4.05- Dvt And Pe

Front 1

What is Virchow's triad?

Back 1

The three factors that contribute to thrombosis:
- Hypercoagulability
- Static blood / abnormal flow
- Endothelial damage

Front 2

What is the difference in colour between arterial and venous thromboses and why is this?

Back 2

Arterial thrombus = full of platelets -> white
Venous thrombus = more rich in RBCs -> red

Front 3

What is THE main thing that activates platelets?

Back 3

Thrombin (II)

Front 4

What is clopidogrel?

Back 4

An ADP receptor antagonist _. inhibits platelet function

Front 5

What is the GPIIa-IIIa complex?

Back 5

GP = glycoprotein
It's on the surface of platelets
Involved in lots of things, namely:
- Platelet aggregation
- Fibrinogen binding (its the receptor to which fibrinogen binds)
- Platelet activation

Front 6

Which is more likely to result in a PE, distal or proximal DVT?

Back 6

Obviously proximal

Front 7

What are some of the mechanisms by which tumours promote venous clotting?

Back 7

- They might be blocking the vessel to some extent -> blood stasis
- They can result in higher conc of proteins and WBCs in blood -> more viscous blood
- Can invade BVs -> endo damage
- The tumour cells can release pro-coagulant that's able to directly activate X without VII

Front 8

What does lupus anticoagulant do to the APTT?

Back 8

It prolongs the APTT -> suggests that it would increase bleeding in the body but it's actually the opposite ie it increases thrombosis (it's a misnomer!)

Front 9

Who would we recommend to take LMWH before a flight of longer than 5 hours duration?

Back 9

Anyone who's have a thrombus previously
Pregnant woman
Someone who's had recent trauma or surgery

Front 10

What does thrombophilia mean?

Back 10

Tendency to clot

Front 11

By how many times does heparin potentiate anti-thrombin's effects?

Back 11

1000 fold!

Front 12

What three major groups of inherited abnormalities can we have that increase thrombosis? and some egs in each group

Back 12

- Reduction in inhibitors eg decreased ATIII, decreased prot C and/or S
- Increase in procoagulants eg factor V Leiden, prothrombin mutation
- Increased homocysteine

Front 13

What are some acquired causes of thrombophilia?

Back 13

Surgery = definitely the most common / main one
Lupus anticoagulant and anti-cardiolipin antibody
Pregnancy
Malignancy
OCP

Front 14

What is the difference in oral bioavailabilities of unfractionated and LMW heparins?

Back 14

Unfractionated -> very low oral bioavailability
LMWH -> much higher

Front 15

Which has better dose-response predictability: unfractionated heparin or LMWH?

Back 15

LMWH - this means that we don't need to do so much monitoring because we can much more effectively predict their response based on weight etc

Front 16

What test do we use to monitor warfarin levels / effects?

Back 16

INR ie the PT

Front 17

Which factor is the INR / PT most sensitive to?

Back 17

Factor VII

Front 18

With warfarin therapy, what INR are we aiming for?

Back 18

About 2.5 usually (might be higher in some cases)

Front 19

How many days do we need cross-over between heparin and warfarin therapy?

Back 19

Must cross-over for at least FOUR DAYS!
This is even if the INR gets up to the therapeutic range in that time

Front 20

Someone in hospital on heparin and you want to switch them to warfarin. Monitoring INR - after 2 days it reaches therapeutic range. Are we now safe to take them off the heparin?

Back 20

NOOOOOO

must have cross-over for 4 days regardless of what the INR is saying

Front 21

Which type of BVs are called the 'capacitance vessels' and why?

Back 21

The veins
Because they usually store about 60% of the circulating blood

Front 22

What are the three major venous pathways in the leg?

Back 22

Deep veins - in the muscle compartments (ie venae commitantes)
Superficial veins - in the subcutaneous tissue
Communicating veins

Front 23

What direction does blood flow in the communicating veins?

Back 23

from superficial to deep

Front 24

Which blood vessels have more 'sluggish flow'?

Back 24

The veins

Front 25

What are the three main consequences of a DVT in the leg?

Back 25

1. Local venous congestion
2. Organisation - ingrowth of endo cells and fibrous tissue - could result in the formation of a new little channel in the vessel so blood can flow through still
3. Embolism = the most severe

Front 26

What are the effects of a DVT on the local area?

Back 26

Limb become oedematous and painful
There's an increase risk of infections if there's a little trauma and increase risk of ulcers forming

Front 27

Other than location and size of the PE, what impacts its severity?

Back 27

The ability of the systemic bronchial artery to compensate for the blockage

Front 28

What is factor V Leiden

Back 28

a gene defect -> V is less susceptible to cleavage by activated protein C -> hypercoagulability

Front 29

How much does factor V Leiden increase your risk of clotting? give values for both homos and heterozygotes

Back 29

hetero - increases 7-8 times
homo - about 50 times

Front 30

What would we consider 'abnormal sites' for thrombosis?

Back 30

In the cerebral or mesenteric vessels

Front 31

In a patient who was moderate-high risk of a thrombosis during surgery, what would we do in terms of prophylaxis?

Back 31

Would give them HEPARIN prophylactially - it decreases the risk of DVT and PE by 75%

Front 32

What are the three main clinical signs of DVT?

Back 32

Painful calf
Leg swelling
Positive Homan's test (but this isn't very sensitive or specific)

Front 33

What are our two main options for imaging a suspected DVT?

Back 33

- Venogram (x-ray the veins after injecting contrast)
- Ultrasound

Front 34

What are the disadvantages associated with a venogram?

Back 34

Radiation dose
Invasive (need to inject contrast)
Potential for an allergic reaction to contrast
Because of these, we prefer to do an US of the suspected DVT rather than venogram

Front 35

What is a duplex ultrasound?

Back 35

Implies that we have a combination of doppler information (on the speed of the blood flow) and structural info

Front 36

By how much does plasma volume increase in pregnancy?

Back 36

40-50%

Front 37

By how much does red cell volume increase during pregnancy?

Back 37

10-20%

Front 38

By how many g/L does Hb change in pregancy?

Back 38

It decreases ie being diluted out by the increased BV
Decreases by 10-20g/L

Front 39

How much more iron do we need each day during pregnancy?

Back 39

800-1000mg MORE than the normal (normal is 1-1.5g -> need about 2-2.5g)

Front 40

Why do we need extra iron during pregnancy? ie what's it used for?

Back 40

1/3 goes to the placenta and 2/3 is needed for the increased red cell mass

Front 41

What happens to iron absorption during pregnancy?

Back 41

It increases. But this often isn't enough to prevent iron deficiency anaemia - the mum's often start at borderline low iron levels then increased Fe needs in pregnancy will tip them into being deficient

Front 42

By how much do folate requirements change in pregnancy?

Back 42

They double

Front 43

What evidence is there for the benefits of folate and iron supplementation in pregnancy?

Back 43

Folate - definitely beneficial
Iron supplementation hasn't been shown to be beneficial to mum or baby

Front 44

What happens to transferrin levels in pregancy?

Back 44

They are increased

Front 45

What happens to serum iron and serum folate levels in pregnancy?

Back 45

They are decreased even in the case of no deficiency

Front 46

Which of these should and shouldn't we look at when looking for iron and folate deficiencies in pregnancy?
Serum iron, serum folate, red cell folate, serum ferritin, serum transferrin

Back 46

serum iron and serum folate - fall in pregnancy naturally -> not good indices
transferrin - increased -> not good index
serum ferritin - good index for iron!
red cell folate = good for folate

Front 47

What happens to coagulability in pregnancy?

Back 47

You become hyper-coagulable!

Front 48

Which clotting factors' levels change during pregnancy

Back 48

Fibrinogen - rises 2-3 fold
II, VII, X, VIII and vWF

Front 49

Why do mothers with vWD not have frequent and serious bleeds during pregnancy / birth?

Back 49

Both vWF and VIII increase during pregancy, but VIII increases the most out of the two

Front 50

70kg man has how much iron (in grams) in his body?

Back 50

4.5g

Front 51

What form is all the iron in your body in?

Back 51

1/2 is contained in haemoglobin
1/3 is stored as ferritin and haemosiderin
Remainder is in myoglobin and other enzymes etc

Front 52

How much iron is in the average person's diet each day? How much of this gets absorbed?

Back 52

10-15mg p/day
But you only absorb about 10% of this ie 1-1.5mg p/day approx

Front 53

Where in the GIT does iron get absorbed?

Back 53

The duodenum

Front 54

what are the two types of iron in our diet?
what's difference in absorbance?

Back 54

haem iron - from animal sources. Better absorbed (fe2+ form)
non-haem iron - from veggies, eggs etc. Not as well absorbed (fe3+ form)

Front 55

What increases and what decreases non-haem iron absorption?

Back 55

Increased by: acidic pH, vitamin C
Decreased by: tannates, alkaline conditions in the stomach

Front 56

How do we absorb non-haem iron?

Back 56

It's in 3+ form -> needs to be reduced to 2+ this is done b duodenal cytochrome B (DcytB) on apical mem of enterocyte
Then the 2+ form can bind to DMT1 (divalent metal transporter 1) transporter and get taken into enterocyte
Ferroportin takes iron across basal membrane

Front 57

What is DcytB and what's its role in Fe absorption?

Back 57

duodenal cytochrome B
It's a reductase that converts 3+ heam to 2+ so it can get absorbed
On apical mem of enterocytes

Front 58

What is DMT1 and what's its role in Fe absorption?

Back 58

divalent metal transporter 1
Carries Fe2+ across apical mem of enterocytes

Front 59

What's ferroportin and what's its role in Fe absorption?

Back 59

On the basement membrane of teh enterocytes - transports Fe out of the enterocyte and into the blood

Front 60

What transporter takes a) haem and b)non-heam iron into the enterocyte

Back 60

Non-haem crosses apical membrane via DMT1 (divalent metal transporter1)
we're not sure what receptor takes haem iron across

Front 61

What form of iron does transferrin bind?

Back 61

Fe3+ ie once Fe2+ is transported out of the enterocyte via ferroportin, it needs to be converted to Fe3+

Front 62

Where is hepcidin produced?

Back 62

The liver

Front 63

What does hepicidin do?

Back 63

Controls release of iron from enterocytes AND release from RES macros.
Negative regulator ie up hepcidin -> down release of Fe
(we have lots of hepcidin if the body stores of iron are increased)

Front 64

How does hypoxia affect iron absorption?

Back 64

Hypoxia -> hypoxia inducible factor 1 -> upregulation of DcytB and DMT1

Front 65

What happens to serum ferritin, transferrin and transferrin saturation in Fe deficiency?

Back 65

Ferritin low
Transferrin high
Saturation low

Front 66

What happens to serum ferritin, transferrin and transferrin saturation in chronic disease?

Back 66

Ferritin low
Transferrin low
Saturation - normal

Front 67

What happens to serum ferritin and transferrin saturation in iron overload

Back 67

ferritin high
saturation high

Front 68

What is the thing we have to be aware of when we're looking at a person's ferritin levels?

Back 68

It's an acute phase reactant! -> levels will be elevated in inflammation, infection or neoplasia. Will also be increased if Fe is released from its stores (eg liver damage)

Front 69

What is the relationship between synthesis of transferrin + body iron stores?

Back 69

They're inversely proportional
Low stores -> icnreased transferin

Front 70

What happens to transferrin receptor levels in a) Fe deficiency and b) chronic disease?

Back 70

fe deficiency -> increased receptor levels
chronic disease -> they're not increased (because transferrin isn't increased in chronic disease -> cells aren't increasing their expression of the receptor)

Front 71

What is the Perl's stain?

Back 71

= How we assess iron levels in the BM
ie the perl's stain stains iron containing material blue. Absence or decrease in blue = iron deficiency

Front 72

What are the three clinical features of DVT?

Back 72

Painful calf
Leg swelling
+ve Homan's sign

Front 73

What might make us suspicious that a person has inherited clotting disorders?

Back 73

family Hx of DVT / PE
past history of thrombosis, particularly if it was in weird location, unexplained and/or at early age

Front 74

What is our principle aim with treating a DVT?

Back 74

Totally inhibit clot formation ASAP - this prevents further extension (hence decreases risk of embolus) and allows fibrinolysis and clot organisation to start occuring

Front 75

What drug do we give to someone with a DVT?

Back 75

HEPARIN immediately
Would probably start an oral anti-coagulant soon as well ie warfarin (this learning topic says you need 5 days overlap, others have said 4)

Front 76

What does warfarin inhibit

Back 76

II VII IX and X
protein C and S
ie the vitK dep factors

Front 77

What is the time scale of warfarin's effects?

Back 77

The inhibition of C and S is the net effect of warfarin in the first few days. This makes the person HYPER COAGULABLE -> need another anticoag drug over the top at this time

Front 78

Which test do we use to monitor warfariN?

Back 78

PT ie INR
Aiming for 2-2.5

Front 79

When is it safe to stop heparin after the combo of heparin and warfarin?

Back 79

Must wait 4 days ie need four days of warfarin treatment WITH heparin before we can do warfarin alone

Front 80

T/F: when we're administering heparin and warfarin, we stop the concurrent heparin once INR has reached therapeutic range

Back 80

FALSE !!!! need to wait at least 4 days regardless of the INR is saying
Once we've had those 4 days, we need the INR to be in therapeutic range as well

Front 81

Do we usually use fibrinolytic agents with DVTs?

Back 81

Not usually. Benefits don't usually outweigh the risks (haemorrhage)

Front 82

Because of the big rate of recurrence of DVTs and PEs, how do we treat someone in LT post a DVT? (hint: 2 diff groups of people will be treated differently)

Back 82

- If there was a clear predisposing factor (eg post op / immobilisation) that's been removed, then we anti-coagulate for 6 weeks
- if there wasn't such a clear predisposing factor that we can remove, we anticoagulate for at least 3 months

Front 83

During pregnancy, what is the time when you're most at risk of a clot?

Back 83

The puerperium ie 6 week period post giving birth

Front 84

What is coumadin?

Back 84

warfarin

Front 85

What groups of people is warfarin contra-indicated in?

Back 85

- The very old
- People who are confused / demented
- People on multiple meds (because it has lots of rxns)
- People with liver disease
- people with potential focal bleeding eg peptic ulcer
- pregnant women

Front 86

If someone is suspected of having a DVT / PE, what tests would we run and in which order?

Back 86

First do D-dimers - if it's above 500, we start on heparin immediately. Below -> they don't have either DVT or PE
Then for DVT do a lower limb ultrasound
For PE, do V/Q lung scan

Front 87

If you have a PE, what will the V/Q scan show?

Back 87

ventilation is normal
perfusion is abnormal

Front 88

What does heparin act on?

Back 88

Potentiates the actions of anti-thrombin III
- the unfractionated acts on both Xa and IIa (thrombin)
- LMWH only acts on Xa

Front 89

What's the difference between unfractionated heparin and LMWH?

Back 89

Unfractionated = big mix of polysacc chains that vary significantly in size - lots are long enough to interact with both ATIII and IIa -> can inhibit both Xa and IIa
Fractionated - much smaller chains -> most can't bind both ATIII and IIa -> only acts on Xa

Front 90

What is the size range of molecules in unfractionated heparin?

Back 90

3k-30k

Front 91

What is the administration route of unfractionated heparin?

Back 91

IV or deep SC - can't do intermuscular because would cause a big haematoma

Front 92

What are the advs of LMWH over UFH? (5)

Back 92

- no need for lab monitoring because response is much more predictable
- higher oral bioavailability
- longer plasma half life
- less inhibition of platelet function
- less chance of HITs though still possible!

Front 93

What is the different in oral bioavailability of LMWH cf UFH?

Back 93

LMWH = 90%
UFH = 30%

Front 94

What is the pathogenesis of HITs?

Back 94

PF4 (platelet factor 4) forms complex with heparin -> IgG antibodies against this complex bind and then activate the platelets --> thrombosis and thrombocytopenia

Front 95

What do we monitor heparin with?

Back 95

APTT

Front 96

Why do we need to monitor someone on unfractionated heparin so regularly?

Back 96

There isn't a very predictable dose-response relationship with UFH -> need to always do their APTT and adjust dosage as requried

Front 97

What is the difference in the anti-Xa:IIa ration between UFH and LMWH?

Back 97

LMWH - can't bind to IIa as well as ATIII --> higher action on Xa compared to IIa
UFH - more equal -> smaller ratio

Front 98

How do we reverse the action of warfarin?

Back 98

Give them plasma ie we're replacing all the factors - rapid response but short lasting
Vitamin K replacement - takes longer to get a response but then it lasts longer (1-2 weeks)

Front 99

what are the effects of warfarin on baby in utero a) first trimester? b) 2nd and 3rd trimesters

Back 99

first trimester -> 10% chance of mental retardation, nasal hypoplasia, stippled cartilage and small fingers and hands
Later on, there's no developmental risks, just increased risk of intracranial haemorrhage (particularly at time of birth)

Front 100

Do we use warfarin during pregnancy and/or breast feeding?

Back 100

No for pregnancy - particularly in first trimester because causes birth defects
Ok for breast feeding - inactive form only in the breast milk -> doesn't affect the baby

Front 101

What does heparin bind to?

Back 101

Anti-thrombin III
which then inhibits Xa and IIa (inhibition of IIa requires that IIa also binds to the heparin molecule - only possible with the big heparin molecules)