Cardio - Thrombosis, anticoaguants, antiplatelets Flashcards
what kind of thrombus is an arterial thrombus and how are they treated?
white thrombus - platelets in a fibrin mesh
treated with antiplatelets
what kind of thrombus is a venous thrombus and how are they treated?
red thrombus - white head, red tail, fibrin rich
treated with anticoagulants
where an embolus from an arterial thrombus likely to lodge?
artery in brain or other organ
where is an embolus from an arterial thrombus likely to lodge?
lungs (PE)
what is the role of vitamin K in blood clotting?
Required in its reduced form as an essential cofactor for the carboxylase enzyme that mediates carboxylation of clotting factors II, VII, IX and X to their active forms that act as serine proteases
how does warfarin work?
blocks action of Vitamin K reductase which reduces viamin K to its reduced form rendering clotting factors II, VII, IX and X inactive
Slow onset over 2-3 days
what are the risks with warfarin?
low therapeutic index
delay to maximum effect
effect must be monitored regularly via INR
how can warfarin overdose be treated?
Vit K1 (as phytomenadione) concentrate of plasma clotting factors
what increases warfarin risk?
liver disease
high metabolic rate
drug interactions (antiplatelets etc)
what lessens warfarin risk of haemorrhage (increases thrombosis risk)?
pregnancy
hypothyroidism
Vit K consumption
Drug interactions (ones that increase warfarin metabolism rate)
what is antithrombin III?
inhibitor of coagulation which neutralises serine proteases (active clotting factors) in coagulation cascade by binding to active site in 1:1 ratio
how does heparin work?
binds to antithrombin III increasing its affinity for serine proteases clotting factors increasing rate of inactivation
what do LMWHs do?
inhibit factor Xa (prothrombinase) but not thrombin (IIa)
how is heparin administered?
LMWH = Subcutaneous
Heparin = IV or SC
heparin dose determined via in vitro clotting test
how is LMWH eliminated?
via renal excretion
therefore heparin is preferred in renal failure as it has a different elimination pathway
give some examples of LMWHs
enoxaparin
dalteparin
fondaparinux and idrabiotaparinux are similar to LMWH
what are the risks of heparin and LMWH?
haemorrhage (treat with protamine sulfate IV and stopping drug)
osteoporosis (long term)
hypoaldosteronism
hypersensitivity reactions
how does aspirin work?
irreversibly blocks COX in platelets preventing TXA2 synthesis
blocks COX in endothelial cells inhibiting production of antithrombotic prostaglandin I2 (PGI2)
why does aspirin therapy shift balance in favour of antithrombotic effect?
endothelial cells can synthesise new COX enzymes while enucleate platelets cant
TXA2 synthesis doesn’t recover for 7-10 days until affected platelets are replaced
what is the main adverse affect of aspirin?
GI bleeding and ulceration
how does clopidogrel work?
links to P2Y12 receptor via disulphide bond causing irreversible inhibition
when is clopidogrel used?
if aspirin intolerant
combined with aspirin for combined synergistic effect
when is Tirofiban used?
short term IV to prevent MI in high risk unstable angina
what is the fibrinolytic cascade?
Plasminogen > plasmin catalyses breakdown of fibrin to fibrin fragments
exists endogenously and opposes coagulation cascade
name some fibrinolytics?
streptokinase
Alteplase and Duteplase
when are fibrinolytics used and what is the risk?
used to reopen artery in MI
risk of haemorrhage (controlled via tranexamic acid)
what are the pros and cons of orally active inhibitors (eg - dabigatran etexilate)?
pros
- convenient administration
- predictable degree of anticoagulation
cons
- no agent to treat haemorrhage in overdose
used to prevent thrombosis in hip/knee replacement
what does warfarin block?
factors X and II (prothrombin)
what does rivaroxiban block?
factor Xa
what do heparin, LMWH and fondaparinux block?
factor Xa via antithrombin III
what does dabigatran block?
factor IIa
what does heparin block as well as factor Xa?
IIa via antithrombin III
