Oral and Parenteral Anticoagulants

What is hemostasis?

The process that stops bleeding after vessel injury

What is coagulation?

The process of blood changing from liquid to solid

What factors are in the extrinsic pathway?

Factor VII

What factors are in the intrinsic pathway?

Factors XII, XI, IX

What factors are in the common pathway?

Factors X, II, I

What are natural anticoagulants in the body?

- Antithrombin

- Protein C

- Protein S

- tPA

- TFPI

What are the steps of hemostasis?

1. Vascular Spasm / Vasoconstriction

2. Platelet plug

3. Coagulation

4. Fibrinolysis

What are examples of existing clots requiring anticoagulation?

DVT, PE, atrial thrombus, LV thrombus

What are risk conditions requiring anticoagulation?

Atrial fibrillation, mechanical valve, immobilization, surgery

What is the MOA for Dabigatran?

Direct thrombin (factor IIa) inhibitor that prevents fibrin formation

What is the dosing for Dabigatran?

150 mg BID (nonvalvular AF and DVT/PE treatment)

What is a major boxed warning of Dabigatran?

Increased risk of thrombotic events with premature discontinuation

What serious bleeding risk is associated with Dabigatran?

Spinal/epidural hematoma

What is a key contraindication of Dabigatran?

Mechanical prosthetic heart valve

What renal function cutoff contraindicates Dabigatran in AF?

CrCl < 15 mL/min

What renal function cutoff contraindicates Dabigatran in DVT/PE?

CrCl < 30 mL/min

What are common side effects of Dabigatran?

Dyspepsia, gastritis-like symptoms, bleeding

What labs are monitored for safety with Dabigatran?

Hemoglobin, hematocrit, serum creatinine

What is the antidote for Dabigatran?

Idarucizumab (Praxbind)

What type of drug interactions affect Dabigatran?

P-gp interactions

What should a patient do if a dose of Dabigatran is missed close to the next dose?

Skip it (do not take within 6 hours of next dose)

What is the mechanism of action of Apixaban?

Direct factor Xa inhibitor

What is the standard dose of Apixaban for nonvalvular AF?

5 mg BID

What is the initial treatment dose for DVT/PE with Apixaban?

10 mg BID for 7 days, then 5 mg BID

What boxed warning is shared by DOACs like Apixaban?

Increased clot risk with premature discontinuation

What condition is a contraindication for Apixaban?

Antiphospholipid syndrome

When should Apixaban dose be reduced to 2.5 mg BID in AF?

If patient meets 2 of 3:

- Age ≥80

- Weight ≤60 kg

- SCr ≥1.5

What labs are monitored for safety with Apixaban?

Hemoglobin, hematocrit, LFTs, serum creatinine

What enzyme metabolizes Apixaban?

CYP3A4

What type of drug interactions affect Apixaban?

CYP3A4 and P-gp inhibitors/inducers

What is key counseling for Apixaban?

Do not double missed doses

How is Edoxaban dosed for AF?

Once daily

When is Edoxaban started for DVT/PE?

After 5-10 days of parenteral anticoagulation

When is Edoxaban contraindicated based on renal function?

CrCl > 95 or < 15 mL/min

What are common side effects of Edoxaban?

Bleeding, rash, abnormal LFTs

What is the dose of Rivaroxaban for nonvalvular AF?

20 mg once daily with evening meal

What is the initial dosing of Rivaroxaban for DVT/PE treatment?

15 mg BID for 21 days, then 20 mg daily

What boxed warning is associated with Rivaroxaban?

Increased risk of clot with premature discontinuation

What is the renal dosing cutoff for Rivaroxaban?

< 15 mL/min or < 30 mL/min depending on indication

What should a patient do if they miss a 15 mg BID dose of Rivaroxaban during initial VTE treatment (first 21 days)?

Take 2 tablets at once (30 mg total)

What is the mechanism of action of Warfarin?

Inhibits vitamin K epoxide reductase (VKORC1)

What clotting factors does Warfarin decrease?

II, VII, IX, X

What natural anticoagulants are also decreased by Warfarin?

Protein C and Protein S

Why does Warfarin not affect already activated clotting factors?

It only prevents synthesis of new factors

What is the INR goal for most patients on Warfarin?

2.0-3.0

What is the INR goal for patient's on Warfarin and have a mechanical mitral valve?

2.5-3.5

What is the baseline INR in normal patients?

0.8-1.1

What happens if INR is too low?

Increased risk of clot

What happens if INR is too high?

Increased risk of bleeding

What are the contraindications/warnings of Warfarin?

- Active bleeding

- Pregnancy (except in the presence of mechanical heart valves)

- Recent/potential eye surgery or CNS

- Unsupervised patients

When does Warfarin start to have an effect?

24-72 hours

When is full therapeutic effect reached for Warfarin?

5-7 days

What does Prothrombin Time (PT) measure?

- Time needed to create fibrin after activation of factor VII

- Measures extrinsic and common pathways

What does aPTT measure?

- Time needed to create fibrin from starting the intrinsic pathway

What is INR?

Standardized PT measurement

What is the typical starting dose of Warfarin?

5 mg daily

What starting dose of Warfarin is used in high-risk patients?

2.5 mg daily

How much should the weekly dose of Warfarin be adjusted for subtherapeutic INR?

Increase by 5-20%

How much should the weekly dose of Warfarin be adjusted for supratherapeutic INR?

Decrease by 5-20%

Why is bridging needed when starting Warfarin?

Initial inhibition of protein C/S creates a prothrombotic state

When should bridging therapy to Warfarin be continued?

At least 5 days AND until ≥2 therapeutic INRs

Does warfarin require renal dose adjustment?

No

What are serious side effects of Warfarin?

Bleeding, tissue necrosis, purple toe syndrome

What is the antidote for Warfarin?

Vitamin K and PCC (Kcentra)

What enzyme primarily metabolizes Warfarin?

CYP2C9

What happens to INR with CYP inhibitors?

INR increases (↑ bleeding risk)

What happens to INR with CYP inducers?

INR decreases (↑ clot risk)

What is the key counseling point about vitamin K intake?

Consistency is critical

What should you do if INR is below goal?

Increase dose or give booster

What should you do if INR is above goal?

Hold dose and/or decrease dose

When should INR be rechecked after dose changes?

About 1 week

How often should INR be checked after dose change?

Every 1-2 weeks

How often should INR be checked when stable?

Every 4-12 weeks

Why take Earfarin in the evening?

Easier dose adjustment after INR results

What effect does smoking have on INR?

Decreases

What effect does alcohol have on INR?

Increases

What is bridging therapy?

Using a short-acting anticoagulant when warfarin is interrupted

When is Warfarin stopped before surgery?

5 days prior

When should Warfarin be restarted after surgery?

Within 24 hours

What drugs are used for bridging?

LMWH, heparin, fondaparinux

What dose of Enoxaparin is use in bridging therapy?

1 mg/kg SC Q12H

What is the mechanism of heparin?

Activates antithrombin to inhibit thrombin and factor Xa

What dosing of heparin is used for DVT/PE treatment?

80 units/kg bolus (max 10,000 units), then 18 units/kg/hr infusion (max 2000 units/hr)

What dosing of heparin is used for VTE prophylaxis?

5000 units SC every 8-12 hours

What dosing of heparin is used for ACS (NSTEMI and STEMI)?

60 units/kg IV bolus (4000 units), then 12 units/kg/hr infusion (max 1000 units/hr)

What are the side effects for heparin?

Bleeding, thrombocytopenia, HIT, hyperkalemia

What lab monitors IV heparin efficacy?

aPTT

What alternative monitoring test can be used?

Anti-Xa levels

What is the antidote for heparin?

Protamine

What is the mechanism of LMWH?

Activates antithrombin to inhibit factor Xa > IIa

What is Enoxaparin dosing for DVT treatment?

1 mg/kg BID

What is Enoxparin prophylaxis dosing?

40 mg daily

When is anti-Xa monitoring recommended for Enoxaparin?

Pregnancy, obesity, renal impairment

What is the antidote for LMWH?

Protamine

What is the mechanism of Argatroban?

Direct thrombin inhibitor

What is Argatroban used for?

Heparin-induced thrombocytopenia (HIT)

What is the dosing for Argatroban?

Continuous infusion

What lab monitors argatroban?

aPTT

What is the mechanism of Bivalirudin?

Direct thrombin inhibitor

What Bivalirudin commonly used for?

HIT and PCI