Anticoagulation

Question 1

Warfarin inhibits…

Answer 1

• Factor II
• Factor VII
• Factor IX
• Factor X

Question 2

Direct Xa Inhibitors

Answer 2

• RivaroXAban
• ApiXAban
• EdoXAban

Question 3

Indirect Xa Inhibitor

Answer 3

Fondaparinux (SQ)

Question 4

Heparins and Where They Work

Answer 4

• Unfractionated, UFH (equal Xa and IIa activity)
• LMWH - Enoxaparin, Dalteparin (More Xa than IIa activity)
• Work via antithrombin

Question 5

Direct Thrombin Inhibitors

Answer 5

• IV: Argatroban, Bivalirudin

- PO: Dabigatran

Question 6

UFH Dosings

Answer 6

• VTE Prophylaxis: 5000u SQ Q8-12H
• VTE Treatment: 80u/kg bolus IV, 18u/kg/hr infusion (continuous, short half life)
• ACS/STEMI Tx: 60u/kg IV bolus, infuse 12u/kg/hr
• TBW for dosing!!!
• HIT antibodies cross react with LMWH

Question 7

UFH Information

Answer 7

• SE: HIT (platelets drop >50% from baseline, thrombocytopenia), hyperkalemia, osteoporosis with long-term use
• Monitor: aPTT and anti-Xa level - check Q6H
• aPTT should be between 1.5-2.5 * control
• CAUTION: fatal errors associated with Heparin lock-flushes dosing mix-ups (10x dose. used to keep lines open)
• Antidote: protamine
• Unpredictable anticoagulation response

Question 8

LMWH VTE Dosing

Answer 8

• VTE Prophylaxis: 30 mg SQ Q12H or 40 mg QD
• VTE Tx: 1 mg/kg SQ Q12H or 1.5 mg/kg SQ QD (inpatient only, pref. anticoag for cancer pts)
• CrCl < 30: lower dosing option at Q24H
• TBW for dosing!!!

Question 9

LMWH STEMI Dosing

Answer 9

• Pts < 75 yo: 30 mg IV bolus + 1 mg/kg SQ dose (then Q12H) Only indication for IV administration
• CrCl < 30: same as above except dose is given QD instead of Q12H OR 1mg/kg SQ QD with no bolus
• Patient’s over >=75 yo don’t get bolus
• TBW for dosing!!!

Question 10

LMWH Information

Answer 10

• Boxed warnings: neuraxial anesthesia => hematoma and paralysis risk
• CI: HIT history
• Anti-Xa monitoring only recommended in pregnancy (obtained 4 hours after SQ dose, peak)
• Antidote: protamine
• Don’t expel bubbles from syringe

Question 11

Apixaban Dosing

Answer 11

• Nonvalvular Afib (NVAF): 5 mg PO BID
• IF patient is 2 of following: >= 80 yo, BW =< 60 kg, or SCR >=1.5 then 2.5 mg PO BID for Afib
• DVT/PE Tx: 10 mg PO BID x 7 days then 5 mg PO BID (preferred in pts w/o cancer)

Question 12

Rivaroxaban Dosing

Answer 12

• Doses >= 15 mg need to be taken with food
• Take Afib doses with evening meals
• DVT/PE Tx: 15 mg PO BID x 21 days then 20 mg PO QD with food
• Avoid use in CrCl < 30

Question 13

Rivaroxaban Missed Doses

Answer 13

• If taking 15 mg BID, take two tablets immediately to ensure 30 mg/day, then back to scheduled dosing
• If taking 10/15/20 mg QD: take immediately the same day, otherwise skip

Question 14

Edoxaban

Answer 14

• Direct Xa Inhibitor
• Don’t use if CrCl > 95 (reduced efficacy)
• Start after 5-10 days parenteral anticoagulation

Question 15

DOAC Information

Answer 15

• Boxed Warning: Neuraxial anesthesia => risk of hematomas/paralysis
• Not recommended for prosthetic heart valves or antiphospholipid syndrome
• Antidote: Andexanet alfa (Andexxa) - for Eliquis and Xarelto
• Avoid taking with bleed risk drugs (SSRIs, SNRIs, NSAIDs, herbals) and CYP3A4i

Question 16

Fondaparinux

Answer 16

• Indirect Xa Inhibitor
• Boxed Warning: neuraxial anesthesia => hematoma and paralysis
• CI: severe renal impairment (CrCl < 30)

Question 17

Warfarin to Oral Anticoagulant

Answer 17

Stop Warfarin to switch to:

• Rivaroxaban when INR < 3
• Edoxaban when INR =< 2.5
• Apixaban when INR < 2
• Dabigatran when INR < 2

Question 18

Oral Anticoagulants to Warfarin

Answer 18

• Overlap Xa with warfarin until INR is therapeutic (for 5 days AND INR >=2 for at least 24 hours)
• Stop Xa inhibitor and warfarin at next dose

Question 19

Dabigatran to Warfarin

Answer 19

• Start warfarin 1-3 days before stopping dabigatran

- Determined by renal function

Question 20

Dabigatran Dosing

Answer 20

• Direct Thrombin Inhibitor (oral)
• Dispense in original container and discard 4 mo after opening
• Swallow capsules whole, NO NG TUBE
• Take missed dose immediately unless next dose is within 6 hours, then skip (don’t double)

Question 21

Dabigatran Information

Answer 21

• Boxed Warning: Neuraxial anesthesia => hematoma and paralysis
• CI: mechanical, prosthetic heart valves
• SE: Dyspepsia, gastritis-like sxs, bleeding (including GI)
• No monitoring required
• Antidote: idarucizumab (Praxbind)

Question 22

IV Direct Thrombin Inhibitors

Answer 22

• Argatroban and Bivalirudin (Angiomax)
• Used in patients at risk for HIT
• No cross-reaction with HIT-antibodies
• No antidote

Question 23

Warfarin Dosing

Answer 23

• 10 mg QD for 2 days in health outpatient then adjust per INR
• Lower dose (=<5 mg) for elderly, malnourished, CYP inhibitors, liver disease, HF, or high risk bleeders
• S-enantiomer is 2.7-3.8x more potent
• Don’t double doses if missed, take immediately same day or skip

Question 24

Warfarin Information

Answer 24

• CI: Preggo UNLESS mechanical heart valve
• Warning: tissue necrosis/gangrene, HIT, presence of CYP2C9 2/3 alleles or VKORC1 gene
• SE: Purple toe syndrome, bleed, bruise, necrosis
• Higher INR goal (2.5-3.5) for mechanical mitral or 2+ mechanical valve patients
• Antidote: Vitamin K

Question 25

CYP2C9 Inducers

Answer 25

Decrease INR - Rifampin (large decrease) - PS PORCS - Aprepitant - Bosentant

Question 26

CYP2C9 Inhibitors

Answer 26

Increase INR (MAT) - M: Metronidazole and macrolides - A: Amiodarone and azoles (Fluconazole) - T: TMP/SMX

Question 27

Warfarin DDI

Answer 27

- NSAIDs, antiplatelet agents (clopidogrel), other anticoagulants, and SSRIs/SNRIs increase bleeding risk but not INR - Estrogen and SERMs increase clotting risk

Question 28

Natural Medicines + Warfarin

Answer 28

INCREASE bleeding risk - 5 Gs (garlic, ginseng, ginkgo, ginger, and glucosamine) - Vitamine E - Dong quai - Fish oils (high dose) - Willow bark (natural salicylate) - Wintergreen oil DECREASES Warfarin Efficacy -St. John's Wort

Question 29

Protamine

Answer 29

- Antidote for UFH/LMWH - 1mg of protamine reverses ~100u of heparin - Reverse amount given in last 2-2.5 hours - Max dose: 50 mg - 1:1 for LMWH, only reverse last 8 hours

Question 30

Kcentra

Answer 30

``` -Four Factor Prothrombin Contains: -Factor II -Factor VII -Factor IX -Factor X -Protein C -Protein S ``` -Administer with Vitamin K (usually IV) for warfarin reversal with major bleeding

Question 31

Phytonadione

Answer 31

- Vitamin K, warfarin antidote - Given IV or PO (1-10 mg) - Boxed warning: hypersensitivity (anaphylaxis) - Requires light protection - SQ has variable absorption and IM has risk of hematoma - Don't reverse until INR > 10 and/or bleed (w/o bleed use oral)

Question 32

HIT

Answer 32

- Diagnosis: PLT drop >50% - IgG reaction - Risk for UFH and LMWH (cross-reactive between meds)

Question 33

Praxbind

Answer 33

- Idarucizumab | - Antidote for Pradaxa (dabigatran)

Question 34

Angiomax

Answer 34

- Bivalidurin - Injectable direct thrombin inhibitor (IV) - Mainly used/seen in cardiac/cath. labs

Question 35

Warfarin Colors

Answer 35

``` Please Let Greg Brown Bring Peaches To Your Wedding: P: Pink - 1 mg L: Lavender - 2 mg G: Green - 2.5 mg B: Brown - 3 mg B: Blue - 4 mg P: Peach - 5 mg T: Teal - 6 mg Y: Yellow - 7.5 mg W: White - 10 mg ```

Question 36

Andexxa

Answer 36

- Andexamet alfa | - Antidote for xarelto and rivaroxaban (ONLY)