Drugs Affecting Hemostasis: 2) Anticoagulants

Question 1

Anticoagulants

Answer 1

• Affect body’s ability to form a platelet plug
• Vitamin K antagonists
• vitamin K is needed to make clotting factors
• decreases activity of clotting factors II, VII, IX, X and protein C (endogenous anti-coagulant) and protein S
• clotting factors & bone (osteoblasts/osteoclast)
• activity sensitive to dietary vitamin K- consistent intake is essential

Question 2

Warfarin (Coumadin) 
Rivaroxaban (Xarelto)
Edoxaban (Savaysa)
Apixaban (Eliquis) 
Fondaparinux (Arixtra) 
Dabigatran (Pradaxa) 
-idarucizumab (praxbind-antidote) 
Hirudin derivatives: Leprirudin, Desirudin, Bivalrudin

Answer 2

Anticoagulants

Question 3

Warfarin (Coumadin)

General info

Answer 3

Oldest and most widely used

• PO
• prefects body’s recycling of Vitamin K
• works on clotting factors II and X (in normal cascade)
• paired with heparin: works immediately

Question 4

Warfarin (Coumadin)

MOA

Answer 4

• blocks the formation of Vitamin K dependent clotting factors: II, VII, IX, X, protein C and S
• prevents bodies recycling of Vitamin K
• works on clotting factors II and X

Question 5

Warfarin (Coumadin)

Monitoring information

Answer 5

Monitoring required
-INR blood test (target 2-3) 
⬆️ INR= blood is very thin
⬇️ INR= blood is thick (no warfarin present) 
* highly individualized 
* metabolism is complicated

Question 6

Warfarin (Coumadin)

Risks/cautions

Answer 6

• high drug inx risk
• dietary restrictions: green leafy veg, livers and K supplements
• takes a long time to start dosing
• NO antidote

Question 7

Warfarin (Coumadin)

Adverse effects

Answer 7

Bleeding
Purple toe syndrome
Skin necrosis
Osteoporosis (long term use)

Question 8

To reverse the effects of warfarin if the blood is too thin?

Answer 8

Give vitamin K
Eat a salad
Give fresh frozen plasma

Question 9

Rivaroxaban (Xarelto) 
Edoxaban (Savaysa)
Apixaban (Eliquis)
Fondaparinux (Anitra) 
Dabigatran (Pradaxa) 
Hirudin derivatives: Leprirudin, Desirudin, Bivalrudin 
Argatraban

Answer 9

2nd, 3rd line therapy options
Work right away
* cause more bleeding than warfarin
* much more predictable in effectiveness= low variability patient to patient

Question 10

Rivaroxaban (Xarelto)

Answer 10

Specific Xa inhibitor

• PO, variable bioavailability
• some drug inx risk
• bleeding- avoid 6-8 hrs after surgery
• caution with renal dysfunction

Question 11

Edoxaban ( Savaysa)

Apixaban (Eliquis)

Answer 11

Specific Xa inhibitors

• PO
• drug inx risks
• sensitive to renal fxn
• role in therapy uncertain

Question 12

Fondaparinux (Arixtra)

Answer 12

Specific Xa inhibitor

• injectable
• eliminated renally
• bleeding: avoid 6-8 hrs after surgery
• caution with renal fxn

Question 13

Dabigatran (Pradaxa)

Answer 13

Direct thrombin inhibitor
PO
* use/discard after 120 days after opening container
-sensitive to humidity: ⬇️ drug effectiveness
-given in manufacture container or blister packs
* do not crush, chew or open capsules

Question 14

Dabigatran (Pradaxa)

Answer 14

Drug inx risk

Sensitive to renal fxn

Question 15

Antidote for Dabigatran ( Pradaxa)?

Answer 15

Idarucizumab (praxbind)

• binds to Dabigatran in blood and inactivates it
• specific to Dabigatran
• can receive Dabigatran in 24 hrs

Question 16

Hirudun derivatives: Leprirudin, Desirudin, Bivalrudin

Answer 16

• injectable
  Direct thrombin inhibitor
• irreversible IIa inhibitors
  Renal elimination

Question 17

Argabatran

Answer 17

Direct thrombin inhibitor (IIa)
* injectable
Small synthetic: can bind to IIa in clot
Hepatic metabolism

Question 18

Heparin: unfractionated heparin (UFH)

MOA

Answer 18

Enhance the actions of antithrombin 
-anti Xa, IIa 
-unfavorable PK: variable dose-dependent absorption 
-onset 1-2 hrs 
-dose dependent t1/2: 30-90 min 
Renal metabolism and elimination

Question 19

UFH

Answer 19

Molecules are all different lengths
Each size works differently: more mechanisms than LMWH
* active against clotting factor Xa and IIa (thrombin)

Question 20

Heparin

Monitoring and risks

Answer 20

A PTT- many limitations

• anti Xa activity
• heparin concentration (0.3-0.7 units/mL)
• Bleeding: heparin induced thrombocytopenia
• osteoporosis with long term use

Question 21

LMWH

Answer 21

Short chained- more consistent in length 
MOA: enhance actions of antithrombin 
* more predictable PK and effects 
-primarily renal elimination 
-weight based dosing( even in obese PTs) 
* monitoring is less necessary 
* lower risk of bleeding 
* lower variability from pt to pt

Question 22

What alter UFH and LMWH variability?

Answer 22

Weight and renal fxn