Chest
Managing Oral Anticoagulant Therapy
Section snippets
Initiation and Maintenance Dosing
Following the administration of warfarin, an observableanticoagulant effect occurs within 2 to 7 days, depending onthe dose administered.20, 21 When a rapid effect isrequired, heparin should be given concurrently with warfarin for atleast 4 days. The common practice of initiating warfarin therapy with aloading dose is unnecessary in most patients, and commencing with anaverage maintenance dose of 5 mg warfarin usually results in an INR of2.0 in 4 or 5 days.21 Heparin treatment is
Management of Nontherapeutic INRs
Some patients receiving long-term warfarin therapy are difficultto manage because they have unexpected fluctuations in doseresponse.28 These unexpected fluctuations could be due toa number of variables, including inaccuracy in PT testing, changes invitamin K1 intake (ie, increased ordecreased vitamin K1 in the diet), changes invitamin K1 or warfarin absorption (eg, GI factors or drug effects), changes in warfarin metabolism(eg, liver disease or drug effects), changes in vitaminK1-dependent
Management of Oral Anticoagulation During Invasive Procedures
Clinicians often are required to assess the risk of bleeding froma procedure if anticoagulation therapy is continued vs the risk ofthrombosis if anticoagulation therapy is discontinued, as well as thecost of alternative anticoagulation options. This subject has beenreviewed with suggested alternative options based on an estimate of thepreoperative and postoperative daily risk of bleeding orthrombosis.40 With each of the following options, the length of time for warfarin dosage reduction and for
Definition of Major and Minor Hemorrhage
Precise estimates of hemorrhagic event rates are complicated bythe inconsistency between classification schemes in clinical researchstudies.12 The goal of classification is to place ableeding episode on a continuum of severity ranging from minor events, such as brief epistaxis that would not have been reported to aphysician (but would, for example, be recorded as part of a clinicaltrial), to a fatal or life-threatening episode of bleeding. Fihn etal12 established the following three categories:
Management of the Patient Who Bleeds During Warfarin Therapy
The short-term management of patients who bleed with anexcessively prolonged INR has been discussed above. The long-termmanagement of patients who bleed but who require ongoing protectionagainst systemic embolism (eg, patients with mechanicalheart valves or with atrial fibrillation and other risk factors) isproblematic. There are two general principles that should be followed:(1) to attempt to identify and reverse the cause of bleeding; and (2)to examine the possibility of lowering the
Models of Anticoagulation Management
The effectiveness and safety of warfarin are critically dependenton maintaining the INR in the therapeutic range. This objective isfacilitated by aiming for an INR that is in the middle of the INR range(ie, a goal of 2.5 for a designated range of 2.0 to 3.0, anda goal of 3.0 for a designated range of 2.5 to 3.5). The impact ofmaintaining good anticoagulant control was highlighted by reanalysis ofthe primary prevention trials in atrial fibrillation using anon-treatment analysis.1 The results of
Pregnancy
Oral anticoagulants cross the placenta and can produce acharacteristic embryopathy, CNS abnormalities, fetal bleeding, orincreased rates of fetal death.152, 153 These complications are discussed in detail elsewhere in this supplement (see page 122). The incidence of warfarin embryopathy is greatest during 6to 12 weeks' gestation, and warfarin should be avoided during thisperiod of pregnancy.152 Since CNS abnormalities, fetalbleeding, and fetal death may occur throughout pregnancy,
Practical Dosing
- 1.
For the initiation of and maintenance dosing of warfarin, commence therapy with an average maintenance dose of 5 mg (grade 2Acompared to a dose of 10 mg). Starting doses of < 5 mg might beappropriate for elderly patients, patients with impaired nutrition orliver disease, and in patients with a high risk for bleeding.
Management of Nontherapeutic INRs
- 1.
For patients with INRs greater than the therapeutic levelbut < 5.0 who do not have significant bleeding, lower the dose oromit a dose and resume therapy at a lower dose when the INR
References (168)
- et al.
Randomized comparison of two intensities of oral anticoagulant therapy after tissue heart valve replacement
Lancet
(1988) - et al.
Comparison of two levels of anticoagulant therapy in patients with substitute heart valves
J Thorac Cardiovasc Surg
(1991) - et al.
Major bleeding in outpatients treated with warfarin: incidence and prediction by factors known at the start of outpatient therapy
Am J Med
(1989) - et al.
Bleeding in outpatients treated with warfarin: relation to the prothrombin time and important remedial lesions
Am J Med
(1989) - et al.
Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range
Chest
(1998) - et al.
Use of enoxaparin for the chronically anticoagulated patient before and after procedures
Am J Cardiol
(1999) - et al.
Oral surgery in anticoagulated patients without reducing the dose of oral anticoagulant: a prospective randomized study
J Oral Maxillofac Surg
(1996) - et al.
Prospective evaluation of an index for predicting the risk of major bleeding in outpatients treated with warfarin
Am J Med
(1998) - et al.
Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective collaborative study (ISCOAT)
Lancet
(1996) - et al.
Bleeding and thromboembolism during anticoagulant therapy: a population based study in Rochester, Minnesota
Mayo Clin Proc
(1995)
Prediction of hemorrhage during long-term oral coumarin anticoagulation by excessive prothrombin ratio
Am Heart J
Anticoagulation clinics and the monitoring of anticoagulant therapy
Int J Cardiol
Low intensity anticoagulation in mechanical cardiac prosthetic valves
Chest
Canadian atrial fibrillation anticoagulation (CAFA) study
J Am Coll Cardiol
Placebo-controlled, randomized trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation: the Copenhagen AFASAK Study
Lancet
Warfarin versus aspirin for prevention of thromboembolism in atrial fibrillation: stroke prevention in atrial fibrillation II study
Lancet
Atrial fibrillation and stroke: three new studies, three remaining questions
Arch Intern Med
Fifth ACCP Consensus Conference on Antithrombotic Therapy
Chest
The international normalized ratio: a guide to understanding and correcting its problems
Arch Intern Med
Different intensities of oral anticoagulant therapy in the treatment of proximal-vein thrombosis
N Engl J Med
Trial of different intensities of anticoagulation in patients with prosthetic heart valves
N Engl J Med
Risk factors for intracranial hemorrhage in outpatients taking warfarin
Ann Intern Med
An analysis of the lowest effective intensity of prophylactic anticoagulation for patients with nonrheumatic atrial fibrillation
N Engl J Med
The optimal intensity of oral anticoagulant therapy in patients with mechanical heart valve prostheses: the Leiden artificial valve and anticoagulation study
N Engl J Med
Optimal oral anticoagulant therapy in patients with nonrheumatic atrial fibrillation and recent cerebral ischemia
N Engl J Med
Risk factors for complications of chronic anticoagulation: a multicenter study
Ann Intern Med
Calibration of reference thromboplastins and standardization of the prothrombin time ratio
Thromb Haemost
Anticoagulation management as a risk factor for adverse events: grounds for improvement
J Thromb Thrombolysis
Quality of anticoagulation management among patients with atrial fibrillation: results from a review of medical records from two communities
Arch Intern Med
The quality of anticoagulation management
Arch Intern Med
Studies on coumarin anticoagulant drugs: initiation of warfarin therapy with a loading dose
Circulation
Comparison of 5 mg and 10 mg loading doses in initiation of warfarin therapy
Ann Intern Med
Aging and the anticoagulant response to warfarin therapy
Ann Intern Med
The association of age with dosage requirement for warfarin
Age Ageing
Factors affecting the maintenance dose of warfarin
J Clin Pathol
Aging and warfarin therapy
Ann Intern Med
Stereoselective disposition of warfarin in young and elderly subjects
Clin Pharmacol Ther
Long-term anticoagulation therapy for atrial fibrillation in elderly patients: efficacy, risk, and current patterns of use
J Thromb Thrombolysis
Interindividual differences in the response to oral anticoagulants
Drugs
Temporary discontinuation of warfarin therapy: changes in the international normalized ratio
Ann Intern Med
Evaluation of excessive anticoagulation in a group model health maintenance organization
Arch Intern Med
Effective reversal of warfarin-induced excessive anticoagulation with low dose vitamin K1
Thromb Haemost
Anaphylactoid reactions and vitamin K [letter]
Med J Aust
Comparing different routes and doses of phytonadione for reversing excessive anticoagulation
Arch Intern Med
Time course of reversal of anticoagulant effect of warfarin by intravenous and subcutaneous phytonadione
Arch Intern Med
Reversal of excessive effect of regular anticoagulation: low oral dose of phytonadione (vitamin K1) compared with warfarin discontinuation
Blood Coagul Fibrinolysis
The effectiveness of an oral vitamin K1 in controlling excessive hypoprothrombinemia during anticoagulant therapy
Ann Intern Med
Small doses of vitamin K1 for correction of reduced prothrombin activity
Proc Mayo Clin
Correction of excessive anticoagulation with low dose oral vitamin K1
Ann Intern Med
Low dose oral vitamin K reliably reverses over anticoagulation due to warfarin
Thromb Haemost
Cited by (546)
Safety and efficacy of low-dose non-vitamin K antagonist oral anticoagulants versus warfarin after left atrial appendage closure with the Watchman device
2022, Journal of the Formosan Medical AssociationA turbulence in vitro assessment of On-X and St Jude Medical prostheses
2020, Journal of Thoracic and Cardiovascular SurgeryRecommendations for the post-operative management of an existing Warfarin therapy after lower limb joint arthroplasty
2019, SurgeonCitation Excerpt :Postoperatively, lower limb arthroplasty surgery itself is associated with a high VTE risk5 and Warfarin can be restarted to address the combined risk. There is clear guidance to treat patients with a prophylactic dose of LMWH until the INR reaches a therapeutic value and to overlap for 2 more days.1,3 For patients on an already established dose, restarting them on their anticoagulant poses few challenges as sensitivity to Warfarin is already known.
Being precise with anticoagulation to reduce adverse drug reactions: are we there yet?
2024, Pharmacogenomics Journal