Anticoagulants Flashcards
What are coagulation factors present in the blood as?
Zymogens
What is an endogenous inactivator of clotting factors?
Antithrombin III
What is an important cofactor in the coagulation cascade?
Calcium
Type of heparin
- Unfractionated heparin
- Low molecular weight heparins e.g. dalteparin, enoxaparin
Compare the administration of unfractionated heparin + LMWH
- UFH: IV bolus + infusion or s.c. For prophylaxis
- LMWH: s.c.
What is the mechanism of action of unfractionated heparin?
- Binds to antithrombin III > confirmation change > increases activity of ATIII > Xa inhibiton
- to catalyse inhibition of thrombin, binding to ATIII and IIa is needed
What is the mechanism of action of LMWH
- inhibition of factor Xa by enhancing ATIII activity
- no affect on thrombin
Why does LMWH have no affect on thrombin?
It is too short so cannot bind to both IIa and ATIII
What is the mechanism of action of fondaparinux?
inhibition of factor Xa by enchanting ATIII
Compare the half life of unfractionated heparin + LMWH
- UH: 20 mins low dose, 2hrs high dose
- LMWH: 2+ hours
Why is heparin not given orally?
Large negatively charged molecules > would have very poor GI absorption
Uses of hepatitis + fondaparinux
- prevention of venous thromboembolism - DVT + PE
- ACS with dual anti platelet therapy
What are adverse drug reactions of heparins?
- bruising + bleeding
- herparin induced thrombocytopenia (more likely in UFH)
- osteoporosis
- hyperkalameia (due to inhibition of aldosterone secretion)
What is heparin induced thrombocytopenia?
- antibodies to heparin platelet factor 4 complex produced
- depletion of platelets
- paradoxically can lead to thrombosis as more platelets activated by damaged endothelium
What are important drug drug interactions of heparins?
Other antithrombotic drugs
ACEi/ARBs
K+ sparing diuretics
Outline heparins monitoring
- aPTT used to monitor UFH
- less monitoring for LMWH as more predictable in action
Outline the reversal of heparins
protamine sulphate
- forms inactive complex with heparin
- heparin dissociates from ATIII
- greater effect with UFH than LMWH + no affect on fondaparinux
Example of vitamin K antagonist
Warfarin
What are the uses of warfarin?
- venous thromboembolism
- PE
- DVT + secondary prevention
- superficial vein thrombosis
- AF when DOAC not suitable
- pre cardio version
- in heart valve replacement
What is the mechanism of action of warfarin?
- inhibits activation of vitamin K decent clotting factors II, VII, IX + X
- inhibits conversion of vitamin K to active reduced form
What clotting factors are vitamin K dependent?
II
VII
XI
X
What is the onset of action + half life of warfarin?
- delayed onset of action
- t1/2 - 36-48 hours
What are contraindication for warfain?
Crosses placenta so avoid in pregnancy (especially 1st trimester)
What are adverse drug reactions of warfarin
- bleeding
- epistaxis
- spontaneous retroperitoneal bleeding
Outline the reversal of warfarin
- vitamin K
- prothrombin complex concentrate IV
- stop warfarin
What does a high and low INR mean?
High INR - more anti coagulate
Low INR - less anti coagulated
What are important drug drug interactions with warfarin?
- CYP2C9 inhibitor
- other anticoagulants
- phenytoin, barbiturates, rifampicin, St John’s warts: increase [plasma]
- NSAIDs: both bind to albumin
Examples of DOACs
Apixaban
Edoxaban
Rivaroxaban
Dabigatran
What are the uses of DOACs?
Indicated in most situations where warfarin used to be the only option
What DOACs affect factor Xa and what is their mechanism of action?
- Apixaban, Rivaroxaban, edoxaban
- inhibtion free Xa and bound to ATIII
- do not directly effect thrombin
What is the mechanism of action of dabigatran?
Competitive thrombin inhibition to both circulation and thrombus bound IIa
What are adverse drug reactions of DOACs?
Bleeding
Skin reactions
What are important drug drug interactions of DOACs
- carbamazepine, phenytoin + barbiturates decrease [plasma]
- Macrolides increase [plasma]
What DOACs is most prescribed + why?
Apixaban
Better side effect profile
What antidotes are available for DOACs
- andexanet alfa - Apixaban + Rivaroxaban
- idarucizumab: dabigatran
When may warfarin be more appropriate than a. DOAC?
Patients with prosthetic valves
Higher risk of GI bleeding
Antiphospholipid syndrome
What bleeding risk score is used in AF patients?
ORBIT score
What factor is used in prothrombin time and why?
Factor VII
Most sensitive to vitamin K deficiency
Which DOAC is a direct thrombin inhibitor?
Dabigatran
