Anticoagulants

Question 1

which type of blood vessels do anticoagulants mainly work in

Answer 1

They work in slower-moving veins where a thrombus is made of fibrin, platelets + red blood cells. They are less useful in arteries because they are faster-flowing and a thrombus would be made of platelets + little fibrin

note: fibrin is a major component of a blood clot. Anticoagulants target fibrin

Question 2

when should patients taking anticoagulants seek immediate medical attention

Answer 2

• bleeding that is severe
• bleeding that does not stop or recurs
• who have other signs or symptoms of concern (e.g. sudden severe back pain or breathlessness)
• patients who have sustained a head injury should be referred to the hospital emergency department

Question 3

how do vitamin k antagonists work as anticoagulants?

name some examples of vitamin-k anticoagulants

Answer 3

They inhibit the formation of the active form of vitamin K which is needed for clotting factors involved in coagulation.

examples of vitamin-K anticoagulants:

• warfarin (drug of choice)
• acenocoumarol
• phenindione

Question 4

how long does it take for the full anticoagulant effect of vitamin-K antagonists to develop

Answer 4

at least 48-72 hours

Question 5

what drug is given if a patient needs an immediate anticoagulant effect but is taking vitamin - k antagonists

Answer 5

vitamin k antagonists anticoagulant effect takes at least 48-72 hours for full effect.

Must give unfractionated or low molecular weight heparin alongside if immediate anticoagulant effect is needed,

Question 6

what is the preferred drug for prophylaxis of venous thromboembolism in patients undergoing surgery

Answer 6

unfractionated or low weight heparin

note warfarin can be used instead for this if a patient has been taking warfarin for a long time and they’re at high risk for thromboembolism. (seek expert advice for this)

Question 7

when might warfarin be used in prophylaxis of venous thromboembolism in patients undergoing surgery

Answer 7

in selected patients that have been taking warfarin long-term and they are at risk for thromboembolism. (seek expert advice for this)

Question 8

what is the base-line prothrombin time and when should it be taken

Answer 8

prothrombin time measures the time it takes for your blood to clot.

it should be taken before treatment (base-line) but treatment with an anticoagulant should not be delayed whilst waiting for result

Question 9

what does INR mean

Answer 9

INR= international normalized ratio (INR). It is how the prothrombin time is expressed.

Prothrombin time= the time it takes for your blood to clot

Question 10

when would you deem an INR result as satisfactory

Answer 10

if it is within 0.5 units of the target value.

note larger deviations from target value than this mean the dose needs to be adjusted

Question 11

what is the recommended time a patient should be taking warfarin for isolated calf-vein deep-vein thrombosis

Answer 11

6 weeks

Question 12

what is the main adverse effect of all oral anticoagulants

Answer 12

haemorrhage (bleeding)

Question 13

what should you do if an anticoagulant is stopped but not reversed

Answer 13

keep monitoring patient to measure the INR every 2-3 days to make sure the INR is falling.

Investigate why INR is elevated

Question 14

what is NOT recommended for emergency anticoagulation reversal in patients taking warfarin

Answer 14

recombinant factor VIIa

Question 15

which patients are considered high risk of thromboembolism prior to surgery

Answer 15

Those with:

• venous thromboembolic event within the last 3 months - - atrial fibrillation with previous stroke or transient ischaemic attack
• mitral mechanical heart valve

Question 16

if a surgery carries a high risk of bleeding + a patient was given low weight molecular heparin. When would you consider restarting the low weight molecular heparin

Answer 16

at least 48 hours after surgery

Question 17

when might a patient be on combined antiplatelet and anticoagulant therapy

name an example of the combined therapy

Answer 17

following an acute coronary syndrome or percutaneous coronary intervention (PCI)

e.g aspirin + warfarin, warfarin + clopidogrel, aspirin + warfarin + clopidogrel (triple therapy)

Question 18

which carries a higher risk of bleeding:

aspirin + warfarin or clopidogrel + warfarin

Answer 18

clopidogrel + warfarin

Question 19

what is a DOAC

name the 4 examples

Answer 19

direct-acting oral anticoagulant

examples: apixaban, dabigatran etexilate, rivaroxaban, edoxaban

Question 20

What is the mechanism of action of dabigatran etexilate as a DOAC

Answer 20

it is a reversible competitive inhibitor that inhibits thrombin (a clotting factor) from converting fibrinogen to fibrin. Fibrin molecules normally combine platelets together to form blood clots (platelets aggregation) dabigatran etexilate prevents this from happening. This is known as thrombin-induced platelet aggregation.

Question 21

what is the mechanism of action of Apixaban, edoxaban, and rivaroxaban as DOACs

Answer 21

they are reversible inhibitors of activated factor X (factor Xa) which prevents thrombin generation and thrombus development.

less/no thrombin generated = less/no fibrinogen converted to fibrin so less/no platelets combined together to form blood clots (platelet aggregation)

Question 22

name some indications for the use of all DOACs: Apixaban, dabigatran etexilate, edoxaban, and rivaroxaban

Answer 22

• prevention of stroke
• prevent systemic embolism in patients with non-valvular atrial fibrillation
• secondary prevention of deep-vein thrombosis and/or pulmonary embolism

Question 23

which DOACs are used for prevention of venous thromboembolism after elective hip or knee replacement surgery

Answer 23

Apixaban, dabigatran etexilate, and rivaroxaban

all of them apart from edoxaban

Question 24

what is the use of rivaroxaban

Answer 24

• prevention of atherothrombotic events in patients with coronary or peripheral artery disease
• acute coronary syndrome with raised biomarkers

note this is part of secondary prevention of cardiovascular events

Question 25

What monitoring do you need for DOACs do they need regular anticoagulation monitoring

Answer 25

monitor for signs or bleeding or anemia (stop treatment if severe bleeding occurs) No they don't need regular anticoagulation monitoring

Question 26

how long does it take for the anticoagulant effect of DOACS to stop what is the consequence of this

Answer 26

12-24 hours after the last dose was taken consequence: if a patient misses or delays a dose, it can have a reduction in the anticoagulant effect

Question 27

what drug can reverse the anticoagulant effect of dabigatran etexilate

Answer 27

Idarucizumab it can be used in life-threatening/ uncontrolled bleeding, emergency surgery/ urgent procedures

Question 28

what drug can reverse the anticoagulant effect of apixaban or rivaroxaban

Answer 28

Andexanet alfa it can be used in life-threatening/ uncontrolled bleeding

Question 29

how do you switch a patient from warfarin to a DOAC

Answer 29

- stop warfarin treatment before starting DOAC. this is to reduce risk of over-anticoagulation + risk of bleeding

Question 30

when should a woman postpartum start taking warfarin again

Answer 30

delay warfarin until risk of bleeding is low (usually 5-7 days after birth delivery)

Question 31

what does it mean if your INR is too high (higher than target INR)

Answer 31

if the INR is too high, it means your blood is taking longer to clot so you are at increased risk of bleeding

Question 32

what does it mean if your INR is too low (lower than target INR)

Answer 32

if the INR is too low, it means your blood is clotting quicker so you are at increased risk of a blood clot

Question 33

why should pregnant women avoid taking vitamin k antagonists in their first + third trimester

Answer 33

because all vitamin k antagonists are teratogenic. highest risk is in the 1st + 3rd trimester

Question 34

when is it advised that pregnant women stop taking vitamin k antagonists

Answer 34

stop vitamin k antagonists before the 6th week of gestation to avoid fetal abnormalities

Question 35

how often should patients on vitamin k antagonists have their INR monitoring

Answer 35

- baseline prothrombin time taken

Question 36

name the contraindications for all DOACs

Answer 36

- antiphospholipid syndrome - a lesion or condition if it is considered a risk factor to major bleeding - concomitant use with any other anticoagulant - previous stroke/ TIA (when indication is for prophylaxis of atherothrombotic events)

Question 37

can you take any other anticoagulant when taking a DOAC

Answer 37

No, must not use any other anticoagulants when taking a DOAC unless you are switching therapy when unfractionated heparin is given

Question 38

TRUE OR FALSE Rivaroxaban should not be used in patients with prosthetic heart valves, including patients who have undergone transcatheter aortic valve replacement (TAVR)

Answer 38

TRUE this is because there is an increased risk of all-cause death and bleeding

Question 39

which has an increased risk of recurrent thrombotic events in patients with antiphospholipid syndrome: - vitamin k antagonists - DOACs

Answer 39

DOACs DOACs are not recommended in patients with antiphosholipid syndrome. If a patient is on a DOAC with antiphospholipid syndrome, consider switching them to a vitamin K antagonist

Question 40

why should you take rivaroxaban with food

Answer 40

because taking rivaroxaban with food increases the efficacy compared to taking it on an empty stomach *note in those who have difficulty swallowing, can crush tablets mixed with water/apple puree then eat food immediately after*

Question 41

can you use DOACs whilst pregnant or breastfeeding

Answer 41

no, manufacturer advises to avoid in pregnancy (toxicity seen in animals) + breastfeeding (present in breast milk)

Question 42

what is the difference between standard/unfractionated heparin vs low molecular weight heparins

Answer 42

standard/unfractionated heparin initiates anticoagulation rapidly but has a short duration of action whereas low molecular weight heparin has a longer duration of action *note low weight heparin is generally preferred*

Question 43

although low weight heparin is usually preferred to unfractionated/standard heparin, why might unfractionated/standard heparin still be used

Answer 43

because the anticoagulant effect of unfractionated/standard heparin can quickly be stopped by stopping the infusion (due to short duration of action* *note low weight heparin has a longer duration of action*

Question 44

name some examples of low weight heparins *they end in "rin"*

Answer 44

- enoxaparin sodium - dalteparin sodium - tinzaparin sodium

Question 45

what low weight heparins used for

Answer 45

- preventing venous thromboembolism (VTE) | - treating deep vein thrombosis (DVT) and pulmonary embolism

Question 46

which type of heparin has a lower risk of causing heparin-induced thrombocytopenia

Answer 46

low weight heparins

Question 47

name some examples of parenteral anticoagulants

Answer 47

- low weight heparin + unfractionated/standard heparin - Bivalirudin (used in NSTEMI or unstable angina patients as an anticoagulant for percutaneous coronary intervention) - Epoprostenol (prostacyclin). Also a potent vasodilator used in primary pulmonary hypertension resistant to other treatment - Danaparoid sodium - Argatroban - Fondaparinux

Question 48

what is Venous thromboembolism (VTE)

Answer 48

includes both deep-vein thrombosis (DVT) and pulmonary embolism (PE), and refers to a blood clot that forms in a vein which partially or completely obstructs blood flow

Question 49

what is Hospital-acquired venous thromboembolism (VTE)

Answer 49

VTE that happens within 90 days of hospital admission

Question 50

name some risk factors for Venous thromboembolism (VTE)

Answer 50

- surgery/trauma - significant immobility - obesity - pregnancy and the postpartum period - hormonal therapy (combined hormonal contraception or hormone replacement therapy) - acquired or inherited hypercoagulable states (blood which has increased tendency to clot)

Question 51

where does deep vein thrombosis (DVT) normally occur what are the symptoms

Answer 51

DVT normally occurs in deep veins of legs or pelvis but may affect other sites. It is the most common type of VTE symptoms: - localised pain/ tenderness - swelling - skin changes - vein distension (bulging)

Question 52

how does a pulmonary embolism (PE) normally occur what are the symptoms

Answer 52

pulmonary embolism (PE) usually happens when a thrombus from DVT travels in the blood (embolus) and obstructs blood flow in the lungs. This causes respiratory dysfunction symptoms: - chest pain - shortness of breath - haemoptysis (coughing up blood)

Question 53

TRUE OR FALSE all patients should be assessed on their risk of venous thromboembolism (VTE) and bleeding on admission to hospital

Answer 53

True

Question 54

describe the two methods of venous thromboembolism prophylaxis

Answer 54

- Mechanical: patients given anti-embolism stockings which provide a graduated pressure of 14-15 mmhg. They are worn day + night until patient is sufficiently mobile. or intermittent pneumatic compression device - pharmacological: started at soon as possible or within 24hrs of admission. patients taking anticoagulants should only receive pharmacological treatment if anticoagulant therapy has been interrupted e.g for surgery.

Question 55

which type of anesthesia (regional or general) should be used to reduce risk of VTE in patients

Answer 55

regional anaesthesia over general anaesthesia should be used if possible

Question 56

which drug can be used all types of general and orthopaedic surgery as prophylaxis to prevent VTE

Answer 56

low molecular weight heparin

Question 57

which drug is preferred as prophylaxis to prevent VTE in patients with renal impairment

Answer 57

unfractionated/ standard heparin preferred but can also use low weight molecular heparin

Question 58

what is the first line treatment option to prevent VTE in medical patients (not at hospital for surgery)

Answer 58

first line is pharmacological treatment: | - low weight molecular heparin first line (fondaparinux sodium as an alternative), for a minimum of 7 days

Question 59

which patients should NOT have mechanical treatment to prevent VTE

Answer 59

- acute stroke or those with conditions such as: - peripheral arterial disease - peripheral neuropathy - severe leg oedema - or local conditions (e.g. gangrene, dermatitis)

Question 60

what are the 3 main drugs used in pharmacological prophylaxis of VTE in surgical patients

Answer 60

- low weight molecular heparin - unfractionated/standard heparin - Fondaparinux sodium *note patients may also be taking anticoagulants if undergoing elective hip/knee surgery*

Question 61

which drug is used for thromboprophylaxis in pregnancy

Answer 61

low weight molecular heparin - elastic graduated compression stocking should be applied on the affected leg as an additional treatment to manage symptoms such as pain and swelling * note this includes all pregnant women (who are not in active labour), or women who have given birth, had a miscarriage or termination of pregnancy during the past 6 weeks, with a risk of VTE that outweighs the risk of bleeding*

Question 62

what are the drug treatment options for patients with confirmed DVT or pulmonary embolism

Answer 62

- first line= apixaban or rivaroxaban. if not tolerated: - low molecular weight heparin (LMWH) for at least 5 days followed by dabigatran etexilate or edoxaban; or - LMWH + vitamin K antagonist for at least 5 days or until the INR is at least 2.0 for 2 consecutive readings, followed by a vitamin K antagonist on its own.

Question 63

how do you reverse the anticoagulant effects of low molecular weight heparin or unfractionated heparin

Answer 63

- usually stopping the low weight heparin or unfractionated heparin is enough to reverse effects. If you need rapid reversal, use protamine sulfate (the antidote)