| (2004 update by mid 2005) |
Chapter 1
- Warfarin characteristic.
- Average Warfarin daily dose.
- Factors effect the Warfarin daily dose.
- Tablet size (Coumadin)
- Generic Warfarin (Update soon)
- Treatment Monitoring, standard and Point of Care
Chapter 2
- Initiation dose.
- Inpatient.
- Outpatient.
- Maintenance dose.
- Weekly dose.
- Daily schedule.
- Dose adjustment.
- Warfarin dose schedule table.
Chapter 3
Chapter 4
Chapter 5
Chapter 6
Chapter 7
Chapter 8
This guidelines are prepared for Central Minnesota Heart Center (CMHC) Anticoagulation Clinic although it should be useful to our medical community as well. It is intended to cover outpatient Warfarin (Coumadin) management, related to cardiology work such as atrial fibrillation and prosthetic heart valve. Other conditions are briefly included. Many patients may have been started on Warfarin as inpatient.
The guidelines follows a few major guidelines, i.e. 6th and 7th ACCP Consensus Conference on Antithrombotic Therapy (Chest 2001and 2004), and ACC/AHA Task Force Report of Guidelines for the Management of Patients with Valvular Heart Disease (Circulation 1998). Some other databases are also listed in the bibliography section.
Several parts of this guideline are not specific to individual case and should not be so, since each patient and their condition are different. Individualization is necessary for better results.
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.
12/01
About 4-5 mg/day or 28-35 mg/week with fair amount of variation.
Generic (Update soon)
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.
- Need quality control for point of care INR measurement.
- Faster INR result. Patients are more willing to wait for the result before they go home.
- Direct patient contact for instruction before the patients leave the clinic is more efficient than phone call for the result later.
- Clinic may be able to reimburse for the service.
Home use (Self monitoring).
- Need more validation for this approach, particular the long term result. Current trials have demonstrated short term safety and clinical accuracy.
- Need quality control for point of care INR measurement.
- Patient selection is essential.
- Patients must have long term indication for anticoagulation therapy..
- Patients and caregivers must be willing and able to perform self-management.
- Patients must be willing to record results accurately and attend clinics regularly for quality assurance.
- Patients must demonstrate competence in using the instrument and interpreting the results.
- Patients must not have shown previous noncompliance in terms of clinic attendance or medication management.
- Can increase INR testing frequency and decrease complications associated with oral anticoagulation therapy.
- Need further clarification for financial arrangement.
Point of Care Instruments
Instrument Company Sample Type CoaguChek Roche Diagnostics Corp. Indianapolis, IN
http://www.roche-diagnostics.com/products_services/coaguchek_s.htmlCapillary or venous whole blood Harmony INR Monitoring System LifeScan Inc., Milpitas, CA
http://www.harmonyinr.com/Capillary or venous whole blood INRatio Prothrombin Time Monitoring System Hemosense, Inc. Milpitas, CA
http://www.hemosense.com/Capillary or venous whole blood ProTime Microcoagulation System International Technidyne Corp. Edison, NJ
http://www.itcmed.com/index.shtmlCapillary or venous whole blood
- These instruments are FDA approved for home use.
- These instruments are small, light weight, and portable devices.
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.
Lower dose (2.5 mg).Higher dose (7.5-10.0 mg).
- >80 yr.
- Concurrent illness.
- On interaction drug.
- S/P major surgery, i.e.. heart valve surgery.
- Chronic malnourished.
- Impaired liver function, liver congestion.
- Young healthy subject.
- In the first two days.
Note that the following guidelines does not have specific number, but rather a range of numbers. Individualization and careful monitoring is necessary.
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 2For #B. of Day 2
- If INR <1.5, suggests a higher than average maintenance dose of 5 mg/day or 35 mg/week will be needed. Give higher dose than 5 mg. i.e.7.5 mg for now.
- If INR 1.5-2.0, suggests an average maintenance dose close to 5 mg/day or close to 35 mg/week will be needed, and continue 5 mg for now.
- If INR >2.0, suggests a lower than average maintenance dose of 5 mg/day or 35 mg/week will be needed. Give less than 5 mg, i.e.2.5 mg or none for now.
- If INR 1.5-2.0, suggests daily dose will be close to or less than 5 mg/day or close to 35 mg/week or less. May give 5 mg or less for now.
- If INR >2.0, suggests daily dose will be significantly lower than 5 mg/day or less than 35 mg/week. May give 2.5 mg or none for now.
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.
- 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).
- Patients during an acute illness, or post operative of major surgeries may be more sensitive to warfarin than when they become more stable.
Out patient (See also "Day 4" above)
Table. Warfarin Initiation
|
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 |
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 | |
Back ground
- 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.
- Using specific days of the week for different daily dose is less confusing. 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)
- Using weekly dose adjustment appears more convenient and it is just as accurate.
- Applying #1, #2 and #3 along with one size tablet (i.e. 5 mg), a table of weekly-daily dose schedule can be constructed for working convenience (see Warfarin dose schedule table)
Note that weekly dose difference can be arranged as low as 2.5 mg per week, equivalent to only o.4 mg per day difference.
Example
Weekly Dose (mg)/ Daily Dose (mg)
- 35 -------------- 5.0 daily
- 37.5 ------------ 7.5 Mon, 5 ROW
- 40 -------------- 7.5 Mon, Fri, 5 ROW
- 42.5 ------------ 7.5 Mon, Wed, Fri, 5 ROW
- 45 -------------- 5.0 Mon, Wed, Fri, 7.5 ROW
- 47.5 ------------ 5.0 Mon, Fri, 7.5 ROW
- ----------------------------
(ROW = Rest Of the Week)
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
ROW ROW ROW ROW ROW Daily ROW ROW ROW ROW ROW ROW Daily ROW ROW ROW Daily ROW ROW ROW ROW ROW ROW Daily ROW ROW ROW ROW ROW ROW
- All doses are in mg.
- M,W,and F - Monday, Wednesday and Friday
- ROW - Rest Of the Week
- May not use the schedule with only Monday dose different.
To change the warfarin weekly dose:
- Change warfarin weekly dose by 10% (5-15%). Use higher percentage in patients with higher warfarin weekly dose, or
- Change warfarin weekly dose by 1 mg for each 0.1 INR. Add or subtract for lower or higher INR.
- Repeat INR in 1-2 weeks.
Example
of computer generated report from a patient using weekly dose
adjustment.
Note that there may be more than one choice for a diagnosis. This will allow different approaches within the database guidelines.
With the same diagnosis, co-morbidity or risk factors may move target INR to the higher level or add low dose ASA (80-160 mg), i.e. bileaflet aortic valve prostheses with recurrent systemic emboli should add ASA 80-160 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
Adapted from 6th Consensus Conference on Antithrombotic Therapy, Chest 2001.
7th ACCP Conference on Antithrombotic and Thrombolytic Therapy.Table 2. Target INR for Atrial Fibrillation and Atrial Flutter.
. ATRIAL FIBRILLATION A fib, <65 yr, no RF *.
. A fib, <65 yr, with RF *.
. A fib, 65-75 yr, no RF *.
A fib, 65-75 yr, with RF *.
. A fib, >75 yr.
. A fib, with recurrent emboli.
. A fib, with continue emboli.
. A fib, following cardiac surgery † 2.5-3.0 † . . A fib, cardiovert <48 hr **
. Pre-cardioversion **
.
Post-cardioversion.
. .
ATRIAL FLUTTER.
- RF* = Risk Factors: History of TIAs, CVA, systemic emboli, hypertension, LV systolic dysfunction, recurrent CHF, DM, rheumatic mitral valve disease, CAD, thyrotoxicosis, left atrial enlargement.
- a = add ASA 80 mg when there are more risk factors or more emboli.
- † = If >48 hours.The anticoagulation treatment should continue for several weeks following reversion to NSR, particularly if patients have risk factors for thromboembolism.
- ** = may consider pre and pericardioversion anticoagulation such as heparin or if the patient is on warfarin at target INR level already (not consistently mention in major guidelines).
Table 3. Target INR for Venous Thromboembolism
VENOUS THROMBOEMBOLIC (VTE)
. Deep vein thrombosis (DVT).
. 12 months in 1st idiopathic DVT Pulmonary emboli.
. .
- Start heparin with warfarin. Prefer Low molecular weight heparin (LMWH) over Unfractionated heparin (UFH).
- Discontinue heparin 2 days after target INR has reached.
- May use thrombolytic treatment in massive or life threatening pulmonary emboli..
- Duration of 12 months or more in cases of recurrent VTE, cancer, antithrombin deficiency, antithrombin antibody syndrome, protein C or protein S deficiency, multiple thrombophilic conditions, hemocystienemia, homozygous factor V Leidin.
- Insert inferior vena caval filter in cases of high risk of VTE and cannot use anticoagulation, recurrent VTE or pulmonary emboli with pulmonary hypertension despite adequate anticoagulation.
Table 4. Target INR for various conditions
. LEFT VENTRICULAR DISEASE Dilated cardiomyopathy (EF<30%).
Dilated cardiomyopathy (EF<30%), & emboli.
S/P anterior MI, LV thrombus.
SYSTEMIC EMBOLI. Systemic emboli.
. VALVULAR DISEASES. Rheumatic MV disease, NSR, LA>5.5 cm, history of systemic emboli.
( MV prolapse, unexplained TIAs.
MV prolapse, systemic emboli.
Mitral annular calcification (MAC).
MAC, systemic emboli (not Ca++ emboli).
Mitral valvuloplasty 2.0-3.0 3 wk before,
4 wk after. . AV disease (No anticoag. Rx by itself) . . . . PFO OR ATRIAL SEPTAL ANEURYSM. Unexplained systemic emboli, TIAs, particular with VTE, pulmonary emboli.
. ENDOCARDITIS. Native valve or bioprotheses, with systemic emboli during endocarditis.
Mechanical protheses, during endocarditis. . . . Nonbacterial thrombotic endocarditis (NBTE) with systemic or pulmonary emboli.
Aseptic vegetation (in patients with disseminated cancer or debilitating disease) . . . . ASCENDING AORTA, AORTIC ARCH. Ascending aorta, aortic arch. Mobile plaque >4 mm (TEE).
- a = add ASA 80 mg when there are more risk factors or more emboli. Use Dipyridamole 400 mg/d or clopidogrel 75 mg/d if the patients can not take ASA.
Target INR for Heart Valve Prostheses
General principles
- Type of prostheses. St. Jude Medical bileaflet, CarboMedics bileaflet, Medtronic-Hall tilting mono disc, Omnicarbon mono tilting disc, and Sorin bileaflet, in aortic position, are less thrombogenic.
- Position. Mitral position is more thrombogenic than aortic position.
- Duration. First few days up to first few months after surgery is more thrombogenic.
- Multiple prostheses have higher thromboembolic risk than single prosthesis.
- High thromboembolic risk cases.
- Tilting disk, ball-caged, disk-caged (except Medtronic-Hall and Starr-Edwards valve in aortic position).
- Risk factors (RF). Atrial fibrillation, severe LV systolic dysfunction, previous thromboembolism, hypercoagulable conditions.
- Continue thromboembolic problem while on treatment.
- Treatment.
- Add ASA 80-160 mg (up to 325).
- Increase the INR target level, i.e.2.0-3.0 to 2.5-3.5, up to 3.0-4.5. The latter is associate with higher bleeding complication.
Table 5. Target INR for Heart Valve Prostheses
Adapted from 6th Consensus Conference on Antithrombotic Therapy, Chest 2001 and 7th ACCP Conference on Antithrombotic and Thrombolytic Therapy.
ACC/AHA Pocket Guidelines. Management of Patients with Valvular Heart Disease, 2000.
GENERAL APPROACH * Mechanical prostheses(1)
May add ASA 80 Mechanical prostheses, others
May add ASA 80 Mechanical prostheses(3) Add ASA 80 Mechanical prostheses, with RF(2)
Add ASA 80 . AORTIC VALVE * AV prostheses, bileaflet*, no RF(2)
May add ASA 80 AV prostheses, bileaflet*, with RF(2)
Add ASA 80 AV prostheses, others, no RF(2)
May add ASA 80 AV prostheses, others, with RF(2)
Add ASA 80 AV bioprostheses, 1st 3 months
. -- After 3 months
. -- After 3 months, with RF(2)
May add ASA 80 . MITRAL VALVE * MV prostheses, mechanical
May add ASA 80 . MV bioprostheses, 1st 3 months
May add ASA 80 -- After 3 months
May add ASA 80 -- After 3 months, with RF(2)
May add ASA 80
- * = Warfarin can be started the day after prosthetic valve replacement. UFH or LMWH should be started about 2 days post surgery (when surgical bleeding has been completely controlled) and continue until INR reaches therapeutic level for 2 consecutive days.
- (1) = In aortic position.: St. Jude Medical bileaflet, CarboMedics bileaflet, Medtronic-Hall tilting mono disc, Omnicarbon mono tilting disc, and Sorin bileaflet.
- (2) = Risk factors: History of TIAs, CVA, systemic emboli, severe LV systolic dysfunction, recurrent CHF.
- (3) = Caged ball or caged disk valve.
Comparison with other 2 guidelines.
I. Table 6. Target INR for heart valve prostheses.
From ACC/AHA Pocket Guidelines. Management of Patients With Valvular Heart Disease. July 2000.
. MECHANICAL PROSTHETIC VALVES A. First 3 months after replacement B. After first 3 months: . . . --1. Aortic valve* . --2. Aortic valve + risk factor** . --3. Mitral valve . --4. Mitral valve + risk factor** . BIOLOGICAL PROSTHETIC VALVES A. First 3 months after replacement . B. After first 3 months: . . . --1. Aortic valve* --2. Aortic valve + risk factor† --3. Mitral valve --4. Mitral valve + risk factor†
- Based on McAnulty JH, Rahimtoola SH, Antithrombotic therapy in valvular heart disease. In Schlant R, Alexander RW, eds. Hurst's The Heart, Arteries, and Veins. 9th ed. New York, NY: Mcgraw-Hill Publishing Co; 1998: 1867-1874.
- Notice the new recommendation of adding ASA 80-100 mg. to all patients with mechanical heart valve prostheses.
- * = St. Jude Medical bileaflet, CarboMedics bileaflet, Medtronic-Hall tilting mono disc, Omnicarbon mono tilting disc, and Sorin bileaflet. For other aortic protheses INR should be maintain between 2.5-3.5.
- ** = Risk factors: Atrial fibrillation, severe LV systolic dysfunction, recurrent CHF, previous thromboembolism, and hypercoagulable conditions.
II. Table 7. Simple guidelines for target INR for various conditions.
From Quick Reference Guide for Clinicians. 6th Consensus Conference on Antithrombotic Therapy. 2001.
Prophylactic of venous thrombosis (high risk surgery). Treatment of venous thrombosis. Treatment of pulmonary embolism. Prevention of systemic embolism. Tissue heart valves. Acute myocardial infarction. Valvular heart disease. Atrial fibrillation. . Mechanical prosthetic valves (high risk). Bileaflet mechanical valve in aortic position. Certain patients with thrombosis and the antiphospholipid syndrome.
General principle
- Check for bleeding history.
- Treat patients with active or recent bleeding, history of easy bleeding or higher INR more aggressive.
- Require admission if there is significant bleeding. Hold warfarin until INR returns to therapeutic range or as long as there is bleeding or potential bleeding.
- Check INR more often during the period of higher INR or bleeding.
- Check for factor(s) effecting warfarin response. Try to correct it, or change dose appropriately.
- Individualization is necessary.
- INR > therapeutic level, but < 5.0 and no bleeding.
- 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.
- May not require warfarin dose change if the factor(s) effecting high INR can be identified and corrected.
- INR 5-9, and no bleeding.
- 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.
- More likely will require warfarin dose change.
- INR < 10, with minor bleeding or high risk for bleeding (i.e. recent surgery).
- Hold warfarin. Check for INR in 12-24 hours.
- Vitamin K, 1-2.5 mg orally.
- May repeat vitamin K in 24 hours.
- Check for factor(s) effecting INR carefully, correct the problem.
- Restart warfarin when at appropriate time. Adjust the dose.
- INR 10-20, and no bleeding.
- Hold warfarin. Check INR in 12-24 hours.
- If there is no admission, patient education is important.
- Vitamin K 2.5-5.0 mg orally.
- Check for factor(s) effecting INR carefully, correct the problem.
- Restart warfarin when INR return to target range. Adjust the dose.
- INR 10-20, with more then minor bleeding.
- Require admission.
- Hold warfarin. Check INR in 12-24 hours.
- 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.
- Restart warfarin when INR return to target range and the bleeding has resolved. Adjust the dose.
- INR > 20, with bleeding tendency or bleeding.
- Require admission. Check INR in 12-24 hours.
- 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.
- Restart warfarin when INR return to target range and the bleeding has resolved. Adjust the dose.
- Serious bleeding with therapeutic or elevated INR.
- Require admission.
- Follow guideline #5 . Be careful when restarting warfarin.
- Patient who requires more rapid or urgent reversal before procedure/surgery.
- 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.
(Large dose of intravenous administration may cause a period of warfarin resistance up to a week, when restart it.)
- The tablet size is 5 mg. The practical smallest dose is 2.5 mg. (Dose of 1.0 mg can be obtained by withdrawing the right amount from a 10 mg vial of injectable vitamin K, then given orally).
- Oral route is effective.
- Subcutaneous route may have unpredictable and delayed response.
- Intramuscular route may cause hematoma at the injection site.
- Intravenous route, utilize when
- Patient is unable to take oral medicine.
- Patient who may have impair absorption.
- Need rapid reversal of the INR. The dose is 5 - 10 mg (dose for patient who does not need rapid reversal of INR is 1-3 mg). Slow rate of infusion, at <1 mg/min, should help decrease the incident of anaphylactic reaction.
- Large dose of intravenous administration may cause a period of warfarin resistance up to a week, when restart it.
Table 8. Managing high INR or bleeding.
Hold ----- Adjust dose
• * or Vitamin K 2.5 mg po.
• FFP - Fresh Frozen Plasma.
Print this table
Problems
- Lack of good database.
- Most physicians use their own approaches which vary and is inconsistent. Some of these approaches have not been based on good principle, but rather a guessing or compromised one.
Guidelines.
- Assess the thromboembolic risk of the condition that requires the anticoagulation treatment.
- Assess the bleeding risk of the procedure/surgery that will be performed.
- Possibility of hypercoagulable state induced by the withdrawal of warfarin (rebound phenominon) or the surgical milieu resulting in greater perioperative thromboembolic events than what would be predicted based on the annual thromboembolic rate during nonsurgical settings (Table 9)
- Post major operative venous thromboemboli are more common, while post operative arterial thromboemboli are rare.
- Permanent disability or death is substantially more common after arterial thromboembolism (70-75%) compare to following venous thromboembolism (4-10%). Permanent disability or death after postoperative major bleeding is lower, at about 1-6%.
- Individualization.
- Select the plan in the "Protocol for managing anticoagulation during procedures/surgeries (5 plans)", then follow the detail of that plan in the "Detail of the protocol for managing anticoagulation during procedures/surgeries (5 plans) "
- Using the protocol will make this management more uniform.
Protocol for managing anticoagulation during procedures/surgeries.
- 5 plans for different days of inadequate anticoagulation ranging from 0 to 7 days. These plans include (1) Continue warfarin; (2) Hold warfarin, pre and post heparin; (3) Hold warfarin, post heparin; (4) Hold warfarin, pre heparin: (5) Hold warfarin only.
- Using low molecular weight heparin allows us to use this protocol out of the hospital both pre and post procedures/surgeries, if necessary.
- Post operative full dose heparin is associated with more bleeding complication, while pre operative heparin rarely causes bleeding, if withheld it at appropriate time.
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".
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).
VENOUS . Acute VTE
. -- Month 0-1
1.3
-- Month 1-3
Recurrent VTE
ARTERIAL
Acute arterial embolism
-- Month 0-1
NVAF
NVAF and previous embolism
Mechanical heart valve
- VTE = Venous thromboembolism.
- NVAF = Non valvular atrial fibrillation.
- * = Average
- † = Varies with type, position, and multiple prostheses.
(Rate of thromboembolism may be higher following holding warfarin and during surgical procedures - "rebound phenominon")
Patients with high risk for thromboembolism.
(1 year risk of arterial embolism > 10%, or 1 month risk of venous thromboembolism > 10 %)
- Known hypercoagulable state: Protein C, protein S and antithrombin III deficiency. Factor V Leiden and prothrombin gene mutation. Antiphospholipid antibody syndrome (APS), SLE with cardiolipin antibodies.
- Recurrent arterial or idiopathic venous thromboembolism events.
- Venous or arterial thromboembolism within the preceding 1-3 months.
- Rheumatic atrial fibrillation.
- Acute intracardiac thrombus visualized by echocardiogram.
- Atrial fibrillation plus mechanical heart valve in any position.
- Older mechanical valve model in mitral position.
- Recently placed mechanical valve (<3 months).
- Atrial fibrillation with history of cardioembolism.
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 %)
- Recurrent CVA or TIAs without risk factors for cardiac embolism.
- Atrial fibrillation without history of cardiac embolism but with multiple risks for cardiac embolism (LV ejection <40%, diabetes, hypertension, nonrheumatic valvular heart disease, transmural myocardial infarction within preceding month)
- Venous thromboembolism 3-6 months.
Patients with low risk for thromboembolism.
(1 year risk of arterial embolism < 5%, or 1 month risk of venous thromboembolism < 2%%)
- Venous thromboembolism >6 months.
- Atrial fibrillation without multiple risks for cardiac embolism.
- Newer model prosthetic valve in aortic position >3 months.
Bleeding Risks
- 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.
- 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.
- Gastroenterologic: Colonoscopic and gastric polypectomy, laser ablation and coagulation, endoscopic sphincterotomy, and those procedures with the potential to produce bleeding inaccessible or uncontrollable by endoscopic means such as pneumatic or bougie dilation of benign or malignant strictures, percutaneous endoscopic gastrostomy, and EUS-guided fine needle aspiration.
- 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.
- Cardiac procedures. Pacemaker/ICD insertion have more bleeding potential than bleeding from cardiac catheterization site.
- Any procedures or surgeries that bleeding can not be controlled or stopped with simple intervention.
- Other major surgeries.
Table 10. Protocol for managing anticoagulation during procedures/surgeries (5 plans)
Continue warfarin Hold warfarin With Pre and Post procedure heparin
Hold warfarin With Post procedure heparin Hold warfarin With Pre procedure heparin Hold warfarin only
* = Mininal days
Detail of protocols for managing anticoagulation during procedures/surgeries (5 plans)
- 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.
- Hold warfarin, post procedure heparin, pre procedure heparin.
- Check INR 7 days before 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.
- Start full dose of unfractionated heparin (UFH) or low molecular weight heparin (LMWH) when INR is 2.0 or less which may take about 24-48 hours for INR of 2.0-3.0.
- 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.
- Stop heparin (6 hours for UFH, or 24 hours for LMWH) before the procedure.
- Start full dose of heparin (UFH or LMWH) 24 hours post procedure (when there is no risk of post operative bleeding). No bolus. (Only apply in patients with low risk for post operative bleeding). Low dose (for venous thromboemboli prevention) may be started 12 hours post procedure. These timing should be varied (delayed) depending on risk of bleeding for that patient.
- 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 1-2 days.
- Hold warfarin, post procedure heparin. (Not suitable for patients with high risk for post procedures/surgeries bleeding)
- 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.
- Start full dose of heparin (UFH or LMWH) 24 hours post procedure (when there is no risk of post operative bleeding). No bolus. (Only apply in patients with low risk for post operative bleeding). Low dose ( for venous thromboemboli prevention) may be started 12 hours post procedure. These timing should be varied (delayed) depending on risk of bleeding for that patient.
- 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 3-4 days.
- Hold warfarin, pre procedure heparin.
- Check INR 7 days before procedure, keep 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.
- Start full dose of unfractionated heparin (UFH) or low molecular weight heparin (LMWH) when INR is 2.0 or less which may take about 24-48 hours for INR of 2.0-3.0.
- 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.
- Stop heparin (6 hours for UFH, or 24 hours for LMWH) before 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 4-6 days.
- 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.
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. Others: |
. |
VTE/pulmonary ** emboli |
. |
. | |
|
Low |
--- < 1 month |
High |
1, (2) † | ||
|
Low |
--- 1-3 months |
High |
1, (2) | ||
|
Low |
--- Recurrent |
Low |
1, (3,4) | ||
|
. |
Acute Arterial Emboli |
. |
. | ||
|
Low |
--- < 1 month |
High |
1, (2) † | ||
|
Low |
--- > 1 month |
Low |
1, (3,4) | ||
|
. |
Non Valvular atrial fibrillarion (NVAF) |
. |
. | ||
|
Low |
Atrial fibrillation |
Low |
1, (3,4) | ||
|
Low |
--- With risk factors (1) |
High |
1, (2,3,4) | ||
|
. |
Heart Valve Prostheses |
. |
. | ||
|
Low |
Bileaflet AV † |
Low |
1, (4) | ||
|
Low |
Other valves, multiple or with additional risk factors (2) |
High |
1, (2,3,4) | ||
| Low | (See "Patients with high, intermediate and low risk for thromboembolism") in "Thromboembolic risk" section above. | Using the above approach as a guide to help select the appropriate protocol for each individual. |
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) | ||
Comparison with other 2 guidelines.
I. Table 13. Guidelines for managing anticoagulation during procedures/surgeries.
Adapted from Nguyen DP, et al. Hosp Pharm 1999, and Mayo Clinic. Regional Anticoagulation Symposium, Rochester, Minnesota. 10/2000.
|
PROCEDURE/ SURGERY |
BLEEDING RISK |
DIAGNOSIS |
THROMBO RISK |
PROTOCOL |
|
. |
VTE/pulmonary emboli |
. | ||
|
NA |
NA |
--- Within 6 weeks |
High |
2† |
|
NA |
NA |
--- 6 wks - 3 months |
High |
2 |
|
NA |
NA |
--- Recurrent |
Low |
5, SC heparin post op |
|
.
|
Acute arterial emboli |
. | ||
|
NA |
NA |
--- Within 6 weeks |
High |
2 |
|
NA |
NA |
--- > 6 weeks |
Low |
NA |
|
. |
Non valvular atrial fibrillation (NVAF) |
. | ||
|
NA |
NA |
--- Uncomplicated |
Low |
5, SC heparin post op |
|
NA |
NA |
--- With risk factors (1) |
High |
4, SC heparin post op |
|
. |
Mechanical heart valve prostheses |
. | ||
|
NA |
NA |
--- Low risk (2) |
Low |
5, SC heparin post op |
|
NA |
NA |
--- High risk (3) |
High |
4, 2 |
II. Table 14. Simple guidelines for managing anticoagulation during procedures/surgeries.
Acute VTE
-- Month 1
-- Month 2-3
Recurrent VTE
Acute arterial embolism
-- Month 1
Mechanical heart valve (1)
NVAF (1)
- No detail in managing patients with different operative bleeding risk, or patients with different thromboembolic risk.
- VTE = Venous thromboembolism.
- NVAF = Non valvular atrial fibrillation
- (1) = For low bleeding risk patients.
- (2) = Unfractionated (UFH) or low molecular weight heparin (LMWH).
- (3) = For prevention of venous thromboembolism only.
Unfractionate heparin (UFH) (Update soon)
- Molecular weight of 3000 to 30000 and mean of 15000
LMWH (Low molecular weight heparin)
- Molecular weight of 2000 to 9000 and mean of 4000-5000.
- FDA has not approved for anticoagulation bridging therapy, but there has been sufficient data that it can be used effectively and safely.
- When compare to UFH, LMWH has better bioviability, more predictable dose responses and longer plasma half-lives. It has less interaction with platelets, endothelial cells. macrophages and plasma proteins.
- Can be given subcutaneously on an outpatient basis.
- Less heparin-induced thrombocytopenia (HIT) than UFH (1% vs 3%).
- Similar rate of bleeding to UFH.
- Require adequate plan and patient education to make it work properly.
Unsuitable conditions for LMWH:
Dosing
Prophylactic doae 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.
- Enoxaparin (Lovenox) 1mg/kg SC q 12 hours or 1.5 mg/kg SC q 24 hours.
- Dalteparin (Fragmin) 120 U/kg SC q 12 hours or 200 U/kg SC q 24 hours
- Tinzaparin (Innohep) 175 U/kg SC q 24 hours
After surgery dosing
- Therapeutic dose at no sooner than 24 hours after the procedure.
- Prophylactic dose may be started 12 hours after the procedure in not high bleeding risk patients.
- Continue heparin therapy until INR reaches therapeutic level for 2 consecutive days.
Heparin-induced thrombocytopenia (HIT)
- Incident of 3% from UFH and 1% from LMWH.
- May associate with thrombosis in 30-80% of the cases.
- May occur as early 1 day into therapy particularly in case with previous heparin exposure.
Table 15. Form for managing anticoagulation during procedures/surgeries.
Section A Section B Patient name: . Age: Rec No: . . 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* 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(es) 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". May also mark those areas picked (underline or yellow mark).May send this marked printout to primary physician or place it in the chart.
Options of anticoagulation management in pregnancy with mechanical prosthetic valve.
- Warfarin throughout pregnancy, with its potential fetal risks. Change to heparin (UFH or LMWH) at 38 weeks, Labor induction at 40 weeks of gestation.
- Heparin throughout pregnancy, with its associated maternal thrombosis risks particularlly mechanical heart valve prosthesis. It is anticipated that heparin dose in the third trimester will be higher.
- 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 innection.
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, carefully.
General.
- 6th ACCP Consensus Conference on Antithrombotic Therapy. Chest 2001; 119 (Suppl): 1S-370S
- 6th ACCP Consensus Conference on Antithrombotic Therapy. Quick Reference Guide for Clinicians.
- Ginsberg JA, Crowther MA, White RH, Ortel TL. Anticoagulation Therapy. Hematology (Am Soc Hematol Educ Program) 2001 Jan; :339-57.
- Sachdev GP, Ohlrogge KD, Johnson CL. Review of the Fifth American College of Chest Physicians Consensus Conference on Antithrombotic Therapy: Outpatient Management for Adults. Am J Health Syst Pharm 1999; 56(15): 1505-1514.
- Ansell JE, Oertel LB, Wittkowsky AK. Managing Oral Anticoagulation Therapy. Clinical and Operational Guidelines. Aspen Publishers, Inc. 1997.
- Ansell JE, Buttaro ML, Thomas VO, et al. Consensus Guidelines for Coordinated Outpatient Oral Anticoagulation Therapy Management. Ann Pharmacother. 1997; 31: 604-615.
- Ansell JE, Becker RC. Guidelines for the Initiation, Monitoring and Clinical use of Anticoagulant Therapy. DuPont Pharmaceuticals, 1999.
- Litin SC, Gastineau DA. Current Concepts in Anticoagulant Therapy. Mayo Clin Proc 1995; 70: 266-272.
- Brigden ML. Oral Anticoagulation Therapy. Practical aspect of management. Postgrad Med 1996; 99: 81-4, 87-9, 93-4.
- ACC/AHA Task Force Report. Bonow RO, et al. Guidelines for the Management of Patients with Valvular Heart Disease. Circulation 1998; 98: 1949-1984.
- Tiede DJ, Nishimura RA, Gastineau DA, et al. Modern Management of Prosthetic Valve Anticoagulation . Mayo Clin Proc 1998; 73: 665-680.
Warfarin Initiation.
- 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.
- Tait RC, Sefcick A. A Warfarin Induction Regimen for Outpatient Anticoagulation in Patients with Atrial Fibrillation. Br J Haematol. 1998; 101(3): 450-454.
- Ageno W, Turpie AG. Exaggerated Initial Response to Wafrarin followint Heart Valve Replacement. Am J Cardiol, 1999; 84(8): 905-908.
Target INR.
- 6th ACCP Consensus Conference on Antithrombotic Therapy. Chest, 2001; 119 (1 Suppl): 1S-370S.
- 6th ACCP Consensus Conference on Antithrombotic Therapy. Quick Reference Guide for Clinicians.
- ACC/AHA Task Force Report. Bonow RO, et al. Guidelines for Management of Patients with Valvular Heart Disease. Circulation 1998; 98: 1949-1984.
- ACC/AHA Pocket guidelines. Management of Patients With Valvular Heart Disease. July 2000.
Vitamin K
- Crowther MA, Donovan D, Harrison L, et al. Low-dose Oral Vitamin K Reliably Reverse Over-anticoagulation due to Warfarin. Thromb Haemost, 1998; 79: 1116-1118.
- Raj G, Kumar R, McKinney WP. Time Course of Reversal of Anticoagulation Effect of Warfarin by Intravenous and Subcutaneous Phytonadione. Arch Int Med, 1999; 159: 2721-2724.
Perioperative Management.
- Kearon C. Perioperative Management of Long-term Anticoagulation. Semin Thromb Hemost 1998; 24 (Suppl 1): 77-83.
- Kearon C, Hirsh J. Managing Anticoagulation Before and After Surgery in Patients Who Require Oral Anticoagulants. N Engl J Med 1997; 336: 1506-1511.
- Shalaby A, Mohiuddin SM. Lowson SM, Hanson EW. Spandorfer J, Merli G.N
Anticoagulation and elective surgery.
N Engl J Med. 1997 Sep 25;337(13):939; author reply 939-40.- Douketis JD. Perioperative anticoagulation management in patients who are receiving oral anticoagulant therapy: a practical guide for clinicians.
Thromb Res. 2002 Oct 1;108(1):3-13.- Shapira Y, Vaturi M, Sagie A. Anticoagulant management of patients with mechanical prosthetic valves undergoing non-cardiac surgery: indications and unresolved issues.
J Heart Valve Dis. 2001 May;10(3):380-7. Review.- Spandorfer J. The management of anticoagulation before and after procedures.
Med Clin North Am. 2001 Sep;85(5):1109-16, v. Review.- Jacobs LG, Nusbaum N. Perioperative management and reversal of antithrombotic therapy.
Clin Geriatr Med. 2001 Feb;17(1):189-202, ix. Review.- Heit JA. Perioperative management of the chronically anticoagulated patient.
J Thromb Thrombolysis. 2001 Sep;12(1):81-7. Review.
- Hewitt RL, Chun KL, Flint LM. Current Concepts in Perioperative Anticoagulation. Am Surg 1999; 65: 270-273.
- Nguyen DP, Hasson NK. Perioperative Management of Patients on Long-term Warfarin Therapy. Hosp Pharm 1999; 34 (1): 103-107.
- Wahl MJ. Dental Surgery in Anticoagulation Patients. Arch Intern Med, 1998; 158: 1610-1616.
- Campbell JH, Alvarado F, Murray RA. Anticoagulation and Minor Oral Surgery: Should the Anticoagulation Regimen be Altered? J Oral Maxillofac Surg. 200l; 58: 131-135.
- Stables G, Lawrence CM. Management of patients taking anticoagulant, aspirin, non-steroidal anti-inflammatory and other anti-platelet drugs undergoing dermatological surgery.
Clin Exp Dermatol. 2002 Sep;27(6):432-5. Review.- American Sociaty for Gastrointestinal Endoscopy. Guideline on the Managenent of Anticoagulation and Antiplatelet Therapy for Endoscopic Procedures. Gastrointest Endosc. 1998; 48: 672-675.
Warfarin Drug Interaction.
- Buckley NA, Dawson AH. Drug Interactions with Warfarin. Med J Aust, 1992; 157: 479-483.
- Freedman MD, Olatidoye AG. Clinical Significant Drug Interactions with the Oral Anticoagulants. Drug Saf 1994; 10 (5): 381-394.
- Kayser SR. Drug Interaction with Coumarin Anticoagulants. Prog Cardiovasc Nurs 1993; 8(1): 40-45.
- Harder S, Thurmann P. Clinically Important Drug Interactions with Anticoagulants. An Update. Clin Pharmacokinet. 1996; 30(6): 416-444.
- Wells PS, Holbrook AM, Crowther NR, hirsh J. Interactions of warfarin with Drugs and Food. Ann Intern Med. 1994; 121(9): 676-683.
- Handbook of Adverse Drug Interactions. The medical Letter, Inc. NY. 1999.
Amoidarone.
- Kerin NZ, Blevins RD, Goldman L, et al. The Incidence, Magnitude, and Time Course of the Amiodarone-warfarin Interaction. Arch Intern Med, 1988; 148: 1779-1781.
- Sanoski CA, Bauman JL.
Clinical observations with the amiodarone/warfarin interaction: dosing relationships with long-term therapy.
Chest. 2002 Jan;121(1):19-23.Propafenone.
- Kates RE, Yee YG, kirsten EB. Interaction Between warfarin and Propafenone in Healthy Volunteer Subjects. Clin Pharmacol Ther, 1987; 42(3): 305-311.
Tylenol.
- Shek KL, Chan LN, Nutescu E. Warfarin-acetaminophen Drug Interaction Revisited . Pharmacotherapy, 1999; 19: 1153-1158.
- Hylek EM, Heiman H, Skates SJ, Sheehan MA, Singer DE. Acetaminophen and other risk factors for excessive warfarin anticoagulation. JAMA. 1998 Mar 4;279(9):657-62.
Low Molecular Weight Heparin.
- 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.
- 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.
- 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.
- 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.
- Magnani HN, Orgaran (danaparoid sodium) Use in the Syndrome of Heparin-induced Thrombocytopenia. Platelets 1997; 8: 74-81.
General
- AHA/ACC. Guide to Warfarin Therapy, 2003
- Jaffer A, Bragg L.
Practical tips for warfarin dosing and monitoring.
Cleve Clin J Med. 2003 Apr;70(4):361-71. Review.- Anticoagulation Therapy Guidelines, 2003 Update.
Institute for Clinical Systems Improvement (ICSI)
Target INR.
- 7th ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126 Number 3 (Suppl): 163S-703S
Warfarin Initiation and dosing
- 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.- Jaffer A, Bragg L.
Practical tips for warfarin dosing and monitoring.
Cleve Clin J Med. 2003 Apr;70(4):361-71. Review.Perioperative Management
- 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.- Jaffer AK, Brotman DJ, Chukwumerije N.
When patients on warfarin need surgery.
Cleve Clin J Med. 2003 Nov;70(11):973-84. Review.- Jafri SM.
Periprocedural thromboprophylaxis in patients receiving chronic anticoagulation therapy.
Am Heart J. 2004 Jan;147(1):3-15. Review.- Watts SA, Gibbs NM.
Outpatient management of the chronically anticoagulated patient for elective surgery.
Anaesth Intensive Care. 2003 Apr;31(2):145-54. Review.Point of Care
- Yang DT, Robetorye RS, Rodgers GM.
Home prothrombin time monitoring: a literature analysis.
Am J Hematol. 2004 Oct;77(2):177-86. Review.- Siebenhofer A, Berghold A, Sawicki PT.
Systematic review of studies of self-management of oral anticoagulation.
Thromb Haemost. 2004 Feb;91(2):225-32. Review.Anticoagulation web sites
- carecr.com
CareInternet.net. Check "Antithrombotic Therapy".
- anticoagulation-advisor.com
A guide for using a slide-chart and figures- Consensus guidelines for warfarin therapy, 2000.
Australian Sociaty of Thrombosis and hematostasis.- Anticoagulation, 1997.
Columbia Presbiterian Medical Center.
- Anticoagulation Therapy
14th Annual Pharmacy Invitational Conference on Anticoagulation Therapy, 12/4/99- TIA or Stroke management.
neuroland.com- The perioperative management of anticoagulation.
Royal Melbourne Hospital
- Antithrombin
University of Illinois hematology resource pages.- Anticoagulant, Fibrinolytic and Antiplatelet Therapy Clinical ...
General hematology resources.- Anticoagulation Therapy Management Certificate Program.
University of Southern Indiana- http://www.strokecenter.org/education/aha_anticoagulant_therapy/
Stroke Center- http://www.aacc.org/divisions/poct/ansell/tsld001.htm
Point of Care. Self Management. Slides program.- http://www.umich.edu/~pharm660/AnticoagAntiplat/tsld001.htm
Management and Prevention of Vascular Thrombosis. Slides program.http://www.acforum.org/
Anticoagulation Forum.
www.coumacare.com
http://www.coumadin.com/
- http://www.google.com/search?hl=en&q=oral+anticoagulation&btnG=Google+Search
Google Search for Oral Anticoagulation- http://search.msn.com/results.asp?FORM=MSNH&RS=CHECKED&q=oral+anticoagulation&v=1
MSN Search for Oral AnticoagulationAcenocoumarolThis medicine contains the active ingredient acenocoumarol (previously known as nicoumalone in the UK). ... Acenocoumarol. Main Use, Active Ingredient, Manufacturer. ...
www.netdoctor.co.uk/medicines/100004007.html - 49k - Cached - Similar pages
Patient education and understanding is essential for successful warfarin management clinic.
- Keep content simple and uniform. It has been recommended that the 5th or 6th grade level is usually more effective.
- Include family member or significant other.
- Evaluate the patient understanding, cooperation and compliance periodically. Repeat education is usually necessary.
- It is a time consuming process and it is more effectively performed by specific personnel with experience and time.
Contents
- Why do they need anticoagulation.
- They have condition-disease with harmful blood clot or potentially harmful blood clot formation. The blood clot may block blood vessel such as in the leg, lung and particularly in the brain and cause stroke.
- What is oral anticoagulation (Warfarin-Coumadin).
- It action is to help reduce the blood clot formation by decreasing the formation of blood clotting factors, not due to thinning of the blood as usually belief.
- Importance of compliance.
- What happen if the patient take too much or too little coumadin.
- Taking too much coumadin will cause bleeding.
- Taking too little coumadin will not prevent blood clot formation.
- Coumadin has narrow therapeutic range and it needs to be monitored carefully.
- How do we know that they take the right dose.
- Blood test to measure INR. There are INR levels that are recommended for various condition-diseases. Coumadin dose will be adjusted to obtain the appropriate INR level.
- Time to take coumadin and blood test.
- If it is possible, they should take coumadin in the afternoon-evening and have blood test in the morning. This will make the INR test result more consistent.
- Interactions.
- Medicine non compliance and drug interaction are the most common causes of fluctuating INR.
- Drugs. This includes both prescription drugs, over the counter medicines and herbal-natural products. The clinic should have adequate list of these products.
- Patient must report to the anticoagulation clinic or the health care provider as soon as they start on new medicine even it is a temporary one. The clinic should have plan or protocol to deal with this problem.
- Food. Recognizing food rich in vitamin K. The clinic should have list of those food for the patient. Patient should try to be on stable eating habit.
- Avoid large amount of alcohol.
- When to contact the clinic.
- New medicine or herbal remedies; concurrent illness; evidence of bleeding;
- Medic alert bracelet.
Prapared by:
Dub Sukhum, MD.
Reviewed by:
- Stephen C Reichl, MD.
- Daniel J Tiede, MD.
- Arne Tilleson, RPH
- Dona Bloch, RN.
- Linda Lloyd, RN.