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Flashcards in Warfarin/UFH Deck (29)
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1
Q

Warfarin MOA

A
  • Antagonizes Vitamin K epOxide Reductase Complex 1 (VKORC1)
  • Inhibits carboxylation of factors II, VII, IX, X (procoags)
  • Inhibits protein C and S (anticoags)
2
Q

Warfarin polymorphism

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

Warfarin Indications

A
  • 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
4
Q

Warfarin dosing

A
  • 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]***
5
Q

Traditional Warfarin Dosing

A
  • 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
6
Q

Newer Warfarin dosing

A

Managed by “anticoagulation specialists”

7
Q

Warfarin Monitoring

A
  • 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
8
Q

Warfarin and LMWH/UFH

A
  • Intrinsic pathway not initially altered by warfarin

- Must overlap w UFH or LMWH for at least 5d if rapid anticoag needed (VTE)**

9
Q

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

A
  • 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)***
10
Q

Warfarin Reversal: non-life threatening

A

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

11
Q

Warfarin Reversal: life threatening

A
  • I.e. intracranial: Iv vit K PLUS PCC&raquo_space; FFP
  • PCC lowers INR faster than FFP–> standard of care**
  • FFP: not concentrated form of coag proteins & [clotting factor] vary**
12
Q

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

A
  • 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
13
Q

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

A
  • 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)
14
Q

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

A
  • Reduce or skip warfarin dose. Monitor INR. Resume warfarin when INR therapeutic
  • Dose reduction may not be needed if only slightly above therapeutic range
15
Q

Warfarin drug interactions

A
  • 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
16
Q

Warfarin ADRs

A
  • 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
  • Teratogen**
17
Q

UFH MOA

A
  • Indirect thrombin inhibitor

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

18
Q

UFH indications

A
  • DVT prophy
  • Systemic anticoag (VTE tx)
  • Anticoag for ECMO/HD
  • ACS with PCI (unlabeled indication)
19
Q

UFH advantages

A
  • 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
20
Q

UFH limitations

A
  • 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
21
Q

UFH dosing

A
  • Situation dependent
  • Usually want pt 1-5-2.5x baseline aPTT
  • Optimal to get anticoagulated within 24 hrs**
22
Q

UFH monitoring

A

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

23
Q

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

A

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

24
Q

Heparin reversal

A
  • Nonurgent: turn down/stop heparin

- Urgent: Protamine by slow IV infusion

25
Q

UFH drug interactions

A

other antiplatelets, anticoags, NSAIDS–> bleeding

26
Q

UFH hemorrhage risk

A
  • 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
27
Q

Who is at risk for Heparin Induced Thrombocytopenia?

A

Pts after MAJOR surgery or trauma&raquo_space; minor surgery or medical therapy

28
Q

What is HIT?

A
  • 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)
29
Q

Dx/Tx HIT

A

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)