Anticoagulation

Question 1

why DOAC over warfarin

Answer 1

• less DDI, less or comparable bleeding, shorter duration of action compared to warfarin
• DOAC dosed based on indication and kidney/liver function, not INR
• DOAC preferred for stroke prevention in AF,
  —-> but if moderate to severe mitral stenosis or a mechanical heart valve, use warfarin
• DOAC for VTE tx
  —-> unless pt has antiphospholipid syndrome use warfarin

Question 2

antithrombin (AT)

Answer 2

body’s natural anticoagulants. it inactivates thrombin (factor IIa) and other proteases (like factor Xa).

UFH, LMWH< fonda[aromix bind to AT, cause conformational change which increases AT activity by 1,000- fold.

LMWH inhibits factors Xa more than UFH.

Fondaparinux binds to AT resulting in selective inhibition of factor Xa

Question 3

inhibiting factor Xa directly

Answer 3

apixaban (eliquis)
rivaroxaban (xarelto)

Question 4

Direct thrombin inhibitors

Answer 4

IV DTIs (e.g. agratroban) are great, do not cross-react with HIT antibodies. Dabigatran is oral DTI

Question 5

UFH

Answer 5

• fatal med errors can occur, verify concentration,
• check anti-Xa level every 6 hrs , until therapeutic
• decrease in platelets >50% from baseline suggest possible HIT
• HIT antibodies have cross-sensitivity with LMWH
• heparin lock-flushes (HepFlush) are used to keep IV lines open
• hyperkalemia

-monitor hematocrit, hemoglobin, aPTT, and platelets

• antidote: protamine

Question 6

Enoxaparin

Answer 6

Leovenox
- dose adjustment after <30….
- box warning: neuraxial anesthesia (epidural).. or spinal puncture are at risk for hematomas and subsequent paralysis
- does not require monitoring
- antidote: protamine
- do not expel air from syringe prior to injection…90% angle, abdomen 5cm/2” from umbilicus

• keep in mind it does not require monitoring but extreme body weight (high or low), renal clearance issues, and prego will need monitoring cause of altered pharmacokinetics

Question 7

Management of HIT

Answer 7

• stop heparin and LMWH
• warfarin should be d/c and vitamin k started
• for immediate tx use non-heparin anticoagulant (e.g. argatroban)
• do not start warfarin until platelet received >150,000, warfarin at a lower dose- 5mg max, overlap with non-heparin anticoagulant for 5 days min, until INR within range for 24 hrs. keep in mind argatroban can increase INR,
• if urgent cardiac surgery such as PCI, bivalirudin preferred

Question 8

Apixaban

Answer 8

Eliquis
nonvalvular AF 5mg BID
DVT/PE 10mgBID x7days, then 5mgBID
- not recommended in prosthetic heart vales or antiphospholipid syndrome
- antidont andexanet alfa
- can be crushed, mixed in water, DW or apple juice…. put on apple sauce for suspended in water for NG tube too.
-neuraxial anesthesia (epidural).. or spinal puncture are at risk for hematomas and subsequent paralysis

Question 9

Rivaroxaban

Answer 9

Xarelto
nonvalvular AF (stroke prophylaxis)
- CrCl >50 20mg w/ evening meals
- CrCl 15-50 15mg w/eveing meals
- CrCL <15 avoid use
DVT/PE
- 15mg BID, then 20daily
- CrCl< 30 avoid use
- put on apple sauce for suspended in water for NG tube
- not recommended in prosthetic heart vales or antiphospholipid syndrome
- antidont andexanet alfa
- neuraxial anesthesia (epidural).. or spinal puncture are at risk for hematomas and subsequent paralysis

Question 10

Edoxaban

Answer 10

Savaysa
- reduced efficacy in nonvalvular AF of pt CrCL >95- do not use
- put on apple sauce for suspended in water for NG tube
- neuraxial anesthesia (epidural).. or spinal puncture are at risk for hematomas and subsequent paralysis

Question 11

Fondaparinux

Answer 11

Arixtra
- contra in renal <30 CrCl
- neuraxial anesthesia (epidural).. or spinal puncture are at risk for hematomas and subsequent paralysis

Question 12

Conversion between anticoagulants
from warfarin to oral anticoagulants

Answer 12

stop warfarin and convert to:
Rivaroxaban INR <3
Edoxaban INR <2.5
Abixaban INR <2
Dabigatran INR <2

READ

Question 13

Conversion between anticoagulants
from oral Xa anticoagulants to warfarin

Answer 13

stop Xa inhibitors, start parental anticoagulants and warfarin at next scheduled dose

Endoxaban only: refer to package insert

Question 14

Conversion between anticoagulants
from dabigatran to warfarin

Answer 14

start warfarin 1-3 days before stopping dabigatran (determine renal function… and refer to package insert)

Question 15

Dabigatran

Answer 15

Paradaxa
- oral direct thrombin inhibitor
- neuraxial anesthesia (epidural).. or spinal puncture are at risk for hematomas and subsequent paralysis
- contra in pt with mechanical prosthetic heart valve
- antidote: idarucizumab (praxbind)
- swallow capsules do not admin by NG tube
- missed dose take immediately unless within 6 hours of next dose

Question 16

argatroban

Answer 16

IV direct thrombin inhibitors
- safe with HIT

Question 17

Bivalirudin

Answer 17

angiomax
- IV direct thrombin inhibitors
- safe with HIT
- use this if undergoing PCO in pt with HIT risk
-

Question 18

Warfarin

Answer 18

Coumadin, Jantoven
- do not double the dose or try to make up for the missed dose..
- contra prego unless pt w/ mechanical heart valves
- contra in tissue necrosis/gangrene, HIT

• highly protein bound. pt with hypoalbumin will have issues…
• presence of CYP2C9*2 or *3 and/or VKORC1 polymorphism gene may increase bleeding risk
• antidote: vitamin K

Question 19

Warfarin INR goal

Answer 19

INR 2-3: most indications (VTE, AF, bioprosthetic mitral valve, mechanical aortic valve, antiphospholipid syndrome)

INR 2.5-3.5: high-risk indications (mechanical mitral valve or 2 mechanical heart valves)

Question 20

warfarin CYP2C9 inducers

Answer 20

warfarin is a major substrate of CYP2C9, inducers decrease INR (includes carbamazepine, phenobarbital, phenytoin, st johns’s wart, rifampin, aprepitant, bosentan, primidone, licorice)

Question 21

warfarin CYP2C9 inhibitors

Answer 21

amiodarone, azole antifungals, capecitabine, cimentidine, fluvastatin, fluvoxamine, metronidazole, TMP/SMX, zariflukast, tamoxifen, tigecycline

when starting amiodarone, decrease the dose of warfarin by 30-50%

Question 22

general increased bleed risk with

Answer 22

NSAID, SSRIs, SNRIs

increased colting risk with estrogen, SERMs

Question 23

supplements and warfarin

Answer 23

• increased bleed risk with “the 5 G’s” (garlic, ginger, ginkgo, ginseng, glucosamine) dong quai, vitamin E, fish oils @high dose, willow bark, wintergreen oil
• decreased effectiveness: green tea, coq10, st. john’s wort, alfalfa

foods w/ high vitamin K: spinach, broccoli, brussle sprouts, cabbage, beef liver, Kale

Question 24

Warfarin tablet color

Answer 24

Pink 1mg
Lavender 2 mg
Green 2.5 mg
Brown/tan 3 mg
Blue 4 mg
Peach 5 mg
Teal 6 mg
Yellow 7.5 mg
White 10 mg

Please Let Greg Brown Bring Peaches To Your Wedding

Question 25

Warfarin Use

Answer 25

healthy outpatient, start less than 10mg for the first two days, then adjust per INR values in pt with acute DVT/PE start warfarin on the same day as parenteral anticoagulentls... continue both for minimum 5 day, and until INR >2 for at least 24 hr

Question 26

Protamine sulfate

Answer 26

IV UFH reversal- 1g will reverse 100 units of heparin (50mg max, heparin half-life is 2-2.5hrs) LMWH reversal- 1mg protamine per 1mg of enoxaparin

Question 27

Idarucizumab

Answer 27

Paxbind reversal for dabigatran

Question 28

Andexanet Alfa

Answer 28

Andexxa reversal for apixaban and rivaroxaban

Question 29

warfarin reversal

Answer 29

Vitamin K or phytonadione (mephyton): PO/IV, protect from light!, four-factor prothrombin (Kcentra): Factors II, VII, IX, X, protein C, protein S- admin with vitamin K there factor prothrombin (Profilnine): factors II, IX, and X. admin with vitamin K. FActor VIIa Recombinant (NovoSeven RT)...off label

Question 30

warfarin over anticoagulation above therapeutic bu INR <4.5

Answer 30

reduce or skip warfarin dose monitor INR

Question 31

warfarin over anticoagulation INR 4.5-10

Answer 31

vitamin K is not needed if there is no evidence of bleeding. Hold 1-2 doses of warfarin vitamin K may be used if urgent surgery is needed or bleeding risk is high <5mg, 1-2mg in 24hr...

Question 32

warfarin over anticoagulation INR >10

Answer 32

hold warfarin give oral vitamin K .25-5mg even if not bleeding. Monitor INR, resume at lower dose when INRO therapeutic

Question 33

warfarin over anticoagulation major bleed

Answer 33

give vitamin K 5-10mg by slow IV injection and four-factor prothrombin complex.

Question 34

warfarin and surgery

Answer 34

warfarin: stop 5 days before surgery LMWH: 24 hrs before UFH: 4-6 hours before

Question 35

anticoagulation for pt w/AF

Answer 35

- AF>48hr, anticoagulation for at least 3 weeks prior to and 4 weeks after cardioversion - AF<48hrs, start full therapeutic anticoagulation at presentation and continue full anticoagulation at least 4 weeks after normal sinus rhythm