Anticoagulants Flashcards
1
Q
what are the treatment options for thromboembolic disease?
A
antiplatelets
anticoagulants
thrombolytics/fibrinolytics
mechanical options
2
Q
what do antiplatelets do?
A
prevent clots
arterial use
3
Q
what do anticoagulants do?
A
prevent clots
arterial and venous use
4
Q
what do thrombolytics/fibrinolytics do?
A
destroy clots
arterial and venous use
5
Q
mechanical options for thromboembolic disease
A
PCI
stents and angioplasty
6
Q
common antiplatelets
A
aspirin clopidogrel dipyridamole prasugrel ticagrelor abciximab tirofiban
7
Q
common anticoagulants
A
warfarin heparins apixaban rivaroxaban dabigatran danaparoid fondaparinux argatroban epoprostenol
8
Q
common thrombolytics and fibrinolytics
A
tissue plasminogen activator
streptokinase
urokinase
9
Q
what is VTE?
A
PE and DVT
10
Q
ACS
A
acute coronary syndrome
MI
11
Q
haemostasis
A
balance between haemorrhage and thrombosis
12
Q
virchow’s triad
A
causes of thrombus formation:
- blood stasis
- hypercoagulability
- endothelial injury
13
Q
what is thrombophilia?
A
pro-thrombotic state
14
Q
what determines thrombosis treatment?
A
where the thrombus is
capillaries, veins or arteries
15
Q
what are the stages of haemostasis?
A
formation of platelet plug
propagation of clotting
termination of clotting
fibrinolysis and clot removal
16
Q
formation of platelet plug
A
platelet adhesion, aggregation, activation and secretion
activation of thrombin
17
Q
propagation of clotting
A
intrinsic and extrinsic pathway activation
clotting cascade
amplification of cascade
recruitment of platelets
18
Q
termination of clotting
A
limitation of clot formation
muting clotting cascade
restoring anti-thrombotic state
19
Q
fibrinolysis and clot removal
A
activation of plasmin
lysis of cross-linked fibrin
production of D-dimer and FDPs
20
Q
end of clotting cascade/ common pathway
A
factor X to Xa
Xa causes Va to convert
prothrombin to thrombin
Thrombin causes fibrinogen to fibrin and XIII to XIIIa which converts fibrin to cross linked fibrin
21
Q
what triggers the coagulation cascade?
A
intrinsic pathway = response to sepsis, toxins and hyperlipidaemia
extrinsic pathway = tissue factor caused by injury
22
Q
lining of blood vessels
A
antithrombotic
deeper down in the vessel wall is more thrombotic
23
Q
fibrinolysis
A
plasminogen is converted to plasmin by tissue plasminogen activator
plasmin breaks down cross linked fibrin into fibrinogen degradation products (FDPs) and D-dimer
24
Q
what are the antithrombotic factors?
A
activated protein C
protein S
anti-thrombin
25
what do anti-thrombotic factors do?
block coagulation cascade
26
How do protein S and C work?
protein S activates protein C
| Protein C inhibits factor Va to prevent prothrombin conversion to thrombin
27
how does anti-thrombin work?
directly inhibits thrombin
28
tombstone ST elevation
```
indicates full thickness
acute
large MI
needs immediate treatment - stent
thrombolytic given to open coronaries
```
29
best treatment for STEMI MI
PCI
| more effective than drugs
30
MI
atheroma causes ischaemia and thrombotic occlusion causes the infarction
31
when to use anti-platelets vs anticoagulants
have similar effects
| can be used in same setting but anti-platelets are used more in arterial disease
32
why are anti-platelets used in arterial disease over anti-coagulants?
in arterial disease platelet plug is already occluding the artery and is a more important factor in the occlusion
platelet rich clots form in arteries
in veins more fibrin than platelets cause occlusion
33
how to treat ischaemic stroke?
antiplatelet
| anticoagulation if in AF
34
what antiplatelets are used in treating ischaemic stroke?
aspirin
clopidogrel
dipyridamole
35
AF
risk of clot formation in left atrial appendage and other parts of heart
clots are clotting factor and fibrin rich
can cause bowel ischaemia or stroke
36
AF treatment
need treatment with anticoagulation
| don't use aspirin
37
who needs AF treatment?
younger people with no other comorbidities = bleeding risk from treatment is greater than risk of thrombus so no anticoagulation indicated
older people and those with comorbidities = risk of thrombus exceeds bleeding risk so treatment required
38
what comorbidities indicate AF treatment?
hypertension
high cholesterol
etc.
39
assessment for AF stroke risk
CHA2DS2-VASc score
40
CHA2DS2-VASc scoring system
- 0 points = no anticoagulation needed
- 1 = needs anticoagulation but may opt out in some circumstances
- >1 = ANTICOAGULATION!! (unless good reason not to)
41
what are the classes of anticoagulants?
DOACs
warfarin
heparins
fondaparinux
42
e.g. of heparin
dalteparin
43
DOACs
direct oral anticoagulants
44
what are the indications for anticoagulants?
treatment of thromboembolism
prevention of thromboembolism
high risk thrombophilias
45
treatment of thromboembolism
```
arterial = warfarin and DOACs
venous = heparins, DOACs and warfarin
```
46
prevention of thromboembolism
in stroke and AF = warfarin and DOACs
| VTE prophylaxis = low does LMWH
47
treatment for high risk thrombophilias
seek specialist advice
48
advantages of DOACs?
fewer interactions with other drugs
no INR monitoring required
simpler for patients and doctors
49
disadvantages of DOACs?
no easy way to reverse them - but there is for warfarin
| less long-term data on efficacy and safety
50
use of DOACs
relatively new
| most people are now started on these and not warfarin
51
examples of DOACs
apixaban
rivaroxaban
edoxaban
dabigatran
52
how do DOACs work?
rivaroxaban and apixaban directly inhibit factor Xa and prevent activation of thrombin from prothrombin
dabigatran directly inhibits thrombin so fibrin cannot be formed
53
rivaroxaban
- caution in renal disease
- no monitoring required
- used for VTE prevention
- used for AF
- cannot be used in people with mechanical heart valve
- apixaban is increasingly common in place of this
54
Dabigatran
- renally excreted – avoid in severe CKD
- careful in acute kidney injury
- no monitoring required
- coagulation tests can demonstrate activity but poorly relate to actual degree of action
- dyspepsia and hepatobiliary disease = common side effect
55
Interactions with dabigatran
drugs that are inhibitors or inducers of P-glycoprotein affect dabigatran levels
56
parenteral anticoagulants
= anticoagulants that cannot be given orally
57
examples of parenteral anticoagulants
LMWH
unfractionated heparin
fondaparinux
58
LMWH administration
subcutaneous injection
59
use of fondaparinux
ACS/ MI
60
how does heparin work?
alone antithrombin is relatively weak at inhibiting thrombin but heparin binds and induces a conformational change that increases the binding of thrombin and Xa and increases activity of anti-thrombin and further inhibits thrombin
61
LMWH
affects Xa inhibition more than thrombin
62
fondaparinux mechanism of action
similar to heparin mechanism of action
63
how is heparin administered?
LMWH = subcutaneous injection of dalteparin
| unfractionated heparin = less commonly used, given by IV injection (can be reversed quickly and titrated up and down)
64
who is LMWH given to?
large number of immobile patients
pregnant women
post-op patients
65
side effects of heparin
- bleeding
- thrombocytopenia – long-term use (need to monitor platelets)
- hypokalaemia
- osteoporosis in long-term use
- can accumulate in renal failure – needs dose reduction depending of eGFR
66
fondaparinux
- similar mode of action to heparin
- given by subcutaneous injection
- causes less thrombocytopenia
- replaced LMWHs for treatment of acute coronary syndromes (MIs)
67
warfarin
- common
- prescription complications are common
- complicated
68
disadvantages of warfarin
- no one dose
- variable doses between individuals and difficult to predict
- lots of interactions with drugs and foods
- dangerous – teratogenic in pregnancy
- non-fatal effects
- initial high-dose therapy is pro-thrombotic
69
normal vitamin K activation of clotting factors
clotting factors = serine protease
Carboxylase requires reduced vitamin K (abundant for activation)
During the process vitamin K is oxidised and no longer able to be used
NADH and vitamin K reductase can then reduce vitamin K again to be recycled and used for activating clotting factors again
70
warfarin mechanism of action
- blocks vitamin K reductase
- once all vitamin K is oxidised
- no more reduced vitamin K is present to activate clotting factors
- new vitamin K needed to activate serine protease/clotting factors
- warfarin keeps vitamin K oxidised
71
diet and warfarin
dietary intake of vitamin K can affect warfarin because warfarin inhibits carboxylation of vitamin K dependent coagulation factors
72
INR
international normalised ratio
73
what is INR?
measure of prothrombin time
74
use of INR
measures anticoagulant effect of warfarin and its effect on the clotting cascade
75
how to calculate INR?
prothrombin time of patient/prothrombin calibrated normal
76
benefit of INR
eliminates assay variation between places
77
INR of 2
prothrombin time is twice that of a normal control using that assay
78
what is the target INR for people on warfarin?
2-3
79
how to prescribe warfarin?
```
dedicated chart
own policies
risk assessment - balance of risk factors for bleeding and indication for use
baseline monitoring
advice on interactions
```
80
warfarin and drug interactions
enzyme inducers increase warfarin metabolism and reduce INR and its effect
enzyme inhibitors decrease metabolism of warfarin and so increase INR and bleeding risk
81
what else can affect warfarin?
other anticoagulants
| protein binding
82
high risk drugs for warfarin interactions
```
anticonvulsants
antibiotics
analgesics - NSAIDs
anticoagulants
antidepressants
anti-platelets
```
83
what common drugs enhance the effect of warfarin?
```
anabolic steroids
antidepressants
antidiabetics
allopurinol
amiodarone
antibiotics
aspirin
NSAIDs
phenytoin
statins
```
84
what other substances enhance the effect of warfarin?
cranberry juice
grapefruit juice
smoking cessation
alcohol
85
what common drugs reduce the effect of warfarin?
```
azathioprine
carbamazepine
rifampicin
oral contraceptive pills
st john's wort
```
86
what other substances reduce the effect of warfarin?
chronic alcohol use
broccoli
green leafed vegetables
87
Initial parenteral treatment
when instant anticoagulation is required
88
initial oral treatment
when slower anticoagulation is needed
89
how to reverse warfarin?
```
depends on urgency and severity
vitamin K oral or IV
IV = 5mg
varied doses
omit the warfarin dose
FFP
prothrombin complex concentrates
```
90
FFP
frozen fresh plasma
instant effect
variable effect
new clotting factors
91
dried prothrombin complex concentrates
instant effect
e.g. octaplex
pooled clotting factors from other patients
given with vitamin K
92
warfarin reversal with vitamin K
slow
93
reversal of DOACs
support measures/resuscitation
normal INR excludes significant dabigatran effect but doesn't exclude therapeutic concentrations of the other DOACs
need to wash out DOACs
if severe = dried prothrombin complex
94
wash out for DOACs
12 hours for dabigatran and apixaban
| 24 hours for rivaroxaban
95
new antidote for dabigatran
idarucixumab
| expensive
96
reversal of heparin
depends on severity and urgency
omit dose of LMWH or stop the infusion of unfractionated heparin
protamine sulphate
97
what are thrombolytics?
clot busters
98
uses of thrombolytics
```
acute ischaemic stroke
PE with cardiovascular collapse
massive DVT
upper limb DVT
other rare uses
```
99
how do thrombolytics work?
activates plasmin
breaks down clot
TPA - tissue plasminogen activator
100
consent for thrombolysis
get verbal consent for administration
risks can be severe
make sure risks are explained
101
what are the risks of thrombolytics?
```
intra-cerebral haemorrhage
other haemorrhages
all clots in the body are broken down
haemorrhagic strokes
massive GI bleed
```
102
Criteria for TP in ischaemic acute stroke
<4.5 hours since clear onset
>18 years old
diagnosis of ischaemic CVE
103
most common PE ECG finding
sinus tachycardia
104
when to consider thrombophilia?
when atypical thrombosis is present or there is recurrent unprovoked disease
105
antiplatelets
irreversible COX inhibitors
P2Y12 receptor antagonists/ ADP receptor inhibitors
glycoprotein inhibitors
106
aspirin
inhibition of thromboxane synthesis in platelets
| inhibits platelet aggregation
107
P2Y12 receptor antagonists examples
clopidogrel
prasugrel
ticagrelor
ticlopidine
108
how do P2Y12 receptor antagonists
inhibits P2Y12 receptor on platelets
inhibits platelet aggregation
no activation of Gp IIb/IIIa receptors
109
glycoprotein inhibitors examples
abciximab
eptifibatide
tirofiban
110
how do glycoprotein inhibitors work?
bind and block glycoprotein IIb/IIIa receptors on platelet surface
prevents platelets binding to fibrinogen
inhibits platelet aggregation and thrombus formation
