Haematology Flashcards
(362 cards)
1
Q
Standard dose of iron supplementation?
A
Ferrous Fumarate 210mg tds for 3 months
Take with food (reduce SE)
2
Q
Standard dose for folate deficiency?
A
Folic acid 5mg od for 4 months
3
Q
Standard dose for B12 deficiency?
A
Loading doses- 3 injections weekly for 2 weeks, them 3 monthly (usually for life)
4
Q
What is microangiopathic haemolytic anaemia associated with?
A
Prosthetic heart valves (malfunctioning)
5
Q
Smoking can cause an increase in?
A
Hb, RBC, WCC
6
Q
What does chronic marrow hyperplasia cause?
A
Short stature
Increase energy demand in marrow= decreased energy for growth
7
Q
What is the test for autoimmune haemolytic anaemia?
A
Direct Coomb’s test
8
Q
What is warm autoimmune haemolytic anaemia?
A
IgG mediated
9
Q
What is cold autoimmune haemolytic anaemia?
A
IgM mediated
10
Q
Lifespan of a neutrophil?
A
7-8 hours in blood
Few days in tissue
11
Q
What are B symptoms?
A
Weight loss, fever, night sweats
12
Q
What does high PV indicate?
A
Increased protein in blood
- immunoglobulins (very high increase- usually malignant),
- acute phase reaction proteins (mild increase) etc.
13
Q
How can high PV be further investigated?
A
Electrophoresis
14
Q
What is rouleaux?
A
Stacks or aggregations of RBC
Occurs when plasma protein concentration is high
15
Q
What is the target INR?
A
2.5 (2-3)
16
Q
What is a leucoerythroblastic blood film?
A
Immature RBC and immature white cells in the blood stream
17
Q
What can interact with warfarin and increase efficacy? (high INR)
A
Antibiotics
18
Q
In haemolysis, what happens to haptoglobin and LDH levels in blood?
A
Haptoglobin decreases- binder for free Hb in RBC
LDH increases - releases from RBC
19
Q
What is MAHA?
A
Increased activation of coagulation forms fibrin mesh- RBC are physically damaged by these networks.
Small vessel damage to organs
20
Q
What 3 things does TTP (Thrombotic Thrombocytopenic Purpura) cause?
A
Low platelets
Low RBC
Kidney Failure
(similar to HUS)
21
Q
What are CRAB criteria for myeloma?
A
Calcium elevation
Renal failure
Anaemia
Bone disease
22
Q
What is Rituximab?
A
Monoclonal antibody than binds CD20 on lymphoma/leukaemia cells and induces lysis and apoptosis
23
Q
What is Imatinib?
A
Tyrosine Kinase Inhibition
For cancers with Philadelphia chromosome (CML, ALL)
24
Q
What can gram negative bacteria cause in neutropenic patients?
A
Fulminant life-threatening sepsis
25
What should everyone with a diagnosis of Non-Hodgkin's Lymphoma be tested for?
HIV
26
Important cause of generalised lymphadenopathy +/- lymphopenia/thrombocytopenia?
HIV
27
What is used to monitor intrinsic pathway?
APTT
| play table tennis INside
28
What is used to monitor extrinsic pathway?
PT
| PT= less extra letters
29
Which pathway does heparin act on?
Intrinsic pathway
| INtrinsic= heparIN
30
Which pathways does warfarin act on?
eXtrinsic
| X-1= Warfarin
31
Red cell fragmentation + polychromasia?
MAHA- microangiopathic haemolytic anaemia
| - can be due to HUS- ecoli (if + renal impairment)
32
What is the best test to use for sickle cell disease?
HPLC- haemoglobin high performance liquid chromatography (of whole blood lysate)
- confirm presence of HbS
33
Macroovalocytes and hypersegmented neutrophils?
B12/folate deficiency
34
Excess of blasts with Auer rods?
Acute Myeloid Leukaemia
35
Where does erythropoiesis take place in embryo?
Spleen
36
Where does erythropoiesis take place at birth?
Bone marrow + liver/spleen if needed
37
Where does erythropoiesis take place in adults
```
Bone marrow of:
Skull
Ribs
Sternum
Pelvis
Proximal head of femur etc.
(more in children, progressive loss of sites in ageing)
```
38
What feature do stem cells have that allow them to remain in good numbers?
Self-renewal
When divide, one stays as stem cell and one differentiates
39
What happens to erythrocytes as they differentiate? (3)
Increased Hb
Decreased nuclear size + RNA
Decreased cell size
40
Describe platelet formation?
In megakaryocytes
| Form in cytoplasm at periphery and bud off
41
What can raised neutrophils?
Infection
Trauma
Infarction
42
What are monocytes?
Precursors to macrophages
43
How to test for specific precursor cells and how does it work?
Immunophenotyping
Studies antigen expression on lymphoid cells
44
Where is bone marrow commonly aspirated from in adults?
Posterior iliac crests
45
RBC energy source?
Glycolysis (no mitochondria)
46
What is haemoglobin made up of?
1 haem group (porphyrin ring + Fe2+)
2 alpha, 2 beta globin chains
4O2
47
How are cells destroyed in the spleen?
Actively phagocytosed by macrophages
48
What do globin chains become after destruction?
Amino acids
49
What do haem groups become after destruction?
Bilirubin
50
How do RBC prevent Fe2+ becoming Fe3+?
Reduced by NADH from glycolysis
51
How do RBC prevent oxidative damage from free radicals?
Glutathione formed from NADPH
52
What is the rate limiting enzyme involved in the conversion of NADPH to glutathione?
G6PD
53
How is CO2 transported in blood?
Mostly bicarbonate (also bound to Hb or dissolved)
54
What is cooperative binding?
O2 binding changes Hb shape to make more binding easier
| SIGMOID CURVE
55
How do small molecules binding to Hb affect O2 affinity and tissue O2 delivery?
e.g. H+, CO2, 2,3-DPG
O2 affinity decreased
More released to tissue
56
Redistributive causes of low blood count?
Portal hypertension- splenomegaly- blood trapped in spleen
57
Redistributive causes of high blood count?
Steroids redistribute neutrophils to centre of vessel
58
What is haematocrit a measure of?
Volume of RBCs as % of total blood volume
59
Do reticulocytes have a nucleus/RNA?
No nucleus
| Still some RNA
60
Cause of microcytic RBCs?
Problem with haemoglobin production (cytoplasmic maturation)
61
Cause of macrocytic RBCs?
Problems with nuclear maturation (cell division)
62
In iron deficiency, what happens to transferrin levels?
Increase (apotransferrin- unbound)
63
Causes of iron deficiency?
Dietary
Blood loss
Pregnancy
Malabsorption
64
What increase in iron should be seen with iron replacement therapy?
7-10g/week
65
What is compensated haemolysis?
Increased RBC production so not anaemic
66
Ways of measuring haemolysis? (2)
```
Reticulocytes
Breakdown products (increased)
```
67
What is extravascular haemolysis?
In spleen+ liver- organomegaly
Release porphyrin-->
JAUNDICE + GALLSTONES
(normal products in excess)
68
What is intravascular haemolysis and causes?
Destroyed within circulation:
- ABO incompatibility
- G6PD deficiency
- Falciparum malaria
69
What is released during intravascular haemolysis? (4)
Abnormal products:
- Free Hb in serum
- Hb + albumin complex
- Pink urine- free Hb (black if oxidised)
- Haemosideruria (iron protein in urine)
70
Warm autoimmune haemolysis?
IgG
71
Cold autoimmune haemolysis?
IgM
72
Diagnosis of autoimmune haemolysis?
Direct Coomb's test- identify antibody bound to own RBCs- agglutination= +ve test
73
Other causes of autoimmune haemolysis? (2)
Haemolytic transfusion reaction
| Haemolytic disease of newborn
74
Mechanical causes of haemolysis?
```
DIC
HUS
TTP
Leaking heart valve- damage membrane
Infections e.g. malaria
```
75
Name 1 acquired cause of abnormal RBC membrane leading to haemolysis?
Vitamin E deficiency
76
Pathology of hereditary spherocytosis?
Mutations in membrane proteins that maintain flexibility/integrity- form spherical shape and spleen destroys
77
Features of G6PD deficiency?
X linked- men only
| Can't generate ATP in RBCs
78
In haemolysis, what happens to serum haptoglobins?
Decreased (bind the excess free Hb released)
79
What should all patients with a form of haemolytic anaemia be given and why?
Folic acid
Stimulate haematopoesis
80
Causes of microcytic anaemia? (7)
```
Iron deficiency
Thalassemia
Sideroblastic anaemia
Anaemia of chronic disease
Lead poisoning
Alcohol/drugs
Haemolysis (hereditary or acquired)
```
81
Causes of macrocytic anaemia? (5)
```
Pernicious anaemia
Folate def.
Alcohol/drugs
Liver disease
Hypothyroidism
Marrow failure
```
82
What is HbA?
Normal Hb- 2 alpha 2 beta
83
What is HbA2?
2 alpha + 2 delta
84
What is HbF?
Foetal Hb- 2 alpha + 2 gamma
85
How is expression of globin changes regulated throughout life?
Genes arranged in order of expression- get turned on/off in right-left pattern
86
What are thalassemias?
Decreased globin synthesis (therefore low haemoglobin)
87
2 types of thalassemias?
Alpha thalassemia= alpha chains affected
| Beta thalassemia= beta chains affected
88
Unbalanced accumulation of globin chains in thalassemias lead to..?
Toxic- leads to ineffective erythropoesis + haemolysis
89
Where are alpha genes found and how many are there?
Chromosome 16
| 4 genes
90
Where are beta genes found and how many are there?
Chromosome 11
| 2 genes
91
Alpha thalassemia affects which types of haemoglobin?
All types (all have alpha chains)
92
Symptoms of alpha thalassemia trait?
Asymptomatic
93
What is HbH disease?
One alpha gene left
| Anaemia, Splenomegaly, Jaundice
94
What is Hb Barts Hydrops Fetalis?
No alpha genes- no HbA
Severe anaemia, cardiac failure, reduced growth, severe hepatosplenomegaly, skeletal abnormalities
most DIE IN UTERO
95
What is beta thalassemia caused by?
Point mutation
| Only affects HbA
96
Symptoms of beta thalassemia major?
Pallor, failure to thrive, hepatosplenomegaly, skeletal changes- forehead/skull enlarged
97
Management of beta thalassemia major?
Regular transfusions
98
How do sickling disorders occur?
Point mutation in beta gene- makes HbS
99
How do sickling disorders cause anaemia?
HbS polymerises in low O2- damage RBC membrane
100
When might people with sickle trait suffer?
In severe hypoxia
101
Features of HbSS (sickle cell anaemia)?
2 abnormal genes- AR
| Haemolysis + hyposplenism
102
What is sickle crisis?
Causes tissue infarction de to vascular occlusion
| Pain- CNS, lung, marrow, hands, feet etc.
103
Precipitants of sickle crisis?
```
Hypoxia
Dehydration
Infection
Cold
Stress
Fatigue
```
104
Management of sickle cell anaemia?
Prophylactic penicillin
Folic acid
Regular transfusion
Hydroxycarbamide
105
Diagnosis of sickle cell anaemia?
Blood film
| Gel ELECTROPHORESIS
106
What does megaloblastic mean?
Abnormally large nucleated red cells with immature nuclei
| failure to become smaller
107
Cause of megaloblastic anaemia?
Defects in DNA synthesis/nuclear maturation + more prone to apoptosis:
B12/folate deficiency
108
Sources of folate?
Veg, cereal, kidney beans, yeast
109
B12 absorption? (5)
1. R-binder protein in mouth + stomach
2. Intrinsic factor from parietal cells
3. Pancreatic proteases in duodenum increase pH
4. Breaks down R-binder, B12 binds to intrinsic factor
5. Through to ileum- endocytosed
110
Body reserves of B12?
2-4 years
111
Causes of B12 deficiency?
```
Veganism
Gastritis
Bypass surgery
Chronic pancreatitis
Coeliac/Crohn's
PERNICIOUS ANAEMIA
```
112
What is pernicious anaemia?
Autoimmune destruction of parietal cells- intrinsic factor deficiency- low B12 absorption
113
What is pernicious anaemia associated with?
Other autoimmune- hypothyroid, vitiligo, Addison's
114
Where is folate absorbed?
Jejunum
115
Causes of folate deficiency?
```
Dietary
Haemolysis
Malignancy
Coeliac/Crohn's
Pregnancy
Anti-convulsants
```
116
Body reserves of folate?
4 months
117
Clinical features of folate deficiency?
```
Anaemia
Weight loss
Diarrhoea
Jaundice
Developmental problems
```
118
Clinical features of B12 deficiency?
Sore (beefy) tongue
| NEUROLOGICAL- neuropathy, dementia, column abnormalities
119
Autoantibodies in pernicious anaemia?
IF- anti-intrinsic factor
| GPC- anti-gastric parietal cell
120
What is non-megaloblastic anaemia?
Due to red cell membrane changes (mature but large cells)
121
Causes of non-megaloblastic anaemia?
Alcohol
Liver disease
Hypothyroidism
Marrow failure
122
When might you get a false macrocytosis (false high MCV)? (2)
1. Reticulocytosis- analysed as RBC but larger so give false large MCV
2. Cold agglutinations- in lymphoma
123
What can cause normocytic normochromatic anaemia? (3)
1. Acute blood loss
2. Early iron def.
3. Hypoproliferative- chronic disease, renal failure, hypothyroid, marrow failure
124
What is renal anaemia?
Lack of erythropoietin in renal failure
125
How does anaemia of chronic disease occur?
Inflammation causes upregulation of HEPCIDIN
- inhibits Fe absorption + release
- low erythropoiesis
126
Where does iron get absorbed?
Duodenum
127
What enhances iron absorption? (3)
1. Haem iron (red meat)- easy to digest
2. Ascorbic acid (vit C)
3. Alcohol
128
What inhibits iron absorption? (3)
1. Tannins (tea)
2. Phytates (cereals, nuts, seeds)
3. Calcium
129
In the duodenum, what converts Fe3 to Fe2?
Duodenal cytochrome B
130
What transports Fe2 into duodenal enterocyte?
DMT 1
131
How is iron exported from the duodenal enterocyte to bind to transferrin in the blood?
Ferroportin
132
What does hepcidin do?
Inhibit iron uptake- trap iron in duodenal cells
| due to inflammation, iron overload etc.
133
How much iron is needed per day?
25mg
134
How much iron is in plasma?
4mg (rest in macrophages/hepatocytes)
135
Skin and nail signs of iron deficiency?
Koilonychia
| Angular stomatitis
136
In iron overload, where is iron kept?
In parenchymal tissue e.g. liver, heart etc.
| Oxidative stress causes organ damage
137
Mutation in hereditary heaemochromatosis?
HFE gene
| Low hepcidin- high iron absorption
138
Bloods in hereditary heaemochromatosis?
Iron >5g
Transferrin sats >50%
Ferritin >300 micrograms/L
139
Presentation of hereditary heaemochromatosis?
In 40s-50s
| Fatigue, joint pain, arthritis, cirrhosis, diabetes, cardiomyopathy, impotence etc.
140
Treatment of hereditary heaemochromatosis?
```
Weekly venesection (450-500ml)
Keep ferritin <50micrograms/L
```
141
Secondary cause of iron overload?
Repeated transfusions
| Thalassemias etc.
142
What does FFP contain?
Clotting factors
143
What does cryoprecipitate contain?
Fibrinogen
144
The genes responsible for ABO are on which chromosome?
9
145
Which plasma antibodies do blood group A- have?
anti-B antibody
| anti-D antibody
146
Which plasma antibodies do blood group O have?
anti-A and anti-B antibodies
147
O blood can be given to?
Anyone
148
A blood can be given to?
A or AB
149
B blood can be given to?
B or AB
150
AB blood can be given to?
AB only
151
Group AB can receive blood from?
Any group
152
Which reagent is used to identify RBC antigens?
Antisera
153
Which reagent is used to identify plasma antibodies?
Reagent red cells
154
In tests to confirm a persons blood type, what is a positive test?
When agglutination occurs
155
In tests to confirm a COMPATIBILITY of blood transfusion (crossmatching), what is a good outcome?
NO agglutination means blood in compatible
156
Indications for RBC transfusion? (2)
Symptomatic anaemia
| Major haemorrhage
157
Indications for platelets transfusion? (3)
Prophylaxis for surgery in thrombocytopenia
Bleeding in thrombocytopenia
Prophylaxis in bone marrow failure
158
Indications for FFP transfusion? (3)
Bleeding in coagulopathy
Prophylaxis for surgery in coagulopathy
Massive haemorrhage
159
Symptoms of acute reaction in transfusion?
```
Chills
Rigors
Rash/itch
Flushing
Fever
Increased HR
Decreased BP
Collapse
PAIN
Sense of impending doom
```
160
Cause of acute haemolytic reaction in transfusion and type of hypersensitivity reaction?
ABO incompatibility- type 2 hypersensitivity
IgM + free Hb released
Cause renal failure!
161
Other cause of severe reactions in transfusion?
Bacterial contamination
162
What is TACO and symptoms?
Transfusion Associated Circulatory Overload
| resp. distress, high BP, high JVP, +ve fluid balance
163
Risk factors for TACO?
```
Elderly
HR failure
Low albumin
Renal impairment
Fluid overload
```
164
Management of TACO?
O2
Furosemide
Slow transfusion rate
165
Steps in massive haemorrhage protocol? (4)
1. Urgent blood samples
2. ABCDE
3. Transfuse blood component
4. Thromboprophylaxis once controlled
166
What is shock?
Tissue hypoperfusion due to circulatory failure
167
What can shock lead to?
Anaerobic metabolism- metabolic acidosis + lactic acid
| Eventually cellular NECROSIS
168
Recognition of shock? (5)
1. BP, HR, RR etc.
2. Mottling
3. GCS
4. Urine output <0.5ml/kg/hr
5. Lactate levels
169
Which types of shock have cold, clammy peripheries?
Cardiogenic
Obstructive
Hypovolaemic
170
Which types of shock have warm, red peripheries?
Distributive (due to vasodilation)
171
Lifespan of platelets?
7-10 days
172
What is primary haemostasis?
Formation of platelet plug
173
Steps of primary haemostasis? (3)
1. Endothelial damage= exposed collagen
2. Release von Willebrand Factor (vWF) which attracts platelets- ADHESION
3. Platelets secretes chemical causing AGGREGATION
174
Typical bleeding in primary haemostasis failure?
```
Spontaneous bruising
Purpura (lower limbs)
Mucosal bleeding- GI, nose, eye, menorrhagia
Intracranial haemorrhage
Retinal haemorrhage
```
175
What is secondary haemostasis?
Formation of fibrin clot- stabilise
176
Steps of secondary haemostasis? (6)
1. Platelet plug secretes calcium to make -ve surface positive
2. Attracts -ve clotting factors- activate each other
3. Endothelium releases tissue factor- activates factor VII
4. Activates factors V + Xa
5. Activates prothrombin (factor IIa) to thrombin (activates factors VIII + IXa to AMPLIFY)
6. Thrombin causes fibrinogen- FIBRIN
177
Typical bleeding in secondary haemostasis failure?
Into joints (ankles, knees etc.) and muscles
178
Prolonged PT=
factor VII deficiency
179
Prolonged APTT=
Haemophilia A/B
| von Willebrand deficiency
180
Vascular causes of primary haemostasis failure? (4)
Age (low collagen)
Connective tissue disorders
Scurvy (vit C needed for collagen)
Vasculitis
181
Platelet function causes of primary haemostasis failure? (2)
```
Drugs- aspirin/anti-platelets, NSAIDs
Renal failure (uraemia interrupts function)
```
182
Platelet number causes of primary haemostasis failure + examples? (3)
Low production- Marrow failure
High destruction- DIC, hypersplenism, immune thrombocytopenic purpura (ITP)
Consumption- bleeding
183
What is von Willebrand's disease and what does it affect?
AD inherited deficiency of vWF
| Affects platelet adhesion (primary haemostasis)
184
Why do men often have undiagnosed von Willebrand's disease?
Asymptomatic (women will have menorrhagia)
185
Which other clotting factor is affected in von Willebrand's disease?
Factor VIII low
| vWF normally carries and protects it
186
Causes of multiple clotting factor deficiency? (4)
Liver failure (no synthesis)
Vitamin K deficiency (no carboxylation of factors)
Warfarin
DIC
187
What is DIC?
Excessive and inappropriate activation of haemostasis
| Causes microvascular thrombus in organs- end organ failure + clotting factor consumption (bleeding)
188
Why is vitamin K important?
Carboxylation of glutamic acid to make factors II, V, IX, X + protein C + S
189
Causes of vitamin K deficiency?
Poor diet
Malabsorption
Obstructive jaundice
Haemorrhagic disease of newborn
190
When can DIC occur?
```
Trauma
Sepsis
Burns
Meningitis
Cancer
Hyovolaemic shock
```
191
What happens to PT and APTT in multiple clotting factor deficiency?
Both prolonged
192
What else is raised in multiple clotting factor deficiency?
D-dimers (fibrin degradation products)
| high in DIC) (low in liver disease
193
What is haemophilia A?
X linked disorder causing prolonged bleeding due to factor VIII deficiency
(x5 as common as B)
194
What is haemophilia B?
X linked disorder causing prolonged bleeding due to factor IX deficiency
195
Why does haemophilia cause prolonged bleeding?
Can't amplify clotting system
196
Symptoms of haemophilia?
Recurrent haemarthroses
Soft tissue bleeds
++ bleeding in surgery and dental extractions
197
How do recurrent haemarthroses occur?
One bleed increases the risk of another due to neovasculisation af the synivium
198
In haemophilia, which blood test will be abnormal?
APTT will be prolonged
199
In venous system, what kind of clots are formed?
FIBRIN rich clots
| NO platelet activation
200
Virchows triad applies to Venous system. What are the components?
vessel Wall (valves cause sluggish flow)
Hypercoaguability
Stasis
(WH Smith)
201
Signs of PE? (4)
SOB
Pleuritic chest pain
Rub
Hypoxia
202
Main differential of DVT?
Cellulitis
203
Risk factors for DVT/PE? (13)
```
Age
Marked obesity
Pregnancy (high clotting factors)
Puerperium
Smoking
Oestrogen therapy
Previous DVT/PE
Surgery/Trauma
Malignancy
Paralysis
Infection
IV drug use/PIC lines
Thrombophilia
```
204
Diagnosis of DVT? (4)
Peripheral pulses
Doppler USS
D dimer (raised in other things- -ve in low risk= exclude DVT)
Scoring systems
205
Treatment of DVT?
```
TED stockings
Early mobilisation
Physiotherapy
Heparin
Rivaroxaban
Warfarin
```
206
What is thrombophilia?
Deficiency in naturally occuring anticoagulants causing increased TENDENCY TO THROMBOSE (high coagulation activity)
207
What are the naturally occuring anticoagulants?
Antithrombin- acts on thrombin and Xa, IX, XI, XII
| Protein C+S- acts on V and VIII
208
Causes of hereditary thrombophilia? (3)
Factor V Leiden
Anti-thrombin deficiency
Protein C/S deficiency
209
What is Factor V Leiden?
Mutation of factor V stopping protein C binding and having its inhibitory effect--> overdrive leads to hypercoaguability
210
When should hereditary thrombophilia be considered? (4)
VTE <45 (esp men)
Recurrent VTE
Unusual VTE e.g. arm
FH of VTE or thrombophilia
211
Name a cause of acquired thrombophilia?
Anti-phospholipid syndrome (higher risk than inherited causes)
212
4 features of anti-phospholipid syndrome?
Activation of primary + secondary coagulation
Recurrent thrombosis
Recurrent pregnancy loss
Mild thrombocytopenia (ITP)
213
What is anti-phospholipid syndrome associated with? (4)
Autoimmune disorders
Lymphoproliferative disorders
Viral infections
Drugs
214
Treatment of thrombosis in anti-phospholipid syndrome?
Aspirin + warfarin
215
In general, what do anti-coagulants do?
Stop FURTHER clotting from occuring/breaking off
| Target fibrin clot formation
216
Indications for anti-coagulants?
Venous thrombosis
| AF
217
How does heparin work?
Increases action of anti-thrombin to prevent amplification of coagulation (with immediate effect)
218
2 forms of heparin?
LMWH- maintain antithrombin + Xa complex to keep switched on
| Unfractionated- needs lots of monitoring
219
How is heparin monitored?
APTT (unfractionated)
or
Anti Xa assay (LMWH)
220
Complications of heparin? (3)
Bleeding
Heparin induced thrombocytopenia
Osteoporosis after long-term
221
How is heparin reversed?
Stop- out of system in 12-24 hrs
| Protamine sulphate
222
How does warfarin work?
Inhibition of vitamin K
223
Steps in starting warfarin therapy? (4)
1. Initiation (Slow for AF, liver failure, elderly. Fast for acute thrombosis)
2. Stabilisation
3. Maintenance (same time each day)
4. Monitoring- PT to calculate INR
224
What is a normal INR and the target for warfarin therapt?
0.9-1.2
Target= 2-3
225
Major adverse effects of warfarin therapy?
Haemorrhage:
mild- brusing, epitaxis, haematuria
severe- GI, intracerebral, low Hb
226
Name some drugs that increase warfarin effect?
```
Antibiotics
Alcohol
Amiodarone
NSAIDS (GI bleeds)
+ pomegranate
```
227
In patients with metallic heart valves, which is the only anticoagulant that can be used?
Warfarin
228
How long should warfarin be stopped for before a surgery?
5-7 days
229
If INR is too high or there is major bleeding, how can the effect of warfarin be reversed? (3)
```
Omit dose(s)
Oral vitamin K
Clotting factors (factor concentrates)
```
230
How long does oral vitamin K take to work?
6 hours
231
What are DOACs?
Direct oral anticoagulants
232
DOACs: How do rivaroxaban, apixaban etc. work?
Activated factor X inhibitors (Xa-ban)
233
DOACs: How does dabigatran work and when can't it be used?
Thrombin inhibitor
Avoid in renal failure
234
What is fragmin?
Dalteparin- another anticoagulant
235
In arterial system, what kind of clots are formed?
Platelet rich clots
236
Cause of arterial thrombosis?
Usually atherosclerosis, recruit foamy macrophages
237
Stable plaques are calcified. What can happen to unstable plaques?
Rupture + recruit platelets --> acute thrombosis
238
Prevention of arterial thrombosis + examples?
Anti-platelets e.g. aspirin, clopidogrel, dipyridamole, abciximab
239
How does aspirin work?
Inhibits cyclo-oxygenase so can't produce thromboxane A2
240
How does clopidogrel work?
ADP receptor antagonist (reduce platelet aggregation)
241
How can the effects of anti-platelets be reversed in the case of severe bleeding?
Platelet infusion
242
What are myelocytes?
Precursor of neutrophils
243
Which cell layer are stem cells derived from?
Mesoderm
244
Where is bone marrow commonly aspirated from in children?
Tibia
245
How do cells exit the bone marrow?
Through fenestrations in the membranes- actively migrate down gradient into sinusoid
246
What is red marrow?
Haemopoietically active
247
What is yellow marrow?
Fatty, less cellular, inactive
| More with age
248
What is the myeloid:erythroid ratio and what is the normal range?
neutrophil precursors:nucleated RC precursors
1.5:1 - 3.3:1
249
When might the myeloid:erythroid ratio reverse?
When increased erythroid production e.g. haemolysis, blood etc.
250
What is a stem cell niche?
The microenvironment in which stem cells are found, which interacts with stem cells to regulate stem cell fate (expansion, differentiation, dormancy)
251
Secondary lymphoid tissue?
Lymph nodes
Spleen
(tonsils)
252
In lymph nodes, where are B cells found?
Follicles (also where antigens are presented)
253
In lymph nodes, where are T cells found?
Trabeculae
254
Causes of lymphadenopathy? (6)
```
Infection (local- e.g. TB or generalised- e.g. virus)
Vaccination
Autoimmune
Connective tissue disorder
Malignancy
Sarcoidosis
```
255
Which artery supplies the spleen?
Splenic artery from the coeliac axis
256
Which vein drains the spleen?
Splenic vein to the portal vein
257
The spleen is made up of red and white pulp. What is the function of each?
Red- sinusoids filters blood with marcophages
| White- antigen presenting cells
258
3 components of hypersplenism?
Splenomegaly
Reduced cellular component in blood
Correction of bloods with splenectomy
259
Causes of hypersplenism? (6)
1. Infection- EBV, malaria, TB
2. Congestion- portal hypertension
3. Haematological- ITP, haemolytic anaemia, leukaemia, lymphoma
4. Inflammatory- SLE, RA
5. Storage diseases
6. Others- amyloid, tumour, cyst
260
Causes of hyposplenism? (4)
Splenectomy
Coeliac disease
Sickle cell disease
Sarcoidosis
261
When might Howell-Jolly bodies be seen and what are they?
Nuclear remnant in RBC
Seen in hyposplenism (splenectomy, sickle cell disease etc.)
262
Characteristics of malignant haematopoiesis? (4)
```
MONOCLONAL
High numbers of abnormal/dysfunctional cells
- increased proliferation
- decreased differentiation
- decreased maturation
- decreased apoptosis
```
263
Why is malignant haematopoiesis monoclonal?
Due to mutated regulatory genes (driver mutations) being selected in evolution- one lineage chosen
264
Feature of acute haematological malignancy?
Primitive cells/precursors
265
Feature of chronic haematological malignancy?
Differentiated/mature cells
266
What can chronic lymphocytic leukaemia affect?
Lymph and blood
267
Features of acute leukaemias?
AGGRESSIVE- usually younger people
| Large cells + nuclei with MATURATION defects- blasts
268
What is the most common childhood cancer and how does it present?
Acute Lymphoblastic Leukaemia (ALL)- malignant lymphoblasts!
| Marrow failure, bone pain (rapid marrow expansion)
269
Which type of acute leukaemia is more common in elderly people (>60) and how does it present??
Acute Myeloid Leukaemia (AML)
May be de novo or following another haematological disorder
Marrow failure
270
How to differentiate between AML + ALL
Immunophenotyping
271
Treatment of AML + ALL?
Chemotherapy (most will go into remission but many will relapse again)
Stem cell transplant
272
Which pathology of lymph nodes will not be hard, but soft/rubbery?
Lymphoma
273
Which pathology of lymph nodes will not be smooth, but irregular?
Metastatic cancers
274
Which pathology of lymph nodes will cause overlying skin inflammation?
Bacterial infection
275
Which pathology of lymph nodes will cause the node to be tethered?
Metastatic cancers, sometimes bacterial infections
276
Ways to biopsy lymph nodes?
Core biopsy or FNA
or
CT guided biopsy of whole node
277
What tests are done to a lymph node biopsy?
```
Histology
Immunohistochemistry- for pattern of proteins
Immunophenotyping
Cytogenetic analysis
Molecular analysis
```
278
What is lymphoma?
Neoplasm of mature lymphocytes (more commonly B cells) in lymphoid tissue
279
What is Hodgkin's lymphoma?
More common in younger patients
Good prognosis
Had REED-STERNBERG (RS) CELLS
280
Treatment of Hodgkin's lymphoma?
Early- radiotherapy
| Late- chemotherapy
281
What is Non-Hodgkin's lymphoma?
No reed-sternberg cells
In elderly
Low or high grade
282
Prognosis of Non-Hodgkin's lymphoma?
Low grade- incurable but indolent (7-10 years)
| High grade- 30-40% survival
283
Treatment of Non-Hodgkin's lymphoma?
Low grade- palliative + supportive chemo
| High grade- combined chemo
284
Presentation of lymphoma?
```
PAINLESS lymphadenopathy
Fever, weight loss, drenching night sweats
Itch (no rash)- hot water
Alcohol induced pain
Hepatosplenomegaly
Bone marrow failure
```
285
How is the variable Ig segment on antibodies generated?
VDJ segment of gene (many combinations)
286
Fate of B cells after lymph node?
Circulate as memory B cells
or
Return to marrow as plasma cell
287
Immunoglobulins contain?
2 heavy + 2 light chains
288
Which immunoglobulin is a pentamer?
IgM
289
Which immunoglobulin is a dimer?
IgA
290
What is the marker of underlying clonal B cell disorder, and how is it detected?
Paraprotein (MONOclonal immunoglobulin in urine/blood)
by ELECTROPHORESIS
291
What is Bence Jones protein?
Immunoglobulin light chain in urine if made in excess (leaks into urine)
292
Causes of paraproteinaemia? (5)
```
MGUS
Myeloma
Amyloidosis
Lymphoma
Waldenstrom's macroglobulinaemia
```
293
What is myeloma and how is it classified?
Monoclonal proliferation of plasma cells (activated B cells)
Classified by type of antibody produced
294
Why does myeloma affect bones and what does it cause?
Causes dysregulated OSTEOCLAST activity
- LYTIC bone lesions
- bone pain
- pathological fracture
- hypercalcaemia
295
Symptoms of myeloma due to paraproteins?
Renal failure (CAST NEPHROPATHY- clumping of light chains)
Amyloidosis
Hyperviscosity
Immune suppression
296
Investigations of myeloma?
```
FBC, PV, U+E
Blood film
Serum Ca
Marrow aspirate
DEXA scan/Xray
Urine- BJP
```
297
What would a blood film show in myeloma?
Rouleaux
298
Treatment of myeloma?
```
Not cureable
Chemotherapy
Dexamethasone/pred
Stem cell transplant
New- thalidomide, bortezomib, lenalidomide
BISPHOSPHONATES
```
299
How is response to treatment monitored in myeloma?
Paraprotein level
300
What is monoclonal gammopathy of undetermined significance (MGUS)?
Paraprotein <30g/L (less than myeloma)
NO evidence of myeloma/organ damage
BENIGN (small chance of myeloma progression)
301
What is AL amyloidosis?
(Amyloid light-chain amyloidosis)
| Abnormal plasma cell- mutation in light chain- form insoluble beta sheet
302
Which stain is used to confirm amyloidosis?
Congo Red Stain (appear apple green)
303
Treatment of amyloidosis?
Chemotherapy (switch off light chain supply)
304
What is Waldenstrom's Macroglobulinaemia and what paraprotein is produced?
Clonal disorder of immediate cell between lymphocytes + plasma cells
IgM paraprotein
305
Presentation of Waldenstrom's Macroglobulinaemia?
```
Lymphadenopathy
Splenomegaly
Marrow failure
Neuropathy
Night sweats, weight loss
HYPERVISCOSITY- bleeding, fatigue, cardiac failure
```
306
Treatment of Waldenstrom's Macroglobulinaemia?
Chemo
| PLASMAPHERESIS- remove own and replace with donor plasma
307
What is pancytopenia?
```
Deficiency in all blood cell lineages
Low RBC
Low platelets
Low white cells
(generally excludes lymphocytes)
```
308
Cause of pancytopenia due to reduced production?
Marrow failure
309
Inherited causes of marrow failure?
Rare
| Fanconi's anaemia- imparied haemopoiesis, congenial abnormalities, cancer pre-disposition
310
Acquired causes of marrow failure?
Primary- idiopathic aplastic anaemia, myelodysplastic syndromes (MDS), acute leukaemia
Secondary- drugs, B12/folate def., infiltrative, viral
311
How does idiopathic aplastic anaemia affect marrow?
Reduced red marrow
312
What can myelodysplastic syndromes (MDS) lead to?
AML
313
Cause of pancytopenia due to increased destruction?
Hypersplenism- blood trapped + increased phagocytic activity
314
Causes of hypersplenism?
Portal hypertension
Rheumatoid arthritis
Splenic lymphoma
315
Presentation of pancytopenia?
Anaemia
Infections
Bleeding
316
Investigations of pancytopenia?
```
FBC + retic count
Blood film
LFT
B12 + folate
Autoantibodies
Aspirate
```
317
When is marrow hypocellular?
Aplastic anaemia
318
When is marrow hypercellular?
B12/folate deficiency
Hypersplenism
Myelodysplastic syndromes
319
Treatment of pancytopenia?
Red cell + platelet transfusion
Antibiotic prophylaxis
Marrow transplant
Consider splenectomy
320
What are myeloproliferative disorders (MPD)?
```
Clonal proliferations (increased production) or one/more lineages
MATURATION preserved
```
321
Name some myeloproliferative disorders (MPD)?
Red cells- polycythaemia rubra vera
Platelets- essential thrombocythaemia
White cells- CML
Reactive fibroblasts- myelofibrosis
322
Which myeloproliferative disorders are BCR-ABL1 positive?
CML
323
What bloods would causes suspicion of myeloproliferative disorders?
```
High granulocytes
High RBC/Hb
High platetetls
Eosinophilia/basophilia
May have splenomegaly
```
324
What does chronic myeloid leukaemia cause?
Proliferation of myeloid (granulocytes + platelets)
325
Presentation of chronic myeloid leukaemia?
```
Peak 40-50 years
Often asymptomatic
Splenomegaly
B symptoms
Gout
Small vessel problems (e.g. eyes)
```
326
3 phases of chronic myeloid leukaemia?
1. Chronic phase
2. Accelerated phase
3. Blast phase (crisis)- like acute leukaemia
327
Hallmark of CML?
PHILADELPHIA CHROMOSOME- produces BCR-ABL 1 gene
| which is a tyrosine kinase
328
Investigation of CML and findings?
FBC- normal/low Hb, leucocytosis, neutrophilia, myelocytes, thrombocytosis,
329
Treatment of CML?
Imatinib- tyrosine kinase inhibitor
330
Common features of BCR-ABL1 negative MPD? (6)
```
Asymptomatic or
B symptoms
Gout
Splenomegaly
Marrow failure
Thrombosis (A+V)
```
331
What polycythaemia rubra vera?
High Hb/haematocrit + ERYTHROCYTOSIS
| may also cause increased WCC/platelets
332
Causes of secondary polycythaemia?
Smoking
Chronic hypoxia
EPO-secreting tumours
333
What is pseudopolycythaemia?
Apparent increase in RBCs due to reduction in plasma volume
| e.g. dehydration, diuretic, obesity
334
Clinical features of polycythaemia rubra vera?
55-60 yrs
Headache, fatigue, dizziness, sweating, plethora, ITCH AFTER WARM WATER
Splenomegaly
Thrombosis + bleeding
335
What is polycythaemia rubra vera associated with?
JAK2 mutations in 95%
Kinase- loss of auto-inhibition of erythropoiesis (increased)
336
Treatment of polycythaemia rubra vera?
Aspirin 75mg/day
Venesection
Hydroxycarbamide (oral chemo)
337
What is essential thrombocythaemia?
Uncontrolled production of abnormal platelets
| Leading to thrombosis
338
Presentation of essential thrombocythaemia?
Peak 50-70yrs
Asymptomatic
Burning in hands/soles, cold peripheries, headache, dizziness, digital ischaemia, gangrene
Epitaxis, menorrhagia
339
What is essential thrombocythaemia sometimes associated with?
acquired vWF deficiency due to excess platelets
| Leads to bleeding
340
Investigation of essential thrombocythaemia?
Exclude reactive causes
Exclude CML
JAK2 mutation (50%)
CALR in those without JAK2
341
Treatment of essential thrombocythaemia?
Aspirin
| Hydroxycarbamide (oral chemo)
342
What is myelofibrosis?
Progressive scarring (fibrosis) in bone marrow
343
2 causes of myelofibrosis?
Idiopathic
or
Secondary (transformed) for PRV or ET
344
Presentation of myelofibrosis?
>50s (60-70)
Extramedullary haemopoiesis (liver + spleen
Marrow failure
Fatigue, weight loss, itch
345
Investigations of myelofibrosis + findings? (4)
Blood film (leukoerythroblastic film + TEARDROP RBCs)
Dry aspirate on attempt
Trephine biopsy (stain for fibrosis)
JAK2/CALR mutation
346
How do teardrop RBCs occur?
Damaged when squeezing through sclerotic bone marrow
347
Treatment of myelofibrosis?
```
Blood/platelet transfusion
Antibiotics
Stem cell transplant
Consider splenectomy
JAK2 inhibitor- Ruxolitinib
```
348
Name a JAK2 inhibitor?
Ruxolitinib
349
How does cytotoxic chemotherapy work?
Damage DNA which promotes apoptosis
350
Name some cell cycle specific (tumour specific) drugs? (3)
Methotrexate
Hydroxyurea
Mitotic spindle inhibitors
351
Name some non-cell cycle specific drugs? (3)
Alkylating agents
Platinum derivatives
Cytotoxic antibiotics
352
Nucleated red cells in blood of a newborn baby may suggest?
NORMAL
353
What are Heinz bodies and some causes? (4)
Formed by damage to Hb (usually oxidative)
1. G6PD def
2. NADPH def
3. Chronic liver disease
4. Alpha thalassemia
354
Name some anticoagulants and what are they used for?
Warfarin, Heparin, DOACs
Venous (red) thrombosis
355
Name some antiplatelets and what are they used for?
Aspirin, Clopidogrel
Arterial (white) thrombosis
356
Giving folate in B12 deficiency can lead to what?
Demyelination!!
| make sure to find out cause of anaemia!
357
How does methotrexate affect heamatopoiesis?
Inhibits folate (monitor levels/give folic acid)
358
Smudge cells?
CLL
359
t(8;14)?
Burkitt's Lymphoma
360
What are schistocytes seen in?
DIC, TTP
361
Which clotting factors are used up first in DIC?
Consume factors V + VIII (and platelets) first
362
Deficiencies of which clotting factors will cause prolonged PT and APTT?
II, V, X (common pathway factors)
