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