TBL 1: Anticoagulants Flashcards
what are anticoagulants?
a class of drugs that work on factors of the coagulation cascade to fight unwanted clot formation in the body
what type of anticoagulants are used to treat acute cases?
parenteral anticoagulants –> they are used in acute settings because they become readily available in the blood
you can then transition these acute cases for long-term management with slower acting oral anticoagulants.
ex. DVT
this means not by the mouth/enteric system so things like intravenous, intramuscular, or subcutaneous injection especially
what type of anticoagulants are used to treat chronic cases?
oral anticoagulants
used for long=term prophylaxis against clot formation in conditions like atrial fibrillation
during A-fib, the atria does not effectively push blood into the ventricles and thus causes stasis of blood in atria. Clots can form in the left atrial appendage, which can embolize into the systemic vasculature, clog an artery feeding the brain, and cause a stroke
when we do we use parenteral anticoagulants versus use oral anticoagulants?
we use parenteral anticoagulants for the management of acute, life-threatening diseases like venous thromboembolism (VTE) due to their more rapid onset compared to oral agents
we then transition to oral anticoagulants for long-term management after the acute phase and for prophylaxis in recurrent VTE or chronic A-fib
what is a common cause of a-fib?
hyperthyroidism
so always check lab T4 levels to check thyroid function!
what are the 4 anticoagulant classes?
- clotting factor synthesis inhibitor
- antithrombin activators
- direct factor Xa inhibitors
- direct thrombin inhibitors
what are clotting factor synthesis inhibitors? what is the delivery method, adverse effects and antidotes?
ex. warfarin
oral
adverse effects: hemorrhage
antidote: FFP, vitamin K
what are antithrombin activators? what is the delivery method, adverse effects and antidotes?
ex. heparin, enoxaprin, dalteparin, fondaparinux
parenteral
adverse effects: hemorrhage, HITT
antidotes: protamine sulfate
what are direct factor Xa inhibitors? what is the delivery method, adverse effects and antidotes?
ex. apixaban, rivaroxaban, edoxaban
oral
side effects: hemorrhage
antidote: activated prothrombin complex concentrate (aPCC)
what are direct thrombin inhibitors? what is the delivery method, adverse effects and antidotes?
ex. dabigatran, agratroban, bivalirudin, lepirudin
dabigatran is oral then rest are parenteral
adverse effects: hemorrhage
antidote: aPCC and idarucizumab specifically for dabigatran
what is the coagulation cascade pathway?
draw it out!!!
what are the vitamin K-dependent clotting factors?
vitamins 2, 7, 9, 10 C and S
what is the MOA of warfarin?
warfarin interferes with the γ-carboxylation of vitamin K-dependent clotting factors by inhibiting epoxide reductase
vitamin K dependent clotting factors = 2, 7, 9, 10, C and S
so it indirectly acts on coagulation cascade factors by acting as a clotting factor synthesis inhibitor
how do we monitor warfarin?
PT aka the extrinsic pathway even though it effects all vitamin K dependent clotting factors which involves both intrinsic and extrinsic pathways, we still just use PT mainly to monitor
we do so because factor VII has the shortest half-life of all the factors, so the PT/INR will become abnormal before the PTT –> this way we can monitor the patient’s coagulation status early in the process, before all of the vitamin-K-dependent factors are all knocked out
what is the antidote to warfarin?
vitamin K
warfarin inhibits the synthesis of vitamin K-dependent factors
but this takes a while to kick in so if you want rapid reversal, we give fresh frozen plasma (FFP), which replenishes the patient’s coagulation factors
what is warfarin-induced skin necrosis?
warfarin blocks vitamin K dependent coagulation factors of which, proteins C and S have the shortest half life and are natural anticoagulants
so they get knocked out first which leaves the coagulation cascade free to go rampant and you have a temporary hyper coagulable state where the anticoagulant concentration is lower than usual and the clotting factors can just wreak havoc
this leads to small vessels clotting which causes the skin to die
how do you avoid warfarin-induced skin necrosis?
give a heparin bridge!
when we administer warfarin to a patient, we also provide heparin to activate antithrombin which is an anticoagulant
what are the common drug interactions associated with warfarin?
warfarin is metabolized by the liver P450 enzymes
so drugs that mess with the P450 system can alter warfarin metabolism…
liver enzyme inhibitors = ↓liver enzymes = ↓warfarin metabolism = ↑[warfarin] = ↑risk of bleeding.
liver enzyme inducers = ↑ liver enzymes = ↑warfarin metabolism = ↓[warfarin] = ↑risk of thrombosis
which outcome, clot or bleed, is more likely when warfarin is combined with a liver enzyme inhibitor?
bleeding
because warfarin is metabolized by P450 so if you inhibit it, warfarin levels will remain higher for longer and continue to block the vitamin K dependent clotting factors
what is the MOA of heparin?
it acts indirectly on coagulation factors by activating the anticoagulant antithrombin
antithrombin acts on IIa, VIIa, IXa, Xa, XIa and XIIa = 2, 7, 9, 10, 11, 12
low molecular weight heparins like enoxaparin, dalteparin, and fondaparinux work mainly on Xa and IIa
which anticoagulant is safe for use during pregnancy?
warfarin is a teratogen
heparin derivatives are safe for use during pregnancy
what is the antidote for heparin?
protamine sulfate
it’s a positively charged molecule that binds to negatively charged heparin
what is the hallmark side effect of heparin?
heparin-induced thrombocytopenia and thrombosis = HITT
heparin binds to platelet factor 4 (PF4) and some individuals form IgG antibodies against the heparin-PF4 complex –> the triad of heparin-PF4-Ig antibody activates platelets, simultaneously causing platelets consumption combined with thrombosis
even though there’s low platelets, to combat the thrombotic effect of HITT, use a direct thrombin inhibitor like argatroban, dabigatran, lepirudin, or bivalirudin
what is the MOA of direct factor Xa inhibitors?
they bind to and directly inhibit coagulation factor Xa
ban on factor Xa = apiXaBAN, rivaroXaBAN, edoXaBAN
what is the antidote for of direct factor Xa inhibitors?
activated prothrombin complex concentrate (aPCC)
what is the MOA of direct thrombin inhibitors?
they inhibit thrombin directly
direct ThRombin inhibitors include argaTRoban, dabigaTRan and the “rudins” – bivalirudin and lepirudin.
what is the main indication for argatroban?
it’s a direct thrombin inhibitor
it’s an alternative to heparin for anticoagulating patients with HITT
what is the antidote for direct thrombin inhibitors?
dabigatran = idarucizumab
the rest can be reversed with aPCC
which drugs are clotting factor synthesis inhibitors?
warfarin
which drugs are activators of antithrombin?
- heparin
- enoxaparin
- dalteparin
- fondaparinux
which drugs are direct factor Xa inhibitors?
- apixaban
- rivaroxaban
- edoxaban
which drugs are direct thrombin inhibitors?
- argatroban
- dabigatran
- bivalirudin
- lepirudin
A patient on chronic warfarin is newly prescribed with a known liver P450 enzyme inhibitor. Which of the following risks is increased in this patient?
A. Budd-Chiari syndrome
B. DVT
C. hemorrhagic stroke
D. PE
E. thrombocytopenia
C. hemorrhagic stroke
warfarin is metabolized by liver enzymes, and if we happen to inhibit these liver enzymes, warfarin’s metabolism is decreased, ultimately increasing warfarin concentration in the blood and increasing the risk of a bleed
