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Phase 3 > Week 3 > Flashcards

Week 3 Flashcards

1
Q

Describe where haemopoiesis occurs in the foetus

A

0-2 months - yolk sac
2-7 months - liver, spleen
5-9 months bone marrow

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2
Q

Where does haemopoeisis occur in infants?

A

bone marrow of all bones

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3
Q

Where does haemopoiesis occur in adults?

A

the axial skeleton bone marrow

vertebrae, ribs, sternum, skull, sacrum, pelvis, ends of femurs

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4
Q

what can pluripotent stem cells become?

A

myeloid stem cells and lymphoid stem cells

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5
Q

What do myeloid stem cells differentiate into?

A

erythroblasts
megakaryoblasts
monoblasts
myeloblasts

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6
Q

What do erythroblasts differentiate into?

A

reticulocytes then erythrocytes

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7
Q

What do megakaryoblasts differentiate into?

A

megakaryocytic then platelets

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8
Q

What do mono blasts differentiate into?

A

monocytes and macrophages

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9
Q

What do myelocblasts differentiate into?

A

myelocytes then neutrophils, eosinophils and basophils

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10
Q

What do basophils differentiate into?

A

mast cells

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11
Q

What do lymphoid stem cells differentiate into?

A

B cells (plasma cells) and T cells

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12
Q

Where are haematopoietic stem cells found?

A

bone marrow
peripheral blood after growth factor treatment
umbilical cord blood

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13
Q

Describe the bone marrow microenvironment

A

Stroma cells - macrophages, fibroblasts, endothelial cells, fat cells, reticulum cells.
Supported by ECM of fibronetin, proteoglycans and collagen

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14
Q

What hormones regulate erythropoiesis?

A

EPO
thyroxine
testosterone

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15
Q

What are the paracrine regulators of granulopoiesis?

A

microenvironment
growth factors
chemokine
cytokines

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16
Q

Describe bone marrow aspirations

A

posterior iliac spine in adults
predominantly granulocytes
best way to look for leukaemias

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17
Q

Describe bone marrow trephine

A

biopsy used to analyse the architecture of the bone marrow

good for looking for marrow infiltration - cancer / fibrosis

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18
Q

Describe the principles of leukaemogenesis

A

multi-step process
neoplastic cell is haematopoietic or early myeloid or lymphoid cell
dysregulation of cell growth and differentiation associated with mutations that confer growth advantage to LSC

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19
Q

What is meant by myeloproliferatve disorders?

A

clonal disorders of haemopoiesis leading to increased numbers of mature blood progeny

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20
Q

What are the classical MPDs?

A

polycythaemia rubra vera
essential thrombocytosis
myelofibrosis

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21
Q

Describe myelodysplastic syndromes

A

characterised by dysplasia and ineffective haemopoiesis of the myeloid series

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22
Q

What can MDS’s lead to?

A

progressive bone marrow failure i.e cytopaenias

some progress to AML

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23
Q

What are the clinical features of MDS?

A

mainly elderly
infarctions or bleeding
fatigue - anaemia

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24
Q

What are the types of stem cell transplant?

A

autologous

allogeneic

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25
Q

What are the types of allogenic stem cell transplants?

A

syngeneic transplant - identical twins
allogeneic sibling - HLA identical
volunteer unrelated
umbilical cord blood

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26
Q

What are the main indications for autologous stem cell transplant?

A

relapsed Hodkin’s disease, non hodgkin’s lymphoma

myeloma

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27
Q

What are the main indications for allogenic stem cell transplant?

A

acute leukaemia, aplastic anaemia, hereditary disorders

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28
Q

How does graft-versus-host disease commonly present?

A

skin rash, jaundice, diarrhoea

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29
Q

What are the advantages of using umbilical cord blood?

A

more rapidly available than VUD

less rigorous matching to patient as immune cells in cord blood are immune naive

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30
Q

What are the disadvantages of using umbilical cord blood?

A

small amount
slower engraftment
if replace can’t go back for DLI

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31
Q

What are the problems with stem cell transplant?

A 
limited donor availability 
not available to old
immunosuppression 
infertility
cataract formation 
hypothyroidism, dry eyes and mouth
risk of secondary malignancy 
osteoporosis / avascular necrosis 
relapse
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32
Q

What is the problem with measuring serum ferritin to determine IDA?

A

it is an acute phase protein

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33
Q

Describe RES storing of iron

A

effete rbcs are removed by macrophages of the RES
500mg stored iron in ferritin/haemosderin
released to transferrin in plasma
Tf iron taken up via Tf receptors on erythroblasts, hepatocytes etc

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34
Q

What does low serum ferritin indicate?

A

low RES iron stores

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35
Q

When can serum ferritin levels appear normal even when IDA exists?

A

in the presence of tissue inflammation - e.g. RA and IBD

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36
Q

What is spooning of the nails called?

A

koilonychia

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37
Q

What are some of the clinical effects noticed in the head and neck in IDA?

A

atrophic glossitis
angular stomatitis
oesophageal web

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38
Q

What are the causes of IDA?

A

dietary
malabsorption
blood loss

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39
Q

What is the golden rule when deciding the cause of IDA?

A

in males and post -menopausal females IDA is due to GI blood loss until proven otherwise

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40
Q

Describe anaemia of chronic disease

A

failure of iron utilisation
iron trapped in RES
common
causes - infection, inflammation, neoplasia

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41
Q

What is the pathophysiology of ACD?

A

RES iron blockade
reduced EPO response
depressed marrow activity; cytokine marrow depression

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42
Q

What is B12 needed for?

A

methylation of homocysteine to methionine

methylmalonyl CoA isomerisation

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43
Q

Describe B12 absorption

A

Ingested as animal protein
gastric parietal cells produce IF
B12 released by acid in stomach and duodenum
IF binds to B12
This binds to cubulin in the ileum
B12 is absorbed and binds to transcobalamin

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44
Q

What are the dietary sources of folate?

A

green veg

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45
Q

how is folate abosorbed?

A

freely (no carrier molecule needed)

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46
Q

What are the tissues effected by B12 or folate deficiency?

A

bona marrow

epithelial surfaces - mouth, stomach, small intestine, female genital tracts, urinary

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47
Q

Describe clinical B12 deficiency

A 
blood abnormalities - megaloblastic anaemia (leukocpaenia, thrombocytopenia)
neurological manifestations (bilateral peripheral neuropathy or demylination of the posterior and pyramidal tracts of the spinal cord
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48
Q

Describe clinical folate deficiency

A 
blood abnormalities - megaloblastic anaemia 
growing foetus (1st 12 weeks - neural tube defects)
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49
Q

How do patients present with folate and B12 deficiency?

A

symptoms of anaemia and cytopaenia - tired
easy brushing
mild jaundice
neurological problems

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50
Q

what is foetal Hb made up of?

A

alpha 2 and gamma 2

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51
Q

What is adult Hb made up of?

A

alpha 2 and beta 2

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52
Q

What are thalassaemias?

A

relative lack of globin genes

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53
Q

Where are alpha and beta globin genes normally found?

A 
4 alpha (on 2 Ch16)
2 beta (on 2 Ch11)
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54
Q

What is the alpha+ trait?

A

one missing alpha gene

mild microcytosis

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55
Q

What is homozygous alpha+ trait?

A

two missing alpha genes (1 from each parent)microcytosis, increased red cell count and sometimes very mild anaemia

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56
Q

What is HbH disease?

A

3 missing alpha genes

significant anaemia and bizarre shaped small red cells - beta tetromeres form

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57
Q

What is alpha thal major?

A

no alpha genes - not compatible with life

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58
Q

What is the alpha 0 trait?

A

2 missing alpha genes (both from same parent)

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59
Q

Describe HbH disease

A

missing 3 alpha chains
excess beta chains
beta chains join together
blood transfusion required during periods of stress

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60
Q

Describe beta thalassaemia major

A 
missing both beta globin genes
autosomal recessive
unable to make adult Hb
significant dyserthropoiesis
transfusion dependent from early life 
iron overload has major effect on life expectancy
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61
Q

Describe the pathogenesis of sickle cell disease

A

chromosome 11
single amino acid substitution on B globin gene at position 6
glutamine >valine = HbS
HbS 2 alpha + 2 beta (sickle) (alpha2betas2)

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62
Q

What does the polymerisation of HbS depend on?

A

deoxygenation rate
Hb concentration
HbF

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63
Q

What is the clinical result of sickle cell disease

A

haemolysis

vaso-oclusion - tissue hypoxia / infarction

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64
Q

How does sickle cell affect the brain?

A

stroke

moya moya

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65
Q

how does sickle cell affect the lungs?

A

acute chest syndrome

pulmonary hypertension

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66
Q

how does sickle cell affect the bones?

A

dactilytis

osteonecrosis

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67
Q

how does sickle cell affect the spleen?

A

hyposplenic

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68
Q

how does sickle cell affect the kidneys?

A

loss of concentration

infarction

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69
Q

how does sickle cell affect the urogenital tract?

A

priapism

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70
Q

how does sickle cell affect the eyes?

A

vascular retinopathy

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71
Q

how does sickle cell affect the placenta?

A

IUGR

foetal loss

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72
Q

What is the treatment of sickle cell disease?

A

prevent crises - hydration, analgesia, early intervention, vaccination and antibiotics, folic acid
prompt management of crises - oxygen, fluids, analgesia, antibiotics, specialist care, transfusion / red cell exchange
bone marrow transplantation

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73
Q

What is haemolytic anaemia?

A

anaemia related to reduced RBC lifespan
no blood loss
no haematinic deficiency

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74
Q

Describe hereditary spherocytosis

A

autosomal dominant
RBCs spherocytic and polychromatic
jaundice
splenomegaly

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75
Q

What should be given to a patient who has had a splenectomy?

A

pneumococcus, meningococcus vaccinations and long term penicillin V

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76
Q

Describe the compensated haemolytic state

A

20-100d
Hb normal
raised reticulocytes
raised bilirubin

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77
Q

Describe non-compensated haemolytic anaemia

A

low Hb
increased reticulocytes
increased bilirubin
splenomegaly

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78
Q

Describe pyruvate kinase deficiency anaemia

A

chronic / extravascular haemolytic anaemia
ATP depletion
autosomal recessive

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79
Q

Describe glucose 6 phosphate dehydrogenase deficiency

A

acute episodic intravascular haemolysis
x linked recessive
acute haemolysis from oxidative stress -fauvism, drugs (antimalarials, sulphonamides etc)

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80
Q

What are the types of acquired haemolytic anaemias?

A

autoimmune- warm and cold
isoimmune - mother on baby
non immune - fragmentation haemolysis

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81
Q

Describe cold AIHA

A

autoantibody IgM (+complement)
mycoplasma infection
idiopathic
forms agglutinins

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82
Q

Describe warm AIHA

A 
autoantibody IgG (+/- complement)
other autoimmune disease
lymphoproliferative disorder (NHL/CLL)
drug induced 
RBCs spherocytic and polychromatic
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83
Q

What is the purpose of a direct coombs test?

A

to detect antibody on RBC surface

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84
Q

What is the purpose of an indirect coombs test?

A

to detect RBC antibodies in plasma

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85
Q

What is the treatment of cold AIHA

A

self limiting mycoplasma

idiopathic -keep warm

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86
Q

What is the treatment for warm AIHA?

A

stop any drugs
steroids
immunosuppression
splenectomy

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87
Q

What is leukaemia?

A

accumulation of abnormal leukocytes in marrow and blood/ other tissues

88
Q

What do the symptoms of chronic leukaemia result from?

A

accumulation of cells

89
Q

What do the symptoms of acute leukaemia result from?

A

from marrow failure

90
Q

What does MDS stand for?

A

myelodysplastic syndrome

91
Q

How is MDS characterised?

A 
failure of effective haemopoiesis (low blood counts)
most common in elderly
dysplastic marrow and blood appearances 
25% transformation to AML
consequences of marrow failure
92
Q

What does MPD stand for?

A

myeloproliferative disorders

93
Q

What is the term for too many platelets?

A

essential thrombocytopaenia

94
Q

What is the word for too many red cells?

A

polycytheamia vera or primary polycythaemia

95
Q

What is the name for too much fibrous tissue?

A

myelofibrosis

96
Q

Describe ET and PRV

A 
good outcome
risk of vascular events (aspirin)
cytoreduction (hydroxycarbamide, venesection or interferon) 
5-10% risk of AML
10% progress to myelofibrosis
97
Q

Describe myelofibrosis

A

difficult, large spleen, systemic symptoms, blood counts high or low, incurable other than SCT. JAK2 inhibitors

98
Q

Describe acute leukaemia

A

clonal disorders
blastic proliferation in bone marrow “maturation arrest”
rapid in onset
serious compromise of normal marrow elements
death within days or weeks if untreated

99
Q

What are the different classes of AML?

A

erythroleukaemia
myeloid leukaemia
monocytic leukaemias
megakaryocytic anaemias

100
Q

What are the different classes of ALL?

A 
T lymphoblastic
B lymphoblastic (more common)
101
Q

Describe the history and examination in acute leukaemia

A 
rapid onset
lethargy
infection
bleeding and bruising
bone pain 
gum swelling
lymphadenopathy
skin rash
102
Q

What is seen in peripheral blood in leukaemia?

A

anaemia
neutropenia
thrombocytopenia
blasts

103
Q

What is the translocation in M3 AML?

A

t(15:17)

104
Q

What is the translocation in m2 AML?

A

(8:21)

105
Q

What are the three choices for the management of AML?

A

intensive chemotherapy +/- SCT
low dose chemotherapy
supportive care only

106
Q

What is the typical clinical presentation of ALL?

A

the limping child
purpuric rash
unexplained, sometimes severe bone pains not uncommon
lumps vs liquid presentation

107
Q

What are common translocations in ALL?

A

(9: 22)

4: 11

108
Q

why is CNS chemotherapy essential in ALL?

A

CNS and testes are common sanctuary sites for leukaemic cells

109
Q

What is the supportive care involved in ALL treatment?

A 
blood transfusions
fresh frozen plasma
platelet transfusion
antibiotics
growth factors
granulocytes
110
Q

Which patients are more likely to receive a transplant for ALL?

A 
relapsed patients 
refractory patients 
poor risk disease in first CR
age less than 60
good performance
111
Q

Describe the presenting features of CLL

A

none
lethargy, night sweats, weight loss
lymphadenopathy
infection

112
Q

Describe 17p deletions in CLL

A

aggressive disease
refractory to chemo
loss in p53
patients may respond to steroids and antibodies

113
Q

What are the immune complications of CLL?

A 
autoimmune haemolytic anaemia
autoimmune thrombocytopenia
at presentation
precipitated by treatment
treat with steroids
treat CLL
114
Q

What are the triggers to treat CLL?

A

symptoms

bone marrow failure

115
Q

What are the symptoms of CML?

A 
fatigue
weight loss
night sweats
abdominal discomfort
splenomegaly is very common
116
Q

What is the main treatment of CML?

A

imatinib - blocks BCR-ABL

tyrosine kinase inhibitor

117
Q

What is lymphoma?

A

malignancy derived from lymphocytes
presents with tumour mass
most commonly in lymph nodes

118
Q

What are the two general categories of lymphoma?

A

hodgkins and non hodgkins

119
Q

Describe low grade lymphoma

A

neoplastic cells mostly small
low proliferation
low apoptosis
slow accumulation of neoblastic lymphocytes
often widely disseminated at presentation
indolent clinical course
incurable

120
Q

Describe high grade lymphoma

A 
large neoplastic cells with activate "blast like" appearance 
dispersed nuclear chromatin
prominent nucleoli
high cell division
tends to be localised at presentation 
often curable
121
Q

What protein can be used to assess the rate that cells are dividing at?

A

Ki67 - expressed by cells in S phase

122
Q

Describe follicular lymphoma

A 
neoplasm of follicle centre B cells - centrocytes, centroblasts 
painless lymphadenopathy 
often generalised 
bone marrow frequently involved 
incurable
123
Q

What is the treatment for follicular lymphoma?

A

alleviating symptoms
low dose chemotherapy
radiotherapy

124
Q

What is a common mutation in follicular lymphoma?

A

t(14;18)
BCL2/IGH
BCL2 is an apoptotic protein

125
Q

Describe Burkitt lymphoma

A

neoplasm of proliferating follicle centre b cells - centroblasts

126
Q

What are the three epidemiological variants of burrito lymphoma?

A

endemic
sporadic
immunodeficiency asssociated

127
Q

Describe endemic Burkitt lymphoma

A

equatorial africa and papa new guinae
malaria
strong associstion with epstein bar virus
most common childhood malignancy in these areas

128
Q

Describe sporadic burkitt lymphoma

A

seen in western europe and north america

children and young adults

129
Q

Describe immunodeficiency associated Burkitt lymphoma

A

HIV

post transplant

130
Q

How does Burkitt lymphoma present?

A 
mainly extranodal disease
jaws and facial bonw
 ileocaecum
ovaries 
kidneys
breast 
CNS involvement is common
131
Q

Describe the genetics in Burkitt lymphoma

A

most have chromosomal translocation involving MYC and IG gene

132
Q

Describe diffuse large B - cell lymphoma

A

heterogeneous group
most common
mainly adults

133
Q

Hows does diffuse large B cell lymphoma usually present?

A

rapidly enlarging mass at single nodal or extra nodal site
mainly at early stage
less responsive to therapy than Burkitt but aim is still to cure disease with aggressive chemo

134
Q

How is hodgkin lymphoma characterised?

A

very large neoplastic B cell
Reed Sternberg cell
prominent background of relative white blood cells - lymphocytes, histiocytes, granulocytes

135
Q

How does classic hodgkin lymphoma typically present?

A

often localised
mediastinal and cervical lymph nodes
contiguous spread

136
Q

Describe the morphology seen in classic hodgkin lymphoma

A

very large b-cell with blast like morphology
abundant cytoplasm
binucleate
prominent nucleolus

137
Q

What are the types of classic hodgkin’s lymphoma?

A

mixed cellularity
nodular sclerosing
lymphocyte rich
lymphocyte depleted

138
Q

Describe the cell signature of reed sternberg cells

A

defective b cell
cd20 negative
PAX5 positive

139
Q

What are the risk factors for lymphoma?

A

immunosupression
infection - EBV, helicobacter pylori
age
close relative

140
Q

How is lymphoma staged?

A

CT
PET CT
bone marrow aspirant and biopsy

141
Q

Describe the Ann Arbor staging system

A

I - single LN region
II - >2 LN areas, same side or diaphragm
III- both sides of diaphragm
IV - extensive disease e.g liver, bone marrow

142
Q

What are B symptoms ?

A

drenching night sweets
significant weight loss
unexplained fever

143
Q

What is myeloma?

A

cancer of the bone marrow plasma cells

144
Q

How does myeloma present?

A 
backache or rib pain
fatiguw 
symptoms of hypercalcaemia
recurrent infections
renal impairment
145
Q

What is meant by paraprotein?

A

abnormal plasma cells produce an abnormal monoclonal protein called paraprotein or M protein

146
Q

What is the classical triad that typifies myeloma?

A

increased plasma cells in bone marrow
clonal immunoglobulin or paraprotein
lytic bone lesions

147
Q

How is myeloma diagnosed?

A

blood tests - FBC, ESR,U&Es. , Calcium,serum protein electrophoersis
urine tests - light chains
bone marrow aspirate
imaging

148
Q

What does MGUS stand for?

A

monoclonal gammopathy of undermined significance

149
Q

What are the CRAB features which make myeloma patients high risk

A

calcium elevation
renal dysfunction
anaemia
bone disease

150
Q

What happens when you cut yourself?

A

blood vessel damage
disrupt endothelium
exposure of tissue factor and collagen
primary haemostats - recruitment of platelets
secondary haemostats - activation of coagulation factos
occur simultaneously

151
Q

What is the cascade of events that occurs in secondary haemostats?

A

initiation - extrinsic
propagation - intrinsic
thrombin generation
fibrin production - the clot

152
Q

What is the main clotting facto involved in the extrinsic pathway?

A

VII

153
Q

What factors are in the prothombinase complex?

A

Xa, II and Va

154
Q

What are required at every step of the coagulation cascade?

A

phospholipid

calcium

155
Q

What are the main factors involved in the intrinsic pathway?

A

XI, IX and VIII

156
Q

How can primary haemostasis be assessed?

A

bleeding time

platelet function

157
Q

How can secondary haemostasis be assessed?

A

prothrombin time
activated partial thromboplastin time
thrombin clotting time
individual coagulation factor assays

158
Q

Why is citrate in a blood sample that is being testing for coagulation?

A

chelates all calcium and prevents a clot formation

159
Q

What does the PT depend on?

A

factors in extrinsic and common pathways
factor VII
and X, V, II and fibrinogen

160
Q

What is the INR?

A

international normalised ration

standardised form of prothrombin time

161
Q

What does APTT depend on?

A

factors VIII, IC, XI and XII

and X< V, II and fibrinogen

162
Q

What is the TCT

A

measurement of conversion of fibrinogen to fibrin clot

163
Q

What does TCT depend on?

A

how much fibrinogen is present

how well it functions

164
Q

What will TCT be prolonged by?

A

inhibitors of thrombin (heparin, dabagitran)
FDPs
inhibitors of fibrin polyerisation (paraproteins)

165
Q

What can a long PT only suggest?

A

low factor VII

166
Q

What can a long APTT only suggest?

A

low VIII, IX, XI or XII

lupus anti-coagulant

167
Q

What does a low PT and APTT suggest

A

common pathway factor low

multiple low factors - liver disease, warfarin

168
Q

What do anticoagulants do?

A

they inhibit one or several components of the coagulation cascade

169
Q

What do fibrinolytic agents do?

A

chance lysis of fibrin clot

170
Q

What do anti-platelet agents do?

A

inhibit platelet activation or aggregation

171
Q

How do hepatitis and fondarinux work?

A

antagonise factor Xa

172
Q

How does oral warfarin work?

A

vitamine K antagonist

lowers factors II, VII, IX and X

173
Q

What is the mechanism of action of heparins?

A

mixture of glycosaminoglycans of differing polysaccharide chain length
augment activity of endogenous antirthrombin
does not cross placenta
short half life
administered parenterally

174
Q

What are the potential side effects of heparin?

A

HIT - heparin induced thrombocytopaenia
osteoperosis
hyperkalcaemia

175
Q

What are the advantages of LMWH?

A 
superior pharmacokinetic profile allowing predictable dose repsonse
safer side effect profile
clinical efficacy atleast as good
no monitoring 
out-patients
176
Q

What are the indications for using heparin?

A 
acute DVT or PE
during cardiac bypass surgery
acute coronary syndroemes 
medium term after VTE in cancer patients 
prophylaxis against VTE
medical and post op patients 
obstetric patients
177
Q

What pathway does warfarin inhibit?

A

vitamin K oxide reductase

178
Q

What factors does warfarin effect?

A

II, VII, IX and X

179
Q

What is the target INF on warfarin?

A

2-3

180
Q

What is warfarin used for?

A

atrial fibrillation
acute DVT or PE
prosthetic heart valve

181
Q

What is warfarin not for?

A

immediate anticoagulation

short term thromboprophylaxis

182
Q

What is the name of the DOAC that inhibits factor IIa?

A

dabigatran

183
Q

What is the name of the DOACs that inhibit Xa?

A

rivaroxaban
apixaban
edoxaban

184
Q

What are contraindications for all DOACs?

A

pregnancy and breast feeding

liver disease with cirrhosis and some drugs

185
Q

What are the 2 classes of fibrinolytic?

A

kinases

tissue plasminogen activators

186
Q

describe the action of kinases

A 
bind to plasminogen 
releases plasmin
enhanced breakdown of fibrin
causes both fibrinolysis and systemic fibrinogenolysis
significant bleeding risk
187
Q

Why is streptokinase antigenic?

A

derived from bacteria

recent strep infection or previous use of drug and render it ineffective

188
Q

How do tPA derivatives work?

A 
activate plasminogen
plasmin cleaned from plasminogen
plasmin breaks down fibrin 
relatively selective for clot bound plasminogen
minimal unwanted fibrogenolysis
189
Q

What are tPA derivatives used for?

A

acute MI (for patients not suitable for PCI)
ishaemic stroke
massive PE with haemodynamic instability

190
Q

What are the uses of catheter directed thromblysis?

A

acute limb ischaemia
massive DVT
blocked CVC

191
Q

What are the actions of anti platelet drugs and how are they achieved?

A

inhibit platelet activation
inhibit platelet aggregation
by receptor inhibition and platelet signalling pathway inhibition

192
Q

Describe the action of clopidogrel and ticlodipine

A

irreversible blockage of ADP receptor
decreased depression of GPIIB/IIIa
reduced binding of fibrinogen

193
Q

Describe the action of abciximab and tirofiban

A

GPIIb/IIIa antagonists
monoclonal antibodies
reduced platelet aggregation
reduced bidding of fibrinogen

194
Q

Describe the action of aspirin

A

irreversible inhibition of cyclooxyrgenase
blocks conversion of arachidonic acid to thromboxane A2
decreased platelet activation

195
Q

Describe the action of phosphodiesterase III inhibitoe

A

dipyrisamole
increased platelet concentration of cAMP
platelet responds less to ADP
reduced activation and aggregation of platelets

196
Q

Describe medication indicated following acute MI

A

aspirin indefinitely

ticagrelor/clopidogrel for up to 12 months

197
Q

What is DIC?

A 
disseminated intravascular coagulation.
acquired consumptive process
activation of coagulation cascade
micro thrombi
exhaustion of coagulation cascade
bleeding
198
Q

What are the causes of DIC?

A 
sepsis 
malignancy
massive haemorrhage
severe trauma
pregnancy complications e.g. pre-eclampsia, placental abruption, amniotic fluid emobolism
199
Q

what can DIC cause?

A

systemic activation of coagulation
intravascular fibrin deposition
thrombosis of small and midsize vessels and organ failure
depletion of platelets and coagulation factors
bleeding

200
Q

What laboratory investigations would you do for DIC?

A

coagulation PT, APPT, fibrinogen
D dimers
FBC + film - reduced platelets and RBC fragments

201
Q

What do you do when INR is too high?

A

stop warfarin or reduce dose
give vitamin K1
give coagulation factors -berpilex

202
Q

Describe coagulopathy in liver disease

A 
poor coagulation factor synthesis 
vit K déficient
poor clearance of activated coagulation factors 
DIC
hypersplenism
reduced thrombopoietin synthesis
203
Q

Describe haemophilia A

A

factor VIII deficiency
x-linked inheritance
prolonged APTT

204
Q

What is the treatment for coagulation factor deficiency?

A

education
desmopressin
replacement therapy - recombinant produced factor concentrate
gene therapy

205
Q

Describe von willebrand disease

A

most common mild bleeding disorder
mostly autosomal dominant with incomplete penetrance
mucosal type bleeding pattern
reduced VWF +/- reduced platelet aggregation +/- reduced FVIII

206
Q

Describe type I VWD

A

partial quantitive deficiency

207
Q

Describe type II VWD

A

qualitative deficiency

208
Q

Describe type 3 VWD

A

virtually complete deficiency

209
Q

Describe severe inherited platelet disorders

A

rare
autosomal recessive
mucosal type bleeding patten

210
Q

What is glansmanns thombasthenia?

A

absent/defective GP IIb/IIIa

normal platelet count

211
Q

What is Bernard soupier syndrome?

A

absent/defective GP Ib/V/IX

macrothrombocytopaeia

212
Q

How is bleeding treated in inherited platelet disorders?

A

pressure
tranexamic acid / desmopresin
platelet transfusion
rFVIIa

213
Q

Describe inherited thrombophilia

A 
deficiencies of natural anticoagulants 
antithrombin
protein C
protein S
Factor V leiden - résistance to APC
prothrombin gene mutation (increased prothrombin)
214
Q

Describe lupus anticoagulant

A

phospholipid dependent antibody
interferes with phospholipid dependent tests
APTT prolonged
if persistent, may be associated with prothrombotic state

215
Q

What is antiphospholipid syndrome?

A

persisting lupus anticoagulant and thrombosis or recurrent fetal loss

216
Q

How do you test for lupus anticoagulant?

A

APTT - prolonged
APTT 50:50 dilution - only partially corrects
DRVVT ratio prolonged
corrects with excess phospholipid

Phase 3 (15 decks)

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