CLINICAL- ANTICOAGULATION Flashcards
(115 cards)
1
Q
VTE is said to have a very variable effect, whys that??
A
It can either be completely resolved with no follow up needed
Or it can be classed as a morbidity (a disease) I.e. It becomes a co morbidity called post-thrombotic syndrome
2
Q
Things like immobility, venous obstruction, raised venous pressure can all lead to STASIS which then leads to thrombosis. Can venous dilatation lead to this?
A
Yes!!
This happens in pregnancy
3
Q
What three factors lead from STASIS to THROMBOSIS??
A
Local vessel injury (injury to inner lining of blood vessels)
Coagulation cascade activation (e.g. With tissue trauma in surgery, inherited thrombophilia)
Generation of FIBRIN (with or without platelet activation)
4
Q
One of the causes of coagulation activation leading to thrombosis is inherited thrombophilia. What are hereditary risk factors for VTE??
A
Deficiency of anticoagulants eg. Antithrombin
Abnormal protein eg. Fibrinogen
Increased pro coagulant e.g. Prothrombin
Abnormal metabolism
5
Q
If the patient has a risk of VTE but heparins are contraindicated what should be used?
A
TEDs (anti-embolism stockings)
Unless also contra indicated!!
6
Q
VTE risk is assessed in all surgical in-patients. What do we do if they come out as low risk?
A
Low risk we don’t do anything!!
This is usually for minor surgery e.g. A laparoscopy or arthroscopy (both involve small incisions)
7
Q
VTE risk is assessed in all surgical in-patients. What do we do if they come out as medium risk?
A
We give them a LMWH. This could be Dalteparin or enoxaparin and the dose is in the BNF under prophylaxis of DVT especially in surgical patients, under moderate risk!!
We don’t use LMWH in people with poor renal function!!!
8
Q
VTE risk is assessed in all surgical in-patients. What do we do if they come out as high risk?
A
We give them a LMWH. This could be Dalteparin or enoxaparin. Their doses are in the BNF under DVT prophylaxis for surgical patients, under high risk.
We don’t use LMWH in people with poor renal function!!
9
Q
When should TEDs stockings or IPC (intermittent pneumatic compression) be used for VTE prophylaxis?
A
When Heparins are contraindicated in the moderate and high risk patients.
TEDs should be used when extended prophylaxis is needed, for certain types of surgery such as major general cancer surgery
10
Q
When may LMWHs be contra indicated?
A
In patients with renal impairment (eGFR under 30ml/min)
Patients that are underweight or overweight
As these patients have increased bleed risk!!
11
Q
What should be used instead of LMWH’s in patients with renal impairment ??
A
UFH
For high risk it’s 3 times a day
For low risk it’s 2 times a day
12
Q
What do we use to make a correct diagnosis of VTE?
A
A colour duplex scan
Or compression ultrasonography
13
Q
How do we diagnose a pulmonary embolism?
A
This is in the lungs
We tend to use CT pulmonary amniography (CTPA)
Or CXR sometimes used
14
Q
If a leg vein had a DVT, what would you expect it to look like?
A
Entire leg Swollen
Or calf swelling 3cm more than the unaffected leg
Pitting oedema (can push your finger it to it and it doesn’t ping back)
15
Q
How is cross-linked fibrin broken naturally by our body when there’s a clot??
A
Fibrin cleaved by the enzyme plasmin
The fragments then dissociate into D-Dimers
This is why D-Dimer tests come out positive: when there’s a clot our body will start trying to break it down itself, producing D-Dimers
16
Q
What would a negative D dimer test tell us?
A
That there is no clot
No further testing is needed!!!
17
Q
What’s a heart rate over 100 Bpm likely to indicate??
A
It scores 1.5 towards to pre test probability calculation of PE
18
Q
If someone has a suspected PE and they are in shock, have hypotension or they collapse what do we do??
A
Consider urgent CTPA and thrombolysis
Seek a seniors opinion
19
Q
Heparins work by increasing anti-thrombin activity. Why do we want to do this??
A
Anti-thrombin (AT) is a natural anticoagulant inside us that inhibits the action of several factors of the clotting cascade, such as factor Xa.
We want to inhibit these factors because they are what make our blood naturally clot, and we don’t want that as it increases our clotting risk.
20
Q
What do we monitor with LMWHs when patients are at extremes of weight?
A
Anti factor Xa
21
Q
Which type of heparin has a longer saccharide sequence?
A
Unfractionated heparin
18 saccharides in length in addition to the standard pentasaccharide sequence that both LMWH and UFH have
(LMWH heparin is smaller- hence the Low molecular weight!)
22
Q
Because UFH is longer in length than LMWH, what can this facilitate the binding between?
A
Thrombin and anti thrombin
It also allows binding between antithrombin and factor Xa but so does LMWH
23
Q
How do the heparins work?
A
They wrap themselves around anti thrombin and squeeze it’s shape so that it can bind to Factor Xa and mop it up so that it can’t contribute to clotting in the coagulation cascade. This is called anti-Xa activity
UFH also does this with Thrombin and antithrombin. This is called antithrombin activity
24
Q
What’s the difference between UFH and LMWH in terms of their routes of administration?
A
UFH can be delivered by IV or SC
LMWH can be delivered by SC only
25
Why is renal impairment such a big issue with LMWH compared to UFH?
With LMWH elimination is by Renal only
So in renal impairment there's less elimination, heparin can accumulate
With UFH elimination is by hepatic and renal
So if someone is renally impaired they can still eliminate some by the liver
26
Which has better biovailability: UFH or LMWH?
LMWH has better bioavailability (100%)
| UFH 50%
27
Which type of heparin, LMWH or UFH has great anti-Xa activity?
LMWH's
They also show little non-specific binding
They have greater inhibition of thrombin generation
28
Which heparin, LMWH or UFH, has greater antithrombin activity?
UFH
They also have more non specific binding
And less inhibition of thrombin generation
29
Which type of heparin is heparin monitoring vital for??
UFH!
APTT should be monitored
Anti-factor Xa monitored in special circumstances (paediatrics, pregnancy, renal failure)
30
What is APTT?
Activated partial thromboplastin time
This test characterises blood coagulation
It is used to monitor treatment effects of UFH
Blood sample sent to the lab and they activate the coagulation pathway and see how long it tamed to clot
Typical reference range between 30-50 seconds
31
What special circumstances is anti-factor Xa monitoring used in?
Paediatrics
Renal failure
Pregnancy
32
So I know heparin is used to prevent VTE in surgery patients. Is it only used prophylactically??
No!!
Can be used to TREAT VTE too
And also in acute coronary syndromes
33
What are some of the complications of UFH use??
Under or overdosage is common, especially with a lack of monitoring
Osteoporosis!!!
Heparin induced thrombocytopenia
34
What is heparin induced thrombocytopenia (HIT)??
This is where the immune system forms antibodies against heparin
Heparin, PF4 and IgG antibodies form immune complexes which bind to platelets
This results in platelet activation and the abnormal clotting of blood, And therefore platelet count falls as they're all used in the formation of clots
It can actually lead to a thrombus (clot) forming an this is called Heparin Induced thrombocytopenia and thrombosis (HITT)
35
Type II of HIT is more serious than type I. Why is this?
It can cause thrombosis
The mortality is 30%
It's only seen after 5-7 days from the initial heparin exposure
36
What does Vitamin K do?
Clots the blood! Used when a patients blood is too thin
37
How does warfarin exert it's anti coagulation actions??
```
Vitamin K (a blood clotter) is converted to vitamin K epoxide (inactive form). Vitamin K epoxide is then converted back to vitamin K by Vit K epoxide reductase.
Warfarin inhibits Vit K epoxide reductase, so it stops the formation of Vitamin K, therefore less clotting!!
```
38
Vitamin K is needed for the coagulation clotting cascade. Which factors are dependent on Vit K?
```
Vitamin K is essential for the platelets phospholipid membrane binding properties of:
Factors:
II 2
VII 7
IX 9
X 10
```
Without Vit K (due to warfarin) none of these coagulation factors can bind to platelets Phosholipid membranes, therefore less clotting occurs
39
Warfarin is an enzyme inhibitor.
| What enzyme does warfarin inhibit??
Vitamin K epoxide reductase
40
Warfarin's anticoagulant response can be extremely variable. What kind of things can effect it?
Drugs
Diet
Hepatic function
clotting factor levels before treatment
41
What is prothrombin time and how does it relate to warfarin?
It's a way of finding how long it takes the blood to clot
Predominantly tests the extrinsic pathway of the clotting cascade.
It is needed to work out a patients INR which is needed in order to dose warfarin
42
How do we work out INR?
```
Prothrombin time (PT) of the patient / PT (mean/normal)
All to the power of the ISI (test thromboplastin)
```
Normal INR is in the range of 1-1.2
43
In an overdosage of warfarin there is a risk of bleeds. What are the percentage risks of life-threatening and minor bleeds?
Risk of life threatening is 0.5% per patient per year
Risk of minor bleeds is 15% per patient per year
44
Warfarin can result in hematomas. What are these?
A collection of blood outside of a vessel
Also known as bruise!!
Heamorrhage= bleeding! So a Brain heamorrhage is a bleed on the brain!!
45
When should we use smaller doses vitamin K in warfarin overdose?
When the INR is over 8 (blood extremely thin)
We should firstly stop the patients warfarin
If there are no other risk factors for bleeding we can give 0.5-2.5mg of vitamin K oral
We investigate all INRs over 6
Restart the warfarin when INR is under 5
Only really need Vit K when patients are actively bleeding
46
When should we use larger doses of vitamin K in warfarin overdose?
When major bleeding is occurring
We should immediately stop warfarin
Then give prothrombin complex concentrate
Then give oral or IV vitamin K 5mg
47
What can we give to treat major bleeding with warfarin overdose??
Stop warfarin immediately
Give prothrombin complex concentrate
Give vitamin K 5mg (oral or IV)
48
With warfarin we are aiming to raise the patients INR.
Low INR= blood thick and at risk of clotting
High INR= blood thin and less risk of Clotting
What tends to happen after discontinuing warfarin therapy?
The INR will start to sneak back down, meaning blood is gradually becoming thicker again.
Patients on warfarin are therefore usually on it for the rest of their life
This is why it's so important to bridge patients on warfarin in surgical patients as their blood will become thicker once you stop their warfarin 6 days before surgery
49
What is the annual incidence of VTE in the over 60's?
1% in over 60's
50
If a patient has suffered from heparin induced thrombocytopenia, what can we use instead of heparin??
Heparinoids
Hirudins
Synthetic heparin-like molecules such as Fondaparinux
51
What is dabigatran?
A direct thrombin inhibitor (says in BNF!)
It's a NOAC
In some cases it can be an alternative or warfarin as an oral anticoagulant
52
For patients who's INR is between 1-2 what are patients at increased risk of??
Stroke!!
| Blood is way too thick so could easily clot in the brain
53
With INRs above 2.5-3, what do patients start to become at increased risk of??
Intracranial bleeds
| Bloods too thin so start to be at risk of bleeds within the skull
54
Warfarin is said to have a challenging therapeutic window. Why is this?
Because when the INR is between 1-2 the patient may be at increased risk of stroke
When the INR starts to rise above 3, the patient is at risk of an intracranial bleed.
So we ideally want the INR between 2-3, but it's whatever is normal for that patient!!
55
What are all the NOACs licensed for?
VTE prophylaxis in hip and knee surgery
56
What are some of the advantages of NOACs??
They are orally active
They have a rapid onset of action
They don't require any monitoring (No INR checks!!)
Less interactions
They're predictable (can reproduce their pharmacokinetics as there's little variation)
57
What are some of the disadvantages of the NOACs?
They're expensive
Difficult to measure effects e.g. In overweight underweight how do we know if they're working if we don't monitor the INR
There's no way of reversing their action in an emergency
Results with mechanical heart valves are disappointing
58
Why are the NOACS abit of a concern for trauma and emergency doctors??
There is a lack of readily available information to determine the degree of anticoagulation in the patient
The Irreversible coagulation of the NOACs is the biggest concern
Trauma/ injured patients are bleeding. We want this bleeding to stop, we want to clot it. If someone is on anticoagulation their blood will be being made thinner. We need to clot the blood but won't know how much clotting agent (e.g. Vitamin K) to use if we don't know how coagulated the blood already is with the NOAC
59
What are the three NOACs ?
Dabigatran
Rivaroxaban
Apixaban
60
Why can't we use prothrombin time (PT) as an assay for dabigatran??
It's insensitive
We can use APTT as a qualitative measure
Or HEMOCLOT as a quantitative measure
61
There is no reversal agent for NOAC so if a bleed occurs we should stop the drug, fluid replacement to ensure good urine output
Reversing agents are being developed for the NOACs
Can you think of an example??
Currently can use activated charcoal for overdose
Monoclonal antibody fragment for dabigatran
Modified anti-FXa variant for Rivaroxaban
62
The inability to reverse the effects of the NOACs is one of the main reasons why they're not always the treatment of choice. There are some reversing agents in the pipeline for NOACs. What will happen once these are available?
Once available, NOACs will have a huge advantage over Vitamin K antagonists such as warfarin and they'll be the treatment of choice whenever anticoagulation is needed!!
63
Fibrin is a fibrous protein involved in the clotting of blood.
It is formed by the action if Thrombin on fibrinogen which is eventually polymerised.
Polymerised fibrin, together with platelets, form a clot.
Fibrinogen + thrombin ---> fibrin monomer ---> fibrin dimer ---> fibrin dimer ---> fibrin polymer + factor XIIIa ---> cross linked fibrin polymer
64
Fibrinolysis is the way our body prevents clots from growing, it's the natural break down of clots.
Plasmin is produced in its inactive form, plasminogen.
tPA (tissue plasminogen activator) converts plasminogen into active plasmin.
Plasmin allows fibrinolysis to occur.
tPA gets released into the blood very slowly by damaged endothelium of the blood vessels.
65
tPA is needed to convert inactive plasminogen into active plasmin that triggers fibrinolysis and break down of clots. Where is tPA released from?
Released VERY slowly by damages endothelium.
Plasminogen becomes entrapped in the clot.
As it is slowly activated, it breaks down the fibrin (clot) over several days (when the bleeding from the wound has stopped and there is no need for a clot any more)
66
Can you think of any examples of thrombolytic agents (clot-busting drugs)??
Streptokinase
Alteplase (rt-PA)
Reteplase
Tenecteplase
All in the section of the BNF called "Fibrinolytic drugs"
67
What do fibrinolytic drugs/ thrombolytic agents/ clot busters do??
They activate plasminogen to form plasmin
This degrades fibrin and breaks up thrombi
They can be used to treat DVT or in acute myocardial infarction.
Only used in DVT if they're absolutely needed and can't be used in patients with high bleed risk eg. recent surgery
68
How do we treat acute DVT?
Most patients just have an uncomplicated course with heparin and warfarin
But occasionally the fibrinolytic drugs such as alteplase may be used
69
What are the risks associated with using fibrinolytic drugs?
There is a high bleed risk with these agents they thin the blood so much
Rate of intracerebral haemorrhage is up to 11%
Many patients find this an unacceptable risk
There are also many contrainications e.g recent surgery, trauma, recent haemorrhage, severe renal impairment (all in BNF)
70
What's the deal with fibrinolytics/ thrombolytic therapy for the treatment of acute stroke??
Alteplase is recommended
Only if treatment is started early enough (within 4.5 hours from when stroke symptoms come on)
Only if intracranial heamorrhage has been excluded by imaging techniques
Should be given under specialist neurology doctor guidance
71
What are the contra indications of fibrinolysis used in acute MI or stroke? Or where could we look in exam if we can't remember?
Recent haemorrhage, trauma, surgery, coagulation defects, peptic ulcer, severe hypertension, severe liver disease
Look in BNF under fibrinolytic drugs section, under contra-indications!!
72
What's a Greenfield Vena Cava Filter?!!
It's a small cone shaped metal device that looks like one of those head massagers.
It is inserted into the vena cava vein to help protect patients against life threatening Pulmonary Embolisms whilst allowing blood to flow through it.
It's usually implanted after surgery to protect them in the post operative period
73
What is the evidence behind vena cava filters?
They do help protect against symptomatic Pulmonary Embolisms
But after 12 days there us no reduction in risk of death than those without the filter as there's high risks of major bleeds
After 2 years there's actually higher risk of death with vena cava filters due to recurrent DVTs
74
Medical patients vs surgical patients: who's more likely to be prescribed anticoagulation therapy for VTE prophylaxis??
```
Medical patient (those that are in hospital beds but aren't having surgery)
Nearly all of them are given LMWH
```
With surgical patients we need to balance the bleed vs risk factor. Obviously in surgery were cutting the person open, if blood is too thin they will bleed everywhere and we want some clotting so that the wound heals. But then after surgery they're bed bound and immobile, so there is risk of clots. So we have to weigh up the risks
75
When would we use UFH over LMWH?
Impaired renal function
In patients at high risk of bleeding (as it has a shorter half life so it a bleed occurs it will be out the system quicker)
These are definitely when UFH is preferred^^
UFH can be used in the following but so can LMWH:
Can be used in treatment of DVT/ PE
Can be used for thromboprophylaxis
76
What is the dose of UFH adjusted according to?
Adjusted according to APTT
With a UFH infusion, the APTT is checked at 6 hours then dose is adjusted according to the result
Also dosed according to weight!
77
What is the loading dose for UFH infusions??
5000 units IV over 3-5 mins
78
What's the initial infusion per 24 hours, after the loading dose, of UFH based on?
Patient weight
Different for under 60kg, 60-80 and over 80kg
79
How does APTT compare to PT??
APTT measures the activity of the intrinsic and common pathways of coagulation.
The PT is for the extrinsic pathways and is used for INR
80
What is the APTT ratio??
The patients APTT divided by the control value which is 30 seconds
E.g. If patients APTT is 45 seconds their APTT ratio is 1.5
Don't get this confused with INR- it's PT needed for INR!
81
Dosing of LMWH is weight adjusted when treating DVT and PE.
Look in BNF for dosing in different body weights
NB: Helena's lecture also has dose banding for VTE prophylaxis, but I can't see this in BNF
82
What drug can be used to reverse HEPARINs (not NOAC or warfarin!)?
Protamine
83
What do we need to check before starting warfarin?
Check baseline INR,
check FBC
Check LFT's
84
Who should we reduce the dose of warfarin in??
Elderly patients
Those with impaired liver function (e.g. ALCOHOLICS- NOACs may be safer)
Also adjust dose in accordance with interacting medications
85
What's the usual loading dose of warfarin for rapid loading??
10mg (if their INR is under 1.4)
86
Warfarin prescribing hints:
Small changes in dose can lead to large changes in INR
Peak effects seen in 2-3 days (48-72 hours). Effect of dose lasts 4-5 days
Consider drug interactions especially with antibiotics!!! Clarithromycin, co-amoxiclav, ciprofloxacin, metronidazole etc
Also AMIODARONE and CARBAMAZEPINE
87
What are the two main reasons for warfarin interactions being common??
Warfarin is metabolised by the cytochrome p450 system
Warfarin is highly bound to plasma proteins like albumin (other protein bound drugs can have a competitive effect)
88
With the time line created for warfarin bridging for surgery, we saw that after surgery a heparin and warfarin overlap was needed. Why is this??
Warfarin inhibits the synthesis of the vitamin K dependent clotting factors (as it inhibits Vitamin K)
It's also inhibits the synthesis of the regulatory factors protein C and protein S.
Protein C and S are natural ANTICOAGULANTs that require vitamin K for their activity
As warfarin initially decreases protein C and protein levels, quicker than it managers to reduce levels of the factors causing clotting, warfarin can actually initially increase the bloods thickness when treatment is first began. That's why we need to keep the heparin on until INR has been in target range for 2 days, to cover this initial increase in coagulation if blood seen with warfarin!!
So if initiating warfarin in hospital should always prescribe heparin before it or with it
89
What's the genetic mutation that can pre dispose to PE/ VTE?
Factor V Leiden thrombophilia
A genetically inherited disorder of blood clotting
90
If starting NOACs what should INR be under?
Should be less than 2
91
What is rivaroxaban?
A direct inhibitor of activated factor Xa
| Says in BNF
92
Although NOACs are seen to not require any monitoring, or at least not as much as Warfarin, what baseline monitoring is needed??
Prothrombin time
Liver function
Renal function
Blood pressure
Also patients still need to monitor for signs of bleeding or aneamia!!
93
How do we switch between rivaroxaban and warfarin? (This isn't in BNF)
For treating patient for DVT, PE and to prevent reoccurrence, warfarin should be stopped and Rivaroxiban (Xarelto) therapy started once INR is below 2.5
Remember the INR is not a valid measure of the anticoagulant activity of Rivaroxiban or the other NOACs!!
94
Can NOACs be given in pregancy? What about warfarin?
NOACs usually avoided
Warfarin not in first trimester and third trimester, try to completely avoid
95
What can be used to manage overdose of NOACs??
Activated charcoal
96
What's the reversal agent used for warfarin??
Prothrombin complex concentrate
Vit k?
97
What's the major unmet clinical need with Rivaroxiban?
There is no reversal agent
| But there is a risk of uncontrolled bleeding needing emergency surgery
98
What should we do if we experience minor bleeding with dabigatran?
Delay the next dose
| Or discontinue treatment
99
What should we do if we experience moderate bleeding with dabigatran?
```
Mechanical compression to stop the bleed
Surgery
Fluid replacement
Blood transfusion to replace lost blood
Oral charcoal
```
100
What should we do if we experience life threatening bleeding with dabigatran?
Consider prothrombin complex concentrate
Charcoal filtration
101
Where can we find the contraindications of NOACs?
Look of one of the NOACs in the BNF e.g. Dabigatran
| They're all next to contraindications!!
102
If a patient had a Hip replacement 2 weeks ago, and they're on Rivaroxiban for 5 weeks, but they come into again for a wound infection... Do they need a heparin for VTE prophylaxis as they're in hospital bed again??
No!!
The Rivaroxiban is enough: Rivaroxiban can be used for VTE prophylaxis after knee or hip surgery (see BNF) for 5 weeks.
She's come in 2 weeks later, so she's still covered by the Rivaroxiban. If she had come in 6 weeks later and was off the Rivaroxiban, we would consider a heparin once assessing the bleed risk
103
With the doses of NOACs, what population of people do we need to think about?
Elderly!! Dose adjusted according to BNF
104
What has NICE draft guidance recently supported the use of Rivaroxiban in??
For the prevention of atherothrombotic (CV) events in combo with aspirin + clopidogrel (or aspirin alone) in people who have had ACS with elevated cardiac biomarkers
105
What are TEDs (anti embolism stockings) contra indicated in?
Patients who have had a STROKE
106
Watch out! The units of LMWH's doses change between Dalteparin and enoxaparin. (Dalteparin is iu/kg, enoxaparin is mg/kg)
Also note that LMWHs have different doses in cardiac patients (unstable coronary artery disease). These are in the BNF below all the stuff on VTE prophylaxis for each heparin, as they require a different injection. For enoxaparin it's under unstable angina and NSTEMI: 1 mg/ kg
Helena said this would be a good MCQ
107
What's the risk with osteoarthritis and anticoagulants?
Osteoarthritis patients probably on alendronic acid
This can cause bleeding in you oesophageal varices
This is not good if we want to anticoagulate
108
Which NOAC is preferred for VTE prophylaxis?
Rivaroxiban
As it's once daily dosing!
109
In terms with where they work, what's the difference with warfarin and the NOACs??
NOACs are actually working on the coagulation cascade.
So they work further down the pathway than warfarin that works at the vitamin K level.
Vitamin K is needed to activate the coagulation factors in the coagulation cascade
110
With the NOACs there's no INR monitoring, but if we want to check the patient is taking it we can check their _____
APTT
this involves taking a blood sample from the patient as does the INR
But wouldn't be done like INR testing is done in anticoagulant clinics, therefore less likely to see how adherent patients are on NOACs
111
Is dabigatran metabolised by the CYP450 enzymes like warfarin?
Nope!!
But Rivaroxiban and Apixaban is metabolised by CYP3A4 which is one of the 450 enzymes
112
What are some of the practical issues with dabigatran?
It's a large capsule so it can be difficult to swallow
It won't go into a Dosette box (as it's effected by moisture)
It can't go down a naso-gastric tube or PEG
Lack of reversibility!!
113
Why is Rivaroxiban slightly preferred by patients?
Once daily dosing
Smaller tablet
Can go down a nasal gastric tube or PEG
Still a problem with lack of reversibility!
114
What's the problem with the short half life's of the NOACs?
It means that Missed doses may increase the risk of events- missed doses more of a problem!!
115
Despite the NOACs, warfarin is still quite often used. How come?
It's a lot cheaper
NOACs are very specifically licensed compared to warfarin
Warfarin can be used for other indications: e.g.
Prosthetic valves
Left ventricular thrombus
