Haematology Full Flashcards
1
Q
What is myeloma?
A
Malignancy of plasma cells leading to progressive bone marrow failure. It is associated with production of characteristic paraprotein, bone disease, anaemia and renal failure.
2
Q
In order to make a diagnosis of myeloma, there must be evidence of mono-clonality. What is mono-clonality?
A
Abnormal proliferation of a single clone of plasma cell leading to immunoglobulin secretion and causing organ dysfunction especially to the kidney.
3
Q
What disease often precedes myeloma?
A
Monoclonal gammopathy of undetermined significance (MGUS).
4
Q
What is MGUS?
A
A common disease with paraprotein present in the serum but no myeloma. Often asymptomatic. <10% plasma cells in the bone marrow.
5
Q
In approximately 2/3 of people with myeloma, what might their urine contain?
A
Bence-jones proteins: light chains in urine
6
Q
Give 3 symptoms of myeloma.
A
- Tiredness.
- Bone/back pain.
- Infections.
7
Q
Give 4 key feature of myeloma.
A
CRAB!
- Calcium is elevated.
- Renal failure.
- Anaemia.
- Bone lesions.
8
Q
Why is calcium elevated in myeloma?
A
There is increased bone resorption and decreased formation meaning there is more calcium in the blood.
9
Q
Why might someone with myeloma have anaemia?
A
- The bone marrow is infiltrated with plasma cells, causing suppression of other blood cell lines.
- Consequences of this are anaemia, neutropenia, and thrombocytopenia –> tiredness, infections and bleeding.
10
Q
Why might someone with myeloma have renal failure?
A
- light chain deposition in the kidney tubules
- calcium deposition within the kidney parenchyma
11
Q
What investigations might you do in someone who you suspect has myeloma?
A
- Blood film: rouleaux formation of RBCs
- Bone marrow aspirate and trephine biopsy: ≥ 10% plasma cell infiltration.
- Electrophoresis of urine and blood serum.
- X-ray.
- CT scan.
- MRI scan.
B–Bence–Jones protein (requesturine electrophoresis)
L– Serum‑freeLight‑chain assay
I– SerumImmunoglobulins
P– SerumProtein electrophoresis
12
Q
What would you expect to see on the blood film taken from someone with myeloma?
A
Rouleaux formation (aggregations of RBC’s).
13
Q
What are you looking for on a bone marrow biopsy taken from someone with myeloma?
A
Increased plasma cells.
14
Q
What are you looking for on electrophoresis in a patient with myeloma?
A
Monoclonal protein band.
15
Q
What are you looking for on an X-ray taken from someone with myeloma?
A
Bone lesions.
16
Q
What is the treatment for MGUS and asymptomatic myeloma?
A
Watch and wait.
17
Q
Describe the treatment for symptomatic myeloma.
A
- chemo
- stem cell transplant
- bisphosphonates for bone treatment
18
Q
What is lymphoma?
A
A malignant growth of WBC’s predominantly in the lymph nodes.
19
Q
Although predominantly in the lymph nodes, lymphoma is systemic. What other organs might it effect?
A
- Blood.
- Liver.
- Spleen.
- Bone marrow.
20
Q
Give 4 risk factors for lymphoma.
A
- family hx.
- Secondary immunodeficiency e.g. HIV.
- EBV Infection.
- Autoimmune disorders e.g. RA.
21
Q
Describe the pathophysiology of lymphoma.
A
There is impaired immunosurveillance and infected B cells escape regulation and proliferate. (This is just a theory).
22
Q
Give 4 symptoms of lymphoma.
A
- Enlarged painless lymph nodes in arm/neck.
- itching.
- General systemic ‘B’ symptoms e.g. weight loss, night sweats, malaise.
- Pain in lymph nodes when drinking alcohol [HL only].
- SoB, cough and dyspnoea due to compression of mediastinal lymph nodes.
also recurrent infection
23
Q
What investigations might you do in someone who you suspect has lymphoma?
A
- Lymph node ultrasound [1st line]
- Lactate dehydrogenase blood test: elevated.
- lymph node biopsy = diagnostic: shows Reed-Sternberg cells.[gold standard]
- CT scan for staging
24
Q
What are the two sub-types of lymphoma?
A
- Hodgkins lymphoma.
2. Non-hodgkins lymphoma.
25
What are the symptoms of Hodgkins lymphoma?
1. Painless lymphadenopathy.
2. Presence of 'B' symptoms e.g. night sweats, weight loss.
3. lymph node pain triggered by alcohol
4. pruritus
26
What is a key feature for diagnosis of Hodgkins lymphoma?
Presence of Reed-sternberg cells.
27
Describe the staging of Hodgkins lymphoma.
1. Stage 1: confined to a single lymph node region.
2. Stage 2: Involvement of two or more nodal areas on the same side of the diaphragm.
3. Stage 3: involvement of nodes on both sides of the diaphragm.
4. Stage 4: Spread beyond the lymph nodes e.g. liver.
Each stage is either 'A' - absence of 'B' symptoms or 'B' - presence of 'B' symptoms.
28
What are the treatment options for Hodgkins lymphoma?
- chemotherapy
- radiotherapy.
- rituximab
29
what are the potential side effects of Hodgkin's lymphoma treatment
Chemotherapy creates a risk of leukaemia and infertility.
Radiotherapy creates a risk of cancer, damage to tissues and hypothyroidism.
30
What are the possible complications of treatment for Hodgkins lymphoma?
1. Secondary malignancies.
2. IHD.
3. Infertility.
4. Nausea.
5. Alopecia.
6. Tumour lysis syndrome
31
Describe low grade non-hodgkins lymphoma.
Slow growing
advanced at presentation
often incurable.
Median survival is 10 years.
32
What is the treatment for low grade non-hodgkins lymphoma?
If symptomless - watchful waiting.
Radiotherapy, combination chemotherapy and mAb and stem cell transplant may be used if symptomatic.
33
Describe high grade non-hodgkins lymphoma.
- Aggressive.
- Nodal presentation, patient unwell with symptoms.
- Often curable.
34
Describe the treatment for high grade non-hodgkins lymphoma.
- Early: short course chemotherapy and radiotherapy.
| - Advanced: combination chemotherapy and mAb.
35
what is bone marrow failure
the decreased production of one or more major hematopoietic lineage -> various cytopenias
36
symptoms of bone marrow failure
* Fatigue.
* Shortness of breath.
* Pale appearance.
* Frequent infections.
* Easy bruising or bleeding.
* Bone pain
37
define pancytopenia
low:
- red blood cellls
- platelets
- white blood cel
38
signs of bone marrow failure on a blood test
- thrombocytopenia
- leukopenia
- anaemia
- neutropenia
39
What is leukaemia?
A malignant proliferation of haemopoietic stem cells.
| can have mixed lineage or heterogenous lineage
40
Name 4 sub-types of leukaemia.
1. AML - acute myeloid leukaemia.
2. CML - chronic myeloid leukaemia.
3. ALL - acute lymphoblastic leukaemia. [Ab]
4. CLL - chronic lymphocytic leukaemia. [Cc]
41
What is acute myeloid leukaemia?
Rapid, neoplastic proliferation of myeloblast cells in the bone marrow and blood.
42
What can increase the risk of developing AML?
1. Preceding myeloproliferative disorders.
2. Prior chemotherapy.
3. Exposure to ionising radiation.
4. increasing age
43
what is a granulocyte
a type of WBC with granules, namely:
- basophils,
- eosinophils
- neutrophils
44
what is a myeloblast
A myeloblast is an immature white blood cell
45
Give 5 symptoms of leukaemia.
1. fatigue.
2. recurrent infection.
3. Bleeding + bruising.
4. Fever.
5. Splenomegaly.
6. Hepatomegaly
46
Why are anaemia, infection and bleeding symptoms of leukaemia?
Because of bone marrow failure.
47
Why are hepatomegaly and splenomoegaly symptoms of leukaemia?
Because of tissue infiltration.
48
What investigations might you do on someone who you suspect has leukaemia?
1. Blood film.
2. Bone marrow biopsy.
3. Lymph node biopsy.
4. Immunophenotyping.
5. Cytogenetics.
6. FBC
49
Describe the treatment for AML.
1. Supportive care.
2. Chemotherapy: curative v palliative.
3. Bone marrow transplant.
50
What is CML?
Chronic myeloid leukaemia, there is uncontrolled clonal proliferation of mature myeloid cells within the bone marrow and blood: basophils, eosinophils and neutrophils [granulocytes]
51
What would the FBC from someone with CML look like?
- LeukocytosisHigh WBC's.
- thrombocytopenia
- anaemia
52
What chromosome is present in >80% of people with CML?
Philadelphia chromosome 9:22
53
What are the treatment options for CML?
- Tyrosine kinase inhibitors +/- interferon alpha inibitors.
- chemo
- stem cell transplant
54
What is ALL?
- Acute lymphoblastic leukaemia.
- There is rapid uncontrolled proliferation of lymphocyte precursor cells.
- usually affects B-cells over T-cells.
55
What is the treatment for ALL?
chemotherapy and stem cell transplant.
56
What is CLL?
Chronic lymphoid leukaemia. Proliferation of B lymphocytes leads to the accumulation of mature B cells that have escaped apoptosis and are incompetent
57
What is the treatment for CLL?
1. watch + wait in early stages.
2. Chemotherapy.
3. Bone marrow transplant.
58
Name the 3 broad categories of red cell disorders.
1. Haemoglobinopathies.
2. Membranopathies.
3. Enzymopathies.
59
What is normal adult haemoglobin made of?
2 alpha and 2 beta chains.
60
What is foetal haemoglobin made of?
2 alpha and 2 gamma chains.
61
What is haemoglobin S?
- Haemoglobin S is a variant of Hb arising from a point mutation in the beta globin gene.
- The mutation causes a single amino acid change, valine -> glutamine.
- causes sickle cell anaemia
62
What is sickle cell disease?
A haemoglobin disorder of quality. HbS polymerises -> sickle shaped RBC.
63
What is the advantage of being a carrier of sickle cell disease?
Carriage offers protection against falciparum malaria.
64
Describe the inheritance pattern of sickle cell disease.
Autosomal recessive.
Sickle cell disease is homozygous SS.
65
If both parents are carriers of the sickle trait. What is the chance that their first child will have sickle cell disease?
Their offspring have a 1/4 chance of being affected with a sickle cell disease. (50% chance of being a carrier).
66
How long do sickle cells last for?
5-10 days - this explains why sickle cell disease is described as haemolytic.
67
Give 4 acute complications of sickle cell disease.
1. Very painful crisis.
2. Stroke in children.
3. Cognitive impairment.
4. Infections.
68
Give 3 chronic complications of sickle cell disease.
1. Renal impairment.
2. Pulmonary hypertension.
3. Joint damage.
69
Describe the treatment for sickle cell disease.
1. Transfusion.
2. Hydroxycarbamide ↑ HbF which is protective against sickling.
3. Stem cell transplant.
4. analgesia
5. Lifelong phenoxymethylpenicillin as prophylaxis due to autosplenectomy. Folic acid supps
70
What is thalassaemia?
A haemoglobin disorder of quantity.
There is reduced synthesis of one or more globin chains -> a reduction in Hb -> anaemia.
71
If someone has beta thalassaemia do they have more alpha or beta globin chains?
They have very few beta chains, alpha chains are in excess.
72
What is the clinical classification of beta thalassaemia?
1. Thalassaemia major.
2. Thalassaemia intermedia.
3. Thalassaemia carrier/heterozygote.
73
Which clinical classification of thalassaemia relies on regular transfusions?
Thalassaemia major.
74
Which clinical classification of thalassaemia is often asymptormatic?
Thalassaemia carrier/heterozygote.
75
When do people with beta thalassaemia major usually present and why?
These patients usually present very young due to having severe anaemia and so a failure to feed/thrive.
76
Why is it important to monitor iron levels in someone with beta thalassaemia major?
There is a risk of iron overload from the regular trasnfusions. Excess iron will be deposited in various organs e.g. the liver and spleen and cause fibrosis.
77
What is the significance of parvovirus for someone with sickle cell disease?
Parvovirus is a common infection in children. It leads to decreased RBC production and can cause a dramatic drop in Hb in patients who already have a reduced RBC lifespan. This can be dangerous for someone with sickle cell.
78
Describe the inheritance pattern for membranopathies.
Autosomal dominant.
79
Name 2 common membranopathies.
1. Spherocytosis.
| 2. Elliptocytosis.
80
Briefly describe the physiology of membranopathies.
Deficiency of red cell membrane proteins caused by genetic lesions
81
What are enzymopathies?
Enzyme deficiencies lead to shortened RBC lifespan.
82
Name a common enzymopathy.
G6PD deficiency.
83
Give 3 signs of G6PD deficiency.
Crises characterised by:
1. Haemolysis.
2. Jaundice.
3. Anaemia.
84
What is anaemia?
A decrease in the amount of Hb in the blood below the reference range.
85
What is the function of Hb?
It carries and delivers oxygen to tissues.
86
What organs are responsible for removal of RBC's?
1. Spleen.
2. Liver.
3. Bone marrow.
4. Blood loss.
87
Give 3 causes of microcytic anaemia.
1. Iron deficiency.
2. Anaemia of chronic disease.
3. Thalassaemia.
88
Give 3 causes of normocytic anaemia.
1. Acute blood loss.
2. Anaemia of chronic disease.
3. Combined hematinic deficiency.
89
Give 3 causes of macrocytic anaemia.
1. B12/folate deficiency.
2. Alcohol excess/liver disease.
3. Hypothyroid.
90
Where is B12 absorbed?
The terminal ileum.
91
Explain how pernicious anaemia leads to B12 deficiency.
Pernicious anaemia leads to a loss of parietal cells -> reduced intrinsic factor production -> vitamin B12 malabsorption.
92
Give 5 causes of iron deficiency.
1. Blood loss.
2. Poor absorption.
3. Decreased intake in diet.
4. Hook worm!
5. Breastfeeding, low iron in breast milk.
93
Give 3 symptoms of anaemia.
1. Fatigue.
2. Faintness.
3. Breathlessness.
4. Reduced exercise tolerance.
94
What investigations might you do in someone with anaemia?
1. Blood tests: FBC and blood film.
2. Biopsies.
3. Reticulocyte count.
4. B12 levels.
5. Serum ferritin.
95
What is the treatment for anaemia?
Treat the underlying cause e.g. if iron deficient give ferrous sulphate.
96
What is polycythaemia?
Too many RBC's, an increase in Hb.
97
What hormone is responsible for regulating RBC production?
Erythropoietin.
98
What stimulates EPO?
Tissue hypoxia.
99
Name a primary cause of polycythaemia.
Polycythaemia rubra vera - over reactive bone marrow.
100
Give 3 secondary causes of polycythaemia.
1. Heavy smoking.
2. Lung disease.
3. Cyanotic heart disease.
4. High altitude.
101
What is the treatment for polycythaemia?
1. If a secondary cause treat the underlying cause.
| 2. If a primary cause, treatment aims to maintain a normal blood count and prevent complications e.g. aspirin.
102
What is neutrophilia?
Too many neutrophils.
103
Give 3 causes of neutrophilia.
1. Infection.
2. Inflammation.
3. CML.
4. Cancer.
104
What is lymphocytosis?
Too many lymphocytes.
105
Give 3 causes of lymphocytosis.
1. Viral infections.
2. Inflammation.
3. Malignancy.
4. CLL.
106
What is thrombocytopenia?
Not enough platelets.
107
Give 2 causes of thrombocytopenia.
1. Production failure e.g. marrow suppression, marrow failure.
2. Increased removal e.g. immune response (ITP), consumption (DIC), splenomegaly.
108
What is thrombocytosis?
Too many platelets.
109
What is neutropenia?
Not enough neutrophils.
110
What is the major risk associated with being neutropenic?
Susceptible to infection.
111
Give 3 causes of neutropenia.
1. Marrow failure.
2. Marrow infiltration.
3. Marrow toxicity.
112
Where are platelets produced?
In the bone marrow. They are fragments of megakaryocytes.
113
What hormone regulates platelet production?
Thrombopoietin - produced mainly in the liver.
114
What is the lifespan of a a platelet?
7 - 10 days.
115
What organ is responsible for platelet removal?
The spleen.
116
What can cause platelet dysfunction.
1. Reduced platelet number (thrombocyotpenia).
| 2. Reduced platelet function.
117
Platelet dysfunction: what can cause decreased platelet production?
1. Congenital causes e.g. malfunctioning megakaryocytes.
2. Infiltration of bone marrow e.g. leukaemia.
3. Alcohol.
4. Infection e.g. HIV/TB.
118
Platelet dysfunction: what can cause increased platelet destruction?
1. Autoimmune e.g. ITP.
2. Hypersplenism.
3. Drug related e.g. heparin induced.
4. DIC and TTP -> increased consumption.
119
Platelet dysfunction: what can cause reduced platelet function?
1. Congenital abnormality.
2. Medication e.g. aspirin.
3. VWF disease.
4. Uraemia.
120
Give 3 symptoms of platelet dysfunction.
1. Mucosal bleeding.
2. Easy bruising.
3. Petechiae/purpura.
121
Give 4 causes of bleeding.
1. Trauma.
2. Platelet deficiency e.g. thrombocytopenia.
3. Platelet dysfunction e.g. aspirin induced.
4. Vascular disorders.
122
What is the definition of febrile neutropenia.
Temperature >38°C in a patient with neutrophil count <1x10^9/L.
123
Give 4 risk factors for febrile neutropenia.
1. If the patient had chemotherapy <6 weeks ago.
2. Any patient who has had a stem cell transplant <1 year ago.
3. Any haematological condition causing neutropenia.
4. Bone marrow infiltration.
124
What is the presentation of febrile neutropenia?
1. Pyrexia, 38°C.
2. Generally unwell.
3. Confusion.
4. Hypotensive.
5. Tachycardic.
125
Describe the management of febrile neutropenia.
1. Thorough history and examination.
2. Bloods.
3. Antibiotics within 1 hour!
126
Give a risk factor for spinal cord compression.
Any malignancy that can cause compression e.g. bone metastasis.
127
Describe the presentation of spinal cord compression.
1. Back pain.
2. Weakness in legs.
3. Inability to control bladder.
4. Spastic paresis.
5. Sensory level.
128
Describe the management of spinal cord compression.
1. Bed rest.
2. High dose steroids.
3. Analgesia.
4. Urgent MRI of the whole spine.
129
What is tumour lysis syndrome?
Break down of malignant cells -> content release -> metabolic disturbances; can cause hyperuricaemia, hyperkalaemia, hypocalcaemia.
130
Give 3 risk factors for tumour lysis syndrome.
1. High tumour burden.
2. Pre-existing renal failure.
3. Increasing age.
131
Describe the treatment of tumour lysis syndrome.
1. Aggressive hydration.
2. Monitor electrolytes.
3. Drugs to reduce uric acid production e.g. allopurinol.
132
What is hyperviscosity syndrome?
Increase in blood viscosity usually due to high levels of immunoglobulins.
133
Give 2 consequences of hyperviscosity syndrome.
1. Vascular stasis.
| 2. Hypoperfusion.
134
Describe the presentation of hyperviscosity syndrome.
1. Mucosal bleeding.
2. Visual change.
3. Neurological disturbances.
4. Breathlessness.
5. Fatigue.
135
What investigations might you do in someone who you suspect has hyperviscosity syndrome?
1. FBC and blood film; look for rouleaux formation.
2. U&E.
3. Immunoglobulins.
136
What is the treatment for hyperviscosity syndrome?
1. Keep hydrated!
2. Avoid blood transfusion.
3. Treat the underlying cause.
137
Give 5 signs/symptoms of hypercalcaemia.
1. Confusion.
2. Bone pain.
3. Constipation.
4. Nausea.
5. Abdominal pain.
138
What might you see in the ECG taken from someone with hypercalcaemia.
Shortened QT interval.
Hypercalcaemia = risk of MI.
139
What is the treatment for hypercalcaemia?
IV hydration and bisphosphonates.
140
What does rituximab target?
Targets CD20 on the surface of B.
141
What is the characteristic genetic abnormality in chronic myeloid leukaemia?
t(9; 22) - philadelphia chromosome.
142
How is myeloma bone disease usually assessed?
X-ray.
143
What is the commonest cause of microcytic anaemia?
Iron deficiency.
144
What is the affect of sickle cell anaemia on reticulocyte count?
Reticulocyte count is raised.
145
Why is reticulocyte count raised in sickle cell anaemia?
Sickle cell disease is haemolytic, there is increased degradation of RBC's. Production therefore increases in order to keep up with degradation and so reticulocyte count is raised.
146
What clotting factors depend on vitamin K?
2, 7, 9 and 10.
147
Haemophilia A is due to deficiency of what clotting factor?
Factor 8 deficiency.
148
Haemophilia B is due to deficiency of what clotting factor?
Factor 9 deficiency.
149
Give 4 symptoms of ALL.
1. Bone pain.
2. Recurrent infections (neutropenia).
3. Pale and tired (anaemia).
4. Bruising (low platelets).
150
Is ALL more common in adults or children?
ALL is mainly a childhood disease.
151
What kind of anaemia could methotrexate cause?
Macrocytic due to folate deficiency.
152
Give 4 causes of folate deficiency.
1. Dietary.
2. Malabsorption.
3. Increased requirement e.g. in pregnancy.
4. Folate antagonists e.g. methotrexate.
153
Give 3 signs of haemolytic anaemia.
1. Pallor.
2. Jaundice.
3. Splenomegaly.
154
Give 4 causes of haemolytic anaemia.
1. GP6D deficiency.
2. Sickle cell anaemia.
3. Spherocytosis/elliptocytosis (membranopathies).
4. Autoimmune haemolytic anaemia.
155
Give 3 things that can cause coagulation disorders.
1. Vitamin K deficiency.
2. Liver disease.
3. Congenital e.g. haemophilia.
156
How does warfarin work?
It antagonises vitamin K and so you get a reduction in clotting factors 2, 7, 9 and 10.
157
How does heparin work?
It activates antithrombin which then inhibits thrombin and factor Xa.
158
What is disseminated intravascular coagulation (DIC)?
Pathological activation of the coagulation cascade -> fibrin in vessel walls. There is platelet (thrombocytopenia) and coagulation factor consumption.
159
Give 3 causes of disseminated intravascular coagulation (DIC).
1. Sepsis.
2. Major trauma.
3. Malignancy.
160
What is the affect on TT, PTT and APTT in someone with disseminated intravascular coagulation (DIC)?
All increased.
161
What is the affect on fibrinogen in someone with disseminated intravascular coagulation (DIC)?
Decreased.
162
Give 5 risk factors for DVT.
1. Increasing age.
2. Obesity.
3. Pregnancy.
4. OCP (hyper-coagulability).
5. Major surgery.
6. Immobility.
7. Past DVT.
163
Give 3 symptoms of DVT.
Unilateral warm, tender, painful, swollen leg.
164
What forms the differential diagnosis for a DVT?
Cellulitis.
165
What investigations might you do in someone to see if they have a DVT?
1. D-dimer in those patients with a low clinical probability.
2. US compression.
166
What is the name of the score used to determine someones probability of having a DVT?
The Wells score.
167
The Wells score determines someones clinical probability of having a DVT. Give 3 factors the score takes into account.
1. Active cancer.
2. Recently bedridden or major surgery.
3. Tenderness along deep venous system.
4. Swollen leg/calf.
5. Unilateral pitting oedema.
168
Describe the management for a DVT.
Aim of management is to prevent a PE!
| - Anticoagulants e.g. warfarin/heparin.
169
Explain why philadelphia chromosome causes CML.
Philadelphia chromosome leads to a fusion gene that has tyrosine kinase activity and enhanced phosphorylating activity -> altered cell growth.
170
Where would you normally take a bone marrow biopsy from?
Posterior iliac crest.
171
What is the most important medical treatment for DVT prophylaxis?
LMWH.
172
What is the affect of iron deficiency anaemia on iron binding capacity?
Iron binding capacity will be raised.
173
Why might measuring serum ferritin be inaccurate for looking at iron levels?
Ferritin is an acute phase protein and so its concentration will increase in response to inflammation.
174
Describe the treatment for iron deficiency anaemia.
Ferrous sulphate tablets.
175
What is aplastic anaemia?
When bone marrow stem cells are damaged -> pancytopenia.
176
Give 3 symptoms of iron-deficiency anaemia.
1. Koilonychia.
2. Brittle hair and nails.
3. Atrophic glossitis.
4. Tiredness, reduced exercise tolerance.
5. SOB.
177
What is the difference between Raynaud's disease and Raynaud's phenomenon?
Raynaud's disease is idiopathic.
| Raynaud's phenomenon can be due to SLE, scleroderma, RA, drugs e.g. beta blockers.
178
Describe the pathophysiological mechanism behind Raynaud's disease.
Peripheral digital ischaemia due to intermittent spasm in arteries that supply the fingers/toes. Precipitated by cold/stress.
179
Describe the colour changes that are seen in Raynaud's.
- Pale - due to vasoconstriction.
- Cyanotic - due to deoxygenation.
- Red - due to hyperaemia.
180
Describe the treatment for Raynaud's disease.
1. Physical protection.
2. Vasodilators.
3. Nifedipine (CCB).
4. Stop smoking.
181
State two features with regards to red blood cell appearance that would make you think a patient had anaemia due to iron deficiency.
1. Hypochromia (pale).
| 2. Microcytosis.
182
Suggest 3 ways in which multiple myeloma can lead to AKI.
1. Deposition of light chain.
2. Hypercalcaemia.
3. Hyperuricaemia.
183
In extreme cases, patients with myeloma can present with blurred vision, gangrene and bleeding. What is the pathology behind this?
Paraproteins form aggregates in the blood and change the viscosity.
184
Why are patients with myeloma susceptible to recurrent infections?
There is a reduction in polyclonal immunoglobulin levels.
185
What kind of anaemia is seen in patients with multiple myeloma?
Normochromic normocytic.
186
What chemotherapy regime is used in patients with myeloma?
VAD or CTD.
187
What combination chemotherapy regime is commonly used in patients with non hodgkin's lymphoma?
RCHOP.
188
Give 3 environmental causes of leukaemia.
1. Radiation exposure.
2. Chemicals e.g. benzene compounds.
3. Drugs.
189
Give 3 signs of anaemia.
1. Pale skin and mucous membranes.
2. Tachycardia.
3. Bounding pulse.
190
Describe the appearance of RBC's seen in iron deficiency anaemia.
Hypochromic microcytic.
191
What might you see on a blood count taken from someone with beta thalassaemia major?
1. Raised reticulocyte count.
| 2. Microcytic anaemia.
192
What can precipitate sickling in sickle cell anaemia?
Trauma, cold, stress, exercise.
193
Why does sickle cell anaemia not present until after 6 months of age?
HbF is not affected by sickle cell anaemia as it is made up of 2 alpha and 2 gamma chains.
194
What drug can be used to prevent painful crises in people with sickle cell anaemia?
Hydroxycarbamide.
195
Give 3 clinical features of a patient with a membranopathy.
1. Jaundice.
2. Anaemia.
3. Splenomegaly.
196
Why does a deficiency in glucose-6-phosphate dehydrogenase lead to shortened red cell lifespan?
G6PD protects cells against oxidative damage.
197
What 3 blood test values would be increased in someone with polycythaemia?
1. Hb.
2. RCC.
3. PCV.
198
Give 3 symptoms of polycythaemia.
1. Itching.
2. Headache.
3. Dizziness.
4. Visual disturbance.
199
What can cause ITP?
1. Viral infection.
| 2. Malignancy.
200
What antibodies are often found in ITP?
IgG.
201
Are PTT and APTT increased or decreased in DIC?
Increased.
202
Are fibrinogen and platelets increased or decreased in DIC?
Decreased.
203
Name 2 things that are increased and 2 that are decreased in DIC.
Increased: PTT and APTT.
Decreased: fibrinogen and platelets.
204
How would you treat haemophilia A?
IV infusion of factor 8.
205
causes of microcytic anaemia
* iron deficiency
* thalassemias - alpha and beta
206
causes of normocytic anaemias
* acute bleeding
* chronic disease
* renal disease
* mixed picture = mix of big and small RBCs → normal mean size.
207
causes of Macrocytic anaemias
* folate deficiency
* B12 deficiency
* haemolysis
* bone marrow disorders
208
what are hypo chromic cells
pale RBCs due to reduced amounts of Hb - iron deficiency
209
what factors lead to decreased RBC production
210
what factors lead to increased increased RBC loss
* Acute bleeding
* Haemolysis
211
define anaemia
* haemoglobin below lower limit of normal
* (sex adjusted Female normal 110-147g/l, male 131 – 166g/l)
212
what other factors would you check in a pt with low Hb
* platelet count
* WBC level
213
define MCV
* Mean Corpuscular [cell] Volume
* average cell size of RBCs = 80-98fl
214
define MCH
* Mean Cell Hb
* amount of Hb in each cell
* hypochromic, normochromic
215
T/F
reticulocyte count is part of a routine FBC
False
has to be requested specially
216
what is a reticulocyte count
* count of the number of young RBCs
* measures the rate of RBC production
217
causes of macrocytosis
NOTE: not necessarily always caused by anaemias.
* Folate deficiency
* B12 deficiency
* Reticulocytosis
* Raised immunoglobulins
* Hypothyroidism
* Alcohol
* Bone marrow failure, especially myelodysplastic neoplasms
* Drugs, e.g. methotrexate,
218
when is reticulocyte count a useful investigation
* in pts with symptoms of anaemia with a normocytic MCV
* increased of decreased reticulocyte count can help narrow down the cause of anaemia
219
what are the 2 main classes of normocytic anaemia
AND
what causes them
* normocytic anaemia with increased reticulocyte count - therefore there is bone marrow response
* acute bleed
* haemolytic anaemias e.g. sickle cell. G6pd deficiency.
* normocytic anaemia with decreased reticulocyte count - thus there is bone marrow failure
* aplastic anaemia - bone marrow disorder
* chronic diseases - esp. CKD
220
recommended iron/ day intake
amount of iron absorbed daily
function of iron
* 15mg/ day
* 1mg absorbed/day
* used for Hb synthesis
221
causes of iron deficiency
* blood loss - GI, menstrual
* pregnancy - a quarter of iron is transferred to foetus
* impaired absorption - gastrectomy, coeliac disease
* dietary deficiency - elderly and vegans
* hookworm - blood loss @ site of attachment
222
where is iron absorbed
SI: duodenum + jejunum
223
T/F ferritin is a good diagnostic tool for iron deficiency anaemia
True BUT:
* Ferritin is used to store iron in the RBCs, so the amount of ferritin in the blood gives an indication of how much iron in the blood.
* BUT ferritin is an acute phase protein so could go up in an infection even if the pt is anaemic
* so normal or high ferritin doesn't rule out Fe-deficient anaemia
224
what is transferrin and how is it used
* A protein that binds iron.
* transferrin saturation is used as a diagnostic tool: reduced saturation = Fe anaemia
* transferrin synthesis is increased in Fe deficiency → reduced saturation as less is occupied by iron.
225
T/F
serum iron is a useful investigative tool for Fe anaemia
FALSE
serum iron is useless as there are day to day fluctuations and circadian variation
226
management of Fe deficient anaemia
* stop bleeding if there is bleeding
* iron replacement - oral is preferred
* Hb should rise 20mg every 3-4 weeks
* oral and IV are equivalent so no benefit to IV
* IV requires hospitalisation + there's risk of extravasation → permanent skin discolouration
* once Hb and MCV levels are normal continue replacement for a further 3 months to ensure bone marrow stores are replenished
227
what are the results of iron studies in Fe deficient anaemia
* ↓ ferritin
* ↓ transferrin saturation
* ↑total iron binding capacity
* ↓ serum iron [not reliable]
228
where is B12 absorbed in the gut
the terminal ileum
229
what is the first stem cell for blood cells that → further cells
multipotent haematopoietic stem cell
230
what cells are produced from the multipotent haematopoietic stem cell
* myeloid stem cells
* lymphoid stemcells
231
what cells are derived from myeloblast cells
* monocyte → macrophage
* eosinophil
* neutrophil
* basophil
232
what cells are derived from common myeloid progenitor cells
* myeloblast
* erythroblast
* megakaryocytic
* mast cells
233
what cell are platelets derived from
megakaryocyte
234
what cells are derived from lymphoid progenitor cells
* B cells
* T cells
* Natural killer cells
235
what is a reticulocyte
AND
what is it derived from
* an immature RBC
* derived from erythroblasts
236
what cells are antigen presenting cells and which is the ‘professional’
* professional = dendritic cell
* APCs
* macrophages, B cells + dendritic cells present using MHC2
* all epithelial cells can present using MHC1.
237
what is the most common inherited bleeding disorder
Von Willerbrand Disease
238
what are the types of von willerbrand disease AND which is the most severe
* type 1,2 and 3
* type 3 is the most severe
239
what is the cause of Von Willerbrand disease
* an autosomal dominant genetic disease that → deficient, absent or malfunctioning Von Willerbrand Factor.
* VWF = a glycoprotein needed for formation of the platelet plug
240
what is Von Willerbrand Factor
a glycoprotein needed for platelet adhesion for the formation of the platelet plug.
241
how does VWD present
* pts present with unusually easy, heavy or prolonged bleeding:
* Bleeding gums with brushing
* Nose bleeds (***epistaxis***)
* Heavy menstrual bleeding (***menorrhagia***)
* Heavy bleeding during surgical operations
* severe post-natal bleeding
242
how is VWD diagnosed
* no single diagnostic test, a combo of:
* abnormal bleeding
* family hx
* bleeding assessment tools such as PT, APTT, FBC
243
how is VWD managed
* not managed on a day to day basis only in preparation for an operation or in response to major bleeding.
* **Desmopressin** can be used to stimulates the release of VWF
* **VWF** can be infused
* **Factor VIII** is often infused along with plasma-derived VWF
244
what are the main causes of bleeding disorders
* over anticoagulation
* heparin, aspirin, clopidogrel, heparins, thrombolytics
* genetic conditions
* VWD
* haemophilia: A +B
* DIC: Disseminated Intravascular Coagulopathy
245
what causes haemophilia
* A
* B
* haemophilia is an X-linked recessive disorder - men only need 1 and women need 2 X Genes.
* haemophilia A is caused by a deficiency in factor 8
* haemophilia B is caused by a deficiency in factor 9
246
who is mostly affected by haemophilia
* men as it is an X-Linked recessive condition.
* women are rarely affected as 2 X-genes are needed
247
symptoms of haemophilia
* excessive bleeding in response to minor trauma
* spontaneous haemorrhage without any trauma
* easy bruising
* epistaxis
248
investigations for diagnosis of haemophilia
* APTT: prolonged
* **plasma factor 8 + 9: decreased or absent = diagnostic**
249
signs of haemophilia
* **haemarthrosis**: bleeding in joints: knees, ankles + elbows especially.
* **Prolonged bleeding following heel prick:** common presentation in neonates
* **Cutaneous purpura:** often first presentation of acquired haemophilia
250
symptoms of haemophilia
* spontaneous bleeding into joints
* excessive bleeding
* easy bruising
* fatigue
251
management of haemophilia
* IV infusion factor 8 or 9 +
* desmopressin
* desmopressin stimulates release of VWF
* tranexamic acid = antifibrinolytic
* reduces bleeding
252
what is disseminated intravascular coagulation
* an acquired syndrome → over-activation of the coagulation cascade → formation of intravascular thrombi + depletion of clotting factors and platelets.
253
what can trigger DIC
* severe infection
* major trauma
* malignancy
* major vascular disorder
* immunological reactions
254
signs of DIC
255
investigations for DIC
* PT: prolonged
* platelet count: decreased
* fibrinogen: decreased
* imaging for sites of thrombosis
256
symptoms of bone marrow failure
* Fatigue.
* Shortness of breath.
* Pale appearance.
* Frequent infections.
* Easy bruising or bleeding.
* Bone pain
257
symptoms of bone marrow failure
* Fatigue.
* Shortness of breath.
* Pale appearance.
* Frequent infections.
* Easy bruising or bleeding.
* Bone pain
