Haematology Flashcards
(166 cards)
1
Q
fully saturated Hb group will bind how much O2?
A
1.34ml
2
Q
Tx of CML?
A
Imatinib
3
Q
what is immunophenotyping?
A
ABs used to detect specific antigens on cells to determine type and numbers
4
Q
what is plasma and how is it obtained?
A
liquid that blood cells are suspended in
obtained by anticoagulation
5
Q
What is serum and how is it obtained?
A
liquid without cells or clotting factors (plasma- fibrinogen)
obtained by clotting blood
6
Q
how much O2 will bind in a fully saturated Hb
A
1.34ml
7
Q
What enzyme facilitates formation of HCO3?
A
carbonic anhydrase
8
Q
where are alpha genes?
A
chromo 16
9
Q
where are beta genes?
A
chromo 11
10
Q
target cells?
A
seen in thalassemias
11
Q
HBh disease characteristics and cause?
A
one alpha globin gene left
severe anemia
HbH on elctrophoresis
beta tetromers
12
Q
HBBarts features?
A
gamma tetramer
death in utero
13
Q
Where are alpha tetrameres seen?
A
b thalassemia major
14
Q
what is raised HbA2 diagnostic of?
A
B thalassemia trait
15
Q
HIV infects what cells and what happens?
A
Cd4 Th cells
Th cell numbers decrease
Viral load increase as virus replicates
16
Q
What do Tc cells bind to?
A
MHC1
so have CD4
17
Q
What causes the acute HIV syndrome?
A
immune cell activation and death
body is trying to fight off the virus
symptoms after 2-3 weeks of infection
very high risk of transmission
18
Q
What is phase 2 of HIV?
A
chronic HIV/latency phase/assymptomatic
body is managing to control viral load however over time the viral load slowly increases and Th lymphocyte count decreases.
usually asymptomatic then start getting symptoms as viral load over takes lymphocyte count
lasts about 10 years
19
Q
What is aids?
A
state of depleted immune system
Th lymphocyte count is so low that the body cant fight the of simplest of virused
20
Q
What are aids defining illnesses?
A
illnesses that wouldnt cause symptoms in anyone else
fungal pneumonias: pneumocytis pneumonia, crytococcus pneumonia
21
Q
What are some main characteristics of AIDS?
A
low CD4 cells in blood
any aid defining illnesses
22
Q
how is HIV spread?
A
breast milk
blood
sexual fluids
23
Q
What is leukopenia?
A
low wbc count in the blood
24
Q
What is leukocytosis?
A
high white cell count in the blood
25
what is neutropenia and when is it classically seen?
low neutrophils
drug toxicity eg chemo
very severe infection (increased production of neutrophils but the majority pass into the tissues to fight the infection)
26
How would you treat neutropenia?
gmcsf- granulocyte monocyte colony stimulating factor
gscf- granulocyte colony stimulating factor
both used to boost granulocyte thus neutrophil production
27
What is lymphopenia and some common causes?
low number of circulating lymphocytes
immunodeficiency
autoimmune destruction (antibodies against WBC)
whole body radiation- lymphocytes are very sensitive to radiation
high cortisol state- induce apoptosis of lymphocytes
28
What happens in Di george syndrome?
failure to develop third and fourth pharengeal pouch thus thymus so t cells cant mature properly
29
What is neutrophilic leukocytosis and when does it occur?
increased neutrophils in the blood
bacterial infection
tissue necrosis
high cortisol state
30
How do you recognise the presence of immature neutrophils in the blood and when does this occur?
decreased fc receptors on the surface- decreased CD16- so they dont function quite as well
in situations when the bone marrow increases production and releases immature cells
31
why does high cortisol state increase neutrophils?
cortisol causes release of the storage pool of neutrophils by disrupting the adhesion of the pool causing them to fall into the blood
32
When does monocytosis occur?
chronic inflammatory states
| malignancy
33
When does oesinophillia occur?
allergies
parasites
hodgkin lymphome (increased IL 5 production)
34
When do you see basophilia?
CML
35
when do you see lymphocytic leukocytosis?
viral infections with the exception of bacteria bordetella pertusis (blocks the lymphocytes from entering tissues so increased numbers in the blood)
36
What causes infectious mononucleosis/glandular fever?
EBV infection
| results in lymphocytic leukocytosis of reactive CD8 Tc cells
37
How do you screen for glandular fever?
monospot test identifies IgM antibodies
38
How do you definately diagnose glandular fever?
Ebv viral capsidantigen
39
What is thrombophilia?
hypercoagulability state
| inherited or acquired abnormality/ deficiency of naturally occuring anticoagulants that increases risk of thrombosis
40
When do you suspect thrombophilia?
Individuals with recurrent DVTs or PEs and not other risk factors
any individual with a DVT <45 years
41
What are the four main inherited thrombophilias?
Activated protein C resistence/Factor V leiden
Prothrombin gene mutation
Protein C and S deficiency
Antithrombin deficiency
42
What is APC resistance/factor V leiden?
factor V leiden is an abnormal/mutated factor V which activated protein C cant break down/anticoagulate
43
What happens in prothrombin gene mutation?
results in high prothrombin levels and increased thrombosis
44
What happens in protein C and S deficiency?
reduced anticoagulant effect on VIII/IXa and V/Xa
45
What activates protein C and S?
thrombin bound to thrombomodulin on surface of endothelial cells
46
What are the Vit K dependent clotting factors/proteins?
```
prothrombin
VII
XI
X
PC&S
```
47
how does warfarin work?
blocks vit k oxide reductsae reducing the activation of vit k which decreases vit k dependant clotting factors
48
How does heparin work?
works as a co factor binding to and potentiating/ increasing the effects of antithrombin by enhancing the binding of antithrombin to factor Xa and II/prothrombin for inactivation
49
What does antithrombin do?
inactivates thrombin and enzymes involved in the coagulation cascade
50
What is the main acquired thrombophilia?
antiphospholipid syndrome
51
What is antiphospholipid syndrome?
autoimmune hypercoaguable state caused by antiphospholipid antibodies
commonly in SLE or preganancy
52
Prophylactic treatment of antiphospholipid syndrome in pregnancy?
heparin and aspirin (this is a disease that increases thrombosis risk in venous and arterial system so anticoagulants and antiplatlets needed)
53
What is management of DVT?
```
acutely- LMWH
long term anticoagulation:
3 months if precipitating factor
6 months is no precipitating factor
warfarin
```
54
What is warfarin INR target?
2-3 if no events
| 3-4 if events
55
What is the treatment of thrombopillia?
life long anticoagulation- warfarin
56
DVT/ PE in pregnancy management?
LMWheparin
57
First line investigationin PE?
CT pulmonary angiogram- high risk
| low risk- D dimer if positive CT
58
What is haemophillia?
impaired ability to make blood clots causing prolonged bleeding and easy bruising
59
What are the main types of haemophilias?
Haemophillia A
Haemophillia B
acquired haemophilia
60
What is haemophilia A?
X linked recessive
| factor VIII deficiency
61
What is haemophillia B?
X linked recessive factor IX deficiency
62
What are the typical clinical presentations of haemophilias and why?
bleeding into joints/haemarthrosis
soft tissue bleeds
bruising in toddlers
prolonged bleeds after surgery or dental extraction
63
When can desmopressin be useful and why?
VWF diesease
haemophillia A
desmopressin can increase the secretion of VWF resultingi n a subsequent increase in VIII
64
Management of haemophillia A?
avoid NSAIDs and IM injections
pressure and elevation
desmopressin
65
What are some examples of acquired multiple clotting factor deficiencies?
liver failure- main site of production for clotting factors
| Vit K deficiency/warfarin use- factors II, VII, IX, X need vit K for production
66
What is acquired haemophilia?
rare
| autoimmune ABs to factor VIII
67
what is another name for clotting factor II?
prothrombin
68
what are the key differences between a venous and an arterial thrombosis?
venous- low pressure system, platelets not activated, activation of coagulation cascade, clots rich in fibrin (red)
arterial- high pressure system, platelets are activated, atherosclerotic process, clots rich in platelets (white)
69
What is virchows triad?
stasis, vessel wall damage, hypercoagulability
70
What is the difference of treatments in venous and arterial thrombosis and why?
arterial - PLATELET RICH CLOT- ANTIPLATELETS- aspirin, clopridogrel
venous- FIBRIN RICH CLOT- ANTICOAGULANTS- warfarin, heparin
71
How does aspirin work?
NSAID- blocks COX activation
| decreased production of prostaglandins and thromboxanes (promote platelet aggregation)
72
When should you consider antiphospholipid syndrome?
recurrent arterial or venous thromboses
recurrent fetal loss
mild thrombocytopenia
73
what is antiphospholipid syndrome?
autoimmune hypercoaguable state
| antiphospholipids ABs which activates hamostasis process
74
When do you give anticoagulants?
venous thrombosis events
| AF- stroke prevention
75
what do anticoagulants target?
formation of the fibrin clot- secondary haemstasis
76
How does heparin work?
potentiates the effect antithrombin
77
what are the two forms of heparin?
LMWH (targets Xa more)
| unfractioned form
78
How do you moniter heparin?
standard- APTT
| LMWH- Antifactor Xa (routine monitoring not required)
79
What are the main side effects of heparin?
bleeding
heparin induced thrombocytopenia with thrombosis (HIIT) initial drop in platelets seen in blood and then antibodies form that bind to heparin and result in platelet activation
osteoporosis
80
How does warfarin work?
inhibit vit K which is needed for the activation of II, XII, IX, X
81
what monitoring is needed for warfarin?
INR (calculation from the PT)
82
What is the management for reversing warfarin?
```
stop warfarin
Vit K (6hrs to effect) and clotting factors (immediate effect)
```
83
Why is warfarin so dangerous?
narrow therapeutic window
84
What is type 1 HIT?
heparin induced thrombocytopenia (decrease in platelets)
| decrease in the first 2 days but normalises with continues heparin
85
What is type 2 HIT?
autoimmune ABs that bind to heparin and actvate platelets and lead to HITT
usually 4-10 days but ABs can persist for months
86
What are D dimers and when are the elavated?
cross linked product of fibrin degradation produced when fibrin is made
high in coagulation
87
What is Von willebrand disease?
deficiency of VWF
| most common inherited bleeding disorder usually AD
88
What is seen in hereditory haemophillia?
prolonged APTT
89
Why is VWF so important?
platelet adhesion
90
What are the typical signs of primary haemostasis problems?
spontaneous bruising and purpura
mucosal bleeds (GI, epitaxes, conjunctival, menorhagia)
intracranial haemorrhage
retinal haemorrhages
91
What are some signs of VWF disease?
primary haemostasis
| prolonged APPT
92
Why do you get prolonged APPT in VWF disease?
vwf binds to factor VIII to stop its breakdown. with dcreased VWF you get decreased VIII with can prolong APTT
93
How do you diagnosis VWF disease?
FH
| quantative and qualitative levels of VWF in blood
94
What causes HSP?
systemic vasculitis with deposition of IgA commonly following a throat infection
95
what is idiopathic thrombocytopenic purpura?
isolated reduction in platelet count due to ABs against platelet antigens
96
What are the two types of idiopathic thrombocytopenic purpura?
acute- following infection. 1-2 weeks
| chronic
97
What is thalassemia?
(MICROCYTIC ANEMIA)
98
What kind of RBCs are present in thalassemia and why?
MICROCYTIC
abnormal production of globin chains that are needed for Hb production. Abnormal Hb results in cells that divide an extra time thus smaller cells
99
How can you diagnose thalassemias?
exclude iron deficiency
blood film- target cells
electrophoresis/high performance liquid chromatographs- quantify the types of Hb presnt
100
what is high HbA2 diagnostic of?
B thalassemia trait
101
How does B thalassemia present?
within first year severe anemia and failure to thrive
hepatosplenomegaly
osteopenia
extramedullary haematopoiesis- skull bossing
102
How do you treat B thalassemia?
trait- usually asymptomatic
intermediate- may require transfussions
major- life long transfussions- iron chlators to prevent iron overload
103
What makes target cells?
decreased volume in RBC means extra membrane forms a middle fistula like portion that looks darker
104
Hbh disease
one alpha gene left
| beta tetramere forms
105
HbBarts disease
hydrops fetalis
no alpha genes
gamma tetramere
106
difference between alpha and beta thalassemia?
alpha gene deletions on chromo 16
| beta gene mutations on chromo 11
107
B thalassemia major
alpha tetromere
108
What is the inheritence pattern in sickle cell disease?
autosomal recessive
109
what happens in sickle cell disease?
amino acid substitution on beta chain gene on chromosome 11 (GLU -VAL) causing abnormal production of beta chains
HbS instead of normal adult HbA. Carrier if one S replacing B and disease if two S
110
When does sickle cell commonly present?
1st year of life
111
What are the classic features and symptoms of sickle cell disease?
```
chronic haemolysis-
anemia
attacks of pain- vasoocclusive crisis (microvascular occlusion- cells aren't as flexible)
swelling in hands and feet
stroke
bacterial infections
aplastic crisis
```
112
What is aplastic crisis and what is it commonly associated with?
temporary cessation of RBC production due to
parvo virus B19 that destroys RBC precursors. this decreased RBC on top of the already chronic haemolysis brings Hb down to very low levels. treated with transfusions
113
How do you treat sickle cell anemia?
hydroxycarbamide- regular crisis's
prophylactic immunisations and ABXs
bone marrow transplant
114
How do sickle cells develop?
Hbs polymerises when deoxygenated and causes rbcs to deform into rigid sickle cells that are fragile
115
What can trigger sickle cell disease attacks?
temperature changes, stress, high altitude, dehydration
116
What is a sickle cell carrier?
someone with one mutated copy
117
What is the consequence of sickle cells?
increased haemolysis
118
What are the signs of sickle cell anemia?
reduced Hb
Increased reticulocytes and bilirubin
sickle cells and target cells
119
What does the sickle cell solubility teast recognise?
presence of HbS but cant distinguish between HbAS and HbSS (use electrophoresis)
120
What is amyloidosis?
accumulation of proteins to form non suluble fibrils of amyloid in extracellular space can be local or widely distributed
symptoms vary massively on affected sites
121
What is diagnosis for amyloidosis?
biopsy- postive congo red staining
| red green birefringemence under polarised light
122
What causessecondary amyloidosis?
underlying chronic inflammation eg RA, TB
| amyloid is derived from serum amyloid A which is an acute phase protein
123
What is amyloidosis?
accumulation of proteins to form non suluble fibrils of amyloid in extracellular space can be local or widely distributed
symptoms vary massively on affected sites
124
What is diagnosis for amyloidosis?
biopsy- postive congo red staining
| red green birefringemence under polarised light
125
What causes secondary amyloidosis?
underlying chronic inflammation eg RA, TB
| amyloid is derived from serum amyloid A which is an acute phase protein
126
What is multiple myeloma?
cancer of plasma cells in the bone marrow. Cells are abnormal and multiply releasing monoclonal ABs of one type (paraprotein)
127
when does multiple myeloma commonly present?
60-70s
128
What are the symptoms of myeloms?
```
initially asymptomatic
CRAB:
Calcium high (breakdown of bone)
renal failure (AB deposition)
anemia (function of normal cells affected)
bone lesions - pain, osteoporosis
```
recurrent bacterial infections
129
What causes the symptoms of myeloma?
build up of abnormal B cells in the marrow
| increasing paraprotein in the blood (kidney problems, thicken blood)
130
What are the key signs in myeloma?
FBC- normocytic normochromic anemia
| Film- rouleaux formation. Increased ESR
131
What is rouleaux formation and why does it occur?
stacks of aggregated RBCs occur when plasma protein concentration is high
132
How do you treat multiple myeloma?
bisphosphonate- reduce fracture risk
anemia- EPO or transfusion
regular IV immunoglobulin infusions
Chemo
133
What is myelofibrosis?
myeloproferative disorder with proliferation of abnormal cells and the precense of fibrosis
134
What is a myeloproliferative disorder and the main examples?
```
excess production of cells in the bone marrow
Chronic mylogenous leukemia
essential thrombocytopenia
polycythemia vera
primary myelofibrosis
```
135
How do you treat multiple myeloma?
bisphosphonate- reduce fracture risk
anemia- EPO or transfusion
regular IV immunoglobulin infusions
Chemo
136
What is myelofibrosis?
myeloproferative disorder with proliferation of abnormal stem cells and fibrosis
137
How do you treat essential thrombocythemia?
aspirin 75mg daily
| Hydroycarbamide if >60 or revious thrombosis (decreases platelets)
138
What is essential thrombocythaemia?
clonal proliferation of megakaryocytes
| high platelets with abnormal function
139
What are the signs and symptoms of essential thrombocythaemia?
```
increased WBC count
Decreased RBC count
thrombosis
headaches
splenomegaly
```
140
How do you treat essential thrombocytopenia?
asprin 75mg daily
| Hydroycarbamide if >60 or revious thrombosis (decreases platelets)
141
What are lymphoproliferative disorders and the main types?
```
excess production of lymphocytes
Acute lymphoblastic leukemia
lymphoma
chronic lymphocytic leukemia
multiple myeloma
```
142
What is polycythaemia vera?
malignant proliferation of RBC and overproduction of WBCs and platelets
143
What causes the malignant proliferation of RBCs in polycythemia vera?
mutation in JAK2
| allows cells to proliferate independent of EPO
144
What are the main symptoms of polycythemia rubra vera?
hyperviscosity- headaches, dizzy,
ITCH AFTER A HOT BATH
erythromelagia- burning sensation in fingers and toes
gout- increased urate from RBC turn over
145
What causes erythromelagia?
increased platelet aggregation forming tiny clots in peripheral small vessels
responds well to aspirin
146
How do you treat polycythemia vera?
daily aspirin - reduce thrombosis risk
venesection if young
>60yrs- hydroxycarbamide
147
What are the signs of polycythemia vera?
decreased serum EPO
| marrow- hypercellularity and erythroid hyperplasia
148
What is acute leukemia?
neoplastic proliferation of blasts (disruption in ability of cell to mature so the precursors build up)
>20% blasts in the bone marrow
149
What happens in acute leukemia?
blasts crowd out normal haematopoiesis
anemia (low Hb) thrombocytopenia (bleeding) and neutropenia (infection)
blasts enter into the blood and increase WBC count
150
What are the characteristics of blasts on blood smear?
large immature cells with punched out nucleoli
151
What is AML (acute myeloid leukemia)?
accumulation of myeloblasts
152
What is ALL (acute lymphoid leukemia?
accumulation of lymphoblasts
153
How do you distinguish between the blasts?
Staining
ALL - tDt +ve (DNA polymerase present only in lymphoblasts)
AML- MPO +ve (myloperoxidase shows are a auer rods)
154
What is ALL associated with?
downsyndrome
155
Who is ALL most common in?
children
156
Who is AML most common in?
adults
157
What are the classic symptoms of ALL?
anaemia
infections
bleeding
lymphadenopathy
158
How do you treat ALL?
transfusions
allopurinol (decrease uric acid levels and prevents tumour lysis syndrome which can occure when large amounts of cells are killed off at same time)
chemo
159
what is diagnostic of AML?
auer rods
160
How do you treat AML?
intensive chemo
bone marrow transplant
allopurinol
161
leukemia?
malignancy in the blood
162
lymphoma?
malignancy forms a mass in lymphoid tissue
163
What is meant by a chronic leukemia?
proliferation of mature circulating blood cells
164
What is meant by acute leukemia?
proliferation of immature blasts (either myeloid or lymphoid lineage)
165
What is CLL (chronic lymphocytic leukemia)?
neoplastic proliferation of niave B cells
increased lymphocytes and smudge cells on film
can involve node as the cells travel there
166
What is a key distinguishing feature of CML?
translocation of 9 and 22 showing tyrosine kinase activity
