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Flashcards in Warfarin/UFH Deck (29)
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Warfarin MOA

-Antagonizes Vitamin K epOxide Reductase Complex 1 (VKORC1)
-Inhibits carboxylation of factors II, VII, IX, X (procoags)
-Inhibits protein C and S (anticoags)


Warfarin polymorphism

-Accounts for 30-40% of interpatient variability in daily warfarin dose**
-CYP2C9*2/3 & VKORC1 A/A require lower doses of warfarin


Warfarin Indications

-Prevention and tx VTE
-Prevention/tx thromboembolism d/t valvular/nonvalvular AF or prosthetic valve (Preferred anticoag for AF with CAD, valvular AF, prosthetic valves**)
-May be used for recurrent TIA


Warfarin dosing

-Start 2-4 mg/d or 5-10 mg/d for younger/healthier --> adjust dose based on INR
-Half life is 40 hrs** --> takes 2 days to see effect
-Large loading dose (>10 mg) create transient hypercoagulable state dt ec [Protein C]***


Traditional Warfarin Dosing

-Lower doses may be required for: hepatic impairment, poor nutrition, HF, elderly**, pts on CYP2C9 inhibitors/polymorphisms of CYP2C9
-Higher doses may be required for: pts on CYP2C9 inducer, polymorphism of VKOR1


Newer Warfarin dosing

Managed by "anticoagulation specialists"


Warfarin Monitoring

-Anemia/bleeding--> H&H
-PT/INR (assess extrinsic, coagulation factors in common pathway)
-Prolongation of PT 1st few days d/t depression of factor VII


Warfarin and LMWH/UFH

-Intrinsic pathway not initially altered by warfarin
-Must overlap w UFH or LMWH for at least 5d if rapid anticoag needed (VTE)**


What should INR be of a patient on Warfarin? How often should you monitor?

-2-3 (AF target is 2.5)
-Daily until stable, then q4wks
-Monitor more frequently if unpredictable response (ex concomitant meds that interact w warfarin)***


Warfarin Reversal: non-life threatening

I.e. epistaxis: Vit K1 (phytonadione)--> PO takes 24-hr to restore factors II, VII, IX, X


Warfarin Reversal: life threatening

-I.e. intracranial: Iv vit K PLUS PCC >> FFP
-PCC lowers INR faster than FFP--> standard of care**
-FFP: not concentrated form of coag proteins & [clotting factor] vary**


**KNOW THIS: INR >10 in Warfarin pt--> whatcha gonna do?

-Hold warfarin and give vit K 2.5-5 mg PO, even if not bleeding
-Monitor INR. Resume warfarin at lower doses with INR therapeutic
-Can give IV formulation of vit K orally. Mix w OJ to improve taste


**KNOW THIS: INR 4.5-10 in Warfarin pt--> whatcha gonna do?

-Hold 1-2 doses of warfarin. Monitor INR. Resume warfarin at lower dose with INR therapeutic
-Vit K not routinely recommended if no evidence of bleeding
-Vit K can be used if urgent surgery needed (<5mg, w additional 1-2 mg in 24 hrs if needed) or bleeding risk high (1-2.5 mg)


**KNOW THIS: INR above therapeutic range but <4.5 in Warfarin pt--> whatcha gonna do?

-Reduce or skip warfarin dose. Monitor INR. Resume warfarin when INR therapeutic
-Dose reduction may not be needed if only slightly above therapeutic range


Warfarin drug interactions

-Pk: drugs that decrease absoprtion and CYP2C9 inhibitors and inducers (antimicrobials are worst--> TMP-SMX, metro, rifampin)
-Pd: other antiplatelet/anticoag--> bleeding
-Assume everything interacts with warfarin


Warfarin ADRs

-Bleeding: don't assume pts on chronic stable warfarin who develop heraturia is always 2ndary to anticoag**
-Skin necrosis/gangrene--> pt may have underlying protein C def**
-Purple toe syndrome



-Indirect thrombin inhibitor
-Converts circulating cofactor from slow to rapid inactivator of thrombin > factor Xa > others


UFH indications

-DVT prophy
-Systemic anticoag (VTE tx)
-Anticoag for ECMO/HD
-ACS with PCI (unlabeled indication)


UFH advantages

-Cheap, familiarity of use
-Rapid/complete reversal by protamine
-Not renally eliminated and may be safer in renal impairment
-Shorter 1/2 life (1.5 hr)--> might be better with high risk of bleeding pts


UFH limitations

-Low therapeutic window
-Anticoag response varies widely
-Reduced ability to inactivate thrombin bound fibrin as well as Xa to activated platelets within a thrombus--> thrombus may grow***
-Possibility of HIT


UFH dosing

-Situation dependent
-Usually want pt 1-5-2.5x baseline aPTT
-Optimal to get anticoagulated within 24 hrs**


UFH monitoring

-aPTT--> intrinsic pathway (XII, XI, IX< VIII) and final common pathways (II, V, X)


How often should you monitor platelets for patients on UFH?**

-q2-3d from day 4-14 or until heparin stopped


Heparin reversal

-Nonurgent: turn down/stop heparin
-Urgent: Protamine by slow IV infusion


UFH drug interactions

other antiplatelets, anticoags, NSAIDS--> bleeding


UFH hemorrhage risk

-Congenital bleeding disorder
-Active ulcerative GI dz
-Severe uncontrolled HTN
-Use after recent brain/eye/spinal surgery***
-Pts on other anti-coag
-Severe liver dz
-Osteoporosis another risk


Who is at risk for Heparin Induced Thrombocytopenia?

Pts after MAJOR surgery or trauma >> minor surgery or medical therapy


What is HIT?

-Immune mediated prothrombotic rxn that occurs when heparin binds to platelet factor 4
-Platelets get consumed and endothelial damage--> thrombi develop at site of damage
-Decline in plts >50%
-Thromboembolic events occur in ~50% of HIT cases (venous > arterial)



1) d/c all UFH/LMWH
2) administer direct thrombin inhibitor (argatroban) --> reduces thrombosis risk
3) Avoid prophy plt transfusion
4)Test for HIT abs (EIA)
5) d/c warfarin if on, give vit K
6) add "heparin allergy" to list, med bracelet
7) dx study for thrombosis (ex VTE)