Anticoagulation II Dr. Covert

Question 1

How is Warfarin reversed?

Answer 1

With bleeding:
Vitamin K 10 mg IV over 30 min + Fresh frozen plasma (15-30 ml/kg)
OR
Prothrombin Complex Concentrate (25-50 IU/kg)

Without bleeding -> INR > 10
Vitamin K oral 2.5 - 5 mg, close outpatient follow

Without bleeding -> INR: 4-10
Interrupt warfarin, close follow
consider oral Vitamin K oral 1 - 2.5 mg in patients with high risk for bleeding

Question 2

Signs of bleeding

Answer 2

-Low hemoglobin (normal: male = 13 female = 12)
-other signs: blood vomiting, blood in urine, bruising

Question 3

DOACS agents
Direct-acting oral anticoagulants

Answer 3

-Xa-inhibitors
Apixaban (Eliquis)
Rivaroxaban (Xarelto)
Edoxaban (Savaysa)

-Direct Thrombin Inhibitors
Dabigatran (Pradaxa)

Question 4

MOA of Xa inhibitors
Onset, duration

Answer 4

-blocking Factor Xa (do not rely on ATIII)

-Onset:
Apixaban (Eliquis): 3-4 h
Rivaroxaban (Xarelto): 2-4 h

-Duration:
Apixaban (Eliquis): 12h
Rivaroxaban (Xarelto): 5-10h

Question 5

How are Xa inhibitors metabolized?

Answer 5

-Metabolism -> Liver (3A4, 2C8, 2C9, 2C19); PGP;
-Renal clearance

Question 6

DDI of Xa inhibitors, monitoring and reversal

Answer 6

-Phenobarbital
-Phenytoin
-Primidone
-Carbamazepine

-no monitoring

-reversal: KCentra/ PCC + Andexanet Alfa (Andexxa)

Question 7

MOA for Dabigatran (Pradaxa)

Answer 7

-direct inhibition of Prothrombin (factor II)
-Onset: 1h
-Duration: 12-14h

Question 8

Metabolism and clearance of Dabigatran

Answer 8

-Metabolism: Hepatic (3A4, 2C8, 2C9, 2C19); PGP;
-Renal clearance

Question 9

DDI of Dabigatran, monitoring and reversal

Answer 9

-Phenobarbital
-Phenytoin
-Primidone
-Carbamazepine

-no monitoring

-reversal: Praxbind (idarucizumab)/ + PCC

Question 10

Which of the DOACS require bridging in a full dose treatment?

Answer 10

-Dabigatran
-Edoxaban

Question 11

Dosing (Full dose) Dabigatran

Answer 11

VTE: 150 mg PO BID (after 5d of parental anticoagulation, BRIDGING)

NVAF: 150 mg PO BID

Question 12

Dosing (Full dose) Edoxaban

Answer 12

VTE: 30-60 mg PO daily (after 5d of parental anticoagulation, BRIDGING)

NVAF: 30-60 mg PO daily

Question 13

Dosing (Full dose) Rivaroxaban
!!!

Answer 13

VTE: 15 mg PO BID X 21 d, 20 mg PO daily
NVAF: 15-20 mg PO daily

Question 14

Which DOAC should be taken with food?

Answer 14

Rivaroxaban
increases the absorption

Question 15

Dosing (Full dose) Apixaban
!!!

Answer 15

VTE: 10 mg PO BID X 7 d, 5 mg PO BID thereafter
NVAF: 2.5-5 mg po BI

Question 16

Monitoring of DOACS

Answer 16

-N/A
-there might be changes in aPTT, Xa, and INR but are not clinically meaningful

Question 17

How would Carbamezapine affect Rivaroxaban concentration?

Answer 17

Carbamazepine is a CYP3A4 inducer -> more CYP metabolism of Rivaroxaban -> less available -> we would need to increase the dose, but there is no way to check for appropriate levels

-> change to Warfarin PO -> start on a higher dose 6.5 mg and check INR after 5d (bridging needed)

Question 18

Can DOACS be used for prophylactic treatment?

Answer 18

Only for post-orthopedic surgery (fe hip replacement), not general medicine

-Apixaban: 10 mg PO daily
-Rivaroxaban: 2.5 mg PO BID

Question 19

Titrating Warfarin down

Answer 19

Hold Warfarin for 1 day then start the new dose + give Vitamin K (10 mg IV when bleeding, 2.5 - 5 mg PO daily with no bleed)

Question 20

Which Anticoagulants require bridging?

Answer 20

Oral Anticoagulants:
Warfarin

Direct Anticoagulants (DOACS):
Dabigatran
Edoxaban

Question 21

What if the patient took a dose of enoxaparin and eliquis?

Answer 21

-reverse with andexxa for eliquis???
-reverse with Protamiine???