(2009 update)

 

 

 

ANTICOAGULATION CLINIC GUIDELINE

Contents

Chapter 1

Chapter 2

Chapter 3

Chapter 4

Chapter 5

Chapter 6

Chapter 7

Chapter 8

Patient Warfarin Booklet (Thai)

Patient Warfarin Personal Book (Thai)

 

Introduction

This guideline was prepared for outpatient Warfarin (Coumadin) management, related to cardiology work such as atrial fibrillation and prosthetic heart valve. Other conditions are briefly included.

This guidelines was first prepared in 2001, for Central Minnesota Heart Center Anticoagulation Clinic. There was an 2004 updated. In 2007 this guidelines has inserted ethnic difference information in few appropriate areas, to be the guidelines for Bangkok Hospital Anticoagulation Clinic program. It follows the major anticoagulation guidelines, i.e. 8th ACCP Consensus Conference on Antithrombotic Therapy (Chest 2008), ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation and ACC/AHA 2006 practice Guidelines for the Management of Patients with Valvular Heart Disease. Some other databases are also listed in the bibliography section. Database on ethnic difference is limited at the present time.

It is expected that physicians may choose different approaches in certain patients for various reasons, however uniform practice will make the anticoagulation clinic run more efficiently.

 


Chapter 1

Warfarin

  1. Long half-life of 20 - 60 hours. The mean half-life is approximately 40 hours. The duration of effect is 2 - 5 days. The maximum effect of a dose occurs up to 48 hours after administration, and the effect last for the next 5 days. Steady State requires 5-7 days.
  2. Blocking hepatic biosynthesis of the Vitamin K dependent anticoagulation factors. These include Factor II (42-72), Factor VII (4-6), Factor IX (21-30), Factor X (27-48), Protein C (8), and Protein S (30).
  3. Indications (Indications are in Target INR chapter).
  4. Contraindication.
  5. Adverse effects.

Average Daily Dose

There are differences among various ethnic

About 4-5 mg/day or 28-35 mg/week for caucasian for target INR of 2.5 (2.0-3.0)

About 3-4 mg/day or 21-28 mg/week for Pacific-Asian (exclude caucasian in this region). This dose will be less if INR level is recommended at <2.0.

Factors Effecting the Daily Dose

  1. Age ( For caucasian)
  2. Genetic. Hereditary warfarin sensitive and resistance.
  3. Medicine noncompliance.
  4. Drugs interaction, including herbal medicine.
  5. Concurrent illness, fever, diarrhea, post op major surgery (i.e.. heart valve replacement), malignancy, lupus anticoagulants.
  6. Impaired liver function, CHF with liver congestion.
  7. Food effect, vitamin K intake, alcohol.
  8. Hyperthyroidism, renal disease.
  9. During heparin and direct thrombin inhibitors treatment.

Tablet Size

Warfarin tablets ( Click here to view warfarin tablets)

Treatment monitoring

Standard

Traditionally patients come into the clinic (or the hospital) to have venous blood drawn for routine laboratory INR determination.

Point of Care

Finger tip capillary blood can be used with small, light weight and portable instruments. The clinical trials result have compared favorably with traditional INR determination.

Use in anticoagulation clinic.

Home use or Patient Self Test (PST)

Point of Care Instruments

InstrumentCompanySample Type
CoaguChekRoche Diagnostics Corp. Indianapolis, IN
http://www.coaguchek.com/landing/		 Capillary or venous whole blood
Harmony INR Monitoring SystemLifeScan Inc., Milpitas, CA
www.lifescan.com		 Capillary or venous whole blood
INRatio Prothrombin Time Monitoring SystemHemosense, Inc. Milpitas, CA
www.hemosense.com		Capillary or venous whole blood
ProTime Microcoagulation SystemInternational Technidyne Corp. Edison, NJ
www.itcmed.com		Capillary or venous whole blood

Back to top.

Chapter 2

Initiation

Inpatient

Day 1

(If there is an active or acute thromboembolic condition, warfarin should be started along with heparin, unless there is a contraindication or patient cannot take medicine orally. Following warfarin initiation, heparin should be continued until INR reaches therapeutic level for 2 days).

5 mg (2.5-7.5). This dose is a good choice since it is known that average daily dose is close to 5 mg. Rapid increase INR (anticoagulant) will not achieve fast full antithrombotic effect since factor II half-life is up to 72 hours. Using higher dose than necessary may lead to bleeding complication due to rapidly and severely reduce factor VII. It may deplete protein C too quick, and theoretically can cause hypercoagulable state. The 5 mg size tablet is recommended for both inpatient and outpatient use, making inpatient to outpatient transition more convenient. It is the most commonly used size tablet by the majority of anticoagulation clinics today. If the dose should be changed, it can be given 0.0, 2.5, 5.0, 7.5, 10.0,---- with this size tablet.

The higher dose warfarin initiation have also been tested successfully by using normogram. It may be considered in patient who may need shorter period of time to reach therapeutic INR. It should be done in patient not in the list of "Lower dose" below. INR have to be done frequently enough to prevent over anticoagulation and bleeding complication

    Lower dose (2.5 mg).Higher dose (7.5-10.0 mg).

Day 2

A. If INR <1.5, continue the same dose.
B. If INR >1.5, give lower dose (2.5 mg or none)

Day 3

    For #A. of Day 2 For #B. of Day 2

Day 4

If there is no need for heparin therapy, the patient may have been discharged by now, and warfarin initiation is continued as an outpatient.
    1. INR 2 times a week until INR is in target range twice in a row, then INR 1 time weekly until INR is in target range twice in a row, then INR 1 time in 2 week until INR is in target range twice in a row, then enter the patient in to maintenance schedule (usually INR every 4 weeks).
    2. Patients during an acute illness, or post operative of major surgeries may be more sensitive to warfarin than when they become more stable.

Frequent INR measurement during warfarin initiation will help:
1. Reaching target INR in shorter period of time
2. Prevent bleeding complication from over anticoagulation

Out patient (See also "Day 4" above)

    1. Obtain baseline INR
    2. Start with 5 mg daily. See more detail for dose variation in "Inpatient guideline"
    3. Check INR 2 times a week, or more often if necessary, during the first week or so. Adjust warfarin dose and timing for INR check as outline in "Inpatient" guidelines.

Ethnic Difference for Chinese-Asian or Pacific-Asian (exclude caucasian in this region)

  1. Average daily dose of Warfarin for Pacific-Asian (exclude caucasian in this region) or Chinese-Asian is about 3 mg. Weekly dose is about 21-28 mg, or lower if "target INR" for various diagnoses are about 0.4-0.5 lower than those of Caucasian-American-European level.
  2. "Target INR" for or Pacific-Asian (exclude caucasian in this region) or Chinese-Asian should be lower than those of Caucasian-American-European. The suggest level for nonvalvular atrial fibrillation is 1.6-2.6, to achieve less combine thromboembolic and major bleeding events. (Need more database for confirmation)
  3. Difference in polymorphism of CYP 2C9 and VKORC1 will influence Warfarin dosage

 

    Table. Warfarin Initiation (for patient with average daily dose of 5 mg and target INR >2.0)

    DAY
    INR
    DOSE
    INPATIENT
    (Usually with daily INR)
    		 OUTPATIENT
    1
    		 Normal
    5.0 mg
    ( 2.5 or 7.5-10.0 mg in patients listed in the text )
    		5.0 mg
    ( 2.5 or 7.5-10.0 mg in patients listed in the text )
    2

    < 1.5
    > 1.5
    5.0 mg
    0.0 - 2.5 mg
    		 5.0 mg
    0.0 - 2.5 mg
    . . [If INR is not measured
    5.0 mg]
    3
    < 1.5
    1.5 - 1.9
    2.0 - 3.0
    > 3.0
    5.0 - 10 mg
    2.5 - 5.0 mg
    0.0 - 2.5 mg
    0.0 mg
    		 5.0 - 10 mg
    2.5 - 5.0 mg
    0.0 - 2.5 mg
    0.0 mg

    .

    .

    		 INR should be measured today. If INR is not measured, may use the same dose as day 2, and should not > 5 mg
    4
    <1.5
    1.5 - 1.9
    2.0 - 3.0
    > 3.0
    10.0 mg
    5.0 - 7.5 mg
    0.0 - 5.0 mg
    0.0 mg
    		 10.0 mg
    5.0 - 7.5 mg
    0.0 - 5.0 mg
    0.0 mg
    . . INR measurement should be done, if INR on day 3 is <1.5 or >3.0
    5
    < 1.5
    1.5 - 1.9
    2.0 - 3.0
    > 3.0
    10.0 - mg
    7.5 - 10.0 mg
    0.0 - 5.0 mg
    0.0 mg
    		 10.0 - mg
    7.5 - 10.0 mg
    0.0 - 5.0 mg
    0.0 mg
    . . INR measurement should be done, if INR on day 4 is <1.5 or >3.0
    6
    < 1.5
    1.5 - 1.9
    2.0 - 3.0
    > 3.0
    7.5 - 12.5 mg
    5.0 - 10.0 mg
    0.0 - 7.5 mg
    0.0 mg
    		 7.5 - 12.5 mg
    5.0 - 10.0 mg
    0.0 - 7.5 mg
    0.0 mg
    . . INR measurement should be done, if INR on day 5 is <1.5 or >3.0
    Note: Frequent INR measurement during warfarin initiation helps prevent bleeding from over anticoagulation and helps reaching target INR sooner.

Print this table

Table. Warfarin Initiation (for patient with average daily dose of 3 mg and target INR >1.6)

    DAY
    INR
    DOSE
    INPATIENT
    (Usually with daily INR)
    		 OUTPATIENT
    1
    		 Normal
    3.0 mg
    ( 1.5 or 3.0-6.0 mg in patients listed in the text )
    		3.0 mg
    ( 1.5 or 3.0-6.0 mg in patients listed in the text )
    2

    < 1.3
    > 1.3
    3.0 mg
    0.0 - 1.5 mg
    		 3.0 mg
    0.0 - 1.5 mg
    . . [If INR is not measured
    3.0 mg (1.5-4.5)]
    3
    < 1.3
    1.3 - 1.6
    1.6 - 2.6
    > 2.6
    3.0 - 6 mg
    1.5 - 3.0 mg
    0.0 - 1.5 mg
    0.0 mg
    		 3.0 - 6 mg
    1.5 - 3.0 mg
    0.0 - 1.5 mg
    0.0 mg

    .

    .

    		 INR should be measured today. If INR is not measured, may use the same dose as day 2, and should not > 3.0 mg
    4
    <1.3
    1.3 - 1.6
    1.6 - 2.6
    > 2.6
    4.5 - 6.0 mg
    3.0 - 4.5 mg
    1.5 - 3.0 mg
    0.0 mg
    		 4.5 - 6.0 mg
    3.0 - 4.5 mg
    0.0 - 3.0 mg
    0.0 mg
    . . INR measurement should be done, if INR on day 3 is <1.3 or >2.6
    5
    < 1.3
    1.3 - 1.6
    1.6 - 2.6
    > 2.6
    6.0 - 7.5 mg
    3.0 - 4.5 mg
    1.5 - 3.0 mg
    0.0 mg
    		 6.0 - 7.5 mg
    3.0 - 4.5 mg
    1.5 - 3.0 mg
    0.0 mg
    . . INR measurement should be done, if INR on day 4 is <1.3 or >2.6
    6
    < 1.3
    1.3 - 1.6
    1.6 - 2.6
    > 2.6
    6.0 - 7.5 mg
    4.5 - 6.0 mg
    1.5 - 3.0 mg
    0.0 mg
    		 6.0 - 7.5 mg
    4.5 - 6.0 mg
    1.5 - 3.0 mg
    0.0 mg
    . . INR measurement should be done, if INR on day 5 is <1.3 or >2.6
    Note: Frequent INR measurement during warfarin initiation helps prevent bleeding from over anticoagulation and helps reaching target INR sooner.

    Print this table

Back to top.

Maintenance Dosing

(Example for patient with average daily dose of 5 mg)

Back ground

  1. Because warfarin has a long half-life and there is a range for INR (i.e. 2.0-3.0) to work with, there is no need to keep an equal daily dose. In fact it is impossible to do that, since the patient will have to use several tablet size to fit to the different daily dose requirement during the long term follow up. This will create confusion.
  2. Using specific days of the week for different daily dose is less confusing.
  3. There is no significant INR swing as long as the daily dose difference is not large (i.e. <2.5 mg, when use 5 mg size tablet).
  4. Using weekly dose adjustment appears more convenient and it is just as accurate.
  5. Applying the above principle along with one size tablet (i.e. 5 mg or 3 mg), a table of weekly-daily dose schedule can be constructed for working convenience (see Warfarin dose schedule table for 5 mg tablet and 3 mg tablet)
  6. Note that weekly dose difference can be arranged as low as 2.5 mg per week, equivalent to only 0.4 mg per day difference.

Example

    Weekly Dose (mg)/ Daily Dose (mg)

    Weekly Dose Mon Tue Wed Thu Fri Sat Sun
    35 5 5 5 5 5 5 5
    37.5 7.5 5 5 5 5 5 5
    40 7.5 5 5 5 7.5 5 5
    42.5 7.5 5 7.5 5 7.5 5 5
    45 5.0 7.5 5.0 7.5 5.0 7.5 7.5
    47.5 5.0 7.5 7.5 7.5 5.0 7.5 7.5

Note: Patient should take warfarin in PM (i.e.5-7 PM), and have INR test in AM, for consistency of the INR result. This also allows time to contact the patient before the patient takes warfarin that day.

Table 1. Warfarin Dose Schedule for 5 mg Tablet (2 mg when eekly dose is < 15 mg)

WEEKLY DOSE
DAILY SCHEDULE DOSE
TABLET SIZE
.
WEEKLY DOSE
DAILY SCHEDULE DOSE
TABLET SIZE
2.0
MF
1.0
0.0
 ROW
2
52.5
.
7.5
.
Daily
5
3.0
MWF
1.0
0.0
 ROW
2
55.0
M
10.0
7.5
ROW
5
4.0
MWF
0.0
1.0
 ROW
2
57.5
MF
10.0
7.5
ROW
5
5.0
MF
0.0
1.0
 ROW
2
60.0
MWF
10.0
7.5
ROW
5
6.0
M
0.0
1.0
 ROW
2
62.5
MWF
7.5
10.0
ROW
5
7.0
.
1.0
.
 Daily
2
65.0
MF
7.5
10.0
ROW
5
8.0
M
2.0
1.0
 ROW
2
67.5
M
7.5
10.0
ROW
5
9.0
MF
2.0
1.0
 ROW
2
70.0
.
10.0
.
Daily
5
10.0
MWF
2.0
1.0
 ROW
2
72.5
M
12.5
10.0
ROW
5
11.0
MWF
1.0
2.0
 ROW
2
75.0
MF
12.5
10.0
ROW
5
12.0
MF
1.0
2.0
 ROW
2
77.5
MWF
12.5
10.0
ROW
5
13.0
M
1.0
2.0
 ROW
2
80.0
MWF
10.0
12.5
ROW
5
14.0
.
2.0
.
 Daily
2
82.5
MF
10.0
12.5
ROW
5
.
.
 . . . .
85.0
M
10.0
12.5
ROW
5
10.0
MWF
0.0
2.5
 ROW
5
87.5
.
12.5
.
Daily
5
12.5
MF
0.0
2.5
 ROW
5
90.0
M
15.0
12.5
ROW
5
15.0
M
0.0
2.5
 ROW
5
92.5
MF
15.0
12.5
ROW
5
17.5
.
2.5
.
 Daily
5
95.0
MWF
15.0
12.5
ROW
5
20.0
M
5.0
2.5
 ROW
5
97.5
MWF
12.5
15.0
ROW
5
22.5
MF
5.0
2.5
 ROW
5
100.0
MF
12.5
15.0
ROW
5
25.0
MWF
5.0
2.5
 ROW
5
102.5
M
12.5
15.0
ROW
5
27.5
MWF
2.5
5.0
 ROW
5
105.0
.
15.0
.
Daily
5
30.0
MF
2.5
5.0
 ROW
5
107.5
M
17.5
15.0
ROW
5
32.5
M
2.5
5.0
 ROW
5
110.0
MF
17.5
15.0
ROW
5
35.0
.
5.0
.
 Daily
5
112.5
MWF
17.5
15.0
ROW
5
37.5
M
7.5
5.0
 ROW
5
115.0
MWF
15.0
17.5
ROW
5
40.0
MF
7.5
5.0
 ROW
5
117.5
MF
15.0
17.5
ROW
5
42.5
MWF
7.5
5.0
 ROW
5
120.0
M
15.0
17.7
ROW
5
45.0
MWF
5.0
7.5
 ROW
5
 . . . . . .
47.5
MF
5.0
7.5
 ROW
5
.
.
.
.
.
.
50.0
M
5.0
7.5
 ROW
5
.
.
.
.
.
.

Table 1. Warfarin Dose Schedule for 3 mg Tablet (2 mg when weekly dose is < 18 mg)

WEEKLY DOSE
DAILY SCHEDULE DOSE
TABLET SIZE
.
WEEKLY DOSE
DAILY SCHEDULE DOSE
TABLET SIZE
2
MF
 1.0
0.0
 ROW 2 31.5 . .
4.5
Daily
 3
3
MWF
 1.0 0.0 ROW 2 33
M
 6.0 4.5
ROW
 3
4
MWF
 0.0 1.0 ROW 2 34.5
MF
 6.0 4.5
ROW
 3
5
MF
 0.0 1.0 ROW 2 36
MWF
 6.0 4.5
ROW
 3
6
M
 0.0 1.0 ROW 2 37.5
MWF
 4.5 6.0
ROW
 3
7 . . 1.0 Daily 2 39
MF
 4.5 6.0
ROW
 3
8
M
 2.0 1.0 ROW 2 40.5
M
 4.5 6.0
ROW
 3
9
MF
 2.0 1.0 ROW 2 42
...
 . 6.0
Daily
 3
10
MWF
 2.0 1.0 ROW 2 43.5
M
 7.5 6.0
ROW
 3
11
MWF
 1.0 2.0 ROW 2 45
MF
 7.5 6.0
ROW
 3
12
MF
 1.0 2.0 ROW 2 46.5
MWF
 7.5 6.0
ROW
 3
13
M
 1.0 2.0 ROW 2 48
MWF
 6.0 7.5
ROW
 3
14
.
 . 2.0 Daily 2 49.5
MF
 6.0 7.5
ROW
 3
15
M
 3.0 2.0 ROW 2 51
M
 6.0 7.5
ROW
 3
16
MF
 3.0 2.0 ROW 2 52.5
.
 . 7.5
Daily
 3
17
MWF
 3.0 2.0 ROW 2 54
M
 9.0 7.5
ROW
 3
18
MWF
 2.0 3.0 Daily 2 55.5
MF
 9.0 7.5
ROW
 3
.
.
 . . . . 57
MWF
 9.0 7.5
ROW
 3
13.5
MF
 3.0 1.5 ROW 3 58.5
MWF
 7.5 9.0
ROW
 3
15
MWF
 3.0 1.5 ROW 3 60
MF
 7.5 9.0
ROW
 3
16.5
MWF
 1,5 3.0 ROW 3 61.5
M
 7.5 9.0
ROW
 3
18
MF
 1.5 3.0 ROW 3 63
.
 . 9.0
Daily
 3
19.5
M
 1.5 3.0 ROW 3 64.5
M
 10.5 9.0
ROW
 3
21
.
 . 3.0 Daily 3 66
MF
 10.5 9.0
ROW
 3
22.5
M
 4.5 3.0 ROW 3 67.5
MWF
 10.5 9.0
ROW
 3
24
MF
 4.5 3.0 ROW 3 69
MWF
 9.0 10.5
ROW
 3
25.5
MWF
 4.5 3.0 ROW 3 70.5
MF
 9.0 10.5
ROW
 3
27
MWF
 3.0 4.5 ROW 3 .
.
 . . . .
28.5
MF
 3.0 4.5 ROW 3
.
.
.
.
.
.
30
M
3.0
4.5
 ROW 3
.
.
.
.
.
.

Print this table

Maintenance Dose, Dose Adjustment

    To change the warfarin weekly dose:

      a) Change warfarin weekly dose by 10% (5-15%). Use higher percentage in patients with higher warfarin weekly dose,

      b) The new Warfarin dose should not be significantly different from many recent adequate doses on patient record.

      c) Repeat INR in 1-2 weeks.

Back to top.

Chapter 3

Target INR

With the same diagnosis, co-morbidity or risk factors may move target INR to the higher level or add low dose ASA (75-325 mg), i.e. bileaflet aortic valve prostheses with recurrent systemic emboli should add ASA 75-325 mg and/or move up target INR from 2.0-3.0 to 2.5-3.5. Remember that INR >4.0 is associated with significant more bleeding.

Target INR for various conditions

This guidelines will offer few approaches based on the published major guidelines. The reader may select any of these approaches.

Adapt From ANTITHROMBOTIC AND THROMBOLYTIC THERAPY, 8TH ED: ACCP GUIDELINES : Executive Summary

Jack Hirsh, Gordon Guyatt, Gregory W. Albers, Robert Harrington and Holger J. Schünemann
Chest June 2008 133 : 71S - 109S ; doi:10.1378/chest.08-0693

Table 2. Target INR for Atrial Fibrillation and Atrial Flutter.

.
INR
DURATION
ALTER NATIVE
ADD
ATRIAL FIBRILLATION
.

A fib, < 75 yr. without RF1 and RF2
.
Long-term
ASA 75-325
.

A fib, with any one of RF2
2.0-3.0
Long-term
ASA 75-325
.

A fib, with two or more of RF2
2.0-3.0
Long-term
.
a

A fib, with RF1
2.0-3.0
Long-term
.
a

A fib, with recurrent emboli.
2.0-3.0
Long-term
.2.5-3.5
Add ASA 75-325

A fib, following cardiac surgery †

 2.0-3.0 †† . .

A fib, <48 hr

Cardiovert w/o anticoag
 .
Recommend Heparin during cardioversion
.

A fib. Pre-cardioversion (>48 hr)
2.0-3.0
3 weeks of target INR
TEE pre-cardioversion

.

Post-cardioversion (>48 hr)
2.0-3.0
4 weeks
.I Long-term ** .
ATRIAL FLUTTER.
Same as atrial fibrillation

For Pacific-Asian (exclude caucasian in this region), The INR range of 2.0-3.0 and 2.5-3.5 may be substituted with INR range of 1.6-2.6 and 2.0-3.0 respectively (Requires more validation)

Print this table

ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation
Circulation. 2006;114:e257-e354.

The 2006 ACC/AHA/ESC guidelines emphasized on risk/benefit of thromboembolism and major bleeding for anticoagulation decision. There are 3 options.

Option 1: Using low, medium and high risk factors for thromboembolic score
Antithrombotic Therapy for Patient With Atrial Fibrillation

Risk Category
Recommended Therapy
No risk factors Aspirin 81-325 mg daily
One moderate-risk factor

Aspirin 81-325 mg daily, or
Warfarin (INR 2.0-3.0), target 2.5

Any high-risk factor,
More than one moderate-risk factor 		Warfarin (INR 2.0-3.0), target 2.5
Less Validated, Weaker Risk Factors
Moderate Risk Factors
High Risk Factors
Female gender,
Age 65-74 y,
Coronary artery disease,
Thyrotoxicosis

Age >75 y,
Hypertension,
Heart failure,
LVEF <35%,
Diabetes mellitus

Previous stroke, TIA,
Systemic embolism
Mitral stenosis,
Prosthetic heart valve*

* If mechanical valve, target INR >2.5

Option 2 : Using CHADS2 Index
Stroke Risk in Patients With Nonvalvular AF Not Treated With Anticoagulation According to the CHADS2, Index

There are several stroke risk scores available and CHADS2 index is a simple and reasonable accurate for clinical use. Warfarin should be prescribed for the patient with CHADS2 score of 2 or higher.

CHADS2, Risk Criteria Score
Prior stroke or TIA
Age >75 y
Hypertension
Diabetes mellitus
Heart failure

2
1
1
1
1

Patients
(N=1723)
Adjusted Stroke Rate (%/y )*
(95% CI)
CHADS2 Score
Warfarin
(INR 2.0-3.0 )
120
463
523
337
220
65
5
1.9 (1.2 to 3.0)
2.8 (2.0 to 3.8)
4.0 (3.1 to 5.1)
5.9 (4.6 to 7.3)
8.5 (6.3 to 11.1)
12.5 (8.2 to 17.5)
18.2 (10.5 to 27.4)
0
1
2
3
4
5
6

.
.
Yes
Yes
Yes
Yes
Yes

Print CHADS2

Option 3:
2006 ACC/AHA/ESC Risk-Based Approach to Antithrombotic Therapy in Patients With Atrial Fibrillation

Patient Features
Antithrombotic Therapy
<60 yr. No heart disease ( lone AF) ASA 81-325 mg/day
or no therapy
<60 yr with heart disease. No RF* ASA 81-325 mg/day
60-74 yr. No RF* ASA 81-325 mg/day
65-74 yr with DM or CAD Warfarin (INR 2.0-3.0)
>75 yr. Women Warfarin (INR 2.0-3.0)
>75 yr. Men. No RF*

Warfarin (INR 2.0-3.0)
or ASA 81-325 mg/day

>65 yr and heart failure Warfarin (INR 2.0-3.0)
LV ejection fraction <35% and HT Warfarin (INR 2.0-3.0)
Rheumatic heart disease (MS) Warfarin (INR 2.0-3.0)
Prosthetic heart valves Warfarin (INR 2.0-3.0 or higher)
Prior thromboembolism Warfarin (INR 2.0-3.0 or higher)
Persistent atrial thrombus on TEE Warfarin (INR 2.0-3.0 or higher)

AF = Atrial fibrillation. MS = Mitral stenosis. DM = Diabetes mellitus. HT = Hypertension
RF* = Risk factors for thromboembolism: Heart failure (HF), LVEF < 35, and HT

For Pacific-Asian (exclude caucasian in this region), The INR range of 2.0-3.0 and 2.5-3.5 may be substituted with INR range of 1.6-2.6 and 2.0-3.0 respectively (Requires more validation)

Table 3. Target INR for Venous Thromboembolism. Deep Vein Thrombosis (DVT) and Pulmonary Emboli (PE)

Adapt From ANTITHROMBOTIC AND THROMBOLYTIC THERAPY, 8TH ED: ACCP GUIDELINES : Executive Summary

Jack Hirsh, Gordon Guyatt, Gregory W. Albers, Robert Harrington and Holger J. Schünemann
Chest June 2008 133 : 71S - 109S ; doi:10.1378/chest.08-0693

.
INR
DURATION
ALTERNATIVE

Secondary (reversable cause) deep vein thrombosis (DVT) or pulmonary emboli (PE). First episode

2.0-3.0
3 months
 .
Idiopathic DVT or PE. First episode

2.0-3.0
6-12 months

May consider long-term, particularly proximal DVT
Idiopathic DVT or PE. Second episode
2.0-3.0
Long-term
3 months for distal DVT
DVT or PE with cancer
2.0-3.0
Until cancer is resolved
LMWH for the first 3-6 months
DVT or PE with antiphospholipid antibodies. First episode
2.0-3.0
12 months
May consider long- term
DVT or PE with deficiency of coagulation factors *. First episode
2.0-3.0
6-12 months
May consider long-term
Recurrent episodes of DVT or PE
2.0-3.0
Long-term
 .

For Pacific-Asian (exclude caucasian in this region), The INR range of 2.0-3.0 and 2.5-3.5 may be substituted with INR range of 1.6-2.6 and 2.0-3.0 respectively (Requires more validation)

Table 4. Target INR for various conditions

Adapt From ANTITHROMBOTIC AND THROMBOLYTIC THERAPY, 8TH ED: ACCP GUIDELINES : Executive Summary

Jack Hirsh, Gordon Guyatt, Gregory W. Albers, Robert Harrington and Holger J. Schünemann
Chest June 2008 133 : 71S - 109S ; doi:10.1378/chest.08-0693

(
.
INR
DURATION
ALTER NATIVE
ADD
LEFT VENTRICULAR DISEASE .

Dilated cardiomyopathy (EF<30%).
2.0-3.0
Long-term
No Rx
.

Dilated cardiomyopathy (EF<30%), & emboli.
2.0-3.0
Long-term
.
a

S/P anterior MI, LV thrombus.
2.0-3.0
3 months
.
a
.
SYSTEMIC EMBOLI.
.

Systemic emboli.
2.0-3.0
Long-term
.
a
.
VALVULAR DISEASES.
.

Rheumatic MV disease, NSR, LA > 5.5 cm,
2.0-3.0
Long-term
.
a
Mitral valvuloplasty 2.0-3.0 3 wk before,
4 wk after
TEE prior to procedure
.

MV prolapse, unexplained TIA or ischemic stroke

.
Long-term

.ASA 50-100
.

Mitral annular calcification (MAC).
(No anticoag. Rx by itself)
.
.

MAC, systemic emboli (calcific) without atrial fibrillation

.
Long-term

.ASA 50-100

AV disease

(No anticoag. Rx by itself)...
.
PFO OR ATRIAL SEPTAL ANEURYSM.
.

PFO with ischemic stroke

.
Long-term

ASA 50-100

 .

PFO with cryptogenic ischemic stroke particular with DVT

2.0-3.0
Long-term
IVC filter, Close PFO
a
PFO.
ENDOCARDITIS.
.

Native valve or bioprotheses, with systemic emboli during endocarditis.
Uncertain Rx
.
.
.
Mechanical prostheses, during endocarditis.
Continue anticoagulation, should temporary replace warfarin with heparin
..

Nonbacterial thrombotic endocarditis (NBTE) with systemic or pulmonary emboli.
Heparin
.
.
.

Aseptic vegetation (in patients with disseminated cancer or debilitating disease)

Heparin
...
.
ASCENDING AORTA, AORTIC ARCH.
.

Ascending aorta, aortic arch. Mobile plaque >4 mm (TEE).
2.0-3.0
Long-term
.
a

For Pacific-Asian (exclude caucasian in this region), The INR range of 2.0-3.0 and 2.5-3.5 may be substituted with INR range of 1.6-2.6 and 2.0-3.0 respectively (Requires more validation)

 

Target INR for Heart Valve Prostheses

General principles

Table 5. Target INR for Heart Valve Prostheses

Adapt From ANTITHROMBOTIC AND THROMBOLYTIC THERAPY, 8TH ED: ACCP GUIDELINES : Executive Summary

Jack Hirsh, Gordon Guyatt, Gregory W. Albers, Robert Harrington and Holger J. Schünemann
Chest June 2008 133 : 71S - 109S ; doi:10.1378/chest.08-0693

and ACC/AHA Pocket Guidelines. Management of Patients with Valvular Heart Disease, 2006.

.
INR
DURATION
ALTER NATIVE
ADD
GENERAL APPROACH *
.

Mechanical prostheses(1)
2.0-3.0
Indefinite
.
 May add ASA 50-100

Mechanical prostheses, others
2.5-3.5
Indefinite
.
 May add ASA 50-100
Mechanical prostheses(3)
2.5-3.5
Indefinite
.
 Add ASA 50-100

Mechanical prostheses, with RF(2)
2.5-3.5
Indefinite
.
 Add ASA 50-100
.
AORTIC VALVE *
.

AV prostheses, bileaflet (1), no RF(2)
2.0-3.0
Indefinite
.
 May add ASA 50-100

AV prostheses, bileaflet (1), with RF(2)
2.5-3-5
Indefinite
.
 Add ASA 50-100

AV prostheses, others, no RF(2)
2.5-3.5
Indefinite
.
 May add ASA 50-100

AV prostheses, others, with RF(2)
2.5-3.5
Indefinite
.
 Add ASA 50-100
.

AV bioprostheses, 1st 3 months
2.5-3.5
3 months
ASA 325
.

-- After 3 months
ASA 80
Indefinite
.
.

-- After 3 months, with RF(2)
2.0-3.0
Indefinite
.
 May add ASA 50-100
.
MITRAL VALVE *
.

MV prostheses, mechanical
2.5-3.5
Indefinite
.
 May add ASA 50-100
.

MV bioprostheses, 1st 3 months
2.5-3.5
3 months
.
 May add ASA 50-100

-- After 3 months
ASA 80
Indefinite
.
 May add ASA 50-100

-- After 3 months, with RF(2)
2.5-3.5
Indefinite
.
 May add ASA 50-100

For Pacific-Asian (exclude caucasian in this region), The INR range of 2.0-3.0 and 2.5-3.5 may be substituted with INR range of 1.6-2.6 and 2.0-3.0 respectively (Requires more validation)

Chapter 4

Managing High INR or Bleeding

General principle

  1. INR > therapeutic level, but < 5.0 and no bleeding.
    1. Hold warfarin for 1-2 days. Check INR in 1-2 days. Restart warfarin when INR return to target level. Check for factor(s) effecting high INR before changing the warfarin dose.
    2. May not require warfarin dose change if the factor(s) effecting high INR can be identified and corrected.
  2. INR 5-9, and no bleeding.
    1. Hold Warfarin, check INR in 1 day. Restart warfarin when INR return to target level. Check for factor(s) effecting INR carefully, correct the problem.
    2. More likely will require warfarin dose change.
    3. May prescribe small dose of oral vitamin K (1-2.5 mg)
  3. INR < 10, with minor bleeding or high risk for bleeding (i.e. recent surgery).
    1. Hold warfarin. Vitamin K, 1-2.5 mg orally. Check for INR in 12-24 hours.May repeat vitamin K in 24 hours. Check for factor(s) effecting INR carefully, correct the problem.
    2. Restart warfarin when at appropriate time. Adjust the dose.
  4. INR 10-20, and no bleeding.
    1. Hold warfarin. Vitamin K 2.5-5.0 mg orally. Check INR in 12-24 hours. If there is no admission, patient education is important. Check for factor(s) effecting INR carefully, correct the problem.
    2. Restart warfarin when INR return to target range. Adjust the dose.
  5. INR 10-20, with more then minor bleeding.
    1. Require admission.Hold warfarin. Vitamin K 5-10 mg slow IV infusion (not >1 mg/min), and/or FFP (15 ml/kg). Check INR in 6-12 hours or after FFP administration, repeat vitamin K and/or FFP as necessary. Check for factor(s) effecting INR carefully, correct the problem.
    2. Restart warfarin when INR return to target range and the bleeding has resolved. Adjust the dose.
  6. INR > 20, with bleeding tendency or bleeding.
    1. Require admission. Hold warfarin. Vitamin K 5-10 mg slow IV infusion (not >1 mg/min), and/or FFP (15 ml/kg). Check INR in 6-12 hours or after FFP administration, repeat vitamin K and/or FFP as necessary. Check for factor(s) effecting INR carefully, correct the problem.
    2. Restart warfarin when INR return to target range and the bleeding has resolved. Adjust the dose.
  7. Serious bleeding with therapeutic or elevated INR.
    1. Require admission.
    2. Follow guideline #5. Be careful when restarting warfarin.
  8. Patient who requires more rapid or urgent reversal before procedure/surgery.
    1. Hold warfarin. Vitamin K 5-10 mg slow IV infusion (not >1 mg/min), and/or FFP (15 ml/kg).
    2. Check INR in 6-12 hours or after FFP administration, repeat vitamin K and/or FFP as necessary.

      (Large dose of intravenous administration may cause a period of warfarin resistance up to a week, when restarts it.)

Vitamin K

Food with Vitamin K

 

Table 8. Managing high INR or bleeding.

BLEEDING BLEEDING
INR
VITAMIN K
FFP
WARFARIN
NEXT INR
No bleeding
<5
None
None
Hold 1-2 days. -- Adjust dose?
1-2 days
No bleeding
5-9
None (No bleeding risk) *
None
Hold 1-2 days. --Adjust dose
1 day
Minor bleeding
<10
2.5 mg po
None

Hold ----- Adjust dose
1 day
No bleeding or minor bleeding
10-20
2.5-5.0 mg po
None
Hold ----- Adjust dose
12-24 hours
Bleeding tendency or bleeding
>20
5-10 mg IV (<1 mg/min)
(FFP, PCC)
Hold
6-12 hours
Serious bleeding
Target or high INR
10 mg IV (<1 mg/min)
(FFP, PCC)
Hold
Following FFP

• * or Vitamin K 2.5 mg po.
• FFP - Fresh Frozen Plasma.
• PCC - Prothrombin Complex Concentration



Print this table and Vitamin K

Back to top.

Chapter 5

Managing anticoagulation during procedures/surgeries

Problems

Guidelines.

Bridging Therapy is the procedure involving temporary use of heparin when the warfarin is withheld.

Thromboembolic Risks

Table 9. Risk of thromboembolism on patients without anticoagulation therapy. (Not during withholding warfarin for procedure/surgery). (Adapted from Kearon C, Hirsh J. Management of Anticoagulation Before and After Elective Surgery. NEJM 1997; 336:1506-1511).

CONDITIONS
RATE* OF THROMBO- EMBOLISM
RATE PER DAY
RISK REDUCTION WITH THERAPY
VENOUS .

Acute VTE

.

-- Month 0-1
40% / month

1.3
80%

-- Month 1-3
10% / month
0.3
80%

Recurrent VTE
15 % / year
0.04
80%

ARTERIAL
.

Acute arterial embolism
.

-- Month 0-1
15% / month
0.5
66%

NVAF
4.5% (1-20) / year
0.01
66%

NVAF and previous embolism
12% / year
0.03
66%

Mechanical heart valve
8%† / year
0.02
75%

(Rate of thromboembolism may be higher following holding warfarin and during surgical procedures - "rebound phenomenon")

Print this table

Patients with high risk for thromboembolism.
(1 year risk of arterial embolism > 10%, or 1 month risk of venous thromboembolism > 10 %)

Patients with intermediate risk for thromboembolism.
(1 year risk of arterial embolism of 5 to 10%, or 1 month risk of venous thromboembolism of 5 to 10 %)

Patients with low risk for thromboembolism.
(1 year risk of arterial embolism < 5%, or 1 month risk of venous thromboembolism < 2%%)

Bleeding Risks

  1. Low risk.
    • Cutaneous: Local skin surgery, i.e. Mohs micrographic surgery, simple excisions, biopsy and repairs.
    • Oral: Simple dental procedures, i.e. simple tooth extraction, dental hygiene, restorations, endodontics, prosthetics and periodontal therapy. (Some dentists give antifibrinolytic agents such as tranexamic acid or epsilon aminocaproic acid mouthwash to help control local breeding).
    • Joint and soft tissue aspirations and injections.
    • Minor podiatric procedures, i.e. nail avulsions and phenol matrixectomy.
    • Opthalmic: Cataract extraction, trabeculectomy. The rate of retrobulbar hemorrhage, subconjunctival hemorrhage and mild hyphema increases slightly, but with good prognosis. Risk of bleeding in vitreoretinal, complex lid, and orbital surgical procedures has not been adequately studied.
    • Gastroenterologic: diagnostic esophago-gastro-duodenoscopy (EGD) with or without biopsy, flexible sigmoidoscopy with or without biopsy, colonoscopy with or without biopsy, diagnostic endoscopic retrograde cholangio-pancreatography (ERCP) without sphincterotomy, biliary stent insertion without endoscopic sphincterotomy, endosonography (EUS) without fine needle aspiration, and push enteroscopy of the small bowel. (There is the possibility of poIypectomy with endoscopic examination particularly the colonoscopy. Preparing these cases as high bleeding risk may help prevent repeating the procedure.)
    High risk.

Table 10. Protocol for managing anticoagulation during procedures/surgeries (5 plans)

PLAN
PROTOCOL
DAYS OF INADEQUATE ANTICOAGULATION *
1
 Continue warfarin
0
2
 Hold warfarin

With Pre and Post procedure heparin
1
3
 Hold warfarin With Post procedure heparin
3-4
4
 Hold warfarin With Pre procedure heparin
4-6
5
 Hold warfarin only
6-8

Print this table

The section below is for population who require target INR >2.0 (Caucasian). It should be modified for population who require difference target INR.

Detail of protocols for managing anticoagulation during procedures/surgeries (Table 10)

  1. Plan 1: Continue warfarin.
    • Check INR 7 days before the procedure, keep INR in low target range. Communicate with operator who will perform the procedure.
    • This protocol will result in no subtherapeutic anticoagulation day.
  2. Plan 2: Hold warfarin, post procedure heparin, pre procedure heparin.
  3. Plan 3: Hold warfarin, post procedure heparin. (Not suitable for patients with high risk for post procedures/surgeries bleeding)
  4. Plan 4: Hold warfarin, pre procedure heparin.
  5. Plan 5: Hold warfarin only.
    • Check INR 7 days before the procedure, keep INR in target range.
    • Drop INR to 1.5 or less. For INR of 2.0-3.0, it will require about 4(3-5)days. Higher INR will take longer time.
    • Check INR 1 day before the procedure. If INR is 1.8 or higher, give vitamin K 2.5 mg orally, or delay the procedure.
    • Restart the previous maintenance dose of warfarin the evening of the procedure, If it cannot be started - see "Remark" below.
    • This protocol will result in subtherapeutic anticoagulation for 6-8 days.

Subcutaneous unfractionated heparin or low dose low molecular weight heparin may be used for prevention of post operative venous thromboemboli.

For more urgent surgery, please review Section Managing High INR or Bleeding, "8. Patient who requires more rapid or urgent INR reversal before procedure/surgery".Large dose of intravenous Vit K may cause a period of warfarin resistance up to a week, when restart it.

Back to top.

Table 11. Low bleeding risks: Guidelines for managing anticoagulation during procedures/surgeries.

    PROCEDURE/SURGERY
    BLEEDING RISK
    DIAGNOSIS
    THROMBO RISK
    PROTOCOL

    (Low bleeding risk)
    •    Cutaneous: Local skin surgery, i.e. Mohs micrographic surgery, simple excisions, biopsy and repairs.
    • Oral: Simple dental procedures, i.e. simple tooth extraction, dental hygiene, restorations, endodontics, prosthetics and periodontal therapy. (Some dentists give antifibrinolytic agents such as tranexamic acid or Epsilon amino caproic acid mouthwash to help control local bleeding.)
    •     Opthalmic: cataract extraction, trabeculectomy.
    •     GI procedures: EGD w or w/o biopsy, flex sig w or w/o biopsy, colonoscopy w or w/o biopsy, diagnostic ERCP, biliary stent w/o sphincterectomy, endosonography w/o fine needle aspiration, push enteroscopy of the small bowel.
    • Miscellaneous: Joint and soft tissue aspirations and injections. Minor podiatric procedures, i.e. nail avulsions and phenol matrixectomy

    Others:
    .
    		 VTE/pulmonary emboli ** ††
    .
    .
    Low
    		 --- < 1 month
    High
    1, 2
    Low
    		 --- 1-3 months
    High
    1, 2
    Low
    		 --- Recurrent
    Low
    5, 1
    .
    		 Acute Arterial Emboli ††
    .
    .
    Low
    		 --- < 1 month
    High
    1, 2
    Low
    		 --- > 1 month
    Low
    5, 1
    .
    		 Non Valvular atrial fibrillarion (NVAF)
    .
    .
    Low
    		 Atrial fibrillation
    Low
    5, 1
    Low
    		 --- With risk factors (1)
    High
    1,2,3,4
    .
    		 Heart Valve Prostheses
    .
    .
    Low
    		 Bileaflet AV †
    Low
    5, 1
    Low
    		 Other valves, multiple or with additional risk factors (2)
    High
    1,2,3,4
        See "Thrombo embolic Risks" section

Table 12. High bleeding risks: Guidelines for managing anticoagulation during procedures/surgeries.

    PROCEDURE/SURGERY
    BLEEDING RISK
    DIAGNOSIS
    THROMBO RISK
    PROTOCOL

    (High bleeding risk)

    • Cutaneous: More complex procedures, i.e. hair transplantation, blepharoplasty, or facelifts.
    • Oral: More complex procedures such as complicated extractions, gingival and alveolar surgeries.
    • Opthalmic: Retinal surgery, complex lid and orbital surgery, patients who need retrobulbar anesthesia for ophthalmic procedures.
    • GI procedures:     colonoscopic or gastric polypectomy, laser ablation and coagulation, endoscopic sphincterotomy,
    pneumatic or bougie dilation of strictures, percutaneous endoscopic gastrostomy, EUS-guided fine needle aspiration.
    • Cardiac procedures: Pacemaker/ICD insertion have more bleeding potential than bleeding from cardiac catheterization site.
    • Intracavitory surgery: Intraabdominal surgeries, intrathoracic surgeries, intracranial surgeries,
    • Neurosurgical procedures, neuraxial anesthesia and spinal puncture.
    • Orthopedic.
    • Genito-urinary:     Transurethral resection of the prostate?
    • Obstetric-gynecologic.
    • plastic surgery.
    •     Any procedures or surgeries that bleeding can not be controlled or stopped with simple intervention.

    Others:
    .
    		 VTE/pulmonary emboli ** ††
    .
    .
    High
    		 --- < 1 month
    High
    2
    High
    		 --- 1-3 months
    High
    4, 2
    High
    		 --- Recurrent
    Low
    5, 4
    .
    		 Acute Arterial Emboli ††
    .
    .
    High
    		 --- < 1 month
    High
    2, 4
    High
    		 --- > 1 month
    Low
    4, 5
    .
    		 Non Valvular atrial fibrillarion (NVAF)
    .
    .
    High
    		 Atrial fibrillation
    Low
    5, 4
    High
    		 ---With risk factors (1)
    High
    4, 2
    .
    		 Heart Valve Prostheses
    .
    .
    High
    		 Bileaflet AV †
    Low
    5, 4
    High
    		 Other valves, multiple or with additional risk factors (2)
    High
    2, 4
     

Table 13 Simple guidelines for managing anticoagulation during procedures/surgeries.

Adapted from Kearon C, Hirsh J. Management of Anticoagulation Before and After Elective Surgery. NEJM 1997; 336: 1506-1511.

CONDITIONS
PRE PROCEDURE
POST PROCEDURE

Acute VTE
.
.

-- Month 1
*              Heparin (2)
**              Heparin (2)

-- Month 2-3
*
**              Heparin (2)

Recurrent VTE
*.
**         SC heparin (3)

Acute arterial embolism
.
.

-- Month 1
*               Heparin (2)
**              Heparin (2)

Mechanical heart valve

*.
**         SC heparin (3)

NVAF

*.
**         SC heparin (3)

Print this table

Using Heparin for "Bridging Therapy"

Unfractionate heparin (UFH) (Update soon)

LMWH (Low molecular weight heparin)

Unsuitable conditions for LMWH:

Dosing

  Prophylactic dose Therapeutic dose
. . q 12 hours q 24 hours  
Enoxaparin 20-40 mg od 1 mg/kg 1.5 mg/kg  
Delparin 5000 IU od 100 IU/kg 200 IU/kg  
Nadroparin 38 IU od 87 IU/kg   .
Tinzaparin 4500 IU od 175 IU/kg   .

Before surgery dosing. Usually start 24-48 hours after last warfarin dose.

After surgery dosing

Heparin-induced thrombocytopenia (HIT)

 

Table 15. Form for managing anticoagulation during procedures/surgeries.

Section ASection B
 Patient name:.
 Age:Rec No:.
.
(Circle H or L)
 1ry Diagnosis: Thrombo risk: H, L* Bleeding risk: H, L*
 2ry Diagnosis: Thrombo risk: H, L* Bleeding risk: H, L*
 Procedure/surgery: Thrombo risk: H, L* Bleeding risk: H, L*
Section C.
Select the protocol - Plan 1, 2, 3, 4, 5 (Circle the number)

* H = high, Low = low.

(For more urgent surgery, please review Section Managing High INR or Bleeding, "8. Patient who requires more rapid or urgent reversal before procedure/surgery".)
1. Fill in the patient information in Section A. 1ry Diagnosis = Diagnosis that requires anticoagulation. 2ry Diagnosis = Diagnosis ( that may increase thromboembolic or bleeding risks.
2. Determine thromboembolic and bleeding risk in Section B. Then circle the H (high) or L (low). Using Table 9, Table 11, Table 12. for risk stratification.
3. Select the protocol plan. Using Table 11, Table 12, Table 10, and individualization for selection guidelines. Then circle the protocol plan number in Section C.
4. May print "Managing anticoagulation during procedures/surgeries section". M ay also mark those areas picked (underline or yellow mark). May send this marked printout to primary physician or place it in the chart.

Print this table

 

Anticoagulation Guidelines for Endoscopic Procedures.

American Society for Gastrointestinal Endoscopy. Guideline on the management of anticoagulation and antiplatelet therapy for endoscopic procedures.
Gastrointest Endosc . 2002 Jun;55(7):775-9.

Condition Risk for Thromboembolism
Procedure Risk for Hemorrhage
High
Low
High

- Hold warfarin for 3-5 days
- Consider heparin while INR is sub therapeutic *

 - Hold warfarin for 3-5 day
- Re-institute warfarin right after the procedure
Low
 - No change in anticoagulation
- Elective procedures should be delayed while INR is in supratherapeutic range

* Use more detail guidelines for heparin bridging as described in the earlier section.

ASA and other NSAIDs: Endoscopic procedures may be performed in patients taking ASA or other NSAIDs if there is no pre-existing bleeding disorder.

Procedures Risk for Hemorrhage
High Risk
Low Risk
Polypectomy

Diagnostic: EGD +/- biopsy, flex sigmoidoscopy +/- biopsy, colonoscopy +/- biopsy

Billiary sphincterotomy ERCP without sphincterotomy
Pneumatic or bougie dilatation Billiary/pancreatic stent without sphincterotomy
PEG placement Endoscopy without fine needle aspiration
Endosonic guided fine needle aspiration Endoscopy
Laser ablation and coagulation
Treatment of varices

Conditions Risk for Thrombo-embolism
Hgh
low
Atrial fibrillation with valvular heart disease or prior thromboembolic event Deep vein thrombosis
Mechanical valve in mitral position Uncomplicated or paroxysmal non-valvular atrial fibrillation
Mechanical valve and prior thromboembolic event Bioprosthetic valve
Very recent thromboembolic event or multiple and severe thromboembolic events Mechanical valve in aortic position

 

Anticoagulation in pregnancy

Options of anticoagulation management in pregnancy with mechanical prosthetic valve.

  1. Warfarin throughout pregnancy, with its potential fetal risks. Change to heparin (UFH or LMWH) at 38 weeks, Labor induction at 40 weeks of gestation.
  2. Heparin throughout pregnancy, with its associated maternal thrombosis risks particularly mechanical heart valve prosthesis. It is anticipated that heparin dose in the third trimester will be higher.
  3. Heparin during the first trimester. Switch to warfarin in the second trimester. Change back to heparin at 38 weeks. Labor induction at 40 weeks of gestation. Heparin dose in the third trimester is usually higher.

For UFH, start with total daily dose of 35000 U given subcutaneously twice a day. Monitor PTT at least twice a week to keep the level at least 2-3 times of control. For LMWH such as Lavenox, start with 100 mg given subcutaneously twice a day. Monitor anti-Xa to keep the level at 0.5 -1.2 U/ml 4-6 hours after injection.

Risk of mechanical heart valve prosthesis thrombosis in pregnancy continue to be high with heparin therapy. The heparin dose should be kept at high PTT or anti-Xa level.

Back to top.

Chapter 6

Drugs interact with warfarin (Updating)

Back to top.

Chapter 7

Selected oral anticoagulation references (Updating)

General.
  1. 8th ACCP Conference on Antithrombotic and Thrombolytic Therapy.
    http://www.chestjournal.org/content/133/6_suppl
  2. Ginsberg JA, Crowther MA, White RH, Ortel TL. Anticoagulation Therapy. Hematology
    Am Soc Hematol Educ Program) 2001 Jan; :339-57.
  3. AHA/ACC. Foudation Guide to Warfarin Therapy, 2003
    Circulation . 2003 Apr 1;107(12):1692-711. Review.
  4. Ansell JE, Oertel LB, Wittkowsky AK. Managing Oral Anticoagulation Therapy. Clinical and Operational Guidelines. Lippincott Williams & Wilkins; 2 edition (June 1, 2005)
  5. Ansell JE, Buttaro ML, Thomas VO, et al. Consensus Guidelines for Coordinated Outpatient Oral Anticoagulation Therapy Management. Ann Pharmacother. 1997; 31: 604-615.
  6. ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation
    Circulation. 2006;114:e257-e354.
  7. ACC/AHA 2006 Guidelines for the Management of Patients with Valvular Heart Disease
    Circulation . 2006 Aug 1;114(5):e84-231. Review.
  8. Schulman S.
    Clinical practice. Care of patients receiving long-term anticoagulant therapy.
    N Engl J Med . 2003 Aug 14;349(7):675-83. Review.
  9. Jack Ansell, M.D. Jack Hirsh, M.D. Nanette K. Wenger, M.D.
    Postgraduate Education Committee, Council on Clinical Cardiology
    American Heart Association

Warfarin Initiation.

  1. Crowther MA, Ginsberg JB, Kearon C, Hirsh J et al. A Randomized Trial Comparing 5 mg and 10 mg warfarin Loading Doses. Arch Intern Med, 1999; 159: 46-48.
  2. Tait RC, Sefcick A. A Warfarin Induction Regimen for Outpatient Anticoagulation in Patients with Atrial Fibrillation. Br J Haematol. 1998; 101(3): 450-454.
  3. Ageno W, Turpie AG. Exaggerated Initial Response to Wafrarin followint Heart Valve Replacement. Am J Cardiol, 1999; 84(8): 905-908.
  4. Kovacs MJ, Rodger M, Anderson DR, Morrow B, Kells G, Kovacs J, Boyle E, Wells PS.
    Comparison of 10-mg and 5-mg warfarin initiation nomograms together with low-molecular-weight heparin for outpatient treatment of acute venous thromboembolism. A randomized, double-blind, controlled trial.
    Ann Intern Med. 2003 May 6;138(9):714-9.

Target INR.

  1. 8th ACCP Conference on Antithrombotic and Thrombolytic Therapy.
    http://www.chestjournal.org/content/133/6_suppl
  2. ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation
    Circulation. 2006;114:e257-e354.
  3. ACC/AHA 2006 Pocket Guidelines for the Management of Patients with Valvular Heart Disease
  4. Hylek EM, Go AS, Chang Y, Jensvold NG, Henault LE, Selby JV, Singer DE. Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation.
    N Engl J Med . 2003 Sep 11;349(11):1019-26.

Warfarin Requirement for Pacific-Asian ( Exclude caucasian in this region)

  1. Dang MT, Hambleton J, Kayser SR. The influence of ethnicity on warfarin dosage requirement.
    Ann Pharmacother . 2005 Jun;39(6):1008-12. Epub 2005 Apr 26.
  2. El Rouby S, Mestres CA, LaDuca FM, Zucker ML.
    Racial and ethnic differences in warfarin response.
    J Heart Valve Dis . 2004 Jan;13(1):15-21. Review.

Tatget INR for Pacific-Asian (Limited evidence-based)

  1. Yamaguchi T. Optimal intensity of warfarin therapy for secondary prevention of stroke in patients with nonvalvular atrial fibrillation : a multicenter, prospective, randomized trial. Japanese Nonvalvular Atrial Fibrillation-Embolism Secondary Prevention Cooperative Study Group.
    Stroke . 2000 Apr;31(4):817-21.
  2. Yasaka M , Minematsu K , Yamauchi T. Optimal intensity of international normalized ratio in warfarin therapy for secondary prevention of stroke in patients with non-valvular atrial fibrillation.
    Intern Med 2001. Dec;40(12):1183-8.
  3. Cheung CM, Tsoi TH, Huang CY. The lowest effective intensity of prophylactic anticoagulation for patients with atrial fibrillation.
    Cerebrovasc Dis . 2005;20(2):114-9. Epub 2005 Jul 5.

Vitamin K

  1. Crowther MA , Douketis JD , Schnurr T , Steidl L , Mera V , Ultori C , Venco , Ageno W . Oral vitamin K lowers the international normalized ratio more rapidly than subcutaneous vitamin K in the treatment of warfarin-associated coagulopathy. A randomized, controlled trial.
    Ann Intern Med. 2002 Aug 20;137(4):I39.
  2. Wilson SE , Watson HG , Crowther MA . Low-dose oral vitamin K therapy for the management of asymptomatic patients with elevated international normalized ratios: a brief review.
    CMAJ 2004 Mar 2;170(5):821-4.
  3. Gunther KE , Conwy G , Leibach L , Crowther MA . Low-dose oral vitamin K is safe and effective for outpatient management of patients with an INR>10.
    Thromb Res. 2004;113(3-4):205-9
  4. Dentali F, Crowther MA.
    Management of excessive anticoagulant effect due to vitamin K antagonists.
    Hematology Am Soc Hematol Educ Program. 2008:266-70.

Perioperative Management.

  1. Kearon C. Perioperative Management of Long-term Anticoagulation. Semin Thromb Hemost 1998; 24 (Suppl 1): 77-83.
  2. Kearon C, Hirsh J. Managing Anticoagulation Before and After Surgery in Patients Who Require Oral Anticoagulants. N Engl J Med 1997; 336: 1506-1511.
  3. Heit JA. Perioperative management of the chronically anticoagulated patient.
    J Thromb Thrombolysis. 2001 Sep;12(1):81-7. Review.
  4. Wahl MJ. Dental Surgery in Anticoagulation Patients. Arch Intern Med, 1998; 158: 1610-1616.
  5. Randall C . Surgical management of the primary care dental patient on warfarin.
    Dent Update. 2005 Sep;32(7):414-6, 419-20, 423-4 passim.
  6. Eisen GM, Baron TH, Dominitz JA, Faigel DO, Goldstein JL, Johanson JF, Mallery JS, Raddawi HM, Vargo JJ 2nd, Waring JP, Fanelli RD, Wheeler-Harbough J; American Society for Gastrointestinal Endoscopy.
    Guideline on the management of anticoagulation and antiplatelet therapy for endoscopic procedures.
    Gastrointest Endosc . 2002 Jun;55(7):775-9.
  7. Dunn AS, Turpie AG.
    Perioperative management of patients receiving oral anticoagulants: a systematic review.
    Arch Intern Med. 2003 Apr 28;163(8):901-8. Review.
  8. Jaffer AK, Brotman DJ, Chukwumerije N.
    When patients on warfarin need surgery.
    Cleve Clin J Med. 2003 Nov;70(11):973-84. Review.
  9. Dunn A . Perioperative management of oral anticoagulation: when and how to bridge.
    J Thromb Thrombolysis. 2006 Feb;21(1):85-9.

Warfarin Drug Interaction.

  1. Holbrook AM, Pereira JA, Labiris R, McDonald H, Douketis JD, Crowther M, Wells PS.
    Systematic overview of warfarin and its drug and food interactions.
    Arch Intern Med . 2005 May 23;165(10):1095-106. Review.
  2. Wittkowsky AK, Boccuzzi SJ, Wogen J, Wygant G, Patel P, Hauch O.
    Frequency of concurrent use of warfarin with potentially interacting drugs.
    Pharmacotherapy . 2004 Dec;24(12):1668-74.
  3. Greenblatt, D. J., von Moltke, L. L. (2005). Interaction of Warfarin With Drugs, Natural Substances, and Foods. J Clin Pharmacol 45: 127-132

Low Molecular Weight Heparin.

  1. Hirsh J, Warkentin TE, Shaughnessy SG, et al. Heparin and Low-Molecular-Weight Heparin: Mechanisms of Action, Pharmacokinetics, Dosing, Monitoring, Efficacy, and Safety. Chest 2001; 119 (Suppl 1): 64S-94S.
  2. Spandorfer j, Lynch S, Weitz HH, et al. Use of Enoxaparin for the Chronically Anticoagulated Patient Before and After Procedures. Am J Cardiol 1999; 84: 478-480, A10.
  3. Litin SC, Heit JA, Mees KA, et al. Concise Review for Primary-Care Physicians. Use of Low-Molecular-Weight Heparin in the Treatment of Venous Thromboembolic Desease: Answers to frequently asked questions. Mayo Clic Proc 1998; 73: 545-551.

Heparin Induced thrombocytopenia.

  1. Warkentin TE, Levine MN, Hirsh J, et al. Heparin-insuced Thrombocytopenia in Patients Treated with Low-Molecular-Weight heparin or Unfractionated Heparin. N Engl J Med, 1995; 332: 1330-1335.
  2. Magnani HN, Orgaran (danaparoid sodium) Use in the Syndrome of Heparin-induced Thrombocytopenia. Platelets 1997; 8: 74-81.

Anticoagulation During Pregnacy

  1. 8th ACCP Conference on Antithrombotic and Thrombolytic Therapy.
    http://www.chestjournal.org/content/133/6_suppl
  2. Bonow RO, Carabello BA, Chatterjee K, de Leon AC Jr, Faxon DP, Freed MD, Gaasch WH, Lytle BW, Nishimura RA, O'Gara PT, O'Rourke RA, Otto CM, Shah PM, Shanewise JS; 2008 focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: Circulation. 2008;118:e523-e661
  3. Chan WS, Anand S, Ginsberg JS. Anticoagulation of pregnant women with mechanical heart valves: a systematic review of the literature. . Arch Intern Med. 2000;160:191-196.
  4. Geelani MA, Singh S, Verma A, Nagesh A, Betigeri V, Nigam M. Anticoagulation in Patients with Mechanical Valves During Pregnancy. . Asian Cardiovasc Thorac Ann 2005;13:30-33

Anticoagulation web sites

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Chapter 8

Patient education

Patient education and understanding is essential for successful warfarin management clinic.

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Warfarin Tablet