Haematology Flashcards
1
Q
What is the pathophysiology of myeloma
A
Cloned malignant plasma cells all produce the same immunoglobulin in large quantities. Leading to secretion of immunoglobulins
2
Q
What are histological features of a malignant plasma cell
A
Prominent ER, centrally placed nucleus and hof
3
Q
What are plasmocytomas
A
Cancers of the plasma, can be within or outside the bone marrow
4
Q
What is waldenstroms macroglobulinaemia
A
IgM related plasma dysfunction
5
Q
What are the presentations of myeloma
A
CRAB hypercalceamia, Renal disease, anaemia, bone disease
6
Q
What causes anaemia in myeloma
A
Plasma cells infiltrating the bone marrow and also excessive WBC reducing the blood volume or RBC
7
Q
What is rouleaux
A
Stacks of erythrocytes on blood film, caused by high protein. Seen in myeloma
8
Q
What is the most common cause of death in myeloma
A
Infection due to monoclonal Ig causing immune surpression
9
Q
What causes renal disease in myeloma
A
Light chain deposition, high calcium, dehydration and NSAIDS
10
Q
What is amyloidosis
A
Extracellular deposition of fibrillar protein, leads to abnormal clinical signs. Can be due to light chain deposition.
11
Q
When should you suspect myeloma
A
Rouelaux, back pain, high ESR, high calcium and unexplained anaemia
12
Q
What should you do if you suspect myeloma
A
Check immunoglobulins in serum and urine
13
Q
What can cause lumps in the neck
A
Malignancy or reactive lymph nodes due to infection or inflammation
14
Q
What can cause primary immunodeficiency
A
Ataxia telangiectasia or Wiscott-Aldrich syndrome
15
Q
What can cause secodnary immunodeficiency
A
HIV, transplant recipients
16
Q
Which infections can cause lymphoma
A
EBV, HTLI-1 and helicobacter pylori
17
Q
What causes nodal disease in lymphoma
A
Accumulation of cancerous WBC
18
Q
Name 3 systemic B symptoms in Lymphoma
A
Loss of apetite, weight loss, drenching night sweats
19
Q
What causes drenching night sweats in lymphoma
A
Cyotkines from WBC
20
Q
What is classified as weight loss
A
Unintentional loss of 10% in 6 months
21
Q
What is WHO performance score 0
A
Asymptomatic, no restriction
22
Q
What is WHO performance score 1
A
Symptomatic but completely ambulatory, restricted strenuous activity but can carry out light work
23
Q
What is WHO performance score 2
A
Symptomatic, less than 50% in bed (waking hours). No work but self care
24
Q
What is WHO performance score 3
A
Symptomatic, more than 50% in bed, not bed bound. Limited self care
25
What is WHO performance score 4
Bedbound, no self care, limited to bed or chair
26
What is WHO performance score 5
Death
27
Name a low grade NHL
Follicular lymphoma
28
Name a high grade NHL
Diffuse Large B cell lymphoma
29
Name a very high grade NHL
Burkitt's lymphoma
30
What is the treatment of stage 1-2A hodgkins lymphoma
Short course combination chemotherapy followed by radiotherapy
31
What is the treatment of stage 2B-4 hodgkins lymphoma
Combination chemotherapy
32
Which chemotherapy causes cardiomyopathy
Anthracyclines
33
Which chemotherapy causes lung damage
Bleomycin
34
Which chemotherapy causes peripheral neuropathy
Vinca alkaloids
35
Name a monoclonal antibody used for NHL treatment
Rituximab, targets CD-20 on B cells. it is a chimeric antibody with few side effects. CD20 is unique to B cells
36
Name a radioimmunotherapy used for NHL treatment
Zevalin
37
Name a T cell engaging therapy used for NHL treatment
Blinatunomab, bi specific anitbody which targets CD19 on B cells and CD3 on T cells, directing the immune system
38
What is red marrow
Where platelets, rbc and wbc are made
39
What is white marrow
Fat, you get more as you age
40
Which cells are affected in acute leukaemia
Immature
41
Which cells are affected in chronic leukaemia
Mature
42
Which cells are affected in chronic myeloid leukaemia
Basophil, Neutrophil and eosinophil
43
Which cells are affected in chronic lymphatic leukaemia
B lymphocytes
44
Which cells are affected in chronic lymphoblastic leukaemia
Lymphoblast
45
Which cells are affected in chronic myeloid leukaemia
Myeloblast
46
Name a congenital risk factor for leukaemia
Down's syndrome
47
Name environmental risk factors for leukaemia
Radiotherapy, chemotherapy and benzene and other chemicals
48
What are signs of anaemia in leukaemia
Shortness of breath, fatigue, may not be pronounced in the young
49
What are the signs of thrombocytopenia in leukaemia
Bruising, bleeding (usually mucosal) and rash
50
What are the signs of infection in leukaemia
Fever and rigors
51
What type of rash does thrombocytopenia cause
Pin prick, pink rash which does not go away on touch - purpura, petechiae
52
What is a sign of lyphoma/ lymphoblastic leukaemia
Night sweats
53
What do blasts look like
very little cytoplasm and indistinct nucleioli
54
Which specialist investigations are used in leukaemia
Flow cytometry, cytogenetic analysis and bone marrow biopsy
55
Who gets acute lymphoblastic leukaemia
Young children, median age 3.5 (also 16-24 and old age but rare)
56
Who gets acute myeloid leukaemia
Older adults, peak age 70 (much rarer in children)
57
What is supportive leukaemia treatment
Blood products, symptom relief and reduce the chance of infection
58
What is a hickman line
Allows direct blood access, goes straight into the right atrium
59
How does aspergillos behave
It is a fungus which is angioinvasive and targets vessles
60
What causes acute relative polycythaemia
Dehydration
61
What causes chronic relative polycythaemia
Obesity, HTN, high alcohol and tobacco intake
62
What is polycythaemia
an increase in the haematocrit of the blood
63
What is polycythaemia vera
disease in which there are more RBC and also more WBC and platelets, it is treated with blood letting. Symptoms include head aches, thromboses, plethora, itching and cyanosis
64
What disease is caused by excessive proliferation of haematoipoietic myeloid stem cells into RBC
Polycythaemia vera
65
What disease is caused by excessive proliferation of haematopoietic myeloid stem cells into RBC
Chronic myeloid leukaemia
66
What disease is caused by excessive proliferation of haematopoietic myeloid stem cells into platelets
Essential thrombocytopenia
67
What disease is caused by excessive proliferation of haematopoietic stem cells into fibroplasts
Myelofibrosis
68
Which mutation is associated with polycythaemia vera
JAK2
69
What is venesection
Blood letting
70
How is polycythaemia treated in high risk/older people
Hydroxycarbamide
71
How is polycythaemia treated in pregnant women
Alpha interferon
72
How is polycythaemia normally treated
Venesection
73
Which chains are present in adult haemoglobin
2 alpha, 2 beta
74
Which chains are present in foetal haemoglobin
2 alpha, 2 gamma
75
When does foetal haemoglobin switch to adult haemoglobin and what is the effect
At 6 months, reducing the oxygen affinity
76
What causes sickle cell structure
valine to glutamine point mutation (A to T) in 6th codon in beta globin gene causes the formation of haemoglobin S
77
What inheritance pattern do sickle cell and thallasaemia show
Autosomal recessive
78
What is priapism
persistent and painful erection of the penis
79
How does sickle cell disease effect RBC
Causes polymerisation of haemoglobin molecules this precipitates out, damages red blood cells and renders them useless
80
How do the causes of alpha and beta thalassaemia differ
Alpha mainly caused by mutatations, beta caused by deletions
81
Define thalassaemia
Globin chain disorders resulting in diminished synthesis in one or more globin chains with subsequent reduction in the haemoglobin
82
What are the different types of thalassaemia
Major - transfusion dependent, Intermedia - less severe, can survive without transfusions, Carrier/Heterozygote - asymptomatic
83
Which type of anaemia does thalassaemia cause
microcytic
84
What would be the blood results for someone with Beta thallasaemia
Hb, MCV and MCH very low
85
What does MCV stand for
Mean corpuscular volume
86
What does MCH stand for
Mean corpuscular haemoglobin
87
What is a consequence of transfusion
High Iron, this can lead to deposition in organs causing renal, cardiac and pituitary failure
88
What is the result of 4 alpha thalassaemia genes
Hydrops foetalis - not compatible with life (Barts hydrops)
89
What happens with increasing numbers of faulty alpha thalassaemia genes
Increasing severity, 1 is normal or minimal changes, 2 more marked and 3 moderately severe
90
Where is alpha thalassaemia found
Eastern meditteranean or the far east
91
Name disease modifying treatment in sickle cell disease
Transfusion, stem cell transplant, hydroxycarbamide
92
What are membranopathies
Deficiencies of red cell membrane proteins caused by a variety of autosomal dominant genetic lesions
93
Name two membranopathies
Spherocytosis and elliptocytosis (shape changes)
94
What is a spherocyte
Horizontal membranopathy
95
What is an eliptocyte
Vertical membranopathy
96
Which RBC membrane protein is commonly missing in membranopathies
Spectrin
97
What causes slapped cheek syndrome
Parovirus and haemolytic anaemia. Reduced RBC production and there is already reduced lifespan so leads to has large effect. Occurs in children and in epidemics.
98
What are common RBC enzyme deficiencies
Pyruvate kinase and glucose-6-phosphate dehydrogenase
99
How is G6PDH deficiency diagnosed
NADPH screening test
100
What factors can bring on G6PDH deficiency crises
Broad beans, infections, drugs (primaquine, sulphonamides, nitrofurantoin, quinolones and dapsone)
101
Define anaemia
Low haemoglobin concentration which may be due to low red cell mass or increased plasma volume (eg. in pregnancy)
102
What are the three main causes of microcytic anaemia
Iron deficiency, chronic disease, thalassaemia
103
What are the two rarer causes of microcytic anaemia
Lead poisoning and congenital sideroblastic anaemia
104
What are the three main causes of normocytic anaemia
Acute blood loss, anaemia of chronic disease and combined haematinic deficiency
105
What are the four rarer causes of normocytic anaemia
Renal failure, hypothyroidism, haemolysis and pregnancy
106
Name the three main causes of macrocytic anaemia
B12/Folate deficiency, Alcohol excess/liver disease and hypothyroidism
107
What are the four examples of haematological causes of macrocytic anaemia
Haemolysis, bone marrow failure or infiltration and antimetabolite therapy
108
What is the normal male Hb range
131-166g/L
109
What is the normal female Hb range
110-147g/L
110
What are the physiological consequences of anaemia
Reduced oxygen transport, tissue hypoxia and compensatory changes (increased tissue perfusion, oxygen transfer and RBC production)
111
What are the pathological consequences of anaemia
Fatty changes in the myocardium and liver, worsen angina/claudication, skin and nail atrophy, CNS cell death (cortex and basal ganglia)
112
What is intermittent claudication
A cramping pain induced by exercise and relieved by rest. Often in the calf.
113
Name something which causes reduced RBC concentration but constant red cell mass
Dehydration
114
Name four causes of hypoplastic anaemia
Renal failure, endocrine, PRCA, aplastic anaemia
115
Name two causes of dyshaemopoietic anaemia
Defective Hb or DNA synthesis
116
Name a cause of post haemorrhagic anaemia
Intrinsic RBC abnormalities
117
Name a cause of haemolytic anaemia
Extrinsic abnormalities
118
Name some symptoms of anaemia
Fatigue, dyspnoea, faintness, palpitations, headaches, tinnitus, anorexia and worsened angina
119
Is high or low ferritin reliable diagnostically
Low. High could be caused by acute phase reactions
120
Which two causes of anaemia will show increased serum iron and ferritin and low total iron binding capacity
There is iron accumulation. Thalassaemia and sideroblastic anaemia. Both causes of microcytic anaemia
121
Name four causes of iron deficiency
Hookworm, menorrhagia, haemorrhage and diet
122
How can you investigate chronic disease in anaemia
Clinical investigation, laboratory investigation and renal failure
123
What is the normal range for mean cell volume
76-96fL
124
How can you investigate B12 deficiency
IF antibodies, Schilling test, coeliac antibodies.
125
What is the common cause of haematinic deficiency
Malabsorption
126
What does a raised reticulocyte count suggest
Increased removal of RBC
127
What does a low reticulocyte count suggest
Increased production of RBC
128
Which disease can cause RBC fragments
TTP
129
What is the Hb cut off for a transfusion
below 70g/L
130
In severe anaemia with heart failure what is the treatment
Transfusion
131
How does thrombopoietin homeostasis work
Low platelets leads to less bound TPO, therefore more free TPO which stimulates megakaryocytes and increases platelets
132
Where is thrombopoietin made
The liver
133
What is the normal platelet lifespan
7-10days
134
How are platelets removed
By the spleen
135
What is platelet function
Adhesion and aggregation using surface glycoproteins to form a platelet plug by primary haemostasis
136
Name platelet surface proteins
ABO, HPA, HLA class I and glycoproteins
137
Which surface protein is used for adhesion to collagen
GPIa
138
Which surface protein is used for adhesion to vWF
GPIb and IIb/IIa
139
What do platelet alpha granules contain
PDGF, Fibrinogen, vWF and PF4
140
What do platelet dense granules contain
Nucleotides (ADP), Calcium, serotonin
141
Which clotting factors are activated by membrane phospholipids
II (prothrombin), V and X
142
Name five causes of bleeding
Injury, vascular disorders, low platelets, abnormal platelet function and defective coagulation
143
Clinical features of platelet dysfunction
Mucuo-cutaneous features. Mucosal bleeding, easy bruising, petechia, purpura and traumatic haematomas
144
What is epistaxis
Bleeding from the nose
145
What is petechia
Small, round, flat, dark red spots caused by bleeding beneath/into the skin
146
What is purpura
Skin rash from capillaries bleeding into the skin, causes many petechia spots. May be due to either platelet or capillary dysfunction
147
Congenital causes of platelet dysfunction
Platelet disorders (Storage pool disorders, Glanzmann or Bernard Soulier) or von Willebrand disease
148
Acquired causes of platelet dysfunction
Uraemia or drugs
149
Name a cause of production failure causing low platelets
Congenital or acquired(drugs, marrow replacement, suppression, replacement or failure)
150
Name a cause of increased removal causing low platelets
Immune, consumption, splenomegaly
151
Name an artefactual cause of low platelets (normal but looks abnormal because of a testing error)
EDTA (anticoagulant used in test tubes) induced clumping
152
What is thrombocytopenia
A reduction in the number of platelets in the blood
153
What is the cause of congenital thrombocytopenia
Few functioning megakaryocytes in the bone marrow
154
Which diseases can cause infiltration of the bone marrow
Leukaemia, metastatic malignancy, lymphoma, myeloma and myelofibrosis
155
Name factors which would cause reduced production of platelets by the bone marrow
Low B12/folate, Reduced TPO, medication, toxins, infections, aplastic anaemia
156
Name a disease which causes dysfunctional production of platelets in bone marrow
Myelodysplasia
157
Name a disease which causes autoimmune destruction of platelets
Primary or secondary immune thrombocytopenia
158
Name two diseases which cause hypersplenism
Portal hypertension and splenomegaly
159
Name an example of drug related immune platelet destruction
heparin induced thrombocytopenia
160
What are causes of platelet consumptin
Disseminated intravascular coagulopathy (DIC), Thrombotic thrombocytopenic purpura (TTP), Haemolytic uraemic syndrome (HUS), Haemolysis, elevated liver enzymes and low platelts (HELLP), major haemorrhage
161
Which part of platelet function does clopidogrel target
P2Y12
162
Which part of platelet function does Tirofiban target
Gp IIb/IIa
163
Which part of platelet function does aspiring target
Cox inhibitor. Prevents thromboxane production from prostaglandin
164
In immune thrombocytopenia which type of immunoglobulin has formed
IgG
165
What is the cause of primary immune thrombocytopenia
May follow viral infection/immunisation in children
166
What is the cause of secondary immune thrombocytopenia
Malignancy or infection eg HIV
167
What causes cytokine release to initiate DIC
Systemic inflammatory response syndrome. Causes systemic activation of the clotting cascade
168
What are the consequences of systemic activation of the clotting cascade
Consumption of platelets and clotting factors (and therefore bleeding) and microvascular thrombosis (and therefore organ failure)
169
What is thrombotic thrombocytopenic purpura
Spontaneous platelet aggregation in the microvasculature of the brain, kidney and heart. Reduction in protease enzyme ADAMTS13 (cant break down vWF multimers)
170
How is the number of platelets investigated
Full blood count
171
How is the appearance of platelets investigated
Blood film
172
How is the function of platelets investigated
PFA and bleeding time
173
How are the surface proteins of platelets investigated
Flow cytometry
174
What is tranexamic acid used for
Inhibits breakdown of fibrin, so good for mucosal bleeding but not if GU bleeding as causes clot retention
175
What are the common causes of disseminated intravascular coagulation
Sepsis or malignancy or obstetric causes
176
What are schistiocytes
RBC fragments, microangiopathic haemolytic anaemia
177
Which three system's microvasculature is commonly affected by thrombocytopenia
Renal, CNS and cardiac
178
What is the key treatment for TTP
Urgent plasma exchange to replace ADAMTS13 and remove antibodies
179
What is D dimer
A protein which is the result of fibrin degradation
180
What are PT and APTT
Meaures of coagulation factors
181
What is the genetic abnormality in chronic myeloid leukaemia
Philadelphia chromosome
182
What are venous thromboses rich in and what should they be treated with
Fibrin rich, should be treated with anticoagulants
183
What are arterial thromboses rich in and what should they be treated with
Platelet rich, should be treated with antiplatelets
184
Which DVT are clinically important
Proximal thrombosis, between the knee and hip. Large enough to cause fatal PE
185
Risk factors for DVT
Surgery, oestrogen (OC pill, pregnancy, HRT), immobility/long haul flights, inherited thrombophilia
186
Name 4 mechanical preventions of DVT
Hydration, early remobilisation, compression stockings, foot pumps and
187
Name a chemical prevention of DVT
LMW heparin
188
What is a saddle embolus
One which blocks left and right pulmonary arteries, it is the most severe
189
Name consequences of a large pulmonary embolism
Hypotension, cyanosis, severe dyspnoea, right heart strain/failure
190
What is the consequence of a coronary circulation arterial thrombosis
Myocardial infarction
191
What is the consequence of a cerebral circulation arterial thrombosis
CVA or stroke
192
What are the consequences of a peripheral circulation arterial thrombosis
Claudication, rest pain and gangrene
193
Risk factors for atherosclerosis
Smoking, HTN, diabetes, hyperlipidaemia, obesity, stress (type A personality)
194
What are the signs of myocardial infarction
diagnosis history, ECG, cardiac enzymes
195
What are the signs of CVA
history and examination, CT scan/MRI scan
196
What are the signs of peripheral vascular disease
History and examination, ultrasound and angiogram
197
What are the signs of DVT
swollen, warm, tender leg
198
What are the signs of pulmonary embolus
Pleuritic chest pain, breathlessness, cyanosis, death
199
Genetic causes of venous thrombosis
Factor V leiden, PT20210A, antithrombin deficiency, protein C or protein S deficiency
200
Acquired causes of venous thrombosis
Antiphospholipid syndrome, lupus anticoagulant, hyperhomocysteinaemia
201
Investigations for DVT
D dimer and ultrasound compression test
202
Which type of DVT is more likely to recur
Spontaneous rather than provoked
203
What thromboprophylaxis is given to high risk patients
Dalteparin s/c od
204
What are the initial investigations in PE
CXR, ECG and blood gases
205
What is the standard drug therapy following PE or DVT
LMW heparin s/c od for 5 days, Oral warfarin 2.5 INR for 6 months
206
Why are DOACs replacing warfarin
They provide coagulation regulation without bleeding
207
What is the best diagnostic test for PE
An echo showing right heart strain
208
What does CTPA acheive
A 3D moving scan showing the pulmonary arteries either latent or full of filling defect
209
What is thrombosis
Blood coagulation within a vessel
210
Whaty does tissue plasminogen activator do (TPA)
Generates plasmin and degrades fibrin. Given in MI treatment
211
Name a DOAC
Rivaroxaban
212
Describe heparin's mechanism
A glycoaminoglycan it binds to antithrombin to increase its activity. Indirect thrombin inhibitor
213
How does LMWH differ from heparin
Smaller molecule with less varation in dose, it is renally excreted and give subcut od
214
Describe aspirin's mechanism
Inhibits COX irreversibly, acts for 7-10 day platelet lifetime. Inhibits thromboxane formation and therefore platelet aggregation
215
Describe clopidogrel's mechanism
Inhibts ADP induced platelet aggregation
216
Describe warfarin's mechanism
Antagonist of Vitamin K it prevents synthesis of factors 1(0)972 and prolongs the prothrombin time
217
How is warfarin measured
by INR which is international normalised ratio, derived from prothrombin time. Should be 2-3
218
Describe new oral anticoagulant drugs (NOAC) or DOAC's mechanism
Orally active, acts directly on factors 2 or 10, not used in pregnancy but no monitoring so used for extended thromboprophylaxis
219
What is the normal range of haemoglobin
131-166
220
What is the normal range of WBC
3.5-9.5
221
What is the normal range of platelets
150-400
222
What is the normal range of MCV
81.8-96,3
223
What is polycythaemia
High RBC
224
Name secondary causes of polycythaemia
(response to low oxygen) Smoking, lung disease, cyanotic heart disease, altitude and EPO excess (doping)
225
Name a primary cause of polycythaemia
Polycythaemia rubra vera
226
What causes polycythaemia rubra vera
JAK2 mutation
227
What is polycythaemia rubra vera
Myeloproliferative disorder, overactive bone marrow. Predominantly affects RBC but WBC and platelets as well
228
Clinical presentation of polycythaemia rubra vera
Plethoric appearance, thrombosis, itching, splenomegaly, abnormal RBC
229
What is the treatment of polycythaemia rubra vera
Aspirin, venesection and bone marrow suppressive drugs
230
What is neutrophilia
High neutrophils
231
Name reactive causes of neutrophilia
Infection, inflammation and malignancy
232
Name a primary cause of neutrophilia
Chronic myeloid leukaemia
233
What is lymphocytosis
High white blood cells
234
Name reactive causes of lymphocytosis
Infection, inflammation, malignancy
235
Name a primary cause of lymphocytosis
Chronic lymphoid leukaemia
236
What is thrombocytopaenia
Low platelets
237
What is thrombocytosis
High platelets
238
Name reactive causes of thrombocytosis
Infection, inflammation and malignancy
239
Name a primary cause of thrombocytosis
Essential thrombocythaemia
240
What is neutropaenia
Low neutrophils
241
What is classed as severe neutropaenia
<0.5 this is a severe infection risk
242
Name two causes of neutropaenia
Underproduction and increased removal
243
Name three causes of underproduction of neutrophils leading to neutropaenia
Marrow failure, marrow infiltration and marrow toxicity eg drugs
244
Name three causes of increased removal of neutrophils leading to neutropaenia
Autoimmune, felty's syndrome and cyclical
