance.
| Refers to excess monoclonal antibody / antibody components without other features of myeloma.
261
What is the link between MGUS and myeloma?
Myeloma is typically preceded by MGUS. Rate of progression from MGUS to malignancy is 1% per year.
262
Which age group is most commonly affected by myeloma?
Older adults - 44% of cases are diagnosed in people aged > 75.
263
Aetiology of myeloma?
Unknown - thought to be a combination of genetics and environmental factors.
264
Risk factors for myeloma?
- increasing age
- Black ethnicity
- MGUS
- family history
- exposure to radiation / petroleum products
265
How does myeloma cause disease?
- genetic mutation results in proliferation of abnormal plasma cells in the bone marrow
- the abnormal cells secrete monoclonal paraprotein (usually IgG)
- abnormal cells may also secrete monoclonal immunoglobulin subunits (light chains)
266
Which immunoglobulin type is most commonly secreted as paraprotein?
IgG
267
What causes myeloma bone disease?
- malignant plasma cells release cytokines which interact with bone marrow stromal cells
- this results in increased osteoclast activity and suppressed osteoblast activity
- this leads to pathological fractures and hypercalcaemia
268
How does myeloma cause renal disease?
- high levels of paraprotein causes damage to the renal tubules
- hypercalcaemia also impairs renal function
269
How does myeloma cause hyperviscosity?
Due to the large amount of immunoglobulins in the blood.
270
Signs and symptoms of myeloma?
- anaemia (fatigue)
- bone pain
- symptoms of hypercalcaemia
- weight loss
- symptoms of hyperviscosity
- pathological fractures
- recurrent infections
271
What are some symptoms of hypercalcaemia?
- bone pain
- abdominal pain
- depression
- confusion
- muscle weakness
- thirst
- polyuria
272
What are some symptoms of hyperviscosity?
- headache
- visual changes
- cognitive impairment
- breathlessness
273
Example of a neurological complication of myeloma?
Spinal cord compression - sensory loss, paraesthesia, limb weakness.
274
What investigations should be done for myeloma?
- serum paraprotein electrophoresis
- Bence-Jones protein (light chain) in urine
- whole body low dose CT / skeletal survey
- bone marrow biopsy (monoclonal plasma cells > 10%)
- serum calcium (elevated)
- FBC (normocytic, normochromic anaemia)
275
Which investigation can inform prognosis?
serum beta2-microglobulin (elevation)
276
What type of disease course does myeloma typically follow?
Relapsing-remitting course.
277
Summary of myeloma management?
- inducing remission (combined chemotherapy and non-chemotherapy agents)
- maintenance therapy
- supportive therapy for bone disease and renal failure
278
How is remission induced in myeloma?
- chemotherapy in combination with another agent such as dexamethasone
- some regimens only involve non-chemotherapy agents (e.g. thalidomide and dexamethasone)
- stem cell transplant
279
Example of a drug used in myeloma maintenance therapy?
Thalidomide
280
How is myeloma bone disease managed?
- bisphosphonates
- denosumab
- radiotherapy to lesions for pain management
- surgical treatment of fractures / prophylactic rod insertion to stabilise bones
- cement augmentation of vertebral lesions / fractures to improve stability and pain
281
Mechanism of action of denosumab?
Monoclonal antibody that binds to and inhibits RANK ligand.
282
How is MGUS monitored?
Serum / urine electrophoresis every 6 - 12 months.
283
What is malaria?
Infectious disease caused by members of the Plasmodium family of protozoan parasites.
284
Which organisms cause malaria in humans?
- plasmodium falciparum
- plasmodium vivax
- plasmodium ovale
- plasmodium malariae
285
Which organism causes the most severe form of malaria?
Plasmodium falciparum
286
What is the pathophysiology (including the life cycle) of malaria?
- feeding mosquito uptakes infected blood
- malaria reproduction produces thousands of sporozoites in the gut of the mosquito
- when the mosquito bites a human, the sporozoites are injected into their blood
- sporozoites mature in the liver and become merozoites
- merozoites infect RBCs over 48 hours, which then rupture and release more merozoites into the blood
- release of merozoites causes haemolytic anaemia and a high fever spike
287
How often do fever spikes occur in malaria?
Every 48 hours (with the reproduction cycle of merozoites).
288
What is meant by hypnozoites?
Sporozoites that lie dormant in the liver for several years (this may occur in infections caused by P. vivax and P. ovale).
289
What are three risk factors for becoming infected with malaria?
- travel to / living in an endemic area
- inadequate chemoprophylaxis
- no bed net use in an endemic area
290
What are four risk factors for severe disease with malarial infection?
- immunocompromised
- older age
- age < 5 years
- pregnancy
291
How long does the incubation period of malaria last?
1-4 weeks
292
What are some signs and symptoms of malaria?
- fever, sweats and rigors
- malaise
- myalgia
- headache
- vomiting
- jaundice
- hepatosplenomegaly
293
Gold standard investigation for malaria?
Malaria blood film - three samples must be taken over three consecutive days (48 hour reproduction cycle of merozoites).
294
How is uncomplicated malaria managed?
- oral quinine sulphate
| - oral doxycycline
295
How is severe / complicated malaria managed?
- IV artesunate
| - IV quinine dihydrochloride
296
Examples of prophylactic anti-malarial medication?
- malarone (proguanil & atovaquone)
- mefloquine
- doxycycline
297
What are some complications of plasmodium falciparum malaria?
- seizures, coma
- AKI
- pulmonary oedema
- disseminated intravascular coagulopathy
- multi-organ failure and death
298
What do bite cells on a blood smear indicate?
G6PD deficiency.
299
What do tear drop cells on a blood smear indicate?
Myelofibrosis
300
What is seen on a blood smear in B12 deficiency anaemia?
- macrocytic, megaloblastic cells
| - hypersegmented neutrophils
301
How long do vitamin B12 stores last?
2 - 5 years
302
What clotting factors are vitamin K dependent?
1972 (factors 10, 9, 7, and 2)
303
Mnemonic for myeloma clinical presentation?
Old CRAB
- hypercalcaemia
- renal injury
- anaemia
- bone destruction
304
Mnemonic for symptoms of hypocalcaemia?
CATs go numb
- convulsions
- arrhythmias
- tetany
- numbness
305
What eponymous signs are seen in hypocalcaemia?
- Chvostek's
| - Trousseau's
306
What is Chvostek's sign?
- facial muscle twitch
| - occurs when tapping an individual's cheek in front of the ear
307
What is Trousseau's sign?
- involuntary contraction of the muscles in the hand and wrist
- occurs after the compression of the upper arm with a BP cuff
308
What do Heinz bodies on a blood smear indicate?
G6PD deficiency
309
What type of autoantibody is usually involved in warm AIHA?
IgG
310
What are some secondary causes of polycythaemia?
- alcohol
- chronic hypoxia (obstructive sleep apnoea, smoking, high altitude)
- EPO secreting tumours
311
What is haemolytic uraemic syndrome?
Triad consisting of:
- microangiopathic haemolytic anaemia
- thrombocytopenia
- renal impairment
312
What causes haemolytic uraemic syndrome?
Diarrhoea-associated. Usually caused by Shiga toxin-producing E. coli.
313
What age group is most commonly affected by haemolytic uraemic syndrome?
Children
314
What is seen on the peripheral blood smear for HUS?
Schistocytes - circulating RBC fragments.
315
In what conditions might schistocytes be seen on a blood smear?
- haemolytic uraemic syndrome
| - thrombotic thrombocytopenic purpura
316
What type of blood film is used to diagnose malaria?
Giemsa stained thin / thick blood films.
317
How is mild malaria treated?
Oral hydroxychloroquine.
318
What is polycythaemia vera?
Inherited myeloproliferative disorder caused by the clonal proliferation of all three blood cell lines. Characterised by an elevation in RBC mass with increased Hb concentration / haematocrit. There may also be an increase in platelets and leucocytes.
319
Causes of primary polycythaemia?
Inherited or acquired mutation - polycythaemia vera is caused by a JAK2 mutation.
320
Causes of secondary polycythaemia?
Hypoxia-induced: smoking, chronic lung disease, obesity, obstructive sleep apnoea.
EPO increase: tumours, illicit EPO use, androgen use.
321
What is relative polycythaemia?
Caused by a decrease in plasma volume - increase in haematocrit / Hb with normal RBC mass.
322
Pathophysiology of polycythaemia?
Elevated red blood cell mass causes increased blood viscosity.
323
Signs and symptoms of polycythaemia?
- headache
- fatigue
- visual blurring / transient blindness
- pruritus
- thrombotic events (portal vein thrombosis)
- microvascular thrombotic events (pain and redness of hands and feet)
- paraesthesia
- splenomegaly
- haemorrhage (faulty platelets made in polycythaemia vera)
324
Investigations for polycythaemia?
- genetic testing for JAK2 mutation
- FBC
- serum EPO (elevated in secondary causes)
- bone marrow biopsy
- LFTs (may be deranged due to Budd-Chiari syndrome)
325
Management of polycythaemia?
- venesection
- cytoreductive therapy with hydroxycarbamide
- low dose aspirin (75mg) for thromboprophylaxis
326
Complications of polycythaemia?
- thrombotic events
- myelofibrosis
- transformation to AML
327
What is immune thrombocytopenic purpura?
Haematological disorder characterised by isolated thrombocytopenia in the absence of an identifiable cause. Occurs secondary to an autoimmune phenomenon in which platelets are destroyed by autoantibodies.
328
What type of hypersensitivity reaction is immune thrombocytopenic purpura?
Type III
329
Signs and symptoms of ITP?
- bleeding (from the gums, epistaxis, menorrhagia)
- bruising
- petechial / purpuric rash (non-blanching lesions)
330
Petechial vs purpuric?
Petechial - 1mm spots.
| Purpuric - 3-10mm spots.
331
Typical patient with ITP?
Child under 10 with preceding viral illness.
332
Investigations for ITP?
FBC - low platelet count.
333
Management of ITP?
```
Watchful waiting in stable patients.
Active bleeding / severe thrombocytopenia:
- prednisolone
- IVIG
- blood transfusions
- platelet transfusion (temporary fix)
```
334
Contradindications in ITP?
- IM injection
- lumbar puncture
- NSAIDs / aspirin
- blood thinning medications
335
What is thrombotic thrombocytopenic purpura?
Microangiopathy in which tiny blood clots develop throughout the small vessels of the body. This uses up platelets, resulting in thrombocytopenia.
336
Cause of TTP?
Deficiency in ADAMTS13 protein due to genetic mutation or autoimmune disease.
337
Pathophysiology of TTP?
- ADAMTS13 normally inactivates von Willebrand factor, reducing platelet adhesion to vessel wall and reducing clot formation
- deficiency leads to vWF overactivity, with clots forming in small vessels causing thrombocytopenia
- haemolytic anaemia occurs due to red blood cell damage when blood flows around the clots
338
Management of TTP?
- plasma exchange
- steroids
- rituximab
339
What is von Willebrand disease?
Autosomal dominant disorder causing haemophilia due to vWF deficiency.
340
Pathophysiology of von Willebrand disease?
Deficiency of vWF, which normally acts to:
- bind to factor VIII, platelet surface glycoproteins, and connective tissue constituents
- stabilise factor VIII in the circulation
- mediate platelet adhesion and aggregation in response to endothelial damage
Results in bleeding!
341
Clinical manifestations of von Willebrand disease?
- bleeding gums
- menorrhagia
- epistaxis
342
Day-to-day management of von Willebrand disease?
Does not require day-to-day management.
343
Management of major bleeding in vWF disease?
- desmopressin stimulates vWF release
- vWF infusion
- factor VIII infusion
344
Management of menorrhagia in vWF disease?
- tranexamic acid
- combined oral contraceptive pill
- hysterectomy
345
What is haemophilia?
Inherited severe bleeding disorders caused by clotting factor deficiencies.
346
What group of patients are almost exclusively affected by haemophilia?
Males - due to X-linked inheritance.
347
Genetic cause of haemophilia A?
Factor VIII deficiency
348
Genetic cause of haemophilia B?
Factor IX deficiency
349
How does haemophilia present?
Neonates or early childhood:
- intracranial haemorrhage
- haematoma
- cord bleeding
350
Where might abnormal bleeding occur in haemophiliacs?
- joints (causing damage and deformity)
- muscles
- gums
- GI tract
- urinary tract (causing haematuria)
- retroperitoneal space
- intracranial
- procedures / surgery
351
Investigations for haemophilia?
- bleeding scores
- coagulation factor assays
- genetic testing
352
Management of haemophilia?
- IV clotting factor infusions
| - also desmopressin and tranexamic acid in acute episodes of bleeding
353
Causes of thrombocytopenia?
- sepsis
- B12 / folate deficiency
- liver failure
- leukaemia
- drugs (methotrexate, sodium valproate)
- alcohol
- ITP / TTP
- haemolytic-uraemic syndrome
354
Clinical manifestations of thrombocytopenia?
- easy / spontaneous bruising
- prolonged bleeding
- epistaxis
- bleeding gums
- menorrhagia
- haematuria
- blood in stool
With very low platelet count (< 10):
- high risk of spontaneous bleeding
- intracranial haemorrhage
- GI bleeding
355
What is beta thalassaemia?
Reduced / absent production of the beta globin chains in haemoglobin.
356
What is beta thalassaemia minor?
Patients have one abnormal copy of the beta globin gene. They are usually asymptomatic with mild anaemia.
357
What is beta thalassaemia intermedia?
Patients have two abnormal copies of the beta globin gene: both associated with reduced (not absent) production. Usually non-transfusion dependent.
358
What is beta thalassaemia major?
Patients have two abnormal copies of the beta globin gene: both associated with absent production. Patients are transfusion dependent.
359
Cause of beta thalassaemia?
Autosomal recessive inheritence.
360
Pathophysiology of beta thalassaemia?
- absence of beta globin chain production leads to an alpha/beta chain imbalance and chronic haemolytic anaemia (excess alpha chains form unstable tetramers, causing premature RBC destruction)
- erythropoiesis is ineffective and RBC survival is reduced
- increased iron absorption results in iron overload
- extramedullary haematopoiesis occurs in the spleen, liver and skull
- there is production of HbA2 (with delta chains) and HbF (gamma chains) but this is insufficient to meet the demands of the body
361
Signs and symptoms of beta thalassaemia?
- anaemia (pallor, dyspnoea, dizziness, lethargy)
- jaundice
- gallstones
- bone pain
- osteopenia / osteoporosis
- facial deformity (frontal bossing) due to extramedullary haematopoiesis
362
Complications of beta thalassaemia?
- iron overload (hepatic impairment, heart failure, arrhythmias)
- thrombotic events
- obstructive / restrictive pulmonary disease
363
Investigations for beta thalassaemia?
- FBC (low Hb, low MCV, low reticulocytes)
- blood film (hypochromic, microcytic RBCs)
- haemolysis screen (raised LDH, low haptoglobin, negative DAT)
- genetic testing
- Hb electrophoresis
364
Screening for beta thalassaemia?
Level of maternal HbA2 measured at 10 weeks gestation.
365
Management of beta thalassaemia?
- blood transfusions every 2-3 weeks
- iron chelation therapy
- splenectomy
- manage hepatic / cardiac / pulmonary complications
366
What Hb levels are considered anaemic?
Men < 130
| Women < 120
367
Blood film sideroblastic anaemia?
Ringed sideroblasts
368
Primary haemostasis vs secondary haemostasis?
Primary - formation of platelet plug.
| Secondary - formation of fibrin clot via activation of the coagulation cascade.
369
What initially activates platelets?
Collagen binds to GPVI / GPIIbIIIa receptors on platelets via von Willebrand factor.
370
How is platelet activation amplified?
- ADP binds to P2Y12 / P2Y1 receptors
- platelets form GPIIb/IIa cross bridges
- thrombin binds to PAR1 / PAR4 receptors
- thromboxane binds to TPa receptors
371
Effects of platelet activation?
- platelets change shape and become spiculated, with projections increasing interlinking with other platelets
- dense granules are released, containing ADP for further P2Y12 activation
- alpha granules are released, containing inflammatory mediators and clotting factors
372
Mechanism of clopidogrel / ticagrelor?
Inhibit P2Y12 binding
373
How do NSAIDs inhibit clotting?
Inhibit thromboxane formation.
374
Intrinsic pathway of the coagulation cascade?
12 > 11 > 9 > 8 > 10 > 10a
375
What initiates the intrinsic pathway of the coagulation cascade?
Endothelial collagen exposure
376
What initiates the extrinsic pathway of the coagulation cascade?
Tissue factor (III) expressed by immune cells and endothelium.
377
Extrinsic pathway of the coagulation cascade?
Trauma activates factor VII.
| VIIa and tissue factor activate X.
378
Common pathway of the coagulation cascade?
10a > prothrombin > thrombin > fibrinogen > fibrin (reinforced by factor 13)
379
Function of factor 13?
Reinforces fibrin.
380
What would be seen on a blood smear in TTP?
Schistocytes
381
What is disseminated intravascular coagulation?
Widespread activation of the clotting cascade and platelets, caused by systemic inflammation or infection. Characterised by microvascular thrombosis.
382
Presentation of DIC?
- bleeding (epistaxis, bruising, rash, GI bleeding)
| - acute respiratory distress syndrome
383
Investigations for DIC?
Bloods: low platelets, low fibrinogen, D-dimer elevated, long prothrombin time.
Blood smear - schistocytes.
384
Treatment of DIC?
- treat underlying cause
- cryoprecipitate for low fibrinogen
- platelet transfusion
385
When is lymphadenopathy in Hodgkin's lymphoma painful?
Drinking alcohol
386
What drug can be used as chemotherapy in ALL?
Methotrexate
387
Which leukaemia has CNS infiltration?
ALL
- headaches
- cranial nerve palsies
388
Hallmarks of AML?
- gum hypertrophy
| - Auer rods
389
How is splenic sequestration treated?
Oxygen, IV morphine, IV fluids.
| Blood transfusion / splenectomy.
390
What does antithrombin inhibit?
II, IX, X
391
What is the most common inherited thrombophilia?
Factor V Leiden
392
Inheritance of factor V Leiden?
Autosomal dominant with incomplete penetrance.
393
Skin sign of antiphospholipid syndrome?
Livedo reticularis
394
What is heparin-induced thrombocytopenia?
Following heparin administration, antibodies bind to the heparin-platelet factor 4 complexes. This results in a prothrombotic state, leading to thrombocytopenia.
395
Management of heparin-induced thrombocytopenia?
- stop heparin
| - give anticoagulation
396
Investigations for heparin-induced thrombocytopenia?
- low platelet count
| - high D-dimer
397
Clinical features of tumour lysis syndrome?
- hyperuricaemia
- hyperkalaemia
- hyperphosphataemia
- hypocalcaemia
- AKI
398
What is essential thrombocythaemia?
Elevated platelet count - 50% have a JAK-2 mutation resulting in constant stimulation of platelet production by thrombopoietin.
399
Stimulator of platelet production?
Thrombopoietin (made by the liver).
400
Investigations for essential thrombocytaemia?
- FBC (elevated platelets)
- genetic testing for JAK2 mutation
- bone marrow biopsy
