Anaemia Flashcards
1
Q
Basics of what blood does?
A
supply O2 to tissues
supply of nutrients (e.g. glucose, amino acids, and fatty acids)
removal of waste such as CO2, urea and lactic acid
immunological functions (white cells and immunoglobulins)
coagulation
messenger functions (e.g. transport of hormones, signalling of tissue damage)
2
Q
Composition of blood
A
plasma (55%) - includes water, proteins and other solutes
cells (45%) - platelets, red blood cells, white blood cells (including - lymphocytes, monocytes, granulocytes - basophils, neutrophils and eosinophils)
3
Q
red blood cell function
A
responsible for transporting oxygen from your lungs to your body’s tissues
4
Q
lymphocytes function
A
determine the specificity of the immune response to infectious microorganisms and other foreign substances.
- type of white blood cell
5
Q
granulocyte function
A
Granulocytes work together to rid your body of infection or allergens. Each type of granulocyte has its own combination of chemicals and enzymes in its granules
-type of white blood cell
6
Q
basophil function
A
they have the ability to help detect and destroy some early cancer cells. Another important function of basophils is that they release the histamine in their granules during an allergic reaction or asthma attack
- type of granulocyte, which is a type of white blood cell
7
Q
eosinophil function
A
movement to inflamed areas, trapping substances, killing cells, anti-parasitic and bactericidal activity, participating in immediate allergic reactions, and modulating inflammatory responses.
-type of granulocyte, which is a type of white blood cell
8
Q
hematopoiesis
A
process of making blood cells
9
Q
FBC
A
full blood count
check the types and numbers of cells in your blood, including red blood cells, white blood cells and platelets.
10
Q
describe reticulocyte count
A
a blood test that measures the amount of these cells in the blood. In the presence of some anemias, the body increases production of red blood cells (RBCs), and sends these cells into the bloodstream before they are mature.
normal range is from 0.5% to 1.5%
11
Q
what does a blood film show
A
the evaluation of white blood cells (WBCs, leucocytes), red blood cells (RBCs, erythrocytes), and platelets (thrombocytes)
12
Q
basic properties of red blood cells (erythrocytes)
A
smooth biconcave disc shape
anucleate
life span: 90-120 days
clearance by the reticuloendothelial system (mainly the spleen)
13
Q
development of red blood cells (erythrocytes)
A
stimulated by erythropoietin (EPO)
oxygen levels sensed by kidney which modulates EPO production
androgens also increase red cell production
14
Q
basic properties of platelets
A
small and anucleate
life span: 7-10 days
normal clearance by reticuloendothelial system (mainly the spleen)
15
Q
Development of platelets
A
stimulated by thrombopoetein (TPO) produced by the liver
TPO increases number / differentiation megakaryocytes
arise through fragmentation of megakaryocytes cytoplasm
16
Q
function of platelets
A
blood coagulation upon vasculature injury
surface coated with glycoproteins for adhesion/aggregation
bind to fibrinogen for platelet-platelet aggregation
release granules and active clotting cascade
17
Q
basic properties of neutrophils
A
multi lobed nucleus , granular cytoplasm
lifespan - 6-10 hours
normal clearance by reticuloendothelial system (mainly spleen)
18
Q
Development of neutrophils
A
mature in bone marrow prior to circulation
require G-CSF (granulocyte colony stimulating factor)
19
Q
neutrophil function
A
detect microbial invasion via inflammatory mediators
engulf microbes (bacteria) by phagocytosis
kill/digest microbes using reactive oxygen species (H2O2) and enzymes (myeloperoxidases)
20
Q
basic properties of monocytes
A
largest leucocyte
diverse subsets and functions
life span 1-2 days
21
Q
development of monocytes
A
require GM - CSF (granulocyte - macrophage colony stimulating factor) and M- CSF (macrophage colony stimulating factor) for development
share common progenitor with granulocyte
develop into macrophages and dendritic cells in tissue
22
Q
function of monocytes
A
phagocytosis of bacteria/virus
antigen presenting cells
replenish tissue macrophages/dendritic cells
23
Q
basic properties of lymphocytes
A
small highly specialised subsets; B cells, T cells, NK cells
life span varies depending on subtype
24
Q
Development of lymphocytes
A
initially develop in the bone marrow
development completed in circulation and secondary lymphoid organs
25
describe plasma cells
derived from mature B cells
reside in bone marrow
produce antibody
eccentric round nucleus, basophilic cytoplasm
26
What does a full blood count measure
```
concentration of haemoglobin: Hb
red cell to plasma ratio: Hct or PCV
Cell size (mean cell volume = MCV)
amount of Hb/ RBC
cell numbers (RBC)
```
27
Describe mean cell volume (MCV)
indicates red cell volume
| normal range: 80-100fL
28
microcytic anaemia MCV
<80fL
29
normocytic anaemia MCV
80-100fL
30
macrocytic anaemia MCV
>100fL
31
what does it mean if reticulocytes are increased
reduced RBC survival
| - haemolysis (premature destruction) or bleeding (loss)
32
what does it mean if reticulocyte numbers are decreased
there is a problem with production
33
Four components of normal haemostasis
blood vessel wall
platelets and von willebrand factor
coagulation factor
fibrinogen
34
platelets 3 main roles in haemostasis
1. to adhere to subendothelial proteins after vascular damage to initiate haemostasis
2. activate and aggregate with other platelets
3. support the activation of coagulation factors
35
von willebrand factor
complex adhesive plasma protein synthesised by vascular endothelium
36
von willebrand factor main role in haemostasis
binds platelet surface proteins to mediate platelet adhesion
37
endothelial cells in haemostasis
| negative regulators - soluble and surface
critical negative regulators of haemostasis
- soluble mediators: prostacyclin, NO
- surface mediators: endothelial protein c receptor, thrombomodulin, heparans
( Negative feedback occurs when a change in a. variable triggers a response. which reverses the initial change.)
38
sub-endothelium in haemtostasis
contains activators of haemostasis:
| -collagen, tissue factors, von willebrand
39
describe coagulation factors
series of inactive zymogen proteins in plasma
assemble into functional 'tenase' and 'protrombinase' complexes on surface of activated platelets
results in rapid burst conversion of prothrombin (FII) to thrombin
40
what is fibrinogen
complex high molecular weight protein abundant in plasma
41
2 Main roles of fibrinogen in haemostasis
1. binds platelet surface integrins to mediate platelet aggregation
2. polymerised by thrombin to form fibrin clot
42
define haemostasis
process to prevent and stop bleeding, meaning to keep blood within a damaged blood vessel.
43
describe the steps in haemostasis
step 1: trigger
- collagen and tissue factors are exposed
- von willebrand factor (vWF) binds collagen
step 2: primary haemostasis
- platelets adhere to vWF-collagen
- platelets activate and aggregate
step 3: thrombin generation
- TF (tissue factor) initiates rapid thrombin generation on activated platelets
step 4: thrombin consolidates clot formation
- thrombin converts fibrinogen to fibrin and completes platelet activation
- stable fibrin- platelet clot is formed
44
two parts of regulation of homeostasis
clot formation
| fibrinolysis
45
describe clot formation in the regulation of homeostasis
- vWF (von willebrand factor) adhesivity is regulated by ADAMTS 13
- thrombin is regulated by antithrombin and the activated protein C system
46
describe fibrinolysis in regulation of homeostasis
- thrombin activates the protease plasminogen to plasmin
- fibrin cleaved by plasmin into fibrin degradation products (incl. D dimer)
Fibrinolysis is a process that prevents blood clots from growing and becoming problematic. Primary fibrinolysis is a normal body process, while secondary fibrinolysis is the breakdown of clots due to a medicine, a medical disorder, or some other cause.
47
4 core laboratory tests of haemostasis
1. platelet count and blood film
2. Coagulation screen (including prothrombin time (PT) and activated partial thromboplastin time (APTT))
3. fibrinogen level
4. D dimer level
48
3 things a prolonged PT or/and APTT indicate??
1. reduced levels of coagulation factor(s) (from genetic or acquired bleeding disorders)
2. Reduced function of coagulation factor(s) (most anticoagulant drugs)
3. Laboratory artefact ( could be from: wrong blood tube, incompletely filled blood tube, heparin contamination of samples, antiphospholipid syndrome)
49
what does it mean if just the PT interval is prolonged (what factor/ pathway?)
Factor VII
(extrinsic pathway)
This may be caused by conditions such as liver disease, vitamin K deficiency, or a coagulation factor deficiency (e.g., factor VII deficiency).
50
what does it mean if just APTT interval is prolonged
| what factor/pathway?
Factors VIII, IX, XI
| intrinsic pathway
51
what does it mean if PT and APTT are both prolonged in terms of factor involved and pathway
means multiple factor defects
factors II, V, X, fibrinogen
(common pathway)
52
what does high fibrinogen levels indicate
acute phase response
pregnancy
(is a prominent systemic reaction of the organism to local or systemic disturbances in its homeostasis caused by infection, tissue injury, trauma or surgery, neoplastic growth or immunological disorders)
53
what is acute phase response
group of proteins whose concentrations in blood plasma either increase or decrease due to inflammation
54
describe how fibrinogen levels are measured
plasma levels are usually measured using a clotting assay similar to PT or APTT
normal levels are ~1.5-4.0g/dL
55
what does low fibrinogen levels indicate
some important acquired bleeding disorders
| liver disease, massive transfusion, disseminated intravascular coagulation (DIC)
56
what is DIC
disseminated intravascular coagulation
- serious disorder in which the proteins that control the blood become overactive
- small blood clots develop throughout the bloodstream, blocking small blood vessels. The increased clotting depletes the platelets and clotting factors needed to control bleeding, causing excessive bleeding.
57
what causes DIC
inflammation in response to an infection, injury or illness
severe tissue damage from burns, or trauma
clotting factors caused by some cancers or pregnancy complications
58
describe D-dimer level
D-dimer is a fibrin degradation product
plasma levels measured by immunoassay
normal levels ~<500ng/mL
59
3 things that elevated D-dimer indicate
1. DIC (disseminated intravascular coagulation)
2. VTE (venous thromboembolism)
3. pregnancy, liver or kidney disease, sepsis, malignancy, inflammation, increasing age
60
what is Thromboelastography
is a viscoelastic hemostatic assay that measures the global viscoelastic properties of whole blood clot formation under low shear stress. TEG shows the interaction of platelets with the coagulation cascade (aggregation, clot strengthening, fibrin cross-linking and fibrinolysis)
61
some specialist laboratory tests for the blood (factors)
1. levels of coagulation factors
2. von willebrand factor levels
3. platelet function tests
4. Bone marrow morphology
5. anticoagulant drug levels
62
5 signs of DVT
```
leg pain
swelling
tenderness
discolouration
pitting oedema
```
63
6 signs of PE
```
SOB
Cough (haemoptysis)
chest pain
tachycardia
hypotension
low-grade fever
```
64
two long term consequences of VTE
PTS - post thrombotic syndrome
| CTEPH - chronic thromboembolic pulmonary hypertension
65
what is PTS (post thrombotic syndrome) / describe it
-chronic venous stasis with swelling, discomfort, skin -changes, and sometimes skin ulceration
-caused by damage to venous valves by thrombus in DVT
(20-50% of patients develop PTS after DVT)
66
what is CTEPH (chronic thromboembolic pulmonary hypertension)/describe it
chronic breathlessness, hypoxia, and right sided heart failure
caused by obstruction of major pulmonary arteries
(affects up to 9.1% patients who have had symptomatic PE)
lifelong anticoagulant is recommended
67
3 factors in virchows triad
hyper coagulability
venous stasis
endothelial injury
68
what does virchows triad do?
describes 3 factors that are important in the development of a venous thrombus
69
what is venous stasis
loss of proper vein function of the legs that would usually carry blood back towards the heart
70
6 risk factor categories for VTE
1. physiological factors (dehydration, obesity, pregnancy, older age)
2. medications (HRT, some cancer treatments, oestrogen containing contraception)
3. cancer (cancer type, stage)
4. VTE and thrombophillia (VTE personal history, first degree relative with VTE, thrombophillia (inherited or acquired))
5. hospitalisation/ surgery (surgery with general anaesthetic >90mins, critical care admission, hospital admission especially infection, inflammation, reduced mobility, etc. )
6. other factors (medical comorbidities, significant reduction in mobility, vascular access and devices)
71
3 different clinical circumstance of VTE
1. provoked by transient significant factor within the last 3 months (such as recent hospitalisation/surgery, pregnancy, oestrogen therapy, lower limb immobilisation)
2. provoked by transient minor risk factor (e.g. long haul flight)
3. unprovoked (no obvious precipitant)
72
Steps to diagnose DVT
- two level DVT wells score
- D-dimer (screening tool)
- Confirmatory tests (venous ultrasonography, MRV or CTV for VTE at unusual sites)
(MRV - magnetic resonance venography- used contrast dye to visualise veins)
(CTV - computed tomography venography)
73
where are the unusual sites for a VTE
upper limb
cerebral
portal or hepatic vein
IVC or SVC
74
steps to diagnose a PE
```
two level PE wells score
D-dimer (Screening tool )
ECG
chest radiograph (CXR)
confirmatory tests: (CTPA - computer tomography pulmonary angiogram, VQ scan)
```
75
what can give you a false negative D dimer
if someone is on anticoagulants
| late VTE presentation
76
what is thrombophilia
condition that increases your risk of blood clots
77
inherited causes of thrombophilia
- Factor V Leiden (most common)
- prothrombin gene mutation
- natural anticoagulant deficiencies (antithrombin, protein C and S - all rare)
78
what to do if suspected acquired thrombophilia
screen for antiphospholipid syndrom
79
what is antiphospholipid syndrome
a condition in which the immune system mistakenly creates antibodies that attack tissues in the body. These antibodies can cause blood clots to form in arteries and veins.
80
6 clinical features of antiphospholipid syndrome
1. arterial thrombosis
2. VTE
3. microvascular thrombosis
4. pregnancy loss (recurrent early or late)
5. livedo reticularis
6. thrombocytopenia
livedo reticularis - refers to various conditions in which there is mottled discolouration of the skin.
81
VTE treatment
DOAC - direct oral anticoagulants
82
4 most common clinical indications for anticoagulants
1. VTE treatment (therapeutic dose)
2. VTE prevention ( lower prophylactic dose)
- Primary (in hospital)
- Secondary (after 3-6 months treatment after VTE)
3. stroke prevention in AF (therapeutic dose)
4. mechanical heart valves (therapeutic dose)
83
LMWH stands for?
| A little bit about it...
low molecular weight heparin
derived from unfractionated heparin
acts longer and more predictably in the body than UFH
can be administered at home (subcut.) and doesn't require monitoring like UFH
84
UFH stands for?
| a little bit about it..
unfractionated heparin
fast acting blood thinner
binds to antithrombin and enhances bodies ability to inhibit factors xa and IIa (most potent clot forming factors)
it doesn't breakdown clots but stop them growing and new ones forming
rapidly reversed by protamine
85
what is UFH reversed by
protamine
| With UFH meaning unfractionated heparin
86
what is warfarin
oral anticoagulant
| a coumarin derivative
87
how does warfarin work
inhibits vitamin K metabolism
| reduces levels of vitamin K dependent clotting factors II, VII, IX, X
88
describe a bit about warfarin
| onset and half life, causes increased what? monitoring using? what is it reversed with?
slow onset and long half life
causes increased PT and APTT
monitoring using INR test (range 2-3)
reversed with vitamin K
89
When would you prescribe warfarin
- obviously no contra indications
-mechanical heart valve
-severe renal failure
_APLS
-AF with rheumatic mitral stenosis
90
mechanism of warfarin
inhibitor of vitamin K - dependent factors
91
mechanism of Apixaban (DOAC)
direct inhibitor of Xa factor
92
mechanism of dabigatran (DOAC)
direct thrombin inhibitor
93
mechanism of rivaroxaban (DOAC)
direct factor Xa inhibitor
94
mechanism of edoxaban (DOAC)
direct factor Xa inhibitor
95
known risk factors for anticoagulant related bleeding
```
previous major bleed
increasing age
renal impairment
uncontrolled hypertension
concurrent anti platelet medication
excess alcohol
high risk of injury
bleeding disorder
```
96
rank the renal clearance of these drugs from highest to lowest:
Warfarin, Apixaban , dabigatran, rivaroxaban , edoxaban
```
Dabigatran (88%)
Edoxaban (50%)
Rivaroxaban (33%)
Apixaban (27%)
Warfarin (8%)
```
97
rank the half life of these drugs from longest to shortest:
| Warfarin, Apixaban, Dabigatran, Rivaroxaban, Edoxaban
```
Warfarin (40hrs)
Dabigatran (12-18 hrs)
Apixaban (12hrs)
Edoxaban (10-14hrs)
Rivaroxaban (5-9hrs in young, 11-13 elderly)
```
98
Are these things more common in primary haemastosis disorders or coagulation disorders?
- Haemarthrosis (bleeding into joints)
- Haematoma (bleeding into soft tissue)
- Bruises/petechiae/purpura/eccyhymosis
- epistaxis, oral bleeds (nose and mouth)
- heavy menstrual bleeding
- obstetric and surgical bleeding
- CNS and gut
- Haemarthosis: Coagulation disorder
- Haematoma: Coagulation disorder
- Bruises/petechiae:primary haemastosis disorders
- Epistaxis:primary haemastosis disorders
- Heavy menstrual bleeding: both
- Obstetric and surgical: both
- CNS and gut: both
99
What is ISTH score used for
used to determine DIC (disseminated intravascular coagulation)
100
What deficiency does haemophilia A have?
factor VIII
101
what deficiency does haemophilia B have?
Factor IX
102
Haemophilia clinical and laboratory features
soft tissue and joint bleeding (haematoma/haemarthosis)
bleeding after surgery and dental extraction
lab results:
increased APTT but normal PT and PLT
decreased factor VIII OR factor IX
103
what happens in terms of haemostasis in liver disease
- decreased clotting factors, fibrinogen and regulator levels because of reduced protein synthesis
- decreased clotting factor function because of vitamin K malabsorption in cholestasis
- decreased PLT numbers because of reduced thrombopoietin synthesis
- decreased PLT function because of metabolic disturbance
- increased fibrinolysis
104
what is cholestasis
decrease in bile flow due to impaired secretion by hepatocytes or to obstruction of bile flow through intra-or extrahepatic bile ducts. Therefore, the clinical definition of cholestasis is any condition in which substances normally excreted into bile are retained.
105
what is PLT count
count of platelets
106
clinical and lab features of liver disease (thinking ABC cycle)
```
bleeding in skin, soft tissue and GI tract
lab results:
increased PT and APTT
decreased fibrinogen
decreased platelet count (PLT)
increased D dimer
```
107
lab features of patient in DIC
increased PT and APTT (partial thromboplastin time)
decreased platelet count (PLT)
++ increased D dimer
Plus: usually anaemia and evidence of organ dysfunction
108
two pro-haemostatic drugs
tranexamic acid - major haemorrhage
Desmopressin (DDAVP) - minor
(allows blood to form clots)
109
describe tranexamic acid
what does it do and what is it effective in treating
- blocks plasmin binding and activation on fibrin and reduces fibrinolysis
- effective in genetic and acquired bleeding disorders and in major haemorrhage
110
describe Desmopressin (DDAVP)
- releases endogenous factor VIII and vWF
| - effective in mild haemophilia A and vWF deficiency, but also in other mild bleeding disorders
111
3 main indications to use FFP (fresh frozen plasma)
1. bleeding in severe liver disease
2. massive transfusion
3. DIC (disseminated intravascular coagulation)
112
4 main indications to transfuse platelet concentrates
1. bone marrow failure
2. exposure to anti-PLT drugs
3. Trauma, DIC, massive transfusion
4. genetic PLT disorders
113
4 risks of transfusion
1. unavailable blood
2. transfusion transmitted infection
3. immunological reactions
4. overloading (iron, fluid)
114
5 steps to achieving blood safety
1. donor selection
2. testing of blood
3. pathogen inactivation
4. appropriate use of blood
5. Haemoviligance (monitoring system)
115
What to screen in blood donors
healthy volunteers
aged 17-70
medically assessed (history, medication, travel)
fingerprick Hb (women > 125, men >135 g/l)
116
Uses of red cell transfusion
blood loss
| anaemia
117
red cell transfusion (what's needed.. i.e. shelf life etc.)
they have 35 day shelf life at 4 degrees
| transfuse < 4 hrs after removing from fridge
118
reasons for using platelet concentrate transfusions
thrombocytopenia
bleeding with low plt
preventing bleed (v low plt, before procedures)
119
FFP (what's needed.. shelf life etc.)
plasma frozen to -30 degrees celsius
2 yr storage
for clotting factor replacement if bleeding
pre thawed for major haemorrhage
120
dose of plasma infusion for major haemorrhage
1 unit FFP and 2 units RBC
121
alternatives to transfusion
treat underlying cause
reduce surgical bleeding (stopping aspirin/anticoags before surgery, pro-coag drugs ex. tranexamic acid)
minimise use of blood (follow transfusion thresholds, transfuse minimum required)
autologous blood transfusion(intraoperative cell salvage)
122
what is major incompatibility in transfusion
when the recipient has antibodies against transfused blood (e.g. group A given to group O patient)
123
what is. minor incompatibility in transfusion
transfused blood contains antibodies against recipient cells
(e.g. group O blood transfused to group A patient)
124
```
recipient blood group O:
antibodies formed
red cells chosen for transfusion
antigens on red cells
plasma chosen for transfusion
```
anti-A and anti-B antibodies
Group O red cell transfusion only
no antigens on red cells
any plasma for transfusion
125
```
recipient blood group A:
antibodies formed
red cells chosen for transfusion
antigens on red cells
plasma chosen for transfusion
```
anti-B antibodies
Group A or O red cell transfusion
antigen A on red cells
Group A or AB for plasma transfusion
126
```
recipient blood group B:
antibodies formed
red cells chosen for transfusion
antigens on red cells
plasma chosen for transfusion
```
Anti-A antibodies
Group B or O red cell transfusion
Antigen B on red cells
Group B or AB for plasma transfusion
127
```
recipient blood group AB:
antibodies formed
red cells chosen for transfusion
antigens on red cells
plasma chosen for transfusion
```
No ABO antibodies
Group A, B, O, AB red cell transfusion
AB antigens on red cells
Group AB for plasma transfusion
128
what is cryoprecipitate used for
used to prevent or control bleeding in people whose own blood does not clot properly.
129
layers of normal arterial structure from innermost to outermost
Intima (endothelial layer)
internal elastic lamina
media (smooth muscle cells, matrix - elastic, collagen, proteoglycans)
external elastic lamina
adventitia (loose connective tissue, vaso vasorum)
In Ireland Men eat apples
130
sequences in a progression of an atherosclerosis
- initial lesion (histologically normal, macrophage infiltration, isolated from cells)
- fatty streak (mainly intracellular lipid accumulation)
- intermediate lesion (intracellular lipid accumulation, small extracellular lipid pools)
- atheroma (intracellular lipid accumulation, core of extracellular lipid)
- firboatheroma ( single or multiple lipid cores, fibrotic/calcific layers)
- complicated lesions (surface defect, haematoma-haemorrhage, thrombosis)
131
risk factors for atherosclerosis
```
high cholesterol and triglyceride levels
high BP
smoking
diabetes
obesity
eating saturated fats
```
132
main diseases/conditions caused by atherosclerosis
stroke
| MI
133
novel markers of atherosclerosis
high sensitivity CRP
homocysteine
lipoprotein A
134
heart consequences of atherosclerosis
angina
ACS (plaque rupture, plaque erosion, calcific nodule)
AF
135
Brain consequences of atherosclerosis
```
cerebrovascular accident (CVA/TIA/ Stroke) - carotid stenosis, thromboembolic, haemorrhage
vascular dementia
```
136
peripheral consequences of atherosclerosis
renal artery stenosis
aortic aneurysm
peripheral arterial disease ( claudication, acute ischaemia)
impotence (erectile dysfunction)
137
what happens in acute thrombosis
```
plaque disruption
collagen exposure
platelet activation
platelet aggregation
vessel occlusion
```
138
management of acute St elevation MI therapy
thrombolysis (pre-hospital or hospital)
| PCI - percutaneous coronary intervention (primary or facilitated)
139
drugs to reduce platelet activation
aspirin
P2Y12 receptor antagonist (either irreversible: ticlopidine, clopidogrel, prasugrel or reversible: ticagrelor, cangrelor)
𝝰IIb𝛃3 antagonist (abciximab, tirofiban)
140
clinical use of drugs to reduce platelet activation
```
acute MI
In patients with risk of MI
following coronary bypass
unstable coronary syndrome
following coronary artery angioplasty
TIA or thrombotic stroke
```
141
side effects of drugs used to reduce platelet activation
oral drugs - GI disturbances, indigestion
bleeding - GI, nose bleeds, bruising, major bleeding
SOB - ticagrelor specifically
142
what are fibrinolytic drugs
the clot busterrrs
143
examples of fibrinolytic drugs
- steptokinase : from streptococci , forms complex with plasminogen to produce plasmin, 1 yr must elapse before reuse, cheap
-recombinant tissue plasminogen activator (tPA): Alteplase ; more active at fibrin bound plasminogen so "clot" specific. short half life so iv infusion
Reteplase; longer half-life so can give as IV bolus / penetrate inside thrombus more clot specific
(fibrinolytic drug, also called thrombolytic drug, any agent that is capable of stimulating the dissolution of a blood clot (thrombus).
144
clinical use of fibrinolytic drugs
in acute MI within 12 hrs of onset, sooner the better
acute thrombotic stroke
clearing thrombus shunts/cannulae
acute arterial thromboembolism
145
unwanted effects of fibrinolytic drugs
GI haemorrhage/stroke (treat with tranexamic acid)
low grade allergic reactions/fever
burst of plasmin generated by steptokinase can generate kinins causing hypotension
146
contraindications of fibrinolytic drugs (absolute and relative)
absolute:
-active or recent internal bleeding
-recent cerebrovascular event
-invasive procedures where haemostasis is important
relative:
-trauma
-pregnancy
-peptic ulcers
-bacterial endocarditis
147
antifibrinolytic drugs examples
- tranexamic acid (inhibits plasminogen activity, oral or IV administration, clinical use when increased risk of bleeding, side effects of nausea and vomiting)
- aprotinin (proteolytic enzyme inhibitor of plasmin, slow iv, used in patients with high risk of blood loss, usually well tolerated - no side effects)
148
define anaemia
a condition in which there is a deficiency of red cells or of haemoglobin in the blood, resulting in pallor and weariness.
149
3 general symptoms of anaemia
fatigue
dyspnoea - SOB
headaches
150
history to elicit when seeking cause of anaemia
blood loss
weight loss
diet
comorbidities and medications
151
general examination features of anaemia
```
pallor
peripheral oedema
tachycardia/arryhtmias
flow murmur
SOB
confusion (especially in elderly)
```
152
investigations for anaemia
FBC needed to confirm diagnosis, MCV will guide further tests
blood films and haemanitics , renal function, LFTs,
153
microcytic anaemia
MCV <83fL
iron deficiency
thalassaemia
anaemia of chronic disease
(ita like pobrecITA smalllll)
154
Normocytic anaemia
```
MCV 83-96fL
acute blood loss
haemloysis
anaemia of chronic disease
bone marrow infiltration
combined haeminitic deficiency
```
155
macrocytic anaemia
```
MCV>96fL
B12/folate deficiency
haemolysis
hypothyroidism
liver diseae
alcohol excess
myelodysplasia
```
156
what are haeminitic deficiencies
iron
vitamin B12
folate
157
Describe iron absorption and amount needed
total body iron should be 4g (Hb 3g, RE cells 1g)
| Fe absorption through duodenum
158
causes of iron deficiency
dietary (80% from meat, 20% from vegetables)
physiological (infancy, adolescence, pregnancy)
blood loss (most common cause in UK)
malabsorption (e.g. coeliac disease)
159
clinical features of iron deficiency
- angular stomatitis (red swollen patches in corners of mouth)
- sore mouth
- Koilonychia (spoon nails)
- pharyngeal and oesophageal webs
160
laboratory features of iron deficiency
| type of anaemia, low serum what? elevated what?
- microcytic hypochromic anaemia (hypochromic meaning RBCs have less Hb than normal)
- low serum ferritin (beware:acute phase protein)
- low serum iron
- elevated TIBC (total iron binding capacity) and serum transferrin saturation
- absent iron stores in bone marrow
161
talk about Vitamin B-12 (daily requirement, body stores, synthesised by, absorption, type of anaemia)
daily requirement: 1-2µg
body store: 2-3mg mainly in liver
synthesised by micro-organisms: only present naturally in animal products
absorption: combines with intrinsic factor secreted by gastric parietal cells and absorbed in terminal ileum
megaloblastic anaemia (bone marrow produces unusually large, structurally abnormal, immature red blood cells) (macrocytic anaemia)
162
causes of vitamin B-12 deficiency
- dietary: veganism, rare
- intrinsic factor deficiency: pernicious anaemia (an autoimmune condition that affects your stomach, most common in UK), gastrectomy, congenital
- intestinal malabsorption: disease of terminal ileum(e.g. chrons), blind loops and small bowel diverticulae
163
clinical features of vitamin B-12 deficiency
jaundice
glossitis ( inflammation of the tongue.)
neurological deficit
164
laboratory features of vitamin B-12 deficiency
| antibodies against what? what changes in bone marrow? features of what?
- anaemia, neutropenia (occurs when you have too few neutrophils, a type of white blood cells.), thrombocytopenia (a condition in which you have a low blood platelet count.)
- low serum vitamin b12
- antibodies against parietal cells or intrinsic factors
- megaloblastic change in bone marrow
- features of haemolysis
165
talk about folate (folic acid) (daily requirement, body stores, dietary sources, where its absorbed, type of anaemia)
daily requirement: 100-200 µg
body stores: 10-15mg
dietary sources: green vegetables, liver, nuts, cereals
absorbed in jejunum
megaloblastic anaemia (bone marrow produces unusually large, structurally abnormal, immature red blood cells)
166
causes of folate (folic acid) deficiency
- dietary: common in elderly, poor diet related to alcohol misuse
- increased utilisation: e.g. in pregnancy, malignancy, haematological disorders with rapid cell turnover
- malabsorption e.g. coeliac disease
- drugs e.g. anticonvulsants
- excessive loss e.g. renal dialysis
167
clinical features of folate (folic acid) deficiency
```
extreme tiredness
a lack of energy
pins and needles (paraesthesia)
a sore and red tongue
mouth ulcers
muscle weakness
disturbed vision
psychological problems, which may include depression and confusion
problems with memory, understanding and judgement
```
similar to vitamin B-12 deficiency but neurological symptoms do not occur
(jaundice
glossitis ( inflammation of the tongue.))
168
laboratory features of folate (folic acid) deficiency
peripheral blood and bone marrow features identical to vitamin B-12 deficiency
diagnosis made by measuring low serum(and sometimes red cell) folate levels
169
treatment of B12/folate deficiency
- consider underlying cause
- vitamin B12 replacement as IM injection most common: 3x per week or alternate days for 2 weeks then maintenance phase
- oral folic acid replacement
- care: risk worsening neurological symptoms if folic acid is supplemented in b12 deficiency: check both and if in doubt replace B before F
170
RBC breakdown can be.... (location)
intravascular (within the vessels releasing free Hb)
| extravascular (by reticuloendothelial system)
171
describe inherited haemolytic anaemia
| membrane causes, enzyme causes, haemoglobin causes
- membrane: hereditary spherocytosis (autosomal-dominant)
- enzymes: glucose 6 phosphate dehydrogenase deficiency (X linked recessive), pyruvate kinase deficiency (autosomal recessive)
- haemoglobin: sickle cell anaemia, thalassaemia(autosomal recessive)
172
describe causes of acquired haemolytic anaemia
- Immune: i)autoimmune (primary or secondary to lymphoproliferative, autoimmune disorders, drugs, infections) ii) alloimmune (e.g. haemolytic disease of the newborn, incompatible blood transfusion)
- infections: many mechanisms
- drugs and chemicals: many mechanisms
- mechanical: MAHA (microangiopathic haemolytic anaemia) prosthetic heart valves
173
alloimmune meaning in anaemia
red blood cells and immune system don't match
174
7 clinical features of haemolytic anaemia
1) anaemia
2) jaundice
3) splenomegaly
4) skeletal abnormalities (congenital forms)
5) gallstones (pigment stones suggests chronic haemolysis)
6) dark urine (increased urobilnogen)
7) haemoglobinuria (denotes intravascular haemolysis)
175
what is reticulocytosis
| and what it could indicate
high reticulocyte count
this is when there is an increase in production of red blood cells to compensate for the loss of mature red blood cells. This could indicate: hemolytic anemia, acute bleeding, chronic blood loss or a kidney disease.
176
what is polychromasia
occurs on a lab test when some of your red blood cells show up as bluish-gray when they are stained with a particular type of dye. This happens when red blood cells are immature because they were released too early from your bone marrow.
177
What indicates microangiopathic haemolytic anaemia (MAHA)
red cell fragments (schistocyte)
| broken down within the micro-vasculature (intravascular
178
causes of microangiopathic haemolytic anaemia (MAHA)
- thrombotic thrombocytopenic purpura (TTP)
- haemolytic uremic syndrome (HUS)
- DIC
- Malignant hypertension
- Vasculitis
- metastatic adenocarcinoma
179
what are haemoglobinopathies?
| two common examples
- inherited genetic defects of globin
- sickle cell anaemia and thalassaemias are most clinically important
- mutations of the ɑ globin genes affect both foetal and adult life
- sickle cell anaemia is an altered βglobin protein structure
180
3 clinical types of beta thalassemia
- beta thalassemia trait (Carrier): β0/β0
asymptomatic and normal life span
(where β - normal beta globing gene and β0- non functioning beta globin gene)
-beta thalassemia intermedia
variable genotype, phenotype, and life span
-beta thalassemia major: β0/β0
no beta globin and therefore no HbA
181
beta thalassemia major (β0/β0) pathophysiology
- complete absence of HbA (as no β globin)
- excess ɑ chains accumulate and damage red cells
- ineffective erythropoiesis
- excessive RBCs destruction
- iron overload (increased absorption and transfusion dependence)
- extra-medullary haematopoeisis
182
beta thalassemia major clinical features
1. asymptomatic at birth
2. symptomatic anaemia in the first few months of life
3. jaundice
4. growth retardation failure to thrive
5. medullary hyperplasia - bony abnormalities especially on the facial bones
6. extra-medullary haematopoiesis - enlarged liver and spleen
7. increased risk of thromboses
8. pulmonary hypertension and congestive heart failure
183
treatment of beta thalassemia major
1. regular blood transfusions (life long)
2. iron chelation ( drugs that help the body excrete iron)
3. folic acid
4. bone marrow transplantation
184
ɑ thalassemia silent carrier explained
one gene not working
asymptomatic
minority showing reduced MCV and MCH
185
ɑ0 thalassemia trait
| ɑ+/ɑ+ thalassemia trait both explained
```
two genes not working
Hb normal or slightly reduced
MCV and MCH reduced
no symptoms
for both phenotype is indistinguishable
```
186
```
HbH disease
(what is it? how many genes don't work? how would someone present? what is the treatment?)
```
type of ɑ thalassemia
three genes not working
decreased ɑ chains
display: jaundice, hepatosplenomegaly, leg ulcers, gallstones
treatment: folic acid, occasional transfusions, +/- splenectomy
187
Hb Barts hydrops
```
type of ɑ thalassemia
four genes not working
no ɑ chains produced
mainly ɣ chains in utero: form tetramers
intrauterine death and stillborn
```
188
normal vs. sickle red cells
normal:
disc-shaped
deformable
life span of 120 days
sickle:
sickle-shaped
rigid
lives away for 20 days or less
189
3 points on sickle cell anaemia
haemolysis: chronic anaemia, increased reticulocytes, increased LDH and bilirubin
vaso-occlusion: acute episodes and chronic deterioration
hyposplenism: (reduced function of the spleen) risk of infection with encapsulated bacteria
190
acute complications of sickle cell anaemia
```
hand-foot syndrome
splenic sequestration
infections
acute chest syndrome
stroke
venous thrombosis
priaprism
aplastic crisis (pavovirus)
```
191
what is priaprism
persistent and painful erection of the penis.
192
chronic complications of sickle cell anaemia
```
delayed growth and puberty in children
gallstones
blindness
kidney failure
leg ulcers
pulmonary arterial hypertension
hip problems - avascular necrosis
```
193
types of genetic damage
| in anaemia cycle
```
point mutations
chromosomal translocations
chromosomal inversions
chromosomal deletions
chromosomal duplication
epigenetic alterations
microRNAs
```
194
Cancers in haematology
```
acute lymphoblastic leukaemia
CLL (chronic lymphoblastic leukaemia) and lymphomas
myeloma
acute myeloid leukaemia
CML + myeloproliferative disorders
```
195
brief description of term leukaemia
can be myeloid or lymphoid, acute or chronic
"runny" cancer of white cells
predominately affects bone marrow and blood
196
brief description of term lymphoma
only lymphoid, Hodgkins or non-Hodgkins, high grade or low grade, B or T cells
"solid" cancer of lymphocytes
predominately affects lymph nodes but can be extra nodal
197
brief description of myelodysplasia
bone marrow dysfunction
198
brief description of myeloproliferative neoplasms
increased number of normal myeloid cells (RBC, platelets, neutrophils)
199
brief description of myeloma
cancer of plasma cells within the bone marrow
200
difference between acute and chronic leukaemia
acute - undifferentiated
| chronic - differentiated
201
how may haematological cancer present
incidental abnormal FBC or other blood test
lymphadenopathy
splenomegaly
symptoms due to too few cells (anaemia symptoms, bleeding/bruising, infection/fever)
symptoms due to too many cells
constitutional symptoms (weight loss, lethargy, itching, fever, sweats)
Other: bone pain or pathological fracture, hypercalcaemia, renal failure, mass due to lymphoma
202
what does lymphadenopathy mean
swollen lymph nodes
203
if myeloma suspected what tests would you do
```
immunoglobulins
SPE (Serum protein electrophoresis)
serum free light chains
BJP (Bence jones protein)
renal function
calcium
```
204
if lymphoma suspected what laboratory tests would you do
lymph node biopsy
| imaging (CT, MRI , PET scan)
205
What does LDH look at
its a marker of cell turnover
206
what does a grade of cancer mean
how aggressive the cancer is
207
what does stage of cancer mean
how far along the cancer is
208
5 treatment options for haematological cancers
- supportive care (blood transfusions, infection management, etc.)
- chemotherapy (not specific, also kills healthy cells)
- radiotherapy (some lymphomas or myeloma local symptoms)
- targeted therapies aimed at specific molecular targets (includes immunotherapies)
- haematopoetic stem cell transplant HSCT
209
briefly cover splenomegaly in anaemia
- typically causes no symptoms
- Pain or fullness in left upper belly that can spread to the left shoulder
- a feeling of fullness without eating or after eating a small amount because the spleen is pressing on your stomach
- splenomegaly from any cause can lower blood cell numbers (hypersplenism)
- can palpate on an abdominal exam
- confirm with USS
210
causes of splenomegaly
- infections
- cirrhosis of the liver and other liver diseases
- haemolytic anaemia (early destruction of RBCs)
- blood cancers, such leukaemia and myeloproliferative neoplasms, and lymphomas, such as Hodgkins disease
- pressure on the veins in the spleen or liver or a blood clot in these veins
- autoimmune conditions such as lupus or sarcoidosis
211
what is sarcoidosis
is a disease characterized by the growth of tiny collections of inflammatory cells (granulomas) in any part of your body — most commonly the lungs and lymph nodes. But it can also affect the eyes, skin, heart and other organs
212
reactive causes of lymphadenopathy
infection
non haematological cancer (breast cancer)
inflammatory
213
clonal causes of lymphadenopathy
lypmhoma
| leukaemia
214
where to look for lymphadenopathy
```
neck
axilla
inguinal
liver
spleen
```
215
how to assess lymphadenopathy
- clinically divide into localised (one lymph node group) or generalised (several lymph node groups)
- if localised is there a local infective or neoplastic cause?
- duration of lymph node enlargement and any change in size?
- any accompanying B symptoms (>10% weight loss in 6 months, soaking sweats, unexplained fevers?)
- any hepatosplenomegaly, lymphocytosis, cytopenias
216
when is it abnormal lymphadenopathy
-lymphadenopathy >1cm persisting for >6weeks with no obvious infective precipitant
-small volume inguinal lymphadenopathy is a common normal finding. refer if >2cm
-lymphadenopathy for <6 weeks associated with:
B symptoms, rapidly enlarging nodes, generalised lymph, splenomegaly or hepatomegaly, anaemia, thrombocytopenia, or neutropenia , hypercalcaemia
217
out of Hodgkins and non-Hodgkins lymphoma which is more common
Non-Hodgkins
218
is a low grade non-Hodgkins lymphoma more or less curable than a high grade non-hodgkins lymphoma
low grade is slow growing and less curable
| high grade is fast growing and more curable
219
clinical presentation of lymphomas
- usually presents with enlarged lymph nodes
- B symptoms
- bone marrow suppression due to infiltration
- enlarged spleen or liver
- lymphocytosis
- itching
- extranodal lymphoma (e.g. gut, thyroid, parotid, breast, ovary, testis, CNS etc.)
220
brief description of Hodgkin's lymphoma
| incidence, presence of what cell, presents with, histological appearance
- first peak incidence in young adults (20-30yrs), second peak in the elderly
- Presence of Reed-Sternberg cell (B-cell origin)
- usually presents with lymphadenopathy
- May have B symptoms
- may have itching
- defined by histological appearance (looks like owl eyes)
- multinucelated
221
brief description of Non-Hodgkins lymphoma (NHL)
| Which is more common B or T cell? Risk factors? High grade means? Low grade means?
- more common than Hodgkins
- B cell derived NHL more common than T cell derived NHL
- Risk factors include: HIV, EBV, and immunosuppression
- similar staging to Hodgkins
- High grade: short history, fast growing, more curable, needs urgent treatment
- Low grade: slow growing, more indolent (causing little or no pain), less curable, may not need treatment and can be observed
222
what does AML stand for (in anaemia block)
acute myeloid leukaemia
223
What does ALL stand for (in anaemia block)
acute lymphoblastic leukaemia
224
brief overview of acute leukaemias
- proliferation of WBC "blasts"
- accumulate in the bone marrow
- reduced bone marrow production of healthy blood cells
- present with symptoms of reduced production of normal red cells, platelets and neutrophils: anaemia, bleeding, bruising, infection
- general cancer symptoms (weight loss, tiredness, sweats, fevers)
- Acute lymphoblastic leukaemia may have lymphoid mass
- patients have a relatively short history and are often unwell
225
AML incidence
acute myeloid leukaemia incidence increases with age
226
ALL incidence
acute lymphoblastic leukaemia is a disease of the young
227
how to diagnose acute leukaemias
1. FBC results (may be cytopenias)
2. Blood film: blasts, Auer rods (granules clumped together -myeloid sign)
3. Bone marrow: morphology, flow cytometry (differentiate between myeloid and lymphoid precursors). cytogenetics and molecular markers
228
CML stands for
chronic myeloid leukaemia
229
brief description of chronic myeloid leukaemia (CML)
common in who, characterised by what, presents with..
can progress to...
- commoner in adults
- characterised by proliferation WITH differentiation (unlike AML) of myeloid leukocytes including mature neutrophils
- Presentation: High white count (may be detected incidentally)
- may have constitutional symptoms and splenomegaly
- can progress to acute leukaemia's (either AML or ALL)
230
what does CLL stand for and a brief description of it
| who is it most common in? cell origin? rate of growth? increased what on FBC? staged according to? treatment?
Chronic lymphocytic leukaemia
- most common leukaemia in Western world
- most common in elderly
- B-cell origin, small mature lymphocytes on blood film and smear cells
- Slow growing, often asymptomatic/incidental findings
- increased lymphocyte count on FBC
- staged according to lymphocytosis, lymphadenopathy, enlarged spleen/liver, anaemia or thrombocytopenia
- many patients never need treatment
231
what does MGUS stand for
monoclonal gammopathy of undetermined significance
232
Brief overview of MGUS
1. low level of paraprotein
2. a low level of abnormal plasma cells in the bone marrow
3. no indicators of active disease
- all patients with active myeloma once had MGUS
- only 20% of patients with MGUS progresses to active myeloma
- MGUS patients do not need treatment
233
brief overview of Myeloma
| more common in who? accumulation of what? asymptomatic? symptomatic?
- more common in elderly
- incidence 12 per 100,000
- more common in afro-carribean origin
- accumulation of neoplastic plasma cells in the bone marrow
- asymptomatic myeloma: no indicators of active disease (CRABI) but higher level of paraprotein and more bone marrow plasma cells than MGUS
- symptomatic myeloma: one or more indicators of active disease (MGUS)
CRABI: calcium elevation, renal dysfunction, anaemia and bone disease
234
what is a paraprotein
protein found in the blood only as a result of cancer or other disease.
235
symptomatic myeloma presentation (CRABI acronym)
```
C - hypercalcaemia
R - renal dysfunction
A - anemia
B - bone - lytic lesions, fractures, osteoporosis
I - infections
```
236
```
CASE (anaemia case cycle):
84 yo asymptomatic
persistent stable lymphocytosis
otherwise normal FBC
No lymphodenopathy or splenomegaly
Blood film - small immature lymphocytes, smear cells and otherwise normal
diagnosis?
```
CLL
| chronic lymphocytic leukaemia
237
```
CASE (anaemia case cycle):
5 yo boy
malaise, bone pain, fever, rash
FBC: anaemia, neutropenia, thrombocytopenia and high WCC
blood film: circulating blasts
diagnosis?
what if 60yo man and granules in blasts?
```
Child: ALL - acute lymphoblastic leukaemia
Adult: AML - acute myeloid leukaemia
238
```
CASE (Anaemia case cycle):
72 yo man
back pain, renal impairment
femur fracture, no trauma
normocytic anaemia
hypercalcaemia
lytic lesions on XR
Diagnosis?
```
myeloma
239
what are lytic lesions?
An osteolytic lesion is a softened section of a patient's bone formed as a symptom of specific diseases, including breast cancer and multiple myeloma. This softened area appears as a hole on X-ray scans due to decreased bone density, although many other diseases are associated with this symptom
240
CASE (Anaemia case cycle):
55yo woman
fatigue and reduced appetite
splenomegaly
FBC: normal Hb and platelets, very high WCC
blood film: increased neutrophils, other myeloid leukocytes at varying maturity
Diagnosis?
CML
| chronic myeloid leukaemia
241
CASE (anaemia case cycle):
28yo man
recent history of progressive cervical lymphadenopathy over weeks, now 5cm
Fevers, drenching night sweats, weight loss, itching
FBC normal
lactate dehydrogenase high
diagnosis
High grade NHL (non-hodgkins lymphoma)
| Burkitt - highest rate of growing cancer
242
Leukaemia type summary
can be Myeloid: can be acute (AML) or chronic (CML)
| or can be Lymphoid: can be acute (ALL) or chronic (CLL)
243
types of lymphomas
can be Hodgkins
| can be Non-Hodgkins: which can be high grade (either T cell or B cell) or low grade (either T cell or B cell)
244
3 types of myeloproliferative neoplasms
PRV (polycythaemia Rubra Vera)
ET (Essential thrombocytopenia)
PMF (primary myelofibrosis)
245
what is myelodysplasia
Myelodysplastic syndromes are a group of cancers in which immature blood cells in the bone marrow do not mature or become healthy blood cells. The different types of myelodysplastic syndromes are diagnosed based on certain changes in the blood cells and bone marrow
246
difference between monoclonal and polyclonal antibodies
Polyclonal antibodies are made using several different immune cells. They will have the affinity for the same antigen but different epitopes, while monoclonal antibodies are made using identical immune cells that are all clones of a specific parent cell
247
Terminology for too many platelets? too few?
too few: thrombocytopenia
| too many: thrombocytosis
248
terminology for too few neutrophils? too many?
too few: neutropenia
| too many: neutrophilia
249
terminology for too few lymphocytes? too many?
too few: lymphopenia
| too many: lymphocytosis
250
terminology for too few RBCs (haemoglobin)? too many?
too few: anaemia
| too many: polycythaemia
251
reactive causes of neutrophilia
```
infection (esp. bacteria)
inflammation
ischaemia, infarction
smoking
splenectomy
pregnancy
corticosteroids
```
252
clonal causes of neutrophilia
```
myeloproliferative neoplasms (MPN)
chronic myeloid leukaemia
```
253
brief overview of myeloproliferative neoplasms (MPN)
- characterised by excessive proliferation of terminally differentiated myeloid cells (normal differentiation ) - cells look normal
- due to Somatic acquired mutations in haematopoetic stem cells
- lead to cytokine independent restricted growth
254
Clinical features of MPN (myeloproliferative neoplasms)
- incidental finding of an abnormal blood test result (without symptoms)
- thrombosis (arterial or venous), occasionally at an unusual site
- itching, constitutional symptoms (weight loss, fatigue, etc.), increased risk of gout
- symptoms of splenomegaly (more common with PMF) e.g. early fullness
255
what is treatment of MPN usually aimed at?
mainly aimed at reducing risk of blood clots
256
reactive causes of lymphocytosis?
infection (esp. viral or chronic bacterial)
inflammation
smoking
splenectomy
257
clonal causes of lymphocytosis?
lymphoproliferative (chronic lymphocytic leukaemia most common)
258
what does flow cytometry measure in haematological cancer
1) cell type: is it lymphoid, myeloid or non haematological?
2) cell lineage: is it B lymphocyte or T lymphocyte?
3) cell maturity: is it an immature precursor or a more mature cell
4) aberrant antigen patterns which may be specific for some cancers
259
reactive causes of thrombocytosis
```
trauma (e.g. by surgeon)
infection
inflammation
non haematological malignancy
iron deficiency
splenectomy
```
260
clonal causes of thrombocytosis
myeloproliferative neoplasms (MPN): PRV, ET, PMF
261
what does TTP stand for
thrombotic thrombocytopenic purpura
262
5 clinical features of thrombotic thrombocytopenic purpura
1. fever
2. neurological signs
3. Renal failure
4. Low platelets
5. MAHA (microangiopathic haemolytic anaemia)
263
```
thrombocytopenia causes
(broken into non pathological, production, consumption and complex)
```
Not pathological -
- spurious: lab artefact e.g. platelet clumping
- physiological: gestational in pregnancy
Production -
- genetic/inherited: no previous normal results, may have FHx
- substrate deficiency: B12 or folate deficiency can cause any cytopenia
- growth factor deficiency: Liver TPO (thrombopoeitin)
- bone marrow production problem: infiltration, aplasia, dysplasia, fibrosis
consumption-
- reduced survival / consumption : immune destruction or non immune includes MAHA, DIC)
- Loss (Bleeding): only anaemia unless massive haemorrhage/transfusion
- splenomegaly: hypersplenism
complex
- medications
- infections
264
neutropenia causes
| including non pathological, production, consumption and complex
non-pathological-
-physiological: ethnic neutropenia
Production-
- genetic/inherited: no previous normal results, may have FHx
- Substrate deficiency: B12 or folate deficiency can cause any cytopenia
- bone marrow production problem: infiltration, aplasia, dysplasia, fibrosis
Consumption-
- reduced survival /consumption: immune deficiency, non immune
- Loss (bleeding): only anaemia unless massive haemorrhage/transfusion
- splenomegaly: hypersplenism
Complex -
- medications
- infections
265
What does TACO stand for
transfusion associated circulatory overload
266
describe transfusion associated circulatory overload (TACO)
is a common transfusion reaction where pulmonary oedema due to excess volume or circulatory overload results in the patient experiencing acute respiratory distress.
267
What does TRALI stand for
transfusion related acute lung injury
268
Describe transfusion related acute lung injury (TRALI)
is a rare but serious syndrome characterized by sudden acute respiratory distress following transfusion.
The typical presentation of TRALI is the sudden development of shortness of breath, severe hypoxemia (O2 saturation <90% in room air), low blood pressure, and fever that develop within 6 hours after transfusion and usually resolve with supportive care within 48 to 96 hours.
269
signs and symptoms of TACO
appears as acute respiratory distress that begins during or shortly after the administration of a blood product. Symptoms and signs of TACO include dyspnea that worsens as pulmonary edema progresses, orthopnea, chest tightness, cough, tachycardia, hypertension, and widened pulse pressure.
270
signs and symptoms of TRALI
The typical presentation of TRALI is the sudden development of shortness of breath, severe hypoxemia (O2 saturation <90% in room air), low blood pressure, and fever that develop within 6 hours after transfusion and usually resolve with supportive care within 48 to 96 hours.
