Chapter 2 - Blood Clots Flashcards
What drugs are used for treating blocked catheters and lines?
Unfractionated heparin
Urokinase
Epoprostenol
What is a VTE, and what are the two main examples of a VTE?
A VTE is a blood clot in a vein that completely obstructs the flow of blood?
DVT - the blood clot occurs in the deep veins of the legs or pelvis
PE - the blood clot obstructs the flow of blood to the lungs
What is hospital acquired VTE?
A VTE occurring within 90 days of hospital admission?
What are the symptoms of VTE?
Throbbing and/or swelling in one leg
Warm skin around the painful area
Red or darkened skin around the painful area
Swollen veins that are hard or sore when touched
What are the symptoms of PE?
Coughing up blood
SOB/breathlessness
Chest pain/upper back pain
What are the risk factors for VTE?
Surgery Trauma Significant immobility Malignancy Obesity Hypercoagulable states Pregnancy and the postpartum period Hormonal therapy (combined oral contraception, HRT)
What are the two methods of VTE thromboprophylaxis?
Mechanical
Anti-embolism stockings
Intermittent pneumatic compression
Pharmacological
LMWH
UH
Fondaparinux sodium
What calf pressure are we aiming for when using mechanical VTE prophylaxis?
14-15 mmHg
How long is mechanical VTE prophylaxis used for?
Wear day and night for 30 days or until the patient is sufficiently mobile
When should pharmacological VTE prophylaxis be started?
ASAP or within 14 hours of admission
How long is pharmacological VTE prophylaxis used for?
7 days or for the duration of hospital stay, whichever is longer
28 days after major cancer surgery in the abdomen
30 days after spinal injury
What needs to be assessed daily whist a patient is on VTE prophylaxis in hospital?
Bleeding risk (HAS-BLED)
What type of anaesthesia needs to be used for surgical patients requiring VTE prophylaxis?
Regional (not general) if possible
Do surgery patients require VTE prophylaxis?
Patient schedules for surgery are given anti embolism stockings on admission, and are worn until the patient is sufficiently mobile.
If the risk of VTE is high (and higher than the risk of bleeding), pharmacological prophylaxis is also used and continued for 7 days
(28 days abdominal cancer surgery, 30 days spinal injury).
Pharmacological VTE prophylaxis is usually LMWH, but can be UFH or fondaparinux.
What VTE prophylaxis is given in hip replacement?
Usually a LMWH for 10 days then low-dose aspirin for 28 days
What VTE prophylaxis is given in knee replacement?
14 days low-dose aspirin
What should be given to pregnant women or women who have given birth , had a miscarriage or terminated a pregnancy in the last 6 weeks, who’s VTE risk is higher than their bleeding risk?
LMWH e.g. dalterparin
If there is likely to be sufficient immobility, also consider mechanical VTE prophylaxis
First line is intermittent pneumatic compression
What is given for confirmed VTE?
Apixaban or rivaroxaban
For at least 3 months
What is the preferred treatment for VTE in pregnancy and why?
Heparins, LMWH is preferred, because:
It doesn’t cross the placenta
It has a lower risk of osteoporosis
It has a lower risk of heparin-induced thrombocytopenia
LMWH are excreted more rapidly in pregnancy (the dose may need to be altered)
Stop treatment at the end of labour
What do you do in the event of haemorrhage during VTE treatment?
Withdraw the heparin
If necessary, administer protamine (but this only partially reverses the effect of LMWH)
What are the three main types of stroke?
Ischaemic stroke- a blockage cutting off blood supply to the Brian
TIA - same as above, it is temporary and the blood flow returns on its own
Haemorrhagic stroke - bleeding in or around the brain
How is a TIA treated
Patients should immediately receive 300mg aspirin, and should receive secondary prevention
How is an ischaemic stroke managed? Both short and long term
Initial management:
Alteplase should be administered within 4.5 hours of symptom onset
Aspirin should be initiated ASAP and continued for 14 days
Some patients may also require a PPI
Long term management:
Clopidogrel (unlicensed in TIA)
Within 48 hours start a high intensity statin (e.g. atorvastatin) regardless of serum cholesterol (aim to reduce non-HDL cholesterol by more than 40%)
Also monitor BP, and advise lifestyle modifications
What assessment tool is used to assess the likelihood of a VTE?
Two-level Wells Score
Also use the HAS-BLED score to assess the risk of bleeding
In an ischaemic stroke, what is the target BP?
<130/80 mmHg
Don’t use beta-blockers alone
How is a haemorrhagic stroke managed?
Surgery
Aspirin long-term if the patient is at risk of another cardiac event
What is the lifestyle advice to prevent a VTE?
Stay active
Lose weight if overweight
Quit smoking if applicable
Lower BP avoid sitting for long periods of time
Drink plenty of fluids - DVT is more likely when dehydrated
What type of mechanical prophylaxis is used to prevent VTE in patients with
a) an acute stroke?
b) pregnancy?
Both: intermittent pneumatic compression
Do anticoagulants destroy an arterial thrombus?
No, for 2 reasons:
They PREVENT thrombus formation in the VEINS
What is the main adverse event with anticoagulants?
Haemorrhage
What are some risk factors for haemorrhage?
Current or recent GI ulceration Recent surgery Recent intracranial haemorrhage Oesophageal varices Uncontrolled hypertension
What are some symptoms of haemorrhage?
Excessive bleeding e.g. frequent nosebleeds, blood in urine, tarry stools, prolonged bleeding from cuts, heavier than usual menstrual bleeding
Fatigue, dizziness, weakness, headache
What are the main categories of anticoagulants?
Warfarin
DOACs
Heparins
What drugs are vitamin K antagonists, and what is their mechanism of action?
Warfarin
Phenidione
Acenocoumarol
These work by inhibiting the reduction of vitamin K.
Clotting factors require the reduced form of vitamin K, so preventing this stops the coagulation cascade.
How long does the anticoagulant effect of vitamin K antagonists take to develop and why?
48-72 hours.
They prevent the formation of new clotting factors, but clotting factors already present need to be used up.
If rapid anticoagulation is required, use a heparin
What is INR?
A way of standardising the results of prothrombin time (PT)
PT is the time it takes for the blood to clot
Higher INR = it takes longer for the blood to clot, so there’s an increased risk of bleeding
Lower INR = it takes less time for the blood to clot = higher risk of clotting
What is the target INR for most patients?
2.5
But an INR within 0.5 of the target range is usually satisfactory
So usually 2-3 is okay
In patients with a VTE who are already being treated with anticoagulants and have an INR above 2, the target is 3.5
What do you do in the event of bleeding and/or a high INR when on warfarin?
Major bleeding - stop warfarin, give phytomenadione by slow IV injection, give dried prothrombin complex
INR >8 and minor bleeding - stop warfarin, give phytomenadione by slow IV injection, wait 24 hours, if the INR is still high give phytomenadione by slow IV injection again. Restart warfarin when the INR is below 5
INR >8 and no bleeding - stop warfarin, give the IV preparation of phytomenadione orally (unlicensed), wait 24 hours, if the INR is still high give phytomenadione orally again. Restart warfarin when the INR is below 5
INR 5-8 and minor bleeding - stop warfarin, give phytomenadione by slow IV injection. Restart warfarin when the INR is below 5
INR 5-8 and no bleeding - withhold 1-2 doses of warfarin and restart when the INR is in range. Reduce the subsequent dose
How do you manage patients on warfarin who are having surgery?
Stop warfarin 5 days before their surgery (due to the high risk of
If the INR is above 1.5, give phytomenadione by mouth
If the patient is at a high risk of clotting (e.g. recent VTE, heart valve), give LMWH (bridging therapy). This should be stopped 48 hours before surgery
What are the colours and strengths of warfarin tablets?
0.5mg - white
1mg - brown
3mg - blue
5mg - pink
What are the indications of warfarin?
Stoke prevention in AF or rheumatoid heart disease
VTE prophylaxis
VTE management
Prophylaxis after a heart valve
What are the contraindications and cautions of warfarin?
Contraindications: Less than 48 hours postpartum Within 72 hours of major surgery Significant bleeding Recent haemorrhagic stroke
Cautions: Thyroid disease GI ulcer Recent surgery Uncontrolled hypertension High risk of bleeding Recent ischaemic stroke
What are the side effects of warfarin?
Common - haemorrhage
Uncommon - nausea, vomiting, alopecia
Frequently not known - blue to syndrome, altered hepatic function, jaundice, skin reactions, CNS haemorrhage l, fever, diarrhoea
What drugs interact with warfarin?
Warfarin is metabolised by the CYP 450 system
Enzyme inducers
These increase the speed of metabolism of warfarin, reducing its concentration, so there is an increased risk of clots
E.g. phenytoin, carbamazepine, rifampacin, St. John’s wort
Enzyme inhibitors
These reduce the speed of metabolism of warfarin, increasing its concentration, so there is an increased risk of haemorrhage
E.g. macrolide and quinine antibiotics, amiodarone, azole antifungals
What interactions does warfarin have with food?
It can be affected by:
Alcohol
Green tea
Green leafy vegetables e.g. kale, spinach, broccoli
What are the monitoring requirements associated with warfarin?
Baseline: INR, APTT, renal function, hepatic function, FBC
Then INR should be monitored daily or alternate days, then at longer intervals, then up to 3 months
What should a patient do if they miss their warfarin dose?
Warfarin should be taken at the same time every day
Any missed dose should be taken within 6 hours
After this is should be missed
Record this in the yellow book
Should warfarin be taken in pregnancy or breastfeeding?
Pregnancy:
No, warfarin is teratogenic
It can cause congenital malformations, and placental, foetal, and neonatal haemorrhage
It should especially be avoided in the first and third trimester, and in the last few weeks of pregnancy
If warfarin is taken at the time of delivery, the baby needs IM phytomenadione immediately
LMWH is the preferred anticoagulant in pregnancy
Breastfeeding:
Not known to be harmful
What is the effect of antivirals used for hepatitis C on the liver, and if a patient is on warfarin what action should be taken?
It can lead to changes in hepatic function
The INR should be monitored more frequently because this can affect the efficacy of vitamin K antagonists
Why should patients taking warfarin report painful skin reactions?
Could be calciphylaxis (where calcium accumulates in blood vessels)
This in more common in end stage renal disease
What affects INR?
Acute illness, diarrhoea Changes to diet Changes to alcohol intake Changes to smoking habit Changes to medications
Patients should speak to their GP for any of the above
What are the advantages of DOACs over warfarin?
Less monitoring requirements
Lower risk of haemorrhage (but the risk is still high)
Shorter half life (faster onset of action)
Fewer food interactions
What are the advantages of warfarin over DOACs?
Cheaper
Can be used in valvular AF
Which DOAC is most effective?
Apixaban
What is the mechanism of action for DOACs?
Inhibits Factor Xa:
Apixaban
Rivaroxaban
Edoxaban
Inhibits Factor IIa:
Dabigatran
Which DOAC has the lowest risk of haemorrhage?
Apixaban
Which DOACs have the best side effect profile?
Apixaban
Edoxaban
What is the antidotes for DOACs?
Apixaban - anexanet alpha (fridge)
Rivaroxaban - anexanet alpha (fridge)
Dabigatran - idarucizumab
Edoxaban - none
What is the dosing frequency for DOACs?
OD:
Rivaroxaban, edoxaban, dabigatran
BD:
Apixaban
What are the indications and doses of apixaban?
VTE prophylaxis:
2.5mg BD
VTE treatment:
10mg BD for 7 days then 5mg BD
Stroke prevention in patients with AF (in patients with at least one risk factor - diabetes, hypertension, previous stroke/TIA, aged over 75):
5mg BD
2.5mg BD in patients aged over 80, CrCl over 133mg/mL, weight under 61kg
What are the contraindications of DOACs?
Active bleeding or at risk of bleeding
Antiphospholipid syndrome
Prosthetic heart valve
Can NSAIDs be given OTC in patients on an anticoagulant?
No
What are the side effects of apixaban?
Common - haemorrhage, anaemia, nausea, skin reactions
Uncommon - CNS haemorrhage, thrombocytopenia, hypotension, wound complications
Can DOACs be taken in pregnancy?
No, LMWHs are preferred
Can apixaban be taken in patients with renal impairment or hepatic impairment?
Both renal and hepatic impairment increase the risk of bleeding
Renal impairment:
CrCl >30 - okay
CrCl 15-29 - caution
CrCl <15 avoid (may be best to give LMWH and warfarin)
Hepatic impairment:
Mild to moderate - caution
Severe - avoid
What happens if you miss an apixaban dose?
> 6 hours until the next dose - take the dose ASAP
<6 hours until the next dose - omit the dose and take the next one as normal
What is the brand name of apixaban?
Eliquis
What are the indications and doses of rivaroxaban?
VTE prophylaxis:
10mg OD
VTE treatment:
15mg BD for 21 days, then 20mg OD
Stroke prevention in patients with AF (in patients with at least one risk factor - diabetes, hypertension, previous stroke/TIA, aged over 75):
20mg OD
Should rivaroxaban be taken with food?
2.5mg and 10mg - no
15mg and 20mg - yes
What are the side effects of rivaroxaban?
Common - anaemia, haemorrhage, hypotension, GI discomfort, constipation, diarrhoea, renal impairment, menorrhagia, wound complications
Uncommon - thrombocytopenia, tachycardia, dry mouth
What are the monitoring requirements that are associated with DOACs?
FBC, renal and hepatic function done initially and then annually
Can rivaroxaban be given in renal and hepatic impairment?
Renal:
CrCl >30 - yes
CrCl 15-29 - caution
CrCl <15 - avoid
Hepatic:
Avoid
What do you do if you miss a rivaroxaban dose?
> 12 hours until the next dose - take dose ASAP
<12 hours until the next dose - omit and take the next dose as normal
In the initial treatment of VTE, where the dose is 15mg BD, a missed dose should be taken, even if it means taking 2 doses at the same time
What is the brand name of rivaroxaban?
Xarelto
What are the indications and doses of edoxaban?
VTE prophylaxis
VTE treatment (following 5 days of LMWH)
Stroke prevention in patients with AF (in patients with at least one risk factor - diabetes, hypertension, previous stroke/TIA, aged over 75):
Under 61kg - 30mg
Over 61kg - 60mg
With concurrent use of edoxaban and which medications should the dose of edoxaban be reduced to 30mg?
Dronedarone
Erythromycin
Ciclosporin
Ketoconazole
What are the side effects of edoxaban?
Common - anaemia, haemorrhage, nausea, skin reactions
Uncommon - CNS haemorrhage
Can edoxaban be given in renal or hepatic impairment?
Renal:
CrCl >50 -okay
CrCl 15-49 - caution
CrCl <15 - avoid
Hepatic
Mild to moderate - caution
Severe - avoid
What happens if you miss a dose of edoxaban?
> 6 hours until the next dose - take the dose ASAP
<6 hours until the next dose - omit the dose and take the next one as normal
What is the brand name of edoxaban?
Lixiana
What are the indications and doses of dabigatran?
VTE prophylaxis
VTE treatment (following 5 days of LMWH)
Stroke prevention in patients with AF (in patients with at least one risk factor - diabetes, hypertension, previous stroke/TIA, aged over 75):
Aged under 74 - 150mg
Aged 75 and over - 110mg
Concurrent use of verapamil and dabigatran - 110mg
Can dabigatran be given in renal or hepatic impairment?
Renal:
CrCl <50 - avoid
Hepatic:
Mild to moderate - caution
Severe - avoid
What happens if you miss a dose of dabigatran?
> 12 hours until the next dose - take dose ASAP
<12 hours until the next dose - omit and take the next dose as normal
What is the brand name of dabigatran?
Pradexa
Does unfractionated heparin have a short or long half life? And what is the advantage of this?
Short
LMWH is generally preferred
But for patients with a higher risk of bleeding, UFH may be preferred as it can be terminated rapidly by stopping the infusion
What is the mechanical of action of unfractionated heparin?
It binds to antithrombin III, and enhances its ability to inhibit clotting factors
Thereby preventing the coagulation cascade from occurring to produce thrombin
Why is LMWH generally preferred over UFH?
They are as effective, but have a lower risk of heparin induced thrombocytopenia (HIT)
They have a longer duration, so can be OD dosing (but in an emergency situation UFH may be preferred as it has a faster onset of action)
What is the mechanism of action of LMWH
It binds to antithrombin III, and enhances its ability to inhibit clotting factors, except thrombin
Thereby preventing the coagulation cascade from occurring to produce thrombin
Give examples of LMWHs
Dalteparin
Enoxaparin
Tinzaparin
Give an example of a heparinoid
Danaparoid
What are contraindications of heparins?
Majour trauma Peptic ulcer Surgery to eye or nervous system Recent cerebra haemorrhage Thrombocytopenia or history of HIT
What are the side effects of heparins?
HIT
Haemorrhage
Osteoporosis
Hyperkalaemia
What are the signs of heparin induced thrombocytopenia?
30% reduction in platelets
Bleeding
Bruising
Skin allergy e.g. rash at injection site
When does heparin induced thrombocytopenia occur?
Usually within 5-10 days of taking the heparin
But it can occur within 100 days
What should happen if a patient presents with heparin induced thrombocytopenia?
Stop the heparin
Give an alternative e.g. danaparoid
Which patient groups are more susceptible to heparin induced hyperkalaemia?
Diabetics
Renal impairment
Patients taking potassium sparing medications
What should you do if a patient is on a heparin and has haemorrhage
Stop the heparin
Give protamine if necessary
What needs to be monitored when on heparin therapy?
Platelet counts
Plasma-potassium
Renal function
For VTE prophylaxis and treatment, do we give graduated or single dose syringes of fragments?
Single dose syringes
What are the indications and doses of dalteparin?
VTE prophylaxis VTE treatment (for 5 days before oral treatment)
<46kg - 7500 units 46-56kg - 10,000 units 57-68kg - 12,000 units 69-82kg - 15,000 units >83kg - 18,000 units
How do you switch from warfarin to a DOAC?
- Stop the warfarin
- Monitor the INR
- Start the DOAC as follows:
INR <2 - start straight away
INR 2-2.5 - start the next day
INR >2.5 - start when INR is <2
How do you switch from a DOAC to warfarin?
Start the warfarin
Stop taking the DOAC when the INR is in the target range
Monitor the INR closely (once a week for a month)
How do you switch from DOAC to DOAC?
Stop the current DOAC and start the next DOAC when the dose is due
Do antiplatelets work best in arterial or venous thrombosis?
Arterial - the blood is flowing faster in these vessels
Is aspirin recommend for primary or secondary prevention of CVD?
Secondary
When can a PPI be used alongside aspirin?
When there is a high risk of GI bleeding
When there are GI side effects e.g. dyspepsia
Does having hypertension affect treatment with aspirin?
Yes, this must be controlled before treatment with aspirin begins
What is the mechanism of action of aspirin?
It is a COX-1 inhibitor
This leads to a reduction in the production of thromboxane A2, which is a powerful promoter of platelet aggregation
It also reduces prostaglandin production (so a PPI may be required)
What are the indications of aspirin?
Secondary prevention of CVD - 75mg OD
Treatment of TIA/ischaemic stroke - 309mg OD for 14 days
Treatment of angina, nSTEMI r STEMI - 300mg
Pain - 300-900mg every 4-6 hours, maximum 4g daily
Bypass surgery - 75-150mg OD
Precention of Pre-eclampsia in pregnancy in women at moderate to high risk - 75mg OD from 12 weeks gestation until birth
What are the contraindications and cautions of aspirin?
Contraindications:
GI ulcer (active or previous)
Bleeding disorder/at risk of bleeding
Children under 16
Cautions:
Hypertension
Asthma
What are the side effects of aspirin?
Common - haemorrhage, dyspepsia
Other - thrombocytopenia, nausea, vomiting, menorrhagia, GI haemorrhage
Can aspirin be used in breastfeeding?
No - risk of Reye’s syndrome
What is Reye’s syndrome?
A rare disorder that can cause serious brain and liver damage
How many aspirin can be sold OTC?
100
What are the indications of clopidogrel?
TIA/ischahemic stroke if aspirin is contraindicated or not tolerated - 75mg OD
Prevention of atherothrombotic events after PCI, nSTEMI, STEMI, MI (usually alongside aspirin) - initially 300mg then 75mg OD
When can dipyridamole be used?
Alone or alongside aspirin for the secondary prevention of TIA or ischaemic stroke - 200mg BD (with food)
Give three examples of glycoprotein IIb/IIIa inhibitors
Apiximab - a monoclonal antibody, use once to avoid the risk of thrombocytopenia
Tirofiban - use alongside UFH, aspirin and clopidogrel
Eptifibatide - used alongside IFH and aspirin
What is the reversal agent for warfarin?
Phytomenadione
What is the reversal agent for heparins?
Protamine
If a patient is having surgery and is taking LMWH due to a high risk of thromboembolism, when should the LMWH be stopped before surgery and restarted after surgery?
Stop 24h before surgery
Restart 48h after surgery
Which DOACs are black triangle drugs?
Edoxaban, rivaroxaban
These are subject to additional monitoring and any ADRs should be reported
What do you need to do if a patient is taking dabigatran and verapamil or amiodarone?
Reduce the dabigatran dose to 110mg
If a patient is on warfarin, what should they do if they have a nose bleed
Seek medical attention after more than 10 mins
If a patient is on warfarin, what should they do if they have a cut?
Seek medical attention after 30 mins or if there is heavy bleeding
If a patient is on warfarin, what should they do if they have heavier periods than usual?
Seek medical attention
If a patient is on warfarin, what should they do if they hit their head, even if they seem fine?
Seek medical attention
What would you use for prophylaxis of stroke in valvular AF patients?
Warfarin (not DOACs)
What would you use for prophylaxis of stroke in non-valvular AF patients?
Warfarin or DOACs
Which DOACs shouldn’t be used in severe liver disease as they rely on hepatic metabolism?
Apixaban
Rivaroxaban
Which heparin should be used in renal impairment and why?
UFH
LMWH has an increased risk of bleeding in renally impaired patients
What monitoring needs to be done with heparins?
> 4 days - platelets
>7 days or patients at risk of hyperkalaemia - U&E
Post surgery, if a warfarin patient is haemodynamically stable, when can warfarin be restarted?
Evening of the surgery or the day after
What is the antidote for LMWH and UFH?
Protamine
What juice interact with warfarin and should be avoided?
Cranberry juice
What has a shorter duration of action, LMWH or UFH?
UFH
When can LMWH be restarted after surgery in patients with a high risk of thromboembolism?
After at least 48h
Why can’t dabigatran be crushed?
The increases the risk of bleeding
Which heparin is best in renal impairment?
UFH
What does amiodarone contain that could cause thyroid problems?
Iodine
If digoxin is being used alongside amiodarone, dronedarone or quinine what do you do?
Half the dose of digoxin
What should patients immediately receive if they have a suspected ischaemic stroke?
Alteplase if within 4.5h 300mg aspirin (for 2 weeks)
What is the long term management of ischaemic stroke?
Clopidogrel Statin (48h post stroke)
When should a statin be initiated post ischaemic stroke?
48 hours post stroke
Even if their cholesterol is in range
In the long term management of ischaemic stroke, what can be given of clopidogrel if contraindicated or not tolerated?
Dipyramidole (m/r) in combination with aspirin
When should long term anticoagulation be considered post ischaemic stroke?
If the patient has coexisting AF
What trimesters are vitamin k antagonists especially dangerous in?
1st and 3rd
