Anticoagulants Flashcards
What test is used to monitor heparin therapy?
aPTT
What test is used to monitor warfarin therapy?
PT-INR
MOA of heparin
Binds to antithrombin III, enhancing its inhibition of factors IIa (thrombin), Xa, and IXa.
Method of heparin administration
Intravenously or subcutaneously (not absorbed orally).
Primary adverse effect of heparin therapy
Bleeding, followed by heparin-induced thrombocytopenia (HIT)
What is used to Tx heparin overdose?
Protamine sulfate
How does low-molecular weight heparin differ from UFH?
LMWHs are more selective for factor Xa and have more predicatable pharmocokinetics
LMWHs - i.e. Enoxaparin and dalteparin
When is routine monitoring required in LMWH therapy?
Renal impairment
Pregnancy
Obesity
What is fondaparinux and how does it work?
Synthetic heparin derivative that selectively inhibits factor Xa
There is no antidote for bleeding cuased by fondaparinux
Two main types of direct oral anticoagulants
Factor Xa inhibitors and direct thrombin (factor IIa) inhibitors
Name three examples of direct oral anticoagulants that inhibit Xa
- Rivaroxaban
- Apixaban
- Edoxaban
What is an example of a direct thrombin inhibitor
Dabigatran
What should be monitored during direct oral anticoagulant therapy?
Kidney function
What is the antidote for dabigatran
Idarucizumab
Dabigatran = direct thrombin inhibitor
What is the antidote for rivaroxaban and apixaban?
Andexanet alfa
What DOAC has the lowest risk of GI bleeding?
Apixaban
Contraindications for DOAC therapy
Severe renal impairment and CYP450 inhibitors
MOA of warfarin
Inhibits vitamin K epoxide reductase, preventing the synthesis of factors II, VII, IX, and X
Why is warfarin’s onset of action delayed?
It only affects the synthesis of new clotting factors - takes 4-5 days
Rare but serious side-effects of warfarin
Skin necrosis and purple-toe syndrome
Why is warfarin contraindicated in pregnancy?
It is teratogenic and increases the risk of fetal bleeding
What food/supplements increase bleeding risk w/ warfarin
- Garlic
- Ginger
- Ginkgo biloba
- Ginseng
INR target for most warfarin Pt’s
2-3
INR target for Pt’s w/ mechanical heart valves
2.5-3.5
Antidote for warfarin overdose
Vitamin K
In ermergent situations - fresh-frozen plasma or PCC
Most common side-effect of long-term heparin use?
Osteoporosis
Preferred anticoagulant used during pregnancy
LMWHs (i.e. enoxaparin)
Preferred anticoagulant for Pt’s with mechanical heart valves
Warfarin
What anticoagulant is used to Tx heparin-induced thrombocytopenia?
Direct thrombin inhibitors like argatroban
How are DOACs superior to warfarin in atrial fibrillation?
The require no routine monitoring and have fewer drug/food interactions
What is the target range for PTT when using heparin?
1.5-2.5 times the Pt’s baseline PTT
Why is anti-factor Xa activity monitored in some LMWH Pt’s?
To ensure efficacy in special populations (i.e. pregnancy/obesity)
What test is used to monitor dabigatran effects?
Thrombin time or ecarin clotting time (ECT)
Method of excretion of DOACs
Renal - why kidney Fx is monitored
What reversal agent is used for excessive bleeding w/ rivaroxaban
Andexanet alfa
Risk of using idarucizumab to reverse dabigatran
HA
Hypokalemia
Allergic rx’ns
Why does efficacy of warfarin therapy vary between Pt’s?
Genetic differences in CYP2C0 and vitamin K epoxide reductase
Heparin indications
DVT
PE
MI
Dilitazem (used for AF) interacts with what DOACs?
Rivaroxaban and apixaban
Edoxaban and kidney function
Avoid edoxaban if kidney function is too good (i.e. CrCl > 95 mL/min)
What type of bleeding risks is diminished in DOAC therapy compared to other anticoagulation?
Intracranial bleeding
Indications for DOAC therapy
DVT/PE
and prevent clots in A-fib
Parenteral direct thrombin inhibitors
Lepirudin
Bivalirudin
Argatroban
Commonly used in Pt’s w/ prior Hx of heparin-induced thrombocytopenia (HIT) or during angioplasty
Dabigatran
PO direct thrombin inhibitor
Indications for warfarin therapy
DVT/PE
A-fib and rheumatic heart disease to reduce stroke risk
Mechanical heart valves or moderate-to-severe stenosis (warfarin should be selected insteads of DOACs in these Pts)
Blocked coronary arteries (as an adjunctive therapy)
To Tx major bleeding associated w/ warfarin use
Administer vitamin K (aka phytonadione) - slow reversal
Fresh-frozen plasma or prothrombin complex concentrate (PCC)
Hemostatic agents
Tranexamic acid
Aminocarpoic acid
Displace plasminogen from fibrin
How to differentiate between warfarin therapy and DIC?
Only DIC diminishes fibrinogen serum concentration
Warfarin inhibits Vit K epoxide reductase, and consequently diminished production of factors II, VII, IX, and X
Low fibrinogen is one of the hallmarks of DIC - indicates widespread clotting and consumption of clotting factors
How are unfractionated heparin’s actions terminated?
Locally in endothelial cells and liver heparinases
Which of the following is the most likely reason why lepirudin would be selected over heparin?
D) Previous episode of heparin-induced thrombocytopenia
Which of the following inhibits thrombin exclusively?
C. Dabigatran
Why is concurrent Tx w/ clarithromycin and apixiban contraindicated?
Clarithromycin inhibits cyp3A4 and P-glycoprotein which may increase risk of bleeding
