Passmedicine Flashcards
1
Q
What is multiple myeloma a neoplasm of?
A
Bone marrow plasma cells
2
Q
What age group does multiple myeloma mostly affect?
A
60-70 year olds
3
Q
What are the clinical features of MM?
A
Remember using mnemonic CRABBI -
C = Calcium - hypercalcaemia due to increased osteoclast activity
R = Renal - monoclonal production of Ig –> light chain deposition in renal tubules (presents as dehydration + increasing thirst), other causes of renal impairment - amyloidosis, nephrocalcinosis, nephrolithiasis
A = anaemia (due to bone marrow crowding –> suppression of erythropoiesis) –> fatigue, pallor
B = bleeding (bone marrow crowding –> thrombocytopenia –> inc. risk bleeding/bruising)
B = bones (bone marrow infiltration by plasma cells + cytokine mediated osteoclast overactivity –> lytic bone lesions) –> pain + increased risk of fragility fractures
I = infection (a reduction in production of normal Ig –> susceptibility to infection)
Others - hyperviscosity
4
Q
What is the most common type of non-hodgkins lymphoma in the UK?
A
Diffuse large B cell lymphoma
5
Q
Is diffuse large B cell high grade or low grade and what does this mean?
A
It is high grade, i.e. aggressive
6
Q
Who does Burkitt lymphoma tend to affect?
A
Immunocompromised or young patients
7
Q
What is the typical presentation of follicular lymphoma?
A
It is relatively common but low grade and therefore very slow growing
8
Q
How does cutaneous T cell lymphoma present?
A
With skin changes
9
Q
Define lymphoma
A
Malignant proliferation of lymphocytes in lymph nodes/other organs
10
Q
What are the two broad categories of lymphoma
A
Hodgkins
Non-hodgkins
11
Q
What is Hodgkins lymphoma?
A
Specific type of lymphoma characterised by Reed-Sternberg cells
12
Q
How can you further classify non-hodgkins lymphoma?
A
By whether it affects B or T cells
By whether it is high or low grade
13
Q
True or false:
Hodgkins lymphoma is more common than non-hodgkins lymphoma
A
False
14
Q
Who does non-hodgkins lymphoma tend to affect?
A
Older people (>75 especially) Slightly more common in men
15
Q
What are risk factors for developing a non-hodgkins lymphoma?
A
Elderly Caucasian History of viral infections FH Chemical agents, e.g. pesticides, solvents Hx of chemo/radiotherapy Immunodeficiency (HIV, transplant, DM) Autoimmune dx (SLE, Sjogren's, coeliac dx)
16
Q
What virus is associated with non-hodgkins lymphoma?
A
EBV
17
Q
What are the symptoms of non-hodgkins lymphoma?
A
Painless lymphadenopathy (non-tender, rubbery, asymmetrical) Constitutional B symptoms (fever, wt loss, night sweat, lethargy) Extranodal disease (gastric - dyspepsia, dysphagia, wt loss, ab pain, bone marrow - pancytopenia, bone pain, lungs, skin, CNS (nerve palsies))
18
Q
What clinical signs may indicate one of hodgkins or non-hodgkins lymphoma is more likely than the other?
A
Lymphadenopathy in HL can experience alcohol induced pain in the node
B symptoms typically occur earlier in HL
Extra-nodal disease more common in NHL
19
Q
What are the signs of non-hodgkins lymphoma?
A
Wt loss
Lymphadenopathy (esp. cervical, axillary, inguinal)
Palpable abdominal mass - hepatomegaly, splenomegaly or LNs
Testicular mass
Fever
20
Q
What is the diagnostic investigation of choice in non-hodgkins lymphoma?
A
Excisional node biopsy
21
Q
What other investigations should you do in non-hodgkins lymphoma and why?
A
CT chest, abdo, pelvis (staging)
HIV test (risk factor)
FBC + blood film (check for normocytic anaemia which would rule out other haematological malignancy e.g. leukaemia)
ESR (prognostic indicator)
LDH (marker of cell turnover, prognostic indicator)
Others -
LFTs if liver mets suspected, PET CT or bone marrow biopsy to look for bone involvement, LP in neuro involvement)
22
Q
What is the name of the staging system used in non-hodgkins lymphoma?
A
Ann Arbor
23
Q
What is the Ann Arbor classification for staging non-hodgkins lymphoma?
A
Stage 1: 1 node affected
Stage 2: >1 node affected on same side of diaphragm
Stage 3: 1 node affected on either side of diaphragm
Stage 4: extranodal involvement, e.g. spleen, bone marrow, CNS
Stage combined with A/B
A = no B symptoms
B = B symptoms
24
Q
What is the management of non-hodgkins lymphoma?
A
Depends on subtype
Involves watchful waiting, chemo or radio
Patients will get flu/pneumococcal vaccines
Those with neutropenia may req. prophylactic antibiotics
25
What are the possible complications of non-hodgkins lymphoma?
Bone marrow infiltration --> anaemia, neutropenia, thrombocytopenia
SVC obstruction
Mets
Spinal cord compression
Complications related to Rx, e.g. SEs of chemo
26
What is the appearance of the neutrophils in a megaloblastic anaemia?
Hypersegmented neutrophils
27
What do you see on blood film in an intravascular haemolysis?
Schistocytes
28
What do you see on blood film in myelofibrosis?
Tear drop poikilocytes
29
What do you see on blood film in iron deficient anaemia?
Target cells
| Pencil poikilocytes
30
What do you see on blood film in hyposplenism?
```
Target cells
Howell-Jolly bodies
Pappenheimer bodies
Siderotic granules
Acanthocytes
```
31
What test is most likely to confirm the diagnosis of megaloblastic anaemia?
Haematinics (B12 and folate)
32
What are the crises than can occur in sickle cell disease?
```
Thrombotic (painful crises)
Sequestration
Acute chest syndrome
Aplastic
Haemolytic
```
33
What are thrombotic crises? (sickle cell disease)
Aka. painful/vaso-occlusive crises
Precipitated by infection, dehydration deoxygenation
Infarcts occur in various organs + bones (AVN of hip, hand foot syndrome in children, lungs, spleen, brain)
34
What are sequestration crises? (sickle cell disease)
Sickling with organs, e.g. spleen/lungs causes pooling of blood and worsening of anaemia
35
What is acute chest syndrome? (sickle cell disease)
Dyspnoea, chest pain, pulmonary infiltrates, low pO2
36
What is an aplastic crisis? (sickle cell disease)
Caused by infection with parovirus
| Sudden fall in Hb
37
What is a haemolytic crisis? (sickle cell disease)
Rare
| Fall in Hb due to increased rate of haemolysis
38
In which ethnicity is G6PD deficiency most common?
Mediterranean, African
39
How is G6PD deficiency inherited?
X-linked recessive
40
What is the pathophysiology of G6PD deficiency?
Reduced G6PD --> reduced gluthathione --> increased red cell susceptibility to oxidative stress
41
What are the features of G6PD deficiency?
Neonatal jaundice
IV haemolysis
Gallstones
Splenomegaly
42
What can you see on blood films in G6PD deficiency?
Heinz bodies
| Bite + blister cells
43
How do you diagnose G6PD deficiency?
G6PD enzyme assay
44
What drugs can cause haemolysis in G6PD deficiency?
Anti-malarials (primaquine)
Ciprofloxacin
Sulphonamides, sulphasalazine, SUs
45
How is hereditary spherocytosis inherited?
Autosomal dominant
46
What is the typical history of hereditary spherocytosis?
Neonatal jaundice
Chronic symptoms although haemolytic crises may be precipitated by infection
Gallstones
Splenomegaly
47
What do you see on blood film in hereditary spherocytosis?
Spherocytes
48
How do you diagnose hereditary spherocytosis?
Osmotic fragility tests
49
What investigations should you do in suspected MM and what will they show?
FBC - anaemia, thrombocytopenia
U+E - raised urea and creatinine
Bone profile - raised Ca
Serum/urine protein electrophoresis - raised concentrations of monoclonal IgA/IgG (in the urine they are known as Bence Jones Proteins)
50
What investigation is required to make a diagnosis of MM?
Bone marrow aspiration and trephine biopsy
51
Aside from the initial investigations and the bone marrow aspiration to confirm the diagnosis of MM, what other investigation should be done?
Whole body MRI to survey the skeleton for bone lesions
52
What is a common x-ray finding in MM?
Rain-drop skull (due to numerous randomly placed dark spots due to bone lysis)
53
What 3 things define MM?
Monoclonal plasma cells in bone marrow >10%
Monoclonal protein within the serum/urine
Evidence of end organ damage, e.g. hypercalcaemia, elevated Cr, anaemia, lytic bone lesions/fractures
54
How is MM cured?
It cannot be cured - management aims to control symptoms and prolong life
55
For those suitable for autologous stem cell transplantation what is the induction therapy for MM?
Bortezomib and dexamethasone
56
For those unsuitable for autologous stem cell transplantation what is the induction therapy for MM?
Thalidomide and an alkylating agents and dexamethasone
57
What MM patients are typically suitable for autologous stem cell transplant?
Younger, healthier patients
58
What happen after MM patients are treated?
Monitored 3mnthly
| Often go into remission for a long while
59
If an MM patient relapses after initial treatment what is the first line recommended treatment?
Bortezomib monotherapy
Some patients may also be suitable for a repeat autologous stem cell transplant
60
How is pain in MM treated?
Analgesia
61
How are pathological fractures in MM prevented/managed?
Zoledronic acid
62
What prophylaxis/vaccinations do MM patients recieve?
Flu vaccines
| VTE prophylaxis
63
What are the major and minor criteria for diagnosing MM and how many do you need of each for a diagnosis?
MAJOR -
- Plasmacytoma (as demonstrated on biopsy)
- 30% plasma cells in bone marrow sample
- Elevated levels of M protein in blood/urine
MINOR -
- 10-30% plasma cells in bone marrow
- Minor elevations in level of M protein in blood/urine
- Osteolytic lesions
- Low levels of antibodies in blood
1 major + 1 minor or 3 minor in an individual with signs/symptoms of MM
64
What largely causes hypercalcaemia in MM?
Increased osteoclastic bone resorption caused by local cytokines released by myeloma cells
65
What complications may patients develop after a DVT (post-thrombotic syndrome)?
Venous outflow obstruction, venous insufficiency --> chronic venous HTN
66
What features may be seen in post-thrombotic syndrome?
```
Painful, heavy calves
Pruritus
Swelling
Varicose veins
Venous ulceration
```
67
What treatment may be used in post-thrombotic syndrome?
Compression stockings
| Keeping the leg elevated
68
What are the classifications of blood production transfusion complications?
Immunological - acute haemolytic, non-haemolytic febrile, allergic/anaphylaxis
Infective
TRALI
TACO
Others - hyperkalaemia, iron overload, clotting abnormalities
69
What does acute haemolytic transfusion reaction result from?
Mismatch of blood group (ABO) --> massive intravascular haemolysis (usually due to RBC destruction by IgM type antibodies)
70
When do the symptoms of AHTR occur?
Minute after transfusion is started
71
What are symptoms of AHTR?
```
Fever
Abdominal pain
Chest pain
Agitation
Hypotension
```
72
What is the treatment of AHTR?
Immediate transfusion termination
| Generous fluid resus with saline
73
What are complications of AHTR?
DIC, renal failure
74
What causes non-haemolytic febrile reactions?
White blood cell HLA antibodies
| Often the result of sensitization by previous pregnancies or transfusions
75
How is non-haemolytic febrile reaction managed?
Paracetamol
76
When do symptoms of allergic/anaphylactic reactions to blood products begin?
Minutes after starting the transfusion
77
What are symptoms of allergic/anaphylactic reactions to blood products?
Urticaria --> anaphylaxis with hypotension, SoB, wheezing, stridor or angioedema
78
How should simple urticaria as a result of allergic reactions to blood products be treated?
Stop transfusion, antihistamine
| After symptoms resolve, can continue transfusion
79
How should more severe allergic/anaphylactic reactions to blood products be treated?
Permanently discontinue transfusion
IM adrenaline
Supportive care
Consider antihistamines, corticosteroids, bronchodilators
80
What is TRALI?
Transfusion related acute lung injury
| Defined as development of hypoxaemia/acute respiratory distress syndrome within 6 hours of transfusion
81
What are features of TRALI?
Hypoxia
Pulmonary infiltrates on CXR
Fever
Hypotension
82
What causes TACO (transfusion associated circulatory overload)?
Fluid overload --> pulmonaryoedema
83
What are features of TACO?
Features of pulmonary oedema + hypertension (key different from TRALI)
84
What virus may be transmitted by blood transfusion (rarely)?
vCJD
85
What steps have been taken to reduce the risk of vCJD being spread through blood products?
Leuodepletion (all white cells removed)
Plasma derivatives have been fractionated from imported FFP
Children/other group have imported FFP
Recipients of blood components cannot donate blood
86
What are causes of severe thrombocytopenia?
ITP
DIC
TTP
Haematological malignancy
87
What are causes of moderate thrombocytopenia?
```
Heparin induced thrombocytopenia (HIT)
Drug induced (e.g. quinine, diuretics, sulphonamides, aspirin, thiazides)
Alcohol
Liver disease
Hypersplenism
Viral infection (e.g. HIV, EBV, hepatitis)
Pregnancy
SLE/antiphospholipid syndrome
Vit B12 deficiency
```
88
Why is thrombocytopenia in liver disease a common finding?
Splenomegaly (due to portal hypertension) --> larger SA for splenic sequestration of thrombocytes
Thrombopoietin deficiency as liver as damaged
89
In which haematological malignancy is the philadelphia chromosome present in more than 95% of patients?
CML
90
What is the philadelphia chromosome?
Translocation between the long arm of chromosome 9 and 22 (ABL proto-oncogene from chromo9 being fused with BCR gene from chromo22) --> BCR-ABL genes for a fusion protein which has tyrosine kinase activity in excess of normal
91
At what age does CML tend to present?
60-70 years
92
What are the typical features of CML?
Anaemia --> lethargy
Wt loss, sweating
Splenomegaly --> abdominal discomfort
93
Burkitt's lymphoma is a neoplasm of what cells?
B cells
94
Is Burkitt's lymphoma high or low grade?
High grade
95
What are the two forms of Burkitt's lymphoma?
Endemic (African) form - usually involves maxilla and mandible
Sporadic form - abdominal tumours most common, more common in those with HIV
96
What gene translocation is Burkitt's lymphoma associated with?
c-myc gene translocation (usually t(8:14)
97
What virus is strongly associated with Burkitt's lymphoma?
EBV
98
What microscopic findings do you see in Burkitt's lymphoma?
Starry sky appearance (lymphocyte sheets interspersed with macrophages containing dead apoptotic tumour cells)
99
How is Burkitt's lymphoma managed?
Chemotherapy
100
What is a common complication of Burkitt's lymphoma?
Tumour lysis syndrome
101
What drug may be given to those undergoing chemotherapy to prevent tumour lysis syndrome?
Rasburicase (recombinant urate oxidase (an enzyme which catalyses conversion of uric acid to allantoin)
102
What are complications of tumour lysis syndrome?
```
Hyperkalaemia
Hyperphosphataemia
Hypocalcaemia
Hyperuricaemia
Acute renal failure
```
103
What causes tumour lysis syndrome?
Cell breakdown following chemotherapy which leads to release of large amount of intracellular components, e.g. K, phosp, uric acid
104
What is the first line treatment for most individuals with a VTE?
DOACs
105
What score should be calculated if a patient is suspected of having had a DVT?
Two level DVT Wells score
106
What is the two level wells score?
INSERT TABLE FROM PASSMED!!
107
What wells score indicates DVT is unlikely?
1 point or less
108
What wells score indicates DVT is likely?
2+
109
If DVT is 'likely' then what action should follow?
Proximal leg vein USS within 4h
If +ve --> diagnose DVT + start anticoagulants
If -ve --> D-dimer
If D-dimer + scan negative --> DVT unlikely
Scan -ve, d-dimer +ve --> stop interim therapeutic anticoagulation, repeat proximal leg vein USS in 6-8 days
110
If DVT is 'likely' and a proximal leg vein USS cannot be arranged what action should follow?
Give therapeutic anticoagulation in the interm (DOAC)
111
If DVT is 'unlikely' what action should follow?
D-dimer test within 4h (if not interim therapeutic anticoagulation)
If -ve --> DVT unlikely
If +ve --> proximal leg vein USS within 4h
112
What kinds of d-dimer tests do NICE recommend?
Point of care (finger prick) or lab based
113
What DOACs are offered first line for management of DVT?
Apixiban or rivaroxaban
114
If apixiban and rivaroxaban are CI for the treatment of DVT, what can be given?
LMWH, then followed by dagibatran or edoxaban or LMWH followed by vit K antagonist, e.g. warfarin
115
How is DVT in severe renal impairment managed?
LMWH, UF or LMWH followed by a VKA
116
How is DVT in a patient with antiphospholipid syndrome managed?
LMWH followed by VKA
117
All patients with DVT should be anticoagulated for how long?
At least 3 months
118
What is the difference between a provoked and unprovoked DVT?
Provoked - obvious precipitating event, e.g. immobilisation after surgery (implied after this pt no longer at risk)
Unprovoked - absence of obvious precipitating event, i.e. possibility of unknown factors making patient at risk of further clots
119
When is anticoagulation stopped for provoked DVTs?
After initial 3 months
| 3-6m for those with cancer
120
When is anticoagulation stopped for unprovoked DVTs?
Typically continued for a further 3 months
121
What score can be used to help to assess the risk of bleeding in a patient following a DVT?
HAS-BLED
122
What patients are not offered thrombophilia screening after a DVT?
Those on lifelong warfarin as it won't alter the management
123
What might you consider testing for in an unprovoked DVT/PE?
Antiphospholipid antibodies
Or hereditary thrombophilia in those who also have a first degree relative who has had a DVT/PE
124
What is polycythaemia vera?
Myeloproliferative disorder caused by clonal proliferation of marrow stem cell leading to an increase in red cell volume (often accompanied by overproduction of neutrophils and platelets)
125
What mutation is present in 95% of cases of polycythaemia vera?
JAK2
126
When does the incidence of polycythaemia vera peak?
60s
127
What are features of polycythaemia vera?
```
Hyperviscosity
Pruritus, typically after a hot bath
Splenomegaly
Haemorrhage (secondary to abnormal platelet function)
Plethoric appearance
HTN in 1/3rd
Low ESR
```
128
What tests should be performed in those suspected of having polycythaemia vera?
FBC/film (raised haematocrit, neutrophils, basophils and platelets in half of patients)
JAK2 mutation
Serum ferritin
Renal + liver function tests
129
In suspected polycythaemia vera:
| If the JAK2 mutation is negative + there is no obvious secondary cause, what tests should be done?
```
Red cell mass
Arterial O2 saturation
Abdominal USS
Serum erythropoietin
Bone marrow aspiration and trephine
Cytogenetic analysis
Erythroid bursting forming unit culture
```
130
What is the criteria for the diagnosis of polycythaemia vera (JAK2+ve)?
Req both criteria:
A1 - high haematocrit (>0.52 in men, >0.48 in women) or raised red cell mass (>25% above predicted)
A2 - mutation in JAK2
131
What is the criteria for the diagnosis of polycythaemia vera (JAK2-ve)?
Req A1+A2+A3 + either another A or two B criteria
A1 - raised RC mass (>25% above predicted) or haematocrit >0.6 in men, >0.56 in women
A2 - absence of mutation in JAK2
A3 - no cause of secondary erythrocytosis
A4 - palpable splenomegaly
A5 - presence of an acquired genetic abnormality (excluding BCR-ABL) in haematopoietic cells
B1 - thrombocytosis
B2 - neutrophil leucocytosis
B3 - radiological evidence of splenomegaly
B4 - endogenous erythroid colonies or low serum erythropoietin
132
What things may cause a relative polycythaeia?
Dehydration and diuretics
133
What complications are associated with CLL?
Anaemia
Hypogammaglobulinaemia --> recurrent infections
Warm autoimmune haemolytic anaemia (10-15%)
Transformation to high grade lymphoma
134
What is transformation of CLL to high grade lymphoma known as?
Richter's transformation
135
What happens in Richter's transformation?
Leukaemia cells enter the LNs and change into high grade, fast growing non-hodgkins lymphoma + patients suddenly become v. unwell
136
What symptoms may indicate a Richter's transformation has taken place?
```
LN swelling
Fever without infection
Wt loss
Night sweats
Nausea
Ab pain
```
137
What is the most common inherited bleeding disorder?
Von Willebrand's diease
138
How are the majority of cases of Von Willebrand's disease inherited?
AD
139
How does Von Willebrand's disease present?
As a platelet disorder, i.e. epistaxis, menorrhagia are common
140
What is von willebrand factor?
Large glycoprotein which forms massive multimers and promotes platelet adhesion to damaged endothelium
Carrier molecule for factor VIII
141
What are the types of Von Willebrand's disease?
Type 1 - partial reduction in vWF (80% of patients)
Type 2 - abnormal form of vWF
Type 3 - total lack of vWF (AR)
142
What will investigations show in Von Willebrand's disease?
Prolonged bleeding time
APTT prolonged
Factor VIII may be moderately reduced
Defective platelet aggregation with ristocetin
143
What treatments are available for Von Willebrand's disease?
Tranexamic acid for mild bleeding
Desmopressin - raises levels of Von Willebrand's factor by inducing its release from Weibel-Palade bodies in endothelial cells
Factor VIII concentrate
144
Transmission of which type of infection is most likely to occur following a platelet transfusion and why?
Bacterial as platelet concentrations are stored at room temp so there is more of a risk of bacterial proliferation
145
What is Hodgkin's lymphoma?
Malignant proliferation of lymphocytes characterised by the presence of the Reed-Sternberg cell
146
What age group is Hodgkin's lymphoma most common in?
Most common in 3rd and 7th decade
147
What are the histological classifications of Hodgkin's lymphoma?
Nodular sclerosing
Mixed cellularity
Lymphocyte predominant
Lymphocyte depleted
148
What is the most common type of Hodgkin's lymphoma?
Nodular slcerosing
149
What type of Hodgkin's lymphoma has the worst prognosis?
Lymphocyte depleted
150
What cells are associated with nodular sclerosing Hodgkin's lymphoma?
Lacunar cells
151
What type of Hodgkin's lymphoma has the best prognosis?
Lymphocyte predominant
152
What kind of symptoms in Hodgkin's lymphoma imply a poor prognosis?
B SYMPTOMS
Wt loss >10% in last 6 months
Fever >38C
Night sweats
153
What are poor prognostic factors in Hodgkin's lymphoma?
```
Age >45
Stage IV disease
Hb <10.5g/dl
Lymphocyte count <600/ul or <8%
Male
Albumin <40g/l
White blood count >15, 000/ul
```
154
What are indications for cryoprecipitate?
Massive haemorrhage
| Uncontrolled bleeding due to haemophilia
155
What does cyroprecipitate contain?
Factor VIII
Fibrinogen
vWF
Factor XIII
156
What causes CLL?
Monoclonal proliferation of well differentiate lymphocytes which are almost always B cells
157
What is the commonest form of leukaemia in adults?
CLL
158
What are features of CLL?
Often none
Constitutional - anorexia, wt loss
Bleeding, infections
Lymphadenopathy more marked than CML
159
What are complications of CLL?
Anaemia
Hypogammglobulinaemia --> recurrent infections
Warm autoimmune haemolytic anaemia (10-15%)
Transformation to high grade lymphoma (Richter's)
160
What investigations should be done for suspected CLL and what will they find?
Blood film - smudge cells (aka smear cells)
| Immunophenotyping
161
What blood film finding is associated with MM?
Rouleaux formation
162
What are the 3 novel oral anticoagulants (NOACs)?
Dabigatran, rivaroxaban and apixaban
163
What is the mechanism of action of dabigatran?
Direct thrombin inhibitor
164
What is the mechanism of action of rivaroxaban?
Direct factor Xa inhibitor
165
What is the mechanism of action of apixiban?
Direct factor Xa inhibitor
166
How are the NOACs excreted from the body?
Dabigatran - mostly renal
Rivaroxaban - mostly liver
Apixaban - mostly faecal
167
What are indications for NOACs?
Prevention of VTE following hip/knee surgery
Treatment of DVT/PE
Prevention of stroke in non-valvular AF (if prior stroke/TIA, age75+, HTN, DM, heart failure)
168
Should compression stockings be routinely offered to all those with DVT?
No
169
In which ethnicity is hereditary spherocytosis most common?
Northern European
170
What is hereditary spherocytosis?
AD defect of RBC cytoskeleton where the biconcave disc is replaced by a sphere spaced RBC --> reduced RBC survivial due to destruction by spleen
171
How does hereditary spherocytosis present?
```
FTT
Jaundice, gallstones
Splenomegaly
Aplastic crisis precipitated by parovirus (severe anaemia, reduced retic count)
Degree of haemolysis variable
MCHC elevated
```
172
What is the investigation of choice for diagnosing hereditary spherocytosis?
Osmotic fragility test (if equivocal --> cyrohaemolyis test + EMA binding)
(But if someone has a FH of HS, typical clinical features + lab investigations (spherocytes, raised MCHC + increased retics) they do not req. additional tets
173
How is an acute haemolytic crisis in hereditary spherocytosis managed?
Supportive
| Transfusion may be req.
174
What is the long term treatment of hereditary spherocytosis?
Folate replacement
| Splenectomy
175
In which condition(s) do you see the following on blood film:
Target cells?
Sickle cell/thalassaemia
Iron deficiency anaemia
Hyposplenism
Liver disease
176
In which condition(s) do you see the following on blood film:
Tear drop poikilocytes?
Myelofibrosis
177
In which condition(s) do you see the following on blood film:
Spherocytosis?
Hereditary spherocytosis
| Autoimmune haemolytic anaemia
178
In which condition(s) do you see the following on blood film:
Basophilic strippling?
Lead poisoning
Thalassaemia
Sideroblastic anaemia
Myelodysplasia
179
In which condition(s) do you see the following on blood film:
Howell-Jolly bodies?
Hyposplenism
180
In which condition(s) do you see the following on blood film:
Heinz bodies?
G6PD deficiency
| Alpha thalassaemia
181
In which condition(s) do you see the following on blood film:
Schisocytes?
IV haemolysis
Mechanical heart valve
DIC
182
In which condition(s) do you see the following on blood film:
Pencil poikilocytes?
Fe deficient anaemia
183
In which condition(s) do you see the following on blood film:
Burr cells?
Uraemia
| Pyruvate kinase deficiency
184
In which condition(s) do you see the following on blood film:
Acanthocytes?
Abetalipoproteinaemia
185
In which condition(s) do you see the following on blood film:
Hypersigmented neutrophils?
Megloblastic anaemia
186
Basics of lymphatic drainage
Superficial lymphatic vessels drain the skin and follow venous drainage
Superficial lymphatic vessels + drainage of internal organs --> deep lymphatic vessels that follow arteries --> LNs --> lymphatic trunks which unite to form right lymphatic duct/thoracic duct
Right lymphatic duct drains R side of head + R arm, thoracic duct does rest
Both lymphatic ducts drain into venous system
187
Where do the superficial inguinal lymph nodes drain?
```
Anal canal below pectinate line
Perineum
Skin of thigh
Penis
Scrotum
Vagina
```
188
Where do the deep inguinal LNs drain?
Glans penis
189
Where do the para-aortic LNs drain?
Testes, ovaries
Kidney
Adrenal gland
190
Where do the axillary LNs drain?
Lateral breast
| Upper limb
191
Where do the internal iliac LNs drain?
Anal canal above pectinate line
Lower part of rectum
Pelvic structures, incl. cervix + inferior part of rectus
192
Where do the superior mesenteric LNs drain?
Duodenum
| Jejunum
193
Where do the inferior mesenteric LNs drain?
Descending colon
Sigmoid colon
Upper rectum
194
Where do the coeliac LNs drain?
Stomach
195
What do you typically see on blood film in G6PD deficiency?
Blister and bite cells
196
Raised ESR and osteoporosis = what until otherwise proven?
MM
197
What is immune thrombocytopenia (ITP) in adults?
Immune-mediated reduction in platelet count
198
What causes ITP?
Antibodies directed against glycoprotein IIb/IIIa or Ib-V-IX complex
199
What are the two forms of ITP?
Acute
| Chronic
200
Who is acute ITP more commonly seen in ?
Children
201
What is the natural course of acute ITP?
Self-limiting course over 1-2 weeks
202
What may acute ITP follow?
Infection/vaccination
203
Who is chronic ITP more common in?
Young/middle aged women
204
What is the course of chronic ITP?
More relapsing/remitting nature
205
What is Evan's syndrome?
ITP in associated with autoimmune haemolytic anaemia
206
What is the most common cause of an isolated thrombocytopenia?
ITP
207
What are the main causes of Fe deficient anaemia?
Blood loss
Inadequate dietary intake, e.g. vegan
Poor intestinal absorption, e.g. coeliac
Increased Fe requirements, e.g. children growing, pregnancy
208
What is the most common cause of blood loss causing Fe deficient anaemia?
Pre-menopausal women - menorrhagia
Men/post-menopausal women - GI blood loss (always suspect colon cancer)
209
What are clinical features of Fe deficient anaemia?
```
Fatigue
SoBoE
Palpitations
Pallor
Nail changes, incl. koilonychia (spoon shaped nails)
Hair loss
Atrophic glossitis
Post-cricoid webs
Angular stomatitis
```
210
What things are really important to ask about in an Fe deficient anaemia?
```
Changes in diet
Medications
Menstrual history
Wt loss
Change in bowel habit
```
211
What does FBC show in an Fe deficient anaemia?
Hypochromic microcytic anaemia
212
What is the ferritin level in Fe deficient anaemia normally?
Low (as serum ferritin correlates with iron stores)
NB - ferritin increased during inflammation
213
What will the total iron binding capacity (TIBC) be in Fe deficient anaemia?
High (high TIBC reflects low iron stores)
214
What will the transferrin saturation be in Fe deficient anaemia?
Low
215
What might you see on blood film in Fe deficient anaemia?
Anisopoikilocytosis (RBCs of different sizes/shapes)
Target cells
Pencil poikilocytes
216
What other investigation should be done in those with Fe deficiency anaemia who are male/post-menopauseal?
Endoscopy to rule out GI cancer
217
How is Fe deficient anaemia managed?
Treat underlying cause
Oral ferrous sulphate (taken until 3m after anaemia corrected to replenish iron stores)
Iron rich diet
218
What foods are rich in iron?
Dark leafy veg, meat, iron fortified bread
219
What are common SEs of iron supplementation?
Nausea, ab pain, constipation, diarrhoea
220
Can tumour lysis syndrome occur even before starting chemotherapy?
Yes - can occur alone or even on initiation of steroid therapy
221
What cancers is tumour lysis syndrome most common in?
High grade leukaemias/lymphomas
222
What medications should be given to those at high risk of TLS?
IV allopurinol or IV rasburicase prior to and during first days of chemo
223
How does rasburicase work?
Converts uric acid into allantoin
| Allantoin much more water soluble than uric acid so more easily excreted by kidneys
224
What should those at low risk of TLS be given?
Oral allupurinol during chemo cycles
225
How does TLS present?
High K, high Phosp, low Ca
| Suspect in any patient with AKI in presence of high phosphate and high uric acid level
226
What grading system is used for TLS?
Cairo-Bishop
227
How is laboratory tumour lysis syndrome defined?
Abnormality in 2+ of the following occuring within 3 days before or 7 days after chemo:
- High uric acid
- High K
- High phosp
- Low ca
228
How is clinical tumour lysis syndrome defined?
Lab tumour lysis syndrome + 1+ of the following:
- Increased serum CK (>1.5x normal)
- Cardiac arrhythmia/suddnen death
- Seizure
229
What is neutropenic sepsis usually a complication of?
Common complication of cancer treatment (usually chemo)
230
When does neutropenic sepsis tend to occur?
7-14 days after chemo
231
Define neutropenic sepsis
Neutrophil count of <0.5x10^9 in a patient having anticancer treatment and who has 1 of the following:
- Temp 38C+
- Other signs/symptoms consistent with significant sepsis
232
Who should be offered prophylaxis against neutropenic sepsis?
Those who are anticipated to have a neutrophil count of <0.5x10^9 due to their treatment
233
What is the prophylaxis for neutropenic sepsis?
Fluoroquinolone
234
How is neutropenic sepsis managed?
Empirical antibiotics (piperacillin + tazobactam) immediately
If still unwell + febrile >48h meropenem prescribed +/- vancomycin
If not responding within 6-8d investigate for fungal infections
May be role for G-CSF in selected patients
235
Should all patients with sickle cell crises be admitted to hospital?
Yes - unless they are a well adult with mild/moderate pain and temp of <=38C or child with no fever + mild pain
236
Who should you have a low threshold for admitting in sickle cell crises?
A child
If temp >38C (risk of rapid deterioriation)
If person has chest symptoms (as acute chest syndrome can develop quickly)
237
What is the general management of a sickle cell crisis?
Analgesia, e.g. opiates
Rehydrate
Oxygen
Consider antibiotics if evidence of infection
Blood transfusion
Exchange transfusion, e.g. if neurological complications
238
What is the abnormality in beta-thalassaemia major?
Absence of beta chains
| defect on chromo 11
239
How does beta-thalasaemia major present?
In first year of life with FTT and hepatosplenomegaly
Microcytic anaemia
HbA2 and HbF raised
HbA absent
240
How is beta-thalasaemia major managed?
Repeated transfusions (--> iron overload so also req. iron chelation with s/c desferrioxamine)
241
What are the types of polycythaemia?
Relative
Primary - PV
Secondary
242
What are causes of secondary polycythaemia?
COPD
Altitude
Obstructive sleep apnoea
Excessive EPO - cerebellar haemangioma, hypernephroma, heptatoma, uterine fibroids
243
What studies are used to differentiate between true and relative polycythaemia?
Red cell mass studies
| true polycythaemia total RC mass >35ml/kg in men, >32ml/kg in women
244
What are the two categories of causes of a macrocytic anaemia?
Megaloblastic causes --> vit B12 deficiency, folate deficiency
Normoblastic causes --> alcohol, liver disease, hypothyroidism, pregnancy, reticulocytosis, myelodysplasia, drugs - cytotoxics
245
What tests might you do if you are suspecting a megaloblastic anaemia?
FBC
Blood film
Haematinics
246
What is the pathophysiology of G6PD deficiency?
Deficiency of glucose-6-phosphate dehydrogenase means red cells have less ability to respond to oxidative stress + therefore live for less time and are more susceptible to haemolysis (particularly in response to drugs, infection, acidosis and certain foods)
247
Who should be offered platelet transfusion?
Those with platelet count <30x10^9 + clinically significant bleeding
Maximum of <100x10^9 for those with severe bleeding/bleeidng in critical sites (e.g. CNS)
May be given to some patients with thrombocytopenia before surgery
If <10x10^9 if no active bleeding/surgery/no alternative medications for their condition
248
In which conditions is platelet transfusion CI?
Chronic bone marrow failure
Autoimmune thrombocytopenia
Heparin induced thrombocytopenia
TTP
249
What haematological malignancy is h. pylori associated with?
Gastric lymphoma (MALT)
250
What cancers is EBV associated with?
Hodgkin's + Burkitt's lymphoma, nasopharyngeal cancer
251
What cancer is HIV associated with?
High grade B cell lymphoma
252
What cancer is malaria associated with?
Burkitt's lymphoma
253
What are the recommended thresholds for transfusion of red cells in patients with and without ACS?
Without - 70g/L
| With - 80g/L
254
In a non-urgent situation how long is a unit of RBC transferred over?
90-120 minutes
255
At what temperature are RBCs stored prior to infusion?
4C
256
Why is it important to transfuse patients who are anaemia and having an ACS?
Anaemia can worsen ischaemia (as less oxygen is carried by haemoglobin)
257
What factors are affected by heparin?
Prevents activation of factors 2, 9, 10, 11
258
What factors are affected by warfarin?
Affects synthesis of factors 2, 7, 9, 10
259
What factors are affected in DIC?
1, 2, 5, 8, 11
260
What factors are affected in liver disease?
1, 2, 5, 7, 9, 10, 11
261
```
What are the typical findings in the following:
a. APTT
b. PT
c. Bleeding time
In haemophilia?
```
APTT - increased
PT - normal
Bleeding time - normal
262
```
What are the typical findings in the following:
a. APTT
b. PT
c. Bleeding time
in von Willebrand disease?
```
APTT - increased
PT - normal
Bleeding time - increased
263
```
What are the typical findings in the following:
a. APTT
b. PT
c. Bleeding time
in vitamin K deficiency?
```
APTT - increased
PT - increased
Bleeding time - normal
264
When might patients receive packed red cells?
Chronic anaemia and cases where large vols of fluid may --> CV compromise
265
How are packed red cells obtained?
Centrifugation of whole blood
266
Who is platelet rich plasma given to?
Thrombocytopaenic patients who are bleeding/req. surgery
267
How is platelet rich plasma obtained?
Low speed centrifugation
268
How is platelet concentrate obtained?
High speed centrifugation
269
Who is given platelet concentrate?
Thrombocytopaenic patients
270
What is FFP prepared from?
Single units of blood
271
What does FFP contain?
Clotting factors
Albumin
Ig
272
How much is a unit of FFP?
200-250ml
273
When is FFP usually used?
To correct clotting deficiencies in those with hepatic synthetic failure who are due to undergo surgery
274
How is cryoprecipitate prepared?
Formed from supernatant of FFP
275
What is SAG-mannitol blood?
Removal of all plasma from a blood unit + substitute with:
- Sodium chloride
- Adenine
- Anhydrous glucose
- Mannitol
276
How many units of SAG-mannitol blood can be transfused?
Up to 4 (use whole blood thereafter, and consider platelets + clotting factors after 8 units)
277
What are cell saver devices?
Devices that collect patients own blood lost during surgery and re-infuse it
278
What are the two types of cell saver devices?
Those which wash blood cells prior to infusion (reduced risk of contamination)
Those which do not
279
When are cell saver devices CI?
In malignant disease due to risk of facilitating disease dissemination `
280
What should be done in immediate/urgent surgery in a patient taking warfarin?
Stop warfarin
Vit K reversal (IV takes 4-6h, oral up to 24h)
FFP (only if human prothrombin is not available)
Human prothrombin complex (reversal within 1h) - give with vit K
281
What should be given in between every other unit of packed red cells and why?
Furosemide (to prevent fluid overload)
282
Which features should prompt a very urgent FBC in someone 0-24 years old to investigate for leukaemia?
```
Pallor
Persistent fatigue
Unexplained fever
Unexplained persistent infections
Generalised lymphadenopathy
Persistent or unexplained bone pain
Unexplained bruising/bleeding
Hepatosplenomegaly
```
283
What is haemophilia?
X-linked recessive disorder of coagulation
284
What is haemophilia A due to?
Deficiency of factor VIII
285
What is haemophilia B due to?
Deficiency of factor IX
286
What are the clinical features of haemophilia?
Haemoarthroses, haematomas
| Prolonged bleeding after surgery/trauma
287
Up to 10-15% of patients with haemophilia A develop what problem?
Develop antibodies against factor VIII treatment
288
What are granulocyte colony stimulating facotrs?
Factors used to increase neutrophil count in those who are neutropenic secondary to chemo or other factors
289
What are e.g.s of G-CSFs?
Filgrastim
| Pergilgrastim
290
What are RFs for developing febrile neutropenia?
Elderly
Specific malignancies - non-Hodgkin's lymphoma, ALL
Prev neutropenic episodes
Those receiving recombinant chemo + radiation therapy
291
Define acute transfusion reactions
Adverse signs/symptoms during or within 24h of blood transfusion
292
What are the most frequent acute transfusion reactions?
Fever
Chills
Pruritus
Urticaria
293
What are the immune mediated acute transfusion reactions?
```
Pyrexia
Alloimmunisation
Thrombocytopaenia
TRALI
Graft vs host disease
Urticaria
Acute/delayed haemolysis
ABO incompatability
Rhesus incompatability
```
294
What are the non-immune mediated acute transfusion reactions?
Hypocalcaemia
CCF
Infections
Hyperkalaemia
295
What are causes of thrombophilia?
```
Factors V leiden (most common cause)
Prothrombin gene mutation
Antithrombin III deficiency
Protein C deficiency
Protein S deficiency
```
Acquired - antiphospholipid syndrome
Drugs - COCP
296
What is Factor V Leiden aka?
Activated protein C resistance
297
What causes factor V leiden?
Gain of a function mutation in the factor V leiden protein --> activated factor V (a clotting factor) is inactivated 10x more slowly by activated protein C than normal
298
How does being homozygous/heterozygous for factor v leiden affect the risk of having a VTE?
Homozygote - 10x
| Heterozygote - 4-5x
299
What are the thalassaemias?
Group of genetic disorders characterised by reduced production of either alpha or beta chains
300
What is beta-thalassaemia trait?
Autosomal recessive condition characterised by a mild hypochromic, microcytic anaemia (usually asymptomatic)
301
What are the features of beta-thalassaemia triat?
Mild hypochromic, microcytic anaemia
| HbA2 raised
302
What is sickle cell anaemia?
AR condition that results in synthesis of an abnormal Hb chain called HbS
303
In which group of people is sickle cell anaemia more common and why?
People of African descent as the heterozygous condition offers protection against malaria
304
When do the symptoms of sickle cell anaemia in homozygotes present?
After 4-6 months when abnormal HbSS molecules take over from fetal Hb
305
What is the pathophysiology of sickle cell anaemia?
Polar AA glutamate is substituted by non-polar valine in each of the two beta chains --> decreased water solubility of deoxy-Hb --> HbS molecules polyermise and cause RBCs to sickle
Sickle cells are fragile and haemolyse and block small BVs --> infarction
306
How is sickle cell disease definitively diagnosed?
Hb electrophoresis
307
What are causes of massive splenomegaly?
```
Myelofibrosis
CML
Visceral leishmaniasis
Malaria
Gaucher's syndrome
```
308
What are the two subtypes of acquired haemolytic anaemias?
Immune and non-immune causes
309
What are immune causes of acquired anaemias?
Autoimmune - warm/cold antibody type
Alloimmune - transfusion reaction, haemolytic disease of newborn
Drug - methyldopa, penicillin
310
What are non-immune causes of acquired anaemias?
```
Microangiopathic haemolytic anaemia - TTP/HUS, DIC, malignancy, PET
Prosthetic cardiac valves
Paroxysmal nocturnal haemoglobulinuria
Infections - malaria
Drugs - dapsone
```
311
What does thrombin do?
Converts fibrinogen to fibrin
312
What does the fibrinolytic system do?
Breakdown fibrinogen and fibrin by producing plasmin
313
What does the breakdown of fibrinogen and fibrin result in?
Fibrin degradation products
314
What happens in DIC?
Dysregulation of coagulation and fibrinolysis --> widespread clotting with resultant bleeding
Transmembrane glycoprotein (tissue factor) is released. TF is present on surface of many cells and generally is not exposed to the circulation, but after vascular damage it is.
TF binds with coagulation factors that then trigger the extrinsic pathway (via factor VII) which subsequently triggers the intrinsic pathway (XII to XI to IX) of coagulation
315
What are causes of DIC?
Sepsis
Trauma
Obstetric complications, e.g. aminotic fluid embolism, HELLP syndrome
Malignancy
316
What does the typical blood picture look like in DIC?
Low platelets
Prolonged APTT, prothrombin + bleeding time
Fibrin degradation products raised
Schistocytes due to microangiopathic haemolytic anaemia
317
A Hb below what in a man should be referred for upper and lower GI endoscopy as a 2ww?
100g/L
318
What is thought to cause myelofibrosis?
Hyperplasia of abnormal megakaryocytes
| The resultant release of platelet derived growth factor is thought to stimulate fibroblasts
319
Haematopoiesis develops in which two places in myelofibrosis?
Liver and spleen
320
What are features of myelofibrosis?
Tends to be older person presenting with symptoms of anaemia (e.g. fatigue)
Massive splenomegaly
Hypermetabolic symptoms, e.g. night sweats, wt loss
321
What are common lab findings in myelofibrosis?
Anaemia
High WBC and platelet count early in disease
Tear drop poikilocytes on blood film
Unobtainable bone marrow biopsy - dry tap - therefore trephine biopsy req.
High urate + LDH (reflect increased cell turnover)
322
What is aplastic anaemia characterised by?
Pancytopaenia + a hypoplastic bone marrow
323
When is the peak incidence of aplastic anaemia?
30 years old
324
What are features of aplastic anaemia?
Normochromic, normocytic anaemia
Leukopaenia, with lymphocytes relatively spared
Thrombocytopaenia
325
What may aplastic anaemia be a presenting feature of?
ALL or AML
| Minority of patients go on to develop paroxysmal nocturnal haemoglobinuria or myelodysplasia
326
What are causes of aplastic anaemias?
Idiopathic
Congenital - Faconi anaemia, dyskeratosis congenita
Drugs - cytotoxics, chloramphenicol, sulphonamides, phenytoin, gold
Toxins - benzene
Infections - parovirus, hepatitis
Radiation
327
How does Fe deficiency anaemia differ from anaemia of chronic disease in:
- Serum iron
- TIBC
- Transferrin saturation
- Ferritin?
Fe deficient anaemia -
- Serum iron low <8
- TIBC high
- Transferrin saturation low
- Ferritin low
Anaemia of chronic disease -
- Serum iron low <15
- TIBC low
- Transferrin saturation low
- Ferritin high
328
What are presenting features of Hodgkin's lymphoma?
Asymptomatic lymphadenopathy
Cough, Pel Ebstein fever, haemopytsis, SoB
B symptoms - wt loss, fever, night sweats
329
How are patients with Hodgkin's lymphoma staged?
CT chest, abdo, pelvis
| Ann Arbor staging
330
What is Ann Arbor stage 1?
Single LN region
331
What is Ann Arbor stage 2?
2+ regions on same side of diaphragm
332
What is Ann Arbor stage 3?
Involvement of LN regions on both sides of diaphragm
333
What is Ann Arbor stage 4?
Involvement of extra nodal sites
334
How is Hodgkin's lymphoma treated?
Chemo + radio
335
How is Hodgkin's lymphoma diagnosed?
Excision and histological evaulation of a complete LN
336
What virus is associated with Hodgkin's lymphoma?
EBV
337
What is prothrombin complex concentrate mainly used for?
Emergency reversal of anticoagulation in patients with severe bleeding/head injuries
338
What is hand-foot syndrome?
Caused by sickling of red blood cells interfering with circulation to the hands and feet in those with sickle cell disease
Leads to swelling, pain + erythema of sudden onset
339
What types of crises can you get in sickle cell disease?
```
Thrombotic (painful) crises
Sequestration
Acute chest syndrome
Aplastic
Haemolytic
```
340
What are thrombotic crises aka?
Painful/vaso-oclusive crises
341
What can precipitate thrombotic crises?
Infection
Dehydration
Deoxygenation
342
What happens in thrombotic crises?
Infarcts occur in various organs, incl the bones (e.g. avascular necrosis of hip, hand foot syndrome in children, lungs, spleen, brain)
343
What are sequestration crises?
Sickling within organs, e.g. spleen/lungs --> pooling of blood with worsening anaemia
344
What are clinical features of acute chest syndrome?
SoB, chest pain, pulmonary infiltrates, low pO2
345
What causes an aplastic crisis?
Infection with parovirus
346
What happens in aplastic crises?
There is a sudden fall in Hb
347
What happens in haemolytic crises?
There is a fall in Hb due to increased rate of haemolysis
348
What can elicit a haemolytic crisis in someone with hereditary spherocytosis and what features may be suggestive of it?
Parovirus infection
| Features may include splenomegaly, fatigue, jaundice
349
What does repeated sequestration and infarction of spleen in sickle cell disease lead to?
Auto-splenectomy
350
What are features of a sequestration crisis?
Severe anaemia, marked pallor, abdominal pain, CV collapse due to ineffective circulating volume
351
What kind of anaemia does sickle cell disease cause?
Normocytic anaemia with raised reticulocyte count (due to haemolysis)
352
Why are pregnant women more at risk of having a DVT/PE?
Pregnancy is a hypercoagulable state
| Increase in factors VII, VIII, X, fibrinogen, decrease in protein S, uterus presses on IVC --> venous stasis in legs
353
When do the majority of VTEs occur in a pregnancy?
Last trimester
354
How is DVT/PE in pregnancy managed?
S/C LMWH
355
What are causes of hyposplenism?
```
Splenectomy
Sickle cell
Coeliac disease, dermatitis herpetiformis
Grave's disease
SLE
Amyloid
```
356
What drugs can precipitate renal failure in those with MM?
NSAIDs
357
Which of the NOACs has an antedote and what is it called?
Dabigatran
| It is called Idarucizumab
358
What is the universal donor of FFP?
AB RhD
359
What is myelodysplasia?
Acquired neoplastic disorder of haematopoietic stem cells where a line of myeloid blasts are produced rapidly but do not mature + die --> deficiency in that line of cells
360
What may myelodysplasia progress to?
AML
361
How does myelodysplasia present?
Bone marrow failure (anaemia, neutropaenia, thrombocytopaenia)
362
What transfusion gene is seen in acute promyelocytic leukaemia?
t(5;17) - fusion of PML and RAR alpha genes
363
What bone profile will you see in myeloma without metastasis?
High calcium, normal/high phosphate, normal alk phosp
NB alk phosp only elevated in metastatic dx
364
What are causes of microcytic anaemias?
```
Fe deficiency anaemia
Thalassaemia
Congenital sideroblastic anaemia
AOCD
Lead poisoning
```
365
A hx of normal Hb with microcytosis should raise suspicion of what?
Thalassaemia or polycythaemia vera (with bleeding)
366
What is Waldenstrom's macroglobulinaemia?
Uncommon condition seen in elderly men
| Lymphoplasmcytoid malignancy where there is secretion of a monoclonal IgM paraprotein
367
What are features of Waldenstrom's macroglobulinaemia?
```
Monoclonal IgM paraproteinaemia
Systemic upset - wt loss, lethargy
Hyperviscosity syndrome, e.g. visual disturbance
Hepatosplenomegaly
Lymphadenopathy
Cyroglobulinaemia, e.g. Raynauds
```
368
In which type of lymphoma does alcohol consumption cause pain in the enlarged LNs?
Hodgkin's (only in a minority)
369
What does the reticulocyte count do in a sequestration crisis vs an aplastic crisis?
Increased in sequestration, reduced in aplastic
370
What is the major criterion determining the use of cyroprecipitate in bleeding?
Low fibrinogen level
371
What should be given to patients with iron deficiency anaemia prior to surgery who cannot tolerate oral iron/time interval is too short?
IV iron
372
What is the shortest time interval for oral iron to work?
2-4 weeks
373
What general risk factors are associated with an increased risk of VTE?
```
Advancing age
Obesity
FH VTE
Pregnancy
Immobility
Hospitalisation
Anaesthesia
Central venous catheter
```
374
What conditions are associated with an increased risk of VTE?
```
Malignancy
Thrombophilia
Heart failure
Antiphospholipid syndrome
Behcet's
Polycythaemia
Nephrotic syndrome
Sickle cell disease
Paroxysmal nocturnal haemoglobinuria
Hyperviscosity syndrome
Homocystinuria
```
375
What medications increase the risk of having a VTE?
COCP
HRT
Raloxifene, tamoxifen
Antipsychotics, esp olanzopine
376
What are the two types of autoimmune haemolytic anaemia?
Warm
Cold
(according to the temperature at what the antibodies best cause haemolysis)
377
What is the aetiology of autoimmune haemolytic anaemia?
Commonly idiopathic, may be secondary to a lymphoproliferative disorder, infection or drugs
378
What test is always +ve in AIHA?
Direct antiglobulin test (Coombs' test)
379
Where does haemolysis tend to occur in warm AIHA?
IgG causes haemolysis best at room temp and haemolysis tends to occur in extravascular sites, e.g. the spleen
380
What are management options for warm AIHA?
Steroids
Immunosupressants
Splenectomy
381
What are causes of warm AIHA?
Autoimmune dx, e.g. SLE
Neoplasia, e.g. lymphoma, CLL
Drugs, e.g. methyldopa
382
What antibody is usually implicated in warm AIHA?
IgG
383
What antibody is usually implicated in cold AIHA?
IgM
384
At what temperature do the IgM in cold AIHA cause haemolysis?
4C
385
Complete the sentence -
| In cold AIHA - haemolysis is mediated by ____ and is more commonly _______.
Complement
| Intravascular
386
What are features of cold AIHA?
Raynaud's
| Acrocyanosis
387
What are causes of cold AIHA?
Neoplasia, e.g. lymphoma
| Infections, e.g. mycoplasma, EBV
388
What is B12 mainly used for in the body?
RBC development and maintenance of the nervous system
389
How is B12 absorbed in the body?
Binds to intrinsic factor (secreted from parietal cells in the stomach) + actively absorbed in the terminal ileum
390
What are causes of B12 deficiency?
```
Pernicious anaemia (most common)
Post-gastrecomy
Vegan diet/poor diet
Disorders of terminal ileum (e.g. CD)
Metformin (rare)
```
391
What are features of a B12 deficiency?
Macrocytic anaemia
Sore tongue + mouth
Neurological symptoms (dorsal column affected first --> distal paraesthesia)
Neuropsychiatric symptoms, e.g. mood disturbances
392
How is B12 deficiency treated?
No neurological involvemenet --> 1mg IM hydroxocobalamin 3x week for 2 weeks, then 3mnthly
If also deficient in folate must treat B12 deficiency first to avoid precipitating subacute combined degeneration of the cord
393
What kind of anaemia can alcohol excess cause?
Megaloblastic
394
What kind of anaemia does hypothryoidism cause?
Macrocytic
395
What do Reed-Sternberg cells look like?
Mirror image nuclei
396
Which of platelets and packed red cells is more likely to cause iatrogenic septicaemia with a gram positive and which with a gram negative bacteria?
Platelets - gram +ve
| RBC - gram -ve
397
What are negative prognostic factors for Hodgkin's lymphoma?
Presence of B symptoms (wt loss, night sweats, fever)
Male gender
Age >45y at diagnosis
High WCC, low Hb, high ESR or low blood albumin
398
What are causes of a normocytic anaemia?
```
AOCD
CKD
Aplastic anaemia
Haemolytic anaemia
Acute blood loss
```
399
What iron profile is typical of AOCD?
Normocytic anaemia, with low serum iron, low TIBC, raised ferritin
400
What is the pathophysiology of AOCD?
Reduced iron released from bone marrow
Inadequate secretion of EPO
Reduced red cell survival
401
What kind of symptoms does lead poisoning lead to?
Abdominal and neurological
402
What does lead poisoning lead to?
Defective ferrochelatase and ALA dehydratase function
403
What are features of lead poisoning?
```
Abdominal pain
Peripheral neuropathy (mainly motor)
Fatigue
Constipation
Blue lines on gum margin
```
404
What test is used to diagnose lead poisoning?
Blood lead level
Levels greater than 10mcg/dl are considered significant
405
What kind of anaemia do you get in lead poisoning?
Microcytic anaemia
406
What abnormalities do you see on the blood film in lead poisoning?
Basophilic stripping + clover leaf morphology
407
Where can the lead accumulate in children who have lead poisoning?
Metaphysis of bones
408
What chelating agents are used to treat lead poisoning?
Dimercaptosuccinic acid (DMSA)
D-penicillamine
EDTA
Dimercaprol
409
Why do you get anaemia in lead poisoning?
Due to interruption of the haem biosynthesis pathway
410
In which cell is CMV transmitted in during blood transfusion?
Leucocytes
411
Apart from to reduce spread of CMV, what is the other reason that most blood products are irradiated?
To avoid transfusion graft vs host disease
412
What is the lymphadenopathy like in Hodgkin's lymphoma?
Painless, non-tender, assymmetrical
413
What is the preferred NOAC for patients with renal impairment?
Apixiban (due to minimal renal drug clearance)
414
What is thrombocytosis?
An abnormally high platelet count (usually >400x10^9/l)
415
What are causes of thrombocytosis?
```
Reactive, e.g. in response to severe infection, surgery, or Fe deficiency anaemia
Malignancy
Essential thrombocytosis
CML
Hyposplenism
```
416
What is essential thrombocytosis?
A myeloproliferative disorder where megakaryocyte proliferation results in overproduction of platelets
417
What are features of essential thrombocytosis?
Platelet count >600x10^9
Arterial and venous thromboses + haemorrhage
Burning in hands
418
What mutation is found in 50% of patients with essential thrombocytosis?
JAK2
419
What is the management of essential thrombocytosis?
Hydroxyurea (hydroxycarbamide) to reduce platelet count
Interferon-a also used in younger patients
Low dose aspirin to reduce risk of thrombosis
420
All people with Fe deficiency anaemia should be screened for what GI disease?
Coeliac disease (anti-TTG test)
421
What is tranexamic acid a synthetic derivative of?
Lysine
422
What is the mode of action of tranexamic acid?
Antifibrinolytic that reversibly binds to lysine receptor sites on plasminogen or plasmin which prevents plasmin binding to and degrading fibrin
423
When might tranexamic acid be used?
Menorrhagia
| Bleeding trauma <3h (where it is given as an IV bolus followed by a slow infusion)
424
Why is the COCP stopped before surgery?
To reduce risk of having a PE
425
What is involved in the long term management of sickle cell disease?
Hydroxyurea (increases levels of HbF)
| Pneumococcal vaccine every 5 years
426
What are thymomas associated with?
Myasthenia gravis
Red cell asplasia
Dermatomyositis
SLE, SIADH
427
How can thymomas cause death?
Compression of airway
| Cardiac tamponade
428
Non-hodgkins lymphoma affects either of which two cells?
B or T cells
429
What are RFs for non-hodgkin's lymphoma?
```
Elderly
Caucasian
Hx viral infections, esp. EBV
FH
Certain chemicals - pesticides, solvents
Hx chemo/radio
Immunodeficiency, e.g. HIV, transplant, DM
Autoimmune dx (SLE, Sjogren's, coeliac dx)
```
430
What are symptoms of NHL?
```
Painless lympadenopathy (non-tender, rubbery, asymmetrical)
B symptoms
Extranodal dx (dyspepsia, dysphagia, wt loss, ab pain), pancytopenia, bone pain, nerve palsies etc.
```
431
What are the B symptoms?
Fever, night sweats, wt loss, lethargy
432
Are extranodal symptoms more common in NHL or HL?
NHL
433
What are signs of NHL?
Wt loss
Lympadenopathy (typically cervical, axillary, inguinal)
Palpable ab mass - hepatomegaly, splenomegaly, LNs
Testicular mass
Fever
434
What is the diagnostic investigation for NHL?
Excisional node biopsy
435
What is the classical appearance of Burkitt's lymphoma on biopsy?
Starry sky appearance
436
What is used to stage NHL?
CT chest, abdo, pelvis
437
Testing for what virus is often done on diagnosis of NHL?
HIV (RF for NHL)
438
What blood tests may be done in NHL?
FBC + blood film (rule out other haematological malignancy)
ESR (prognostic indicator)
LDH (marker of cell turnover - prognostic indicator)
Other investigations based on symptoms, e.g. LFTs if suspecting liver mets
439
What are infective causes of lympadenopathy?
```
IM
HIV
Eczema with secondary infection
Rubella
Toxoplasmosis
CMV
TB
Roseola infantum
```
440
What are neoplastic causes of lymphadenopathy?
Leukaemia
| Lymphoma
441
What are other causes of lymphadenopathy?
Autoimmune conditions - SLE, RA
Graft vs Host disease
Sarcoidosis
Drugs, e.g. phenytoin
