Anticoagulation Management Policy

PURPOSE:

To ensure the patients at Harris Regional Hospital and Swain Community Hospital who are on anticoagulation therapyreceive safe and effective care by a structured care management program.

POLICY:

All inpatientsthat have an active order for anticoagulation therapy will be followed by pharmacy. The pharmacy service can be consulted to follow and adjust anticoagulation therapy based on patient specific factors, lab values, and indication. Order for consult must have indication listed prior to pharmacy adjustments. Pharmacy will follow attached nomograms as a guide when dosing anticoagulation therapy, which will be reviewed annually through P&T. Pharmacists may use clinical judgment to supersede doses suggested by the attached nomogram. All pharmacists dosing medications will have passed an initial competency exam provided by the designated clinical lead on this program.

PROCEDURE:

Patients at Harris Regional Hospital and Swain Community Hospital who are prescribed anticoagulation will be reviewed by the pharmacy clinical service. All patients on anticoagulation therapy will be tracked for appropriate dosing based on renal function and we will assure that PT/INR is ordered prior to warfarin initiation. Pharmacy can order baseline labs (CBC, CMP, or BMP) if not completed within the last 48 hours. Patients on Coumadin must have an INR at least every 3 days. Pharmacists will work with providers on any recommendations for improved patient care.

Providers can request pharmacy dosing consult along with providing the indication for anticoagulation. The pharmacy consult will include medication dose adjustments as stated in guidelines, ordering of pertinent lab work (PT/INR, CBC, BMP, or CMP), and patient education to include dietary considerations, drug interactions, drug-disease interactions, and signs and symptoms of bleeding/bruising or thromboembolism. Any considerations not directly discussed in the guideline for dosing anticoagulation will be discussed in collaboration with the provider and the pharmacist. Clinical judgment should supersede the dosing nomogram. At any time during the consult duration, if the drug regimen or medical condition changes, the pharmacist may order labs more frequently. The provider can request for the consult at anytime during the patients stay by writing an order for “Pharmacy to manage anticoagulation therapy,” or “Pharmacy to dose Coumadin,” or similar wording.

Pharmacy will provide discharge counseling to anticoagulation patients on an as needed basis only or when consulted by the provider to do so. Please see below for basic workflow:

Coumadin Order
Provider Dosing:
Pharmacy Assures Baseline INR; monitors for interactions
Patient will need an INR orderedat a minimum of every 3 days
Any significant interactions will be discussed with the provider
Any INR4 will have medication held that day by pharmacist, any INR > 3 nurse will call for critical lab.
Pharmacy Dosing:
Pharmacy assures baseline INR; monitors for interactions
Must have indication listed for anticoagulation from provider
Pharmacy will change dose daily based on MEC approved dosing
Provider will be called if INR >4, or signs of bleeding (included but not limited to):
Hbg drop by more than 3 g/dL, Hbg less than 8 g/dL
Platelets less than 100,000
Positive Hemoccult
Injectable Anticoagulant:
Suggest a baseline Scr, H/H, Plt, and a minimum every 5 days thereafter
Renal dose per MEC approved dosing
Heparin will follow the specific guidelines on the heparin orderset

GENERAL GUIDELINES:

Obtain Baseline PT/INR, consider other labs per anticoagulant agent.
Determine indication and target INR for patient
Determine potential drug interactions and adjust starting dose if necessary
Make sure to ask patient about any over the counter medications
Check nurses note for stool or guaiac results, character of urine (clear yellow vs. red tinged, etc), and diet for whether the patient is eating.
Usual starting dose will be 5mg. Standard time for warfarin administration is 1700 daily.
Consider factors that may increase warfarin sensitivity and adjust initial starting dose
See guidelines for a list of factors affecting Coumadin sensitivity/resistance
These may suggest a lower Coumadin starting dose such as 2.5 mg daily.
For young and healthy patients consider starting 5 mg to 10mg daily.
If patient has been on Coumadin before restart at this dose initially.
Unless admission INR is not in range without an identifiable cause
Presence of factors that may affect INR while inpatient may suggest a change
Do not initiate warfarin and contact the physician if patient is on an epidural infusion
The second day’s dose is based on response to the first dose. The prothrombin time would normally be expected to be minimal on day two. If there is a substantial prothrombin time increase on day 2, there would in turn need to be a substantial decrease in warfarin, otherwise, starting dose can be repeated per guidelines.
On day three, there may be movement of prothrombin time toward therapeutic range. If not, consider increasing dose from starting dose. If prothrombin time is supratherapeutic, consider a lower dose. On day three you have not seen the maximal effect of the first two doses.
By day five, if patient is still subtherapeutic, you should evaluate for lab error, missed doses, drug interactions, dietary or pharmaceutical vitamin K intake, and active disease states. True warfarin resistance does occur, but is quite rare.
Remember, the patient must be bridged with an injectable anticoagulant for a minimum of 5 days AND while the INR is >2 for at least 24 hours.
Anticoagulation may be seen within 24 hours due to the sensitivity of the INR to factor VII (shortest half life), but peak anticoagulation is delayed for 72-96 hours due to Factor II inhibition.

Anticoagulation Dosing Guidelines:

1.Factors Identifying Warfarin Sensitive Patients (consider lower starting dose):
Increased INR Response / Increased Bleeding Risk
Baseline INR ≥ 1.5 / Surgery within past 2 weeks
Age > 65 / Thrombocytopenia: platelet <75 K/uL
Actual body weight < 45 kg or actual < ideal / Significant hepatic disease:
cirrhosis or total bilirubin.>2.4 mg/dL
Malnourished/ NPO >3 days / Alcohol abuse history
Hypoalbuminemia <2 g/dl / End stage renal disease
Prolonged diarrhea (>3 days) / GI bleed within past 30 days
Significant drug interactions / Intracranial bleed within past 30 days
Recent alcohol binge / Medications:
Aspirin
NSAIDS
Clopidogrel
Ticlodipine
Hepatic insufficiency/Active Liver disease / Thromocytopenia
Fever (>3 days)
Decompensated heart failure or Acute HF exacerbation
Clinical hyperthyroidism

2. Factors identifyingpossible Warfarin Resistance (consider higher initial dose):

Weight >100kg
African American patients
Clinical Hypothyroidism
Medications (see chart on concomitant medications and interactions)
Heavy smoker
Chronic alcohol use

3. Medications Altering Warfarin Pharmacokinetics and Pharmacodynamics (non inclusive list)

INCREASED WARFARIN EFFECT / DECREASED WARFARIN EFFECT
Acetaminophen (high dose multiple days) / Alcohol (chronic ingestion)
Alcohol (acute ingestion) / Barbituates
Aminosalicylic acid / carbamazepine
Allopurinol / cholestyramine
amiodarone / dicloxacillin
aspirin / griseofulvin
cimetideine / nafcillin
ciprofloxacin / phenytoin
clarithromycin / Rifampin
Disulfiram / sucralfate
erythromycin / Vitamin K (tube feeds and supplements)
Fluconazole
Itraconazole
Isoniazid (600mg/day)
levothyroxine
metronidazole
omeparazole
Phenytoin (chronic)
Quinidine
sulfonylurea
Tamoxifen
Tetracycline
TMP/SMX

4. Warfarin Initiation for Naïve Patients (Target INR 2-3):

DAY OF THERAPY / INR / Dose
Day 1 / 5 mg
Day 2 / <1.5
1.5-1.9
2.0-2.5
>2.5 / 5mg
2.5mg
1-2.5mg
HOLD
Day 3 / <1.5
1.5-1.9
2.0-3.0
>3.0 / 5- 10mg
2.5-5mg
0-2.5mg
HOLD
Day 4 / <1.5
1.5-1.9
2.0-3.0
>3.0 / 10mg
5- 7.5mg
0-5 mg
HOLD
Day 5 / <1.5
1.5-1.9
2.0-3.0
3.0 / 10 mg
7.5 mg- 10 mg
0- 5 mg
HOLD
Day 6 / <1.5
1.5-1.9
2.0-3.0
3.0 / 7.5- 12.5 mg
5-10 mg
0-7.5 mg
HOLD

5. Warfarin Initiation for Naïve Patients starting dose 2.5 mg- 10mg (Target INR 2-3):

DAY OF THERAPY / INR / Dose
Day 1 / 2.5 -10 mg
Day 2 / <1.5
1.5-1.9
2.0-2.5
>2.5 / No dosage change
Decrease dose by 25-50%
Decrease dose by 50-75%
Hold next dose
Day 3 / <1.5
1.5-1.9
2.0-2.5
>2.5 / Increase dose by 0-25%
No dosage change
Decrease dose by 25-50%
Decrease dose by 50% or hold one dose
Day 4 / <1.5
1.5-1.9
2.0-2.5
>2.5 / Increase dose by 0-25%
No dosage change or increase by 10-25%
Decrease dose by 0-25%
Decrease dose by 50% or hold one dose
Day 5 / <1.5
1.5-1.9
2.0-2.5
>2.5 / Increase dose by 25%
Increase dose by 0-25%
No dosage change or decrease 10-25%
Decrease dose by 25-50%

6. Warfarin Initiation for Naïve Patients(Target INR 2.5-3.5)

DAY OF THERAPY / INR / Dose
Day 1 / 5 mg
Day 2 / <1.5
1.5-1.9
>2.0 / 5mg
0-2.5mg
HOLD
Day 3 / <1.5
1.5-1.9
2.0-2.4
>2.5 / 5- 7.5mg
5-7.5 mg
0-2.5mg
HOLD
Day 4 / <1.6
1.6-2.3
2.4- 3.0
3.1-3.4
>3.5 / 7.5-10mg
5- 7.5mg
0-7.5 mg
0-2.5mg
HOLD
Day 5 / <1.5
1.5-1.9
2.0-2.5
2.5-3.5
3.6-3.9
4- 4.4
/=4.5 / 7.5-10 mg
7.5- 10 mg
2.5-7.5 mg
2.5-5 mg
0-2.5 mg
0-1mg
HOLD

7. How to Manage Elevated INRs or bleeding in Patients receiving Warfarin:

INR / Description
INR not within range, but <5
No clinically significant bleeding /

Monitor INR every 24 hours until INR is stable
Reduce or skip warfarin dose
Resume at a lower dose when INR therapeutic (no reduction may be necessary if close to INR goal).

INR = 5-9
No clinically significant bleeding /

Monitor INR every 24 hours until INR is stable
Hold 1-2 doses of warfarin
Resume warfarin at a lower dose when INR therapeutic
Vitamin K not routinely recommended if no evidence of bleeding

INR = 5.0-9.0
No clinically significant bleeding
RAPID REVERSAL NEEDED FOR SURGERY /

Give phytonadione 1mg – 5mg PO once (reversal in 24 hours)
If INR remains high after 24 hours, repeat initial PO phytonadione dose
If INR remains high at 24 hours, may give an phytonadione 2.5 mg PO once orphytonadione 1mg IV in 50 mL of NS by slow infusion over 60 minutes (reversal 6-12 hours)

INR > 10
No clinically significant bleeding /

Repeat INR initially, monitor INR every 24 hours until INR is stable
Hold warfarin only to restart when clinically appropriate
Give Vitamin K 2.5mg- 5mg PO once, even if not bleeding
Resume warfarin at lower dose when INR therapeutic

Life-threatening bleed
OR
Serious warfarin overdose /

Hold warfarin only to restart when clinically appropriate
Mix phytonadione 10mg IV in 50mL of normal saline and administer as a slow IV infusion over 60 minutes—may repeat every 12 hours if indicated.
Consider use of FFP or Kcentra, depending on clinical urgency
Monitor INR every 2 hours

8. Recommendations for Bridge Therapy

For patients with stable therapeutic INRs presenting with a single subtherapeutic INR value, no bridge therapy with LMWH or heparin recommended
Acute DVT/PE Management:
In patients with acute DVT of the leg, we recommend early initiation of VKA (eg, same day as parenteral therapy is started) over delayed initiation, and continuation of parenteral anticoagulation for a minimum of 5 days and until the international normalized ratio (INR) is 2.0 or above for at least 24 h
In patients with acute PE, we recommend early initiation of VKA (eg, same day as parenteral therapy is started) over delayed initiation, and continuation of parenteral anticoagulation for a minimum of 5 days and until the INR is 2.0 or above for at least 24 h
Perioperative Management:
In patients with a mechanical heart valve, atrial fibrillation, or VTE at high risk for thromboembolism, we suggest bridging anticoagulation instead of no bridging during interruption of VKA therapy
In patients with a mechanical heart valve, atrial fibrillation, or VTE at low risk for thromboembolism, we suggest no bridging instead of bridging anticoagulation during interruption of VKA therapy

9. Warfarin Indications
Thrombophilia with Thromboembolic Event
Antiphospholipid Syndrome / 2.5 (2-3) / Chronic
Homozygous Factor V Leiden / 2.5 (2-3) / Chronic
Deficiency of Protein C, S or Anti-Thrombin / 2.5 (2-3) / Chronic
Atrial Fibrillation (AF)/ Atrial Flutter
CHADS2 = 0; Low stroke risk / None / May choose aspirin 75-325 mg daily
CHADS2 = 1; Intermediate stroke risk / 2.5 (2-3) / Chronic / CI anticoagulation: aspirin 75-325 mg and clopidogrel 75 mg daily
CHADS2 ≥ 2; High stroke risk / 2.5 (2-3) / Chronic / CI anticoagulation: aspirin 75-325 mg and clopidogrel 75 mg daily
With mitral stenosis / 2.5 (2-3) / Chronic / CI anticoagulation: aspirin 75-325 mg and clopidogrel 75 mg daily
With stable CAD / 2.5 (2-3) / Chronic / No aspirin needed
Pre-cardioversion (AF or flutter >48 hours) / 2.5 (2-3) / 3 weeks
Post-cardioversion (in NSR) / 2.5 (2-3) / 4 weeks
Ischemic Stroke
Non-cardioembolic stroke or TIA / None / Chronic / Use antiplatelet therapy
Cardioembolic stroke or TIA
-With warfarin CI / None / Chronic / Aspirin 81-325 mg daily
-With cerebral venous sinus thrombosis / 2.5 (2-3) / 3-6 months
- With patent foramen ovale / None / Chronic / Use antiplatelet therapy
- With other indication for
anticoagulation (VTE, AF) / 2.5 (2-3) / Chronic
Heart Valves
Mitral prosthetic / 3.0 (2.5-3.5 / 3 months, then use aspirin
Aortic prosthetic / None / Aspirin 50-100mg daily
Mechanical valve (low bleeding risk) / None / Aspirin 50-100mg daily
Aortic (caged ball or caged disk) / 3.0 (2.5-3.5) / Chronic
Aortic bileaflet or Medtronic Hall tilting disk in NSR with nk LA size / 2.5 (2-3) / Chronic
Mitral bileaflet, tilting disk, caged ball, or caged disk / 3.0 (2.5-3.5) / Chronic
VTE Treatment
VTE- transient risk factor / 2.5 (2-3) / 3 months
VTE- unprovoked / 2.5 (2-3) / At least 3 months- re-evaluate risk/benefit after 3 months treatment
VTE- second episode / 2.5 (2-3) / Chronic

10. Evaluating bleeding risk versus stroke risk:

CHADS2 Score to Estimate Stroke Risk in Atrial Fibrillation
Score / Risk of Thromboembolic Event
Congestive heart failure (1 point) / 0 / 1.9%
Hypertension (1 point) / 1 / 2.8%
Age >/= 75 years (1 point) / 2 / 4.0%
Diabetes (1 point) / 3 / 5.9%
Stroke (2 points) / 4 / 8.5%
5 / 12.5%
6 / 18.2%
HEMMORR2HAGES Bleeding Risk
Hepatic or Renal disease / Score / Bleed Rate
Ethanal abuse / 0 / 1.9
Malignancy / 1 / 2.5
Older (Age >75 years old) / 2 / 5.3
Reduced platelets / 3 / 8.4
Rebleeding risk / 4 / 10.4
Hypertension (uncontrolled) / 5+ / 12.3
Anemia
Genetic factors (CYP2C9)
Excessive fall risk
Stroke

11. Comparison of NOAC medications:

Apixiban / Dabigatran / Edoxaban / Rivaroxaban
Class / Direct selective factor Xa inhibitor / Direct thrombin inhibitor / Direct factor Xa inhibitor / Direct factor Xa inhibitor
Dosing in non valvularA.fib / 5mg PO BID
*If 2 of following: Age >=80 years, <60 kg, or Scr 1.5 give 2.5mg PO BID / 150mg PO BID
*CrCl 15-30 mL/min 75mg PO BID
*CrCl <15 -Avoid / 60mg PO daily
*CrCl 15-50 mL/min reduce to 30mg PO daily
*CrCl >95mL/min- Avoid use
CrCl <15 mL/min- Avoid / 20mg PO daily
*CrCl 15-50 mL/min give 15mg PO daily
*CrCl <15 - Avoid
Dosing PE/DVT Treatment / 10mg PO BID x 7 days, 5mg PO BID x 6 mths / 150mg PO BID
*Must treat with parenteral anticoagulant for 5-10 days first.
*CrCl<30 mL/min-Avoid / >60 kg: 60mg PO daily
<=60kg: 30 mg PO daily
*Must treat with parenteral anticoagulant for 5-10 days first.
*CrCl 15-50 mL/min reduce to 30mg PO daily / 15mg PO BID x 21 days, then 20mg PO daily x 6 months
CrCl<30 mL/min-Avoid
DVT prophylaxis / 2.5 mg PO BID / 150mg-220mg PO daily. / 10mg PO daily
CrCl <30 mL/min- Avoid
Half-life / 8-13 hours / 12-14 hours / 9-11 hours / 7-13 hours
Elimination / 25% renal, 75% fecal / 80% renal / 33% renal, 66% fecal / 67% renal (half inactive drug), 33% fecal
Major Drug Drug Interactions / Check dose with strong CYP3A4 inhibitor and P-glycoprotein inhibitor / Check dose changes with P-glycoprotein inhibitors / Check dose with P-glycoprotein inhibitors and inducers / Check dose with strong CYP3A4 inhibitor and P-glycoprotein inhibitor

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