McDanel Anticoagulation

Venous Thromboembolism (VTE)

Blood clot forming in a vein

Virchow’s Triad - physiologic changes in any of 3 factors increases risk for thrombosis

Decreased blood flow, changes in intrinsic properties of blood, and vessel injury/inflammation

Treatments for VTE

DOACs are preferred

Rivaroxaban or apixaban alone

Dabigatran or edoxaban AFTER 5-10 days parenteral agnet

Warfarin (goal INR 2.0-3.0) + LMWH/heparin for > or = 5 days

Duration of DOACs treatment??

3 months ONLY

PROVOKED by major or minor transient risk factors

Duration of Warfarin treatment??

At least 3 months and then extended-phase

\-unprovoked

\-provoked by a persistent risk factor

Atrial Fibrillation/Flutter (AF)

Irregular contraction of atria → blood pooling → clot formation → embolism → stroke

Most common cardiac rhythm disorder

Men > Women

Do you use a DOAC for a mechanical heart valve?

No dumbbass

Mechanical Heart Valves Require what?

Lifelong warfarin

Bioprosthetic Valve

3-6 months: Aspirin 75-100mg/d or Warfarin (INR 2.5)

If pt has Afib then lifelong and must use warfarin or DOAC based on CHA2DS2-VASc

Which valve has a greater risk of thrombosis? Mitral or Aortic?

Mitral valve!! Much more thrombogenic blood is much more likely to fill as it deals with diastole

Treatment of Thrombus - DVT and PE

All oral agents approved - DOACs preferred

If use of warfarin INR target 2.0-3.0

Duration: All at least 3 months

Prevention of Stroke- AF and Heart Valves

AFib/Flutter all oral agents approved

DOACs preferred

Warfarin (INR goal 2.0-3.0 maintain TTR > 70%

Mechanical Valves

Warfarin ONLY - with INR range depending on position of valve

INR 2.0-3.0 if aortic valve without risk factors

INR 2.5-3.5 if mitral valve or aortic valve with risk factors

Duration: indefinitely (all valves and most AF)

Steady State for Dabigatran

2-2.5 days

Steady State for Apixaban

2-3 days

Steady state for Edoxaban

2\.5-3 days

Steady State for Rivaroxaban

one to two days

Steady State for Warfarin

10-14 days

Renal Elimination of Dabigatran

80%

MOA of Warfarin

Interferes with conversion of vitamin K to antagonize the production of vitamin K dependent clotting factors

MOA of Dabigatran

IIa inhibitor

Inhibits both clot-bound and circulating thrombin (Factor II)

It’s a prodrug

Indications of Dabigatran

Risk reduction of stroke and systemic embolism in non-valvular AFib

Treatment and risk reduction of recurrence of DVT and PE - ADULT AND PEDS (8-17 yo)

Prevention of VTE in total hip replacement surgery

Apixaban

Xa inhibitor

Oral, direct, selective Factor Xa inhibitor

Indications for Apixaban

Risk reduction of stroke and systemic emobolism in NON-VALVULAR AFib

Treatment of DVT and PE

Risk reduction of recurrence of DVT and PE following > or = 6 months of therapy

Prevention of VTE in total hip and knee replacement surgery

Rivaroxaban

Xa inhibitor

Oral, direct, selective Factor Xa inhibitor

Indications for Rivaroxaban

Decreased stroke/systemic embolism risk in non-valvular atrial fibrillation

Treatment and recurrence risk reduction after 6 months of DVT and PE

ADULTS AND PEDS (BIRTH TO

Normal Dosing for Warfarin

Daily

For VTE: Plus > or = 5 days LMWH

Renal Dosing for Warfarin

No

Reversibility of Warfarin

Vitamin K, Kcentra

Pregnancy for Warfarin

Nada don’t do it, bad for babies

Normal dosing for Dabigatran

150mg BID

VTE: After > or = 5 days LMWH

Peds: Weight-based see PI

Renal Dosing for Dabigatran

AF: CrCl 15-30 → decrease 50%

VTE: CrCl

Reversibility for Dabigatran

Praxbind ( Idarucizumab)

Pregnancy for Dabigatran

Level C

Normal Dosing for Apixaban

5 mg BID

VTE: 10mg BID for 7 days

Renal Dosing for Apixaban

AF: ABCs > or = 2 → Decrease 50%

A: Age > or = 80 years

B: Body Weight is < or = 60 kg

C: SCr > or = 1.5 mg/dL

VTE: No

Reversibility of Apixaban

Andexxa (recombinant Factor Xa)

Pregnancy for Apixaban

Level B

Normal Dosing for Rivaroxaban

20 mg daily (BID some)

VTE: 15mg BID x 3 weeks

CAD/PAD: 2.5 mg BID + ASA 81mg/d

Med III 10mg/d x 31-39 days

Peds: Weight-based see PI

Renal Dosing for Rivaroxaban

AF: CrCl < or = 50 → Decrease 25%

CrCl < or = 15,

Reversibility of Rivaroxaban (Xarelto)

Andexxa (recombinant factor Xa)

Pregnancy level for Rivaroxaban

C

Administration Specifics of Warfarin

With or without food

Crushing: Allowed

Generally in the evening for adjusting the INR

Administration Specifics for Dabigatran (Pradaxa)

With or without food

Swallow whole

MUST be in original bottle/blister pack

Not in MED BOXES

Administration Specifics for Apixaban

With or without food

Administration Specifics for Rivaroxaban (Xarelto)

AFib: Evening meal

VTE: with food

Crushing is allowed

Monitoring for Warfarin

INRs and CBC

Monitoring for Dabigatran

Renal Function

CBC/LFTs

Monitoring for Apixaban

Renal Function

CBC/LFTs

Monitoring for Rivaroxaban

Renal Function

CBC/LFTs

Adverse Effects for Dabigatran

Bleeding and Dyspepsia (tartaric acid)

All other DOACs just have bleeding as an adverse

Anticoagulation Initiation with Parenteral agent (LMWH or Heparin)

\+ Warfarin = > or = 5 days AND for warfarin INR > 2.0 for 24 hours

OR

After > or = 5 days add dabigatran 150mg BID with Edoxaban 60 mg daily

Anticoagulation Initiation with Rivaroxaban

15mg BID for 21 days then decrease to 20 mg daily for 21 days

Anticoagulation Initiation with Apixaban

10mg BID for 7 days then decrease to 5 mg daily for 7 days

What effects the onset of action for Warfarin

Depends on vitamin K-dependent clotting factors half life

Onset of action for Warfarin

Protein C and factor VII decline rapidly (12-24 hrs)

Factors IX and X do not occur for 4-6 days

Reduction in Factor II is the most delayed, > 6 days

2-7 days on Initial effect on INR

10-14 days for steady state

Initial Monitoring for INR

2 to 3 days after starting → 2 to 3 times per week for 1 to 2 weeks → Periodically thereafter

FIRST WEEK after initiation INR Increase what happens?

0\.1 to 0.2 levels per day

What are the most common foods with vitamin K

Green, leafy vegetables

Factors that lead to increase in INR values

Alcohol Binge

Medication Changes

Decreased dietary vitamin K intake

Acute illness, persistent fever, and/or diarrhea

Signs of bleeding

Significant weight loss

Factors that lead to Decreased INR changes

Missed doses

Medication changes

Increased dietary vitamin K

New vitamins

Signs of clotting or stroke

Weight gain

Managing High out of Range INR

If NOT bleeding:

One time decrease OR Decrease dose 5-15% and/OR

Hold Doses:

> 1 pt above → hold one dose

> 2 pts above → hold 2 doses

3-5 held doses reverses INR

Excessive INRs > or = 4.5 BLEEDING see reversal of warfarin

RECHECK INR < or = 2 weeks

Managing Low INR

If Missed Dose: Give boost and/or resume normal dose

If consistent change/unknown etiology:

Increase dose by 5-15% and/or Give extra one-half to full dose

Recheck INR < or = 2 weeks

INR Bleeding < 4.5

Omit or lower dose

No dose change if minimally above

INR NO Bleeding 4.5 to 10

Omit 1-2 doses + resume at lower dose when INR in range

Suggest AGAINST routine use of vitamin K

INR No Bleeding > 10.0

Hold warfarin therapy AND give oral vitamin K

\*Dose of vitamin K not defined in the guidelines, most likely oral vitamin K 2.5 - 5 mg per past recommendations

Any Bleeding - Major Bleeding

Hold Warfarin AND rapid reversal with four-factor prothrombin complex concentrate (PCC) instead of FFP ADD vitamin K 5 to 10 mg IV suggested over PCC alone

Induction of Metabolism for Warfarin

Induction of CYP2C9 that metabolizes (S)-warfarin

Synthesis of new drug-metabolizing enzymes

Induction of Metabolism for Warfarin

Decreased INR - upon discontinuation INR increases

Onset: GRADUAL

Few days to 1-2 weeks

Dissipation: 1-2 weeks

Examples for induction for warfarin

Rifampin, Nafcillin, Dicloxacillin, carbamazepine, phenytoin, barbiturates

Examples of Medications Able to Increase INR

Levothyroxine: Increases catabolism of clotting factors

Salicylates (ex: Pepto-bismol, aspirin) and Quinidine

* Decreases production of clotting factors

Examples of what decreases INR values

Propylthiouracil/methimazole

* Reduces circulating thyroid hormone - concentrations → decrease catabolism of clotting factors

\

NSAIDs, Aspirin, Clopidogrel, ticlopidine, ticagrelor, and prasugrel

Drugs that impair platelet function increase bleeding, especially GI bleeds

No effect on INR

Acetaminophen

Salsalate (an non-acetylated salicylate) has minimal effects on platelets and is less likely to cause gastric erosions

No effect on INR

Which antibiotics are Safe for Warfarin

MOST penicillins and cephalosporins

Antibiotics that Increase INR

Unknown: Moxifloxacin and tetracycline

Inhibition: Ciprofloxacin and metronidazole and Bactrim

Antibiotics that May Increase INR - more common in elderly

Azithryomycin, clarithromycin, doxycycline, erythromycin, and levofloxacin

Antibiotics that decrease INR levels

Inductions: Dicloxacillin, nafcillin, rifampin

Herbal and Natural Products

Increase INR: CBD

Decrease INR: Coenzyme Q-10, St. John’s Wort, green tea

Increased bleeding: Garlic, Ginkgo, Ginseng

Alcohol consumption for women and men

1 a day for women and 2 a day for men

Adult ACUTE VTE treatment: Rixaroxaban

21 days: 15mg BID

21 days to 6 months 20mg daily

>6 months/Ongoing 10mg daily (optional\*)

\

Adult ACUTE VTE treatment: Apixaban

7 days: 10mg BID

7 days to 6 months: 5 mg BID

>6 months/ Ongoing: 2.5 mg BID (optional\*)

Adult Acute VTE treatment: Dabigatran

Parenteral Anticoagulant: 5 to 10 days FIRST

Dabigatran: 150 mg BID

Adult ACUTE VTE Treatment

Parenteral Anticoagulant 5 -10 days FIRST

Edoxaban 60mg daily

Risk of Recurrence Reduction: Dabigatran

150mg BID (if CrCl > 30ml/min)

\*After previous treatment

Other dosing for Dabigatran

75mg BID:

P-gp inhibitor AND CrCl 30-50 ml/min

AVOID:

P-gp inhibitor AND CrCl < 30 ml/min

Renal Dosing (ml/min) for Dabigatran

CrCl < 30: DO NOT USE

Risk Recurrence Reduction: Apixaban

2\.5 mg BID

\*After > or = 6 months

Other Dosing for Apixaban

2\.5 mg BID

\-Strong dual P-gp/CYP3A4 inhibitors

AVOID if taking 2.5 mg BID already

Renal Dosing (ml/min) for Apixaban

No dose adjustment

Other dosing for Edoxaban

30mg daily:

< or = 60 kg

On certain P-gp inhibitors

Renal Dosing for Edoxaban

CrCl 15-50: 30 mg

CrCl < 15 : AVOID Risk

Risk of Recurrence Reduction for Rivaroxaban

10 mg daily (with or without food)

* After > or = 6 months

\

Renal Dosing for Rivaroxaban

CrCl < or = 15: AVOID

Normal AFib Dosing for Dabigatran

150mg BID

Normal AFib dosing for Apixaban

5 mg BID

Normal AFib Dosing for Edoxaban

60 mg daily

Normal AFib Dosing for Rivaroxaban

20mg daily with even meals

Renal AFib Dosing (CrCl in ml/min) for Dabigatran

CrCl 15-30: 75 mg BID

CrCl < 15 or Dialysis: AVOID

Renal AFib Dosing (CrCl in ml/min): Apixaban

2\.5 mg BID ONLY if > or = to 2 of the followng:

A: Age > or = 80 years of age

B: Body weight < or = 60 kg

C: Serum Creatinine > or = 1.5 mg/dL