Improving Patient Care - May 2005 - Family Practice Management

May 2005 Table of Contents

Improving Patient Care

A Systematic Approach to Managing Warfarin Doses

Standard protocols make it easy to do the right thing when adjusting warfarin doses.

Mark H. Ebell MD, MS

Covered in FPM Quiz

Tool inside

A 67-year-old patient, Mrs. Leiden is taking 40 mg of warfarin per week (one 5-mg tablet per day on Tuesday, Wednesday, Thursday, Saturday and Sunday, and one and one-half tablets on Monday and Friday). Today her international normalized ratio (INR) is 3.6. Looking back at her records, you notice that her INR trend has gradually risen; her last value was 2.9. How should you adjust her warfarin dose?

What the evidence says

To provide safe, effective care for patients receiving warfarin, practices must follow a systematic process for managing anticoagulation and adjusting warfarin doses. Too often, however, the management of anticoagulation is haphazard because of busy clinical practices and multiple competing demands for physicians' time and attention.

Two alternatives to managing anticoagulation in the primary care office are using anticoagulation management services (AMS) and patient self-monitoring (PSM), which relies on home testing of the INR. A systematic review of the evidence found some support for AMS and PSM over usual care because of increased patient time in the therapeutic range and fewer bleeding complications.1 However, most studies were small, and many were non-randomized. When patients can choose whether to attend an AMS or get usual care, it is possible that more motivated, compliant patients are attracted to the AMS. Large-scale randomized controlled trials with an appropriate duration of follow-up are lacking. Two trials using a before-and-after design (which is still more subject to bias than a prospective randomized trial) found more hemorrhages and recurrent thromboembolia in the usual care group than in the group managed by AMS.2,3 However, the single prospective randomized trial on this topic followed 363 patients for two years and found no difference in complications or time spent in the therapeutic range.4

POINT-OF-CARE SERIES

POC Guides This article is part of a series that offers evidence-based tools to assist family physicians in improving their decision making at the point of care. The series is produced in partnership with American Family Physician. A related article, which also includes the anticoagulation flowsheet and reminder chart, appears in the May 15, 2005, issue of AFP.

Past topics in this series include sore throat, pulmonary embolism, hypertension, acute otitis media, angioplasty risk and knee injury. All tools are available free online at http://www.aafp.org/fpm/toolbox.

What distinguishes AMS and PSM from usual care is that they take a consistent, systematic, protocol-driven approach to monitoring patients. Put another way, they make it easy to do the right thing and hard to do the wrong thing when adjusting warfarin doses. By using standard protocols and making the best possible use of nurses and other staff, physicians should be able to improve outcomes to a similar extent in their own offices.

Unfortunately, no randomized trials exist comparing different dosage adjustment algorithms. The algorithm shown in the accompanying flow sheet is adapted from that of the anticoagulation service at the University of Michigan5 and is consistent with recommendations from the American College of Chest Physicians guideline1 and others. A chart to help patients remember the correct dose of warfarin is also provided. To use it, simply identify the correct weekly warfarin dose, highlight that row in the table, and give the chart to the patient.

The answer

To treat the fictitious patient mentioned earlier, refer to the table at the bottom of the flow sheet on page 79. It suggests that you lower Mrs. Leiden's warfarin dose 5 to 10 percent (e.g., to 36 to 38 mg) and recheck her INR in 7 to 14 days.

If she returns in one week with a therapeutic INR, you would ask her to come back in one week. The next week, if she is in range again, you would ask her to come back in two weeks.

OUTPATIENT ANTICOAGULATION FLOWSHEET

A PDF version of this document is available. Download PDF now. (2 pages/ 84KB. More information on using PDF files.)

Patient's name: _______________________________________________

Date of birth:_____/_____/_____ Medical record #: _____________________

Indication for anticoagulation (check one):		Atrial fibrillation			Deep vein thrombosis			Pulmonary embolism
Indication for anticoagulation (check one):		Mechanical valve			Cerebrovascular accident			Other

Target International Normalized Ratio (INR)*: 2.0 to 3.0 2.5 to 3.5
Other:_____________________

Start date: _____/_____/_____

Therapy duration: 3 months 6 months 1 year Indefinite Other:____________________

Date	Current dose	INR	Complications	New dose	Next INR	Initials

DOSAGE ADJUSTMENT ALGORITHMS

For target INR of 2.0 to 3.0, no bleeding:*

INR	< 1.5	1.5 to 1.9	2.0 to 3.0	3.1 to 3.9	4.0 to 4.9	≥ 5.0
Adjustment	Increase dose 10 to 20%; consider extra dose	Increase dose 5 to 10%†	No change	Decrease dose 5 to 10%†	Hold for 0 to 1 day then decrease dose 10%	See reverse side.
Next INR	4 to 8 days	7 to 14 days	No. of consecutive in-range INRs x 1 wk (max: 4 wks)‡	7 to 14 days	4 to 8 days	See reverse side.

For target INR of 2.5 to 3.5, no bleeding:*

INR	< 1.5	1.5 to 2.4	2.5 to 3.5	3.6 to 4.5	4.5 to 6.0	> 6.0
Adjustment	Increase dose 10 to 20%; consider extra dose	Increase dose 5 to 10%§	No change	Decrease dose 5 to 10%; consider holding one dose§	Hold for 1 to 2 days then decrease dose 5 to 15%	See reverse side.
Next INR	4 to 8 days	7 to 14 days	No. of consecutive in-range INRs x 1 wk (max: 4 wks)‡	7 to 14 days	2 to 8 days	See reverse side.

* - See reverse side for further guidance.

† - If INR is 1.8 to 1.9 or 3.1 to 3.2, consider no change with repeat
INR in seven to 14 days.

‡ - For example, if a patient has had three consecutive in-range INR values, recheck in 3 weeks.

§ - If INR is 2.3 to 2.4 or 3.6 to 3.7, consider no change with repeat INR in seven to 14 days.

ANTICOAGULATION DECISION SUPPORT

Indication	Target INR	Duration of therapy	SORT
DVT or PE1
First episode, transient risk factor	2.0 to 3.0	3 months	A
First episode, idiopathic DVT	2.0 to 3.0	6 to 12 months*	A
First episode, patient with cancer	2.0 to 3.0	LMWH for 3 to 6 months, then warfarin (Coumadin); treat until cancer is resolved*	A
First episode and single risk factor†	2.0 to 3.0	6 to 12 months*	A
First episode, antiphospholipid antibodies or at least two risk factors†	2.0 to 3.0	12 months*	B
Recurrent DVT	2.0 to 3.0	Indefinitely	B
Atrial fibrillation2	2.0 to 3.0	Indefinitely‡	A
Valvular disease3
Rheumatic mitral valve and atrial fibrillation or previous emboli	2.0 to 3.0	Indefinitely	B
Rheumatic mitral valve disease, normal sinus rhythm, and left atrial diameter > 5.5 cm	2.0 to 3.0	Indefinitely	B
Aortic St. Jude Medical bileaflet valve	2.0 to 3.0	Indefinitely	A
Mitral tilting disk valves and bileaflet mechanical valves	2.5 to 3.5	Indefinitely	B
Aortic CarboMedics bileaflet or Medtronic Hall tilting disk valves, normal sinus rhythm, and no LAE	2.0 to 3.0	Indefinitely	B
Mechanical valves with risk factors (atrial fibrillation, myocardial infarction, LAE, endocardial damage, low ejection fraction)	2.5 to 3.5	Indefinitely,* low-dose aspirin	B
Caged ball or disk valve	2.5 to 3.5	Indefinitely,* low-dose aspirin	B
Mechanical valve with breakthrough embolism despite INR 2.0 to 3.0	2.5 to 3.5	Indefinitely,* low-dose aspirin	B
Bioprosthetic valve (mitral)	2.0 to 3.0	3 months after placement	B
Bioprosthetic valve (aortic)	2.0 to 3.0	3 months of warfarin or aspirin	B

Management of Significantly Elevated INR With or Without Bleeding4

INR 5.0 to 8.9, no significant bleeding: Omit 1 to 2 doses; reduce dose 10 to 20 percent; monitor frequently. Alternately consider vitamin K1 1 to 2.5 mg orally.

INR ≥ 9.0, no significant bleeding: Hold warfarin therapy; give vitamin K1 5 to 10 mg orally; monitor frequently. Resume at lower dose when INR is therapeutic.

Serious bleeding, any INR: Hold warfarin; give vitamin K1 10 mg slow intravenous (IV) plus fresh plasma or prothrombin complex concentrate, depending on urgency; repeat vitamin K1 every 12 hours as needed.

Life-threatening bleeding, any INR: Hold warfarin; give prothrombin complex concentrate (or recombinant factor VIIa as an alternate) supplemented with vitamin K1 (10 mg slow IV); repeat as needed.

INR = International Normalized Ratio; SORT = Strength-of-Recommendation Taxonomy; DVT = deep vein thrombosis; PE = pulmonary embolism; LMWH = low-molecular-weight heparin; LAE = left atrial enlargement; A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, opinion, or case series.

* - Consider indefinite therapy for selected patients.

† - Deficiency of antithrombin III, protein C, or protein S; prothrombotic gene mutation such as V Leiden or prothrombin 20210; homocystinemia, or factor VIII levels above the 90th percentile of normal; or persistent residual thrombosis on repeated testing with compression ultrasonography.

‡ - Not indicated in patients younger than 65 years who do not have risk factors (i.e., heart failure, hypertension, previous ischemic stroke or transient ischemic attack, or diabetes mellitus).

1. Buller HR, Agnelli G, Hull RD, Hyers TM, Prins MH, Raskob GE. Antithrombotic therapy for venous thromboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy [published correction appears in Chest 2005;127:416]. Chest 2004;126(3 suppl):401S-28S.

2. Singer DE, Albers GW, Dalen JE, Go AS, Halperin JL, Manning WJ. Antithrombotic therapy in atrial fibrillation: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126(3 suppl):429S-56S.

3. Salem DN, Stein PD, Al-Ahmad A, Bussey HI, Horstkotte D, Miller N, et al. Antithrombotic therapy in valvular heart disease - native and prosthetic: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126(3 suppl):457S-82S.

4. Ansell J, Hirsh J, Poller L, Bussey H, Jacobson A, Hylek E. The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy [published correction appears in Chest 2005;127:415-6]. Chest 2004;126(3 suppl):204S-33S.

Flowsheet developed by Mark H. Ebell, MD, MS. Copyright © 2005 American Academy of Family Physicians. Physicians may photocopy or adapt for use in their own practices; all other rights reserved. "A Systematic Approach to Managing Warfarin Doses." Ebell MH. Family Practice Management. May 2005:77-83; http://www.aafp.org/fpm/20050500/77asys.html.

warfarin dose reminder chart

A PDF version of this document is available. Download PDF now. (1 page/ 76KB. More information on using PDF files.)

Name: ________________________________________________ Date of adjustment:_____/_____/_____

Your doctor has highlighted a row below showing the total amount of warfarin (Coumadin) you should take each week. Look at the highlighted row and find the number under today's day of the week. Take that number of 5-mg warfarin tablets at approximately 5 p.m.

Number of 5-mg tablets to take on each day of the week
Total weekly dose (mg)	Number of tablets on Monday	Number of tablets of Tuesday	Number of tablets on Wednesday	Number of tablets on Thursday	Number of tablets on Friday	Number of tablets on Saturday	Number of tablets on Sunday
2.5	1/2	0	0	0	0	0	0
5.0	1/2	0	0	0	1/2	0	0
7.5	1/2	0	1/2	0	1/2	0	0
10.0	1/2	0	1/2	0	1/2	0	1/2
12.5	1/2	0	1/2	0	1/2	1/2	1/2
15.0	1/2	0	1/2	1/2	1/2	1/2	1/2
17.5	1/2	1/2	1/2	1/2	1/2	1/2	1/2
20.0	1	1/2	1/2	1/2	1/2	1/2	1/2
22.5	1	1/2	1/2	1/2	1	1/2	1/2
25.0	1	1/2	1	1/2	1	1/2	1/2
27.5	1/2	1	1/2	1	1/2	1	1
30.0	1/2	1	1	1	1/2	1	1
32.5	1/2	1	1	1	1	1	1
35.0	1	1	1	1	1	1	1
37.5	1 1/2	1	1	1	1	1	1
40.0	1 1/2	1	1	1	1 1/2	1	1
42.5	1 1/2	1	1 1/2	1	1 1/2	1	1
45.0	1	1 1/2	1	1 1/2	1	1 1/2	1 1/2
47.5	1	1 1/2	1 1/2	1 1/2	1	1 1/2	1 1/2
50.0	1	1 1/2	1 1/2	1 1/2	1 1/2	1 1/2	1 1/2
52.5	1 1/2	1 1/2	1 1/2	1 1/2	1 1/2	1 1/2	1 1/2
55.0	2	1 1/2	1 1/2	1 1/2	1 1/2	1 1/2	1 1/2
57.5	2	1 1/2	1 1/2	1 1/2	2	1 1/2	1 1/2
60.0	2	1 1/2	2	1 1/2	2	1 1/2	1 1/2
62.5	1 1/2	2	1 1/2	2	1 1/2	2	2
65.0	1 1/2	2	2	2	1 1/2	2	2
67.5	1 1/2	2	2	2	2	2	2
70.0	2	2	2	2	2	2	2

Note to the physician: The initial total weekly dose (first column) can be derived using the nomogram published in: Ebell MH. Evidence-based initiation of warfarin (Coumadin). Am Fam Physician. 2005;71:763-765; available online at: http://www.aafp.org/afp/20050215/poc.html.

Chart developed by Mark H. Ebell, MD, MS. Copyright © 2005 American Academy of Family Physicians. Physicians may photocopy or adapt for use in their own practices; all other rights reserved. "A Systematic Approach to Managing Warfarin Doses." Ebell MH. Family Practice Management. May 2005: 77-83; http://www.aafp.org/fpm/20050500/77asys.html.

1. Ansell J, Hirsh J, Poller L, et al. The pharmacology and management of the vitamin K antagonists. Chest. 2004;126:204S-233S.

2. Cortelazzo S, Finazzi G, Viero P, et al. Thrombotic and hemorrhagic complications in patients with mechanical heart valve prosthesis attending an anticoagulation clinic. Thromb Haemost. 1993;69:316-320.

3. Chiquette E, Amato MG, Bussey HI. Comparison of an anticoagulation clinic and usual medical care. Arch Intern Med. 1998;158:1641-1647.

4. Matchar DB, Samsa GP, Cohen SJ, et al. Improving the quality of anticoagulation of patients with atrial fibrillation in managed care organizations: results of the managing anticoagulation services trial. Am J Med. 2002;113:42-51.

5. University of Michigan, Anticoagulation Service. Available online at http://www.med.umich.edu/cvc/prof/anticoag/dose.htm. Accessed April 7, 2005.

Dr. Ebell is in private practice in Athens, Ga., and is associate professor in the Department of Family Practice at Michigan State University College of Human Medicine, East Lansing. He is also deputy editor for evidence-based medicine for American Family Physician. Conflicts of interest: none reported.

Copyright © 2005 by the American Academy of Family Physicians.
This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Contact fpmserv@aafp.org for copyright questions and/or permission requests.