Antiplatelets/Anticoagulants/Thrombolysis Flashcards
hree direct oral anticoagulants (DOACs)
dabigatran, rivaroxaban and apixaban.
Direct factor Xa inhibitor examples
Rivaroxaban Apixaban
Direct thrombin inhibitor examples
Dabigatran
Excretion of DOACs
Majority renal - Dabigatran
Majority liver - Rivaroxaban
Majority faecal - apixaban
Direct factor Xa inhibitor revesal agents
Andexanet alfa
Direct thrombin inhibitor reversal agents
Idarucizumab
Clopidogrel is an anticoagulant/antiplatelet agent
Clopidogrel is an antiplatelet agent
Clopidogrel belongs to a class of drugs known as
thienopyridines
thienopyridines examples
Clopidogrel
prasugrel
ticagrelor
ticlopidine
Clopidogrel mechanism of action?
antagonist of the P2Y12 adenosine diphosphate (ADP) receptor, inhibiting the activation of platelets
Clopidogrel interactions
concurrent use of proton pump inhibitors (PPIs) may make clopidogrel less effective
Aspirin works by
blocking the action of both cyclooxygenase-1 and 2
Cyclooxygenase is responsible for
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.
Aspirin potentiates?
oral hypoglycaemics
warfarin
steroids
Aspirin should not be used in children under 16 due to
risk of Reye’s syndrome
An exception is Kawasaki disease, where the benefits are thought to outweigh the risks.
NICE now recommend what first-line following an ischaemic stroke and for peripheral arterial disease.
NICE now recommend clopidogrel first-line following an ischaemic stroke and for peripheral arterial disease.
first-line for patients with ischaemic heart disease
aspirin
Heparins generally act by
activating antithrombin III.
? forms a complex which inhibits thrombin, factors Xa, IXa, XIa and XIIa.
? however only increases the action of antithrombin III on factor Xa
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
Adverse effects of heparins include:
bleeding
thrombocytopenia
osteoporosis
Adverse effects of heparins include hypokalemia/hyperkalemia
hyperkalaemia - this is thought to be caused by inhibition of aldosterone secretion
Administration Low molecular weight heparin (LMWH)
Subcutaneous
Administration Standard heparin
Intravenous
which heparin has Lower risk of HIT and osteoporosis
LMWH
Monitoring heparins
Standard - Activated partial thromboplastin time (APTT)
LMWH - Anti-Factor Xa (although routine monitoring is not required)
Heparin-induced thrombocytopaenia (HIT) usually does not develop until after? of treatment
usually does not develop until after 5-10 days of treatment
despite being associated with low platelets HIT is actually a prothrombotic condition
true
Heparin overdose may be reversed by
protamine sulphate, although this only partially reverses the effect of LMWH.
Heparin-induced thrombocytopaenia (HIT) mechanism
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
Heparin-induced thrombocytopaenia (HIT) features
50% reduction in platelets
thrombosis
skin allergy
Heparin-induced thrombocytopaenia (HIT) address need for ongoing anticoagulation - what to use?
direct thrombin inhibitor e.g. argatroban
danaparoid
Thrombolytic drugs mechanism
activate plasminogen to form plasmin
What does plasmin do?
degrades fibrin and help breaks up thrombi
Contraindications to thrombolysis
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
s/e thrombolysis
haemorrhage
hypotension - more common with streptokinase
allergic reactions may occur with streptokinase
thrombolysis eg
alteplase
tenecteplase
streptokinase
Dabigatran is an oral anticoagulant that works by being a
direct thrombin inhibitor
What are the known side-effects of dabigatran?
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.
dabigatran Reversing the effects
Idarucizumab cab be used for rapid reversal of the anticoagulant effects of dabigatran.
Dabigatran is currently used for two main indications.
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
Acute coronary syndrome (medically treated)
1st & 2nd line?
Aspirin (lifelong) & ticagrelor (12 months)
If aspirin contraindicated, clopidogrel (lifelong)
Percutaneous coronary intervention
1st & 2nd line?
Aspirin (lifelong) & prasurgrel or ticagrelor (12 months)
If aspirin contraindicated, clopidogrel (lifelong)
TIA
1st & 2nd line?
Clopidogrel (lifelong)
Aspirin (lifelong) & dipyridamole (lifelong)
Ischaemic stroke
1st & 2nd line?
Clopidogrel (lifelong)
Aspirin (lifelong) & dipyridamole (lifelong)
Peripheral arterial disease
1st & 2nd line?
Clopidogrel (lifelong) Asprin (lifelong)
Fondaparinux mechansim
Activates antithrombin III, which in turn potentiates the inhibition of coagulation factors Xa
Fondaparinux is given s/c
true
Direct thrombin inhibitors generally given intravenously.
true
Combination antiplatelet and anticoagulant therapy
Secondary prevention of stable cardiovascular disease with an indication for an anticoagulant
if an indication for anticoagulant exists (for example atrial fibrillation)
it is indicated that anticoagulant monotherapy is given without the addition of antiplatelets
Combination antiplatelet and anticoagulant therapy
Post-acute coronary syndrome/percutaneous coronary intervention
triple therapy (2 antiplatelets + 1 anticoagulant) for 4 weeks-6 months after the event
dual therapy (1 antiplatelet + 1 anticoagulant) to complete 12 months
Combination antiplatelet and anticoagulant therapy
Venous thromboembolism (VTE)
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
