Different types of anticoagulation Flashcards
1
Q
What do anticoagulants do?
A
- Inhibit the body’s own procoagulant clotting proteins.
- They don’t break down any clots that already exist but they reduce the risk of clot growth and embolisation.
2
Q
Indications for anticoagulation
A
Atrial fibrillation (AF)
Prosthetic valve replacement
Deep vein thrombosis (DVT)
Pulmonary embolism (PE)
Post op
3
Q
How does UFH work?
A
Works together with antithrombin to block clot formation by inhibiting factor Xa and factor IIa
4
Q
UFH vs LMWH time to observe effects and blood monitoring
A
- LMWH have longer time of action than UFH, and more predictable therefore no blood monitoring required
- UFH has a quick time of action, but also wears off quickly
5
Q
How is UFH administered?
A
Can be delivered by intravenous infusion or by subcutaneous injection. Intravenous infusion needs regular blood monitoring (check activated partial thromboplastin time ratio (APTR))
6
Q
Reversal of UFH
A
Reversed by protamine
7
Q
Reversal of LMWH
A
Protamine
8
Q
Blood level monitoring for DOAC
A
Do not require blood level monitoring
9
Q
Mechanism of action of DOACs
A
Act on different parts of clotting cascade; for example, dabigatran is a direct thrombin inhibitor whereas apixaban, rivaroxaban and edoxaban inhibit factor Xa
10
Q
Mechanism of Warfarin
A
Warfarin inhibits vitamin K epoxide reductase, the enzyme needed to activate vitamin K. Therefore, warfarin inhibits vitamin K-dependent coagulation factors. These are factors II, VII, IX and X, and proteins C & S
11
Q
Monitoring of warfarin
A
Dosing is very individualised, and requires regular monitoring
International normalised ratio (INR) compares a patient’s prothrombin time (PT) to a control PT value. INR is a standardised result that can be compared between labs
12
Q
How is Warfarin reversed?
A
Reversed slowly by vitamin K, or more urgently by prothrombin complex concentrates (PCC) e.g. Octaplex
13
Q
Warfarin interactions
A
Interacts with vitamin K containing food substances, alcohol and certain medications including antibiotics
14
Q
How is warfarin administered?
A
Orally
15
Q
Treatment of suspected DVT/PE
A
- Patients with a suspected deep vein thrombosis (DVT) or pulmonary embolism (PE) should be started on anticoagulation immediately to reduce the risk of clot growth or embolisation
- The NICE guidelines (2023) state apixaban or rivaroxaban as first-line agents. If these are not suitable, they suggest either 5 days of LMWH followed by dabigatran or edoxaban, or LMWH alongside a vitamin K antagonist for at least 5 days.
- However, before initiating anticoagulation, you need to consider your patient’s bleeding risk. This will be affected by age, comorbidities and renal function. You also need to consider your patient’s treatment preferences.
16
Q
Analgesia in those with anticoagulation
A
Patients should not take aspirin, ibuprofen or other non-steroidal anti-inflammatory drugs (NSAIDs). Paracetamol is the safest analgesic to use
17
Q
Anticoagulation in pregnancy
A
- Heparin and low molecular weight heparin (LMWH) are safe in pregnancy.
- The BNF advises that the effect of LMWH is likely to be negligible is breast milk, but the manufacturers advise avoid. Heparin is safe in breast feeding.
- Warfarin is contra-indicated in pregnancy, but can be taken whilst breast-feeding.
- The BNF advises avoid direct oral anticoagulants (DOACs) in pregnancy and breastfeeding as there is no information available regarding safety.
18
Q
Risk scores used in AF
A
- CHA2DS2VASc score for stroke risk
- ORBIT socring tool for bleeding risk
19
Q
During your attachment in primary care, you see a 70-year-old man with palpitations. His pulse is irregularly irregular and an ECG confirms your clinical diagnosis of atrial fibrillation. His heart rate is 84.
Does he need a beta blocker?
A
No, he does not need rate control at this stage
20
Q
Apixaban dosing in DVT and PE
A
Apixaban is usually prescribed as 10 mg twice daily for 7 days, then 5 mg twice daily.
21
Q
What should be checked before starting DOACs?
A
1- Renal function should be checked before treatment is initiated. LMWH is contraindicated in patients with moderate-severely impaired renal function (creatinine clearance <30 ml/minute). if both DOACs and LMWH are unsuitable for a patient, consider use of unfractionated heparin.
2- Platelet count should be determined on the day treatment is started and then daily in order to detect heparin-induced thrombocytopenia. If the platelet count falls by 50% or more, specialist advice must be sought from haematology.
3- Anti-factor Xa assay is not required routinely, though it may be necessary in special populations, such as patients with mildly impaired renal function and severe obesity. Again specialist advice should be sought.
22
Q
Length of treatment for confirmed DVT
A
At least 6 months for proximal idiopathic DVT.
23
Q
Risks of anticoagulation
A
Increased risk of bruising
Increased risk of internal bleeding
Drug interactions
Bleeding with dental treatment
Risks associated with extended travel
24
Q
Anticoagulation of choice for patients with metallic heart valve
A
Lifelong warfarin
25
Which test is recommended when initiating warfarin?
For rapid anticoagulation with warfarin, daily international normalised ratio (INR) measurements for a minimum of 4 days are recommended.
26
What is essential to do in patients started in warfarin in hospital?
- It is essential that all patients anticoagulated with warfarin are referred for international normalised ratio (INR) monitoring on discharge.
- Discharge arrangements for anticoagulant follow-up must be detailed in the hospital notes.
- All patients should receive their own yellow anticoagulation book, which gives them advice about their treatment and instructs them on the doses they should be taking.
- An appointment should be made for further INR measurement within 7 days of discharge. Responsibility for discharge arrangements lie with the clinician referring the patient.
Referrals should state clearly:
The indication for anticoagulation
The required duration
The required INR range
Concurrent medication
Any other patient factors which will influence anticoagulation management
27
Why should a patient have low molecular weight heparin (LMWH) whilst you are starting warfarin? What is the recommendation
- Full anticoagulation with warfarin may take 2-3 days to become established.
- In addition, the initial period of treatment with warfarin may be associated with a procoagulant state due to rapid reduction in protein C level.
- It is recommended that patients receive heparin (LMWH or unfractionated heparin (UFH)) for at least 5 days and that it should not be discontinued until the international normalised ratio (INR) has been in the therapeutic range for 2 consecutive days.
- This only applies where urgent inpatient anticoagulation with warfarin is required. If warfarin is used for AF in the community, it would not apply (but a DOAC would be first choice)
28
In what circumstances would you consider prescribing an initial dose of oral anticoagulation different from that usually recommended?
- Where there are abnormalities in baseline coagulation results modification in dosage should be considered.
- Modification of dosage should also be considered in patients who may be particularly sensitive to warfarin, e.g:
The elderly
Patients with congestive heart failure
Patients with liver disease
Patients on concurrent interacting drug therapy
Frail and low body weight
High bleeding risk
29
True or False
A. Should not eat vitamin K-containing vegetables
B. Should not breast feed
C. Should not take aspirin unless advised by a doctor
D. Should not drink more than 2-3 units of alcohol a day
E. Should have an international normalised ratio (INR) test within 5-7 days of starting any new medication
A. False. Patients should try to eat the same amount of these foods on a regular basis.
B. False. Patients may breastfeed. Warfarin is not usually detectable in the breast milk of mothers who take warfarin.
C. True. Some patients require low dose aspirin in conjunction with warfarin e.g if they have a history of myocardial infarction. However, patients should not take it unless already agreed with their doctor.
D. True.
E. False. Only needs repeat INR within 5-7 days when the new drug has a potential interaction with Warfarin.
30
NSAIDs in patients on anticoagulation
Use of non-steroidal anti-inflammatory drugs (NSAIDs) should be avoided wherever possible in patients on an anticoagulant.
31
Use of antiplatelets alongside anticoagulants
Drugs which increase the bleeding risk e.g. antiplatelets such as aspirin, clopidogrel and dipyridamole should not be routinely used in conjunction. They should only be used when potential benefit outweighs bleeding risk e.g. in patients who have a history of ischaemic heart disease.
32
Common drugs that increase INR
Amiodarone (profound effect)
Fluconazole and other Azole Antifungals
Ciprofloxacin and other Quinolone antibiotics
Metronidazole
Clarithromycin
Sertraline
Isoniazid
Citalopram
Diltiazem
Cotrimoxazole
Tolterodine
33
Common drugs that decrease INR
Rifampicin (profound effect)
Carbamazepine
Phenytoin
Penicillins, these can also sometimes increase the INR
34
A patient, Mrs Kelly, is admitted to hospital with a community-acquired chest infection. She is taking warfarin 3 mg daily for recurrent deep vein thrombosis (DVT). On admission, she is started on clarithromycin 500 mg bd.
What would you expect to happen to her international normalised ratio (INR) and what actions would you take to prevent over or under anticoagulation?
A. Reduced INR. Check INR again within 5 days
B. Increased INR. Stop warfarin for 2 days
C. Increased INR. Check INR again within 5 days
D. Reduced INR. Increase warfarin dose to 4 mg daily
C is correct.
Clarithromycin enhances the effect of coumarin anticoagulants.
Most drug interactions with warfarin do not necessitate a pre-emptive increase or decrease in warfarin dose. The possible exceptions to this are amiodarone (which can cause a profound increase in INR) and rifampicin (which can cause a profound decrease in INR). It is prudent to check the INR within 5 days of starting any new drug in a patient stabilised on warfarin.
35
Risk factors for bleeding on anticoagulation
The two variables that are most consistently associated with bleeding risks with oral anticoagulation are the:
- Intensity of anticoagulation (international normalised ratio (INR) greater than 5)
- Patient age (older)
Other risk factors include:
Female sex
- Female sex
- Time period on anticoagulants (first year)
- Target INR (higher)
- Actual INR (high, Bleeding episodes also commonly occur while the INR is in the therapeutic range.)
- Indication (arterial disease)
- Previous GI bleed
- CVD
- Hypertension
- Alcoholism
- Liver disease
36
An 82-year-old male patient weighs 39 kg and has been admitted with painful cyanotic foot for angioplasty, followed by bypass graft.
His relevant past medical history is of right above-knee amputation and high alcohol intake, and his medication is simvastatin, aspirin, enoxaparin and ciprofloxacin.
The patient was prescribed and given warfarin loading doses of 10 mg on day 1 and day 2.
On day 3, the patient’s international normalised ratio (INR) was 8.3.
Which of the following immediate actions would you take?
Select one or more options from the answers below, then submit.
Possible answers:
A. Stop warfarin
B. Stop enoxaparin
C. Recheck international normalised ratio (INR) the next day and give vitamin K if still high
D. Check patient for signs of bleeding
E. Give vitamin K
F. Continue warfarin at a lower dose
A, B, D and E are correct.
Stop both the warfarin and enoxaparin.
Check for signs of bleeding.
- If there is evidence of major bleeding seek urgent specialist advice. The patient may need clotting factor replacement (e.g fresh frozen plasma or prothrombin complex concentrate) and vitamin K.
- In patients who are not bleeding, the aim of vitamin K treatment is to partially reverse the level of anticoagulation without rendering the patient resistant to further warfarin therapy.
- Intravenous reversal will have effect on the INR in about 4-6 hours. Oral phytomenadione generally has a slower time of onset, up to 24 hours. Each hospital will have their own guidelines, but NICE guidelines advise:
If INR is greater than 8.0 with no bleeding or minor bleeding – stop warfarin and give 0.5-1 mg phytomenadione (vitamin K) by slow intravenous infusion, or 5 mg by mouth. Repeat the INR the next day. Phytomenadione may be repeated after 24 hours if the INR is still too high. Restart warfarin when INR is less than 5.0
37
An 82-year-old male patient weighs 39 kg and has been admitted with painful cyanotic foot for angioplasty, followed by bypass graft.
His relevant past medical history is of right above-knee amputation and high alcohol intake, and his medication is simvastatin, aspirin, enoxaparin and ciprofloxacin.
The patient was prescribed and given warfarin loading doses of 10 mg on day 1 and day 2.
On day 3, the patient’s international normalised ratio (INR) was 8.3.
What factors potentially led to the over-anticoagulation of this patient?
There were various contributory factors that led to him becoming over-anticoagulated. These include:
Inappropriate initiation of warfarin. The loading dose was too high and the international normalised ratio (INR) was not checked every day
His history of high alcohol intake
His age
Drug interactions: simvastatin, aspirin and ciprofloxacin can increase INR
Low body weight
38
What percentage of medical patients get VTE?
50-70% of symptomatic VTE and 70-80% of fatal pulmonary embolisms (PEs) occur in medical patients
39
Indication of thromboprophylaxis in hospital
- Thromboprophylaxis with low molecular weight heparin (LMWH) is indicated in all medical patients expected to have reduced mobility compared to normal and any associated risk factors.
- All patients should also be considered for antiembolism stockings but essential where anticoagulation is contraindicated.
40
Contraindication for stockings
- Peripheral artery disease
- Peripheral neuropathy
- Sensory impairment
- Local skin or soft tissue condition
- Massive leg edema
- foot ulcers
- recent ischaemic stroke
41
Occurrence of DVT in surgical patients
Deep vein thrombosis (DVT) has previously been shown to occur in 20% of patients undergoing major surgery and up to 40% of patients undergoing major orthopaedic surgery
42
The patient is a 72-year-old with a 10 year history of type 2 diabetes. She presents with bilateral lower limb cellulitis, immobility, and deteriorating diabetic control and is treated with intravenous antibiotics. Laboratory results include:
Platelets 230
Hb 10.1
Creatinine 88
What three risk factors for venous thromboembolism does this patient have?
The patient's three risk factors for venous thromboembolism are:
Age greater than 40
Reduced mobility
Infection/sepsis
43
The patient is a 72-year-old with a 10 year history of type 2 diabetes. She presents with bilateral lower limb cellulitis, immobility, and deteriorating diabetic control and is treated with intravenous antibiotics. Laboratory results include:
Platelets 230
Hb 10.1
Creatinine 88
What type of thromboprophylaxis would you recommend for this patient?
In this case, the best treatment for the patient would be low molecular weight heparin at a medical thromboprophylaxis dose. She cannot wear anti-embolism stockings on account of her cellulitis.
44
A 75-year-old male, weighing 95 kg, BMI 32, is admitted with chest pain. He has a history of ischaemic heart disease. His laboratory results include:
Platelets 354
Hb 13.5
Creatinine 242
What three risk factors for VTE does this patient have?
Risk factors are as follows:
Age
Cardiac disease
Obesity
45
A 75-year-old male, weighing 95 kg, BMI 32, is admitted with chest pain. He has a history of ischaemic heart disease. His laboratory results include:
What thromboprophyalxis would you recommend?
Enoxaparin, dalteparin or tinzaparin in reduced dose can be used in patients with moderate to severe renal impairment (creatinine clearance less than 30 ml/minute).
- An alternative would be to use unfractionated heparin 5000 units bd/tds instead
46
A 79-year-old female patient is admitted for total hip replacement. She has no other past medical history and all her laboratory results are normal.
Would you class her as high, moderate or low risk for venous thromboembolism, and which prophylaxis would you recommend?
This patient is classed as high risk as she is undergoing orthopaedic surgery.
She is also over 40 years of age.
The recommended prophylaxis would be low molecular weight heparin e.g enoxaparin 40 mg daily, dalteparin 5,000 units daily or tinzaparin 3,500 units daily and graduated compression stockings.
47
A 60-yr-old lady has cardiac surgery to replace her aortic valve. A metallic aortic valve is inserted. She has no other past medical history and her laboratory results are normal.
What anticoagulation drug would you offer her and for how long would you advise she needs to continue this medication?
All patients with mechanical heart valves require life-long anticoagulation with warfarin.
Direct oral anticoagulants (DOACs) are currently NOT licensed for use in these patients.
If warfarin is needed to be held for a surgical procedure, the patient will need covering with treatment dose low molecular weight heparin (LMWH) or a heparin infusion. Most hospitals have a bridging protocol for use in this instance.
