Antiplatelets/Anticoagulants/Thrombolysis

Question 1

hree direct oral anticoagulants (DOACs)

Answer 1

dabigatran, rivaroxaban and apixaban.

Question 2

Direct factor Xa inhibitor examples

Answer 2

Rivaroxaban Apixaban

Question 3

Direct thrombin inhibitor examples

Answer 3

Dabigatran

Question 4

Excretion of DOACs

Answer 4

Majority renal - Dabigatran
Majority liver - Rivaroxaban
Majority faecal - apixaban

Question 5

Direct factor Xa inhibitor revesal agents

Answer 5

Andexanet alfa

Question 6

Direct thrombin inhibitor reversal agents

Answer 6

Idarucizumab

Question 7

Clopidogrel is an anticoagulant/antiplatelet agent

Answer 7

Clopidogrel is an antiplatelet agent

Question 8

Clopidogrel belongs to a class of drugs known as

Answer 8

thienopyridines

Question 9

thienopyridines examples

Answer 9

Clopidogrel
prasugrel
ticagrelor
ticlopidine

Question 10

Clopidogrel mechanism of action?

Answer 10

antagonist of the P2Y12 adenosine diphosphate (ADP) receptor, inhibiting the activation of platelets

Question 11

Clopidogrel interactions

Answer 11

concurrent use of proton pump inhibitors (PPIs) may make clopidogrel less effective

Question 12

Aspirin works by

Answer 12

blocking the action of both cyclooxygenase-1 and 2

Question 13

Cyclooxygenase is responsible for

Answer 13

prostaglandin, prostacyclin and thromboxane synthesis.

The blocking of thromboxane A2 formation in platelets reduces the ability of platelets to aggregate which has lead to the widespread use of low-dose aspirin in cardiovascular disease.

Question 14

Aspirin potentiates?

Answer 14

oral hypoglycaemics
warfarin
steroids

Question 15

Aspirin should not be used in children under 16 due to

Answer 15

risk of Reye’s syndrome

An exception is Kawasaki disease, where the benefits are thought to outweigh the risks.

Question 16

NICE now recommend what first-line following an ischaemic stroke and for peripheral arterial disease.

Answer 16

NICE now recommend clopidogrel first-line following an ischaemic stroke and for peripheral arterial disease.

Question 17

first-line for patients with ischaemic heart disease

Answer 17

aspirin

Question 18

Heparins generally act by

Answer 18

activating antithrombin III.

Question 19

? forms a complex which inhibits thrombin, factors Xa, IXa, XIa and XIIa.

? however only increases the action of antithrombin III on factor Xa

Answer 19

Unfractionated heparin forms a complex which inhibits thrombin, factors Xa, IXa, XIa and XIIa.

LMWH however only increases the action of antithrombin III on factor Xa

Question 20

Adverse effects of heparins include:

Answer 20

bleeding
thrombocytopenia
osteoporosis

Question 21

Adverse effects of heparins include hypokalemia/hyperkalemia

Answer 21

hyperkalaemia - this is thought to be caused by inhibition of aldosterone secretion

Question 22

Administration Low molecular weight heparin (LMWH)

Answer 22

Subcutaneous

Question 23

Administration Standard heparin

Answer 23

Intravenous

Question 24

which heparin has Lower risk of HIT and osteoporosis

Answer 24

LMWH

Question 25

Monitoring heparins

Answer 25

Standard - Activated partial thromboplastin time (APTT) LMWH - Anti-Factor Xa (although routine monitoring is not required)

Question 26

Heparin-induced thrombocytopaenia (HIT) usually does not develop until after? of treatment

Answer 26

usually does not develop until after 5-10 days of treatment

Question 27

despite being associated with low platelets HIT is actually a prothrombotic condition

Answer 27

true

Question 28

Heparin overdose may be reversed by

Answer 28

protamine sulphate, although this only partially reverses the effect of LMWH.

Question 29

Heparin-induced thrombocytopaenia (HIT) mechanism

Answer 29

immune mediated - antibodies form against complexes of platelet factor 4 (PF4) and heparin these antibodies bind to the PF4-heparin complexes on the platelet surface and induce platelet activation by cross-linking FcγIIA receptors

Question 30

Heparin-induced thrombocytopaenia (HIT) features

Answer 30

50% reduction in platelets thrombosis skin allergy

Question 31

Heparin-induced thrombocytopaenia (HIT) address need for ongoing anticoagulation - what to use?

Answer 31

direct thrombin inhibitor e.g. argatroban | danaparoid

Question 32

Thrombolytic drugs mechanism

Answer 32

activate plasminogen to form plasmin

Question 33

What does plasmin do?

Answer 33

degrades fibrin and help breaks up thrombi

Question 34

Contraindications to thrombolysis

Answer 34

``` active internal bleeding recent haemorrhage, trauma or surgery (including dental extraction) coagulation and bleeding disorders intracranial neoplasm stroke < 3 months aortic dissection recent head injury severe hypertension ```

Question 35

s/e thrombolysis

Answer 35

haemorrhage hypotension - more common with streptokinase allergic reactions may occur with streptokinase

Question 36

thrombolysis eg

Answer 36

alteplase tenecteplase streptokinase

Question 37

Dabigatran is an oral anticoagulant that works by being a

Answer 37

direct thrombin inhibitor

Question 38

What are the known side-effects of dabigatran?

Answer 38

Unsurprisingly haemorrhage is the major adverse effect. Doses should be reduced in chronic kidney disease and dabigatran should not be prescribed if the creatinine clearance is < 30 ml/min.

Question 39

dabigatran Reversing the effects

Answer 39

Idarucizumab cab be used for rapid reversal of the anticoagulant effects of dabigatran.

Question 40

Dabigatran is currently used for two main indications.

Answer 40

Firstly it is an option in the prophylaxis of venous thromboembolism following hip or knee replacement surgery. Secondly, it is also licensed in the UK for prevention of stroke in patients with non-valvular atrial fibrillation who have one or more of the following risk factors present: previous stroke, transient ischaemic attack or systemic embolism left ventricular ejection fraction below 40% symptomatic heart failure of New York Heart Association (NYHA) class 2 or above age 75 years or older age 65 years or older with one of the following: diabetes mellitus, coronary artery disease or hypertension

Question 41

Acute coronary syndrome (medically treated) | 1st & 2nd line?

Answer 41

Aspirin (lifelong) & ticagrelor (12 months) If aspirin contraindicated, clopidogrel (lifelong)

Question 42

Percutaneous coronary intervention | 1st & 2nd line?

Answer 42

Aspirin (lifelong) & prasurgrel or ticagrelor (12 months) If aspirin contraindicated, clopidogrel (lifelong)

Question 43

TIA | 1st & 2nd line?

Answer 43

Clopidogrel (lifelong) Aspirin (lifelong) & dipyridamole (lifelong)

Question 44

Ischaemic stroke | 1st & 2nd line?

Answer 44

Clopidogrel (lifelong) Aspirin (lifelong) & dipyridamole (lifelong)

Question 45

Peripheral arterial disease | 1st & 2nd line?

Answer 45

Clopidogrel (lifelong) Asprin (lifelong)

Question 46

Fondaparinux mechansim

Answer 46

Activates antithrombin III, which in turn potentiates the inhibition of coagulation factors Xa

Question 47

Fondaparinux is given s/c

Answer 47

true

Question 48

Direct thrombin inhibitors generally given intravenously.

Answer 48

true

Question 49

Combination antiplatelet and anticoagulant therapy Secondary prevention of stable cardiovascular disease with an indication for an anticoagulant

Answer 49

if an indication for anticoagulant exists (for example atrial fibrillation) it is indicated that anticoagulant monotherapy is given without the addition of antiplatelets

Question 50

Combination antiplatelet and anticoagulant therapy Post-acute coronary syndrome/percutaneous coronary intervention

Answer 50

triple therapy (2 antiplatelets + 1 anticoagulant) for 4 weeks-6 months after the event dual therapy (1 antiplatelet + 1 anticoagulant) to complete 12 months

Question 51

Combination antiplatelet and anticoagulant therapy Venous thromboembolism (VTE)

Answer 51

HAS-BLED score should be calculated. Those with a low risk of bleeding may continue antiplatelets. In patients with an intermediate or high risk of bleeding consideration should be given to stopping the antiplatelets