Original Article
Long-Term, Low-Intensity Warfarin Therapy for the Prevention of Recurrent Venous Thromboembolism
N Engl J Med 2003; 348:1425-1434April 10, 2003
- Abstract
Background
Standard therapy to prevent recurrent venous thromboembolism includes 3 to 12 months of treatment with full-dose warfarin with a target international normalized ratio (INR) between 2.0 and 3.0. However, for long-term management, no therapeutic agent has shown an acceptable benefit-to-risk ratio.
Methods
Patients with idiopathic venous thromboembolism who had received full-dose anticoagulation therapy for a median of 6.5 months were randomly assigned to placebo or low-intensity warfarin (target INR, 1.5 to 2.0). Participants were followed for recurrent venous thromboembolism, major hemorrhage, and death.
Results
The trial was terminated early after 508 patients had undergone randomization and had been followed for up to 4.3 years (mean, 2.1). Of 253 patients assigned to placebo, 37 had recurrent venous thromboembolism (7.2 per 100 person-years), as compared with 14 of 255 patients assigned to low-intensity warfarin (2.6 per 100 person-years), a risk reduction of 64 percent (hazard ratio, 0.36 [95 percent confidence interval, 0.19 to 0.67]; P<0.001). Risk reductions were similar for all subgroups, including those with and those without inherited thrombophilia. Major hemorrhage occurred in two patients assigned to placebo and five assigned to low-intensity warfarin (P=0.25). Eight patients in the placebo group and four in the group assigned to low-intensity warfarin died (P=0.26). Low-intensity warfarin was thus associated with a 48 percent reduction in the composite end point of recurrent venous thromboembolism, major hemorrhage, or death. According to per-protocol and as-treated analyses, the reduction in the risk of recurrent venous thromboembolism was between 76 and 81 percent.
Conclusions
Long-term, low-intensity warfarin therapy is a highly effective method of preventing recurrent venous thromboembolism.
Media in This Article
Figure 1
Distribution of International Normalized Ratio (INR) Levels at the Bimonthly Follow-up Visits, According to Randomized Treatment Assignment.Figure 2
Cumulative Risk of the Primary Study End Point of Recurrent Venous Thromboembolism (Panel A) and of the Composite Study End Point of Recurrent Venous Thromboembolism, Major Hemorrhage, or Death from Any Cause (Panel B).Article Activity
- Article
Therapy for idiopathic venous thromboembolism typically includes a 5-to-10-day course of heparin followed by 3 to 12 months of oral anticoagulation therapy with full-dose warfarin, with adjustment of the dose to achieve an international normalized ratio (INR) between 2.0 and 3.0.1-4 After cessation of anticoagulation therapy, however, recurrent venous thromboembolism is a major clinical problem, with an estimated rate of 6 to 9 percent annually.5,6 Unfortunately, no therapy with an acceptable benefit-to-risk ratio is available for long-term management. In particular, although extended use of full-dose warfarin is associated with reduced rates of recurrent venous thromboembolism,2-4 community-based studies have consistently found this approach to be associated with substantial risk of major hemorrhage. For example, in observational studies, full-dose warfarin is associated with rates of major bleeding episodes ranging from 5 to 9 percent annually.7-9 Similarly, an annual rate of major hemorrhage of 3.8 percent was observed in a recent trial of full-dose warfarin despite careful on-site monitoring of anticoagulation therapy.3
By contrast, low-intensity warfarin carries a low risk of bleeding when used on a long-term basis, and such therapy may require less frequent monitoring. Furthermore, low-intensity warfarin is effective in reducing biochemical markers of coagulation, such as factor VII activity and levels of prothrombin fragment 1+2.10,11 There are, however, no clinical data available on the use of low-intensity warfarin therapy for long-term prophylaxis against venous thrombosis, although this approach has been used successfully for the prevention of a first thrombosis among patients with indwelling central venous catheters and among women with metastatic breast cancer.12,13
The Prevention of Recurrent Venous Thromboembolism (PREVENT) trial was initiated in July 1998 to test the hypothesis that long-term, low-intensity warfarin therapy (target INR, 1.5 to 2.0) might provide a safe and effective method of reducing the risk of recurrent venous thromboembolism among patients who have had a previous idiopathic venous thrombosis.14 As a secondary aim, the study was designed to test the hypothesis that patients with thrombophilic mutations such as factor V Leiden or the G20210A prothrombin polymorphism might differentially benefit from long-term, low-intensity warfarin prophylaxis.
Designed to enroll 750 patients for an average follow-up period of four years, our trial was terminated by the independent data and safety monitoring board after 508 patients had undergone randomization, because of the emergence of a large and statistically significant benefit of low-intensity warfarin therapy in the absence of any substantial evidence of harm.
Methods
Study Patients
Men and women 30 years of age or older with documented idiopathic venous thromboembolism were eligible if they had completed at least three uninterrupted months of oral anticoagulation therapy with full-dose warfarin. All index events were confirmed by objective criteria at the central clinical coordinating center on the basis of venography or reports from compression ultrasonography or magnetic resonance imaging (MRI) in the case of deep venous thrombosis and on the basis of ventilation–perfusion scanning, angiography, or computed tomography (CT) of the chest in the case of pulmonary embolism. Idiopathic events were defined as those that did not occur within 90 days after surgery or trauma. Patients were ineligible for the trial if they had a history of metastatic cancer, major gastrointestinal bleeding, hemorrhagic stroke, or a life expectancy of less than three years. Patients who were being treated with dipyridamole, ticlopidine, clopidogrel, heparin, more than 325 mg of aspirin, or drugs that affect the prothrombin time and patients who had known lupus anticoagulant antibodies or antiphospholipid antibodies were excluded.
Study Design
Before randomization, eligible patients participated in a 28-day open-label run-in phase designed to ensure that all participants could have their dose of warfarin titrated to a stable level that achieved an INR between 1.5 and 2.0 without exceeding a dose of 10 mg per day. The run-in phase was also used to exclude patients with a level of compliance of less than 85 percent.
During the run-in phase, at randomization, and throughout the follow-up period, all assessments of the INR at each study site were made with the use of specially designed finger-stick devices with an identical thromboplastin (international sensitivity index, 2.0; CoaguChek, Roche Diagnostics). These devices were altered electronically to provide a coded INR value that was transmitted in a double-blind fashion to the data coordinating center. All dose adjustments were then made according to a simple clinical algorithm (Appendix 2).
Randomization to low-intensity warfarin (Coumadin, provided without charge by Bristol-Myers Squibb; target INR, 1.5 to 2.0) or to matching placebo was performed centrally. Randomization was stratified according to clinical site, time since the index event (≤6 months or >6 months), and whether or not the index event was the patient's first venous thromboembolism. All participants were then followed with office visits once every two months that included blinded evaluations of the INR and adjustments of their dose. To ensure blinding, sham dose adjustments were made in the placebo group.
Follow-up and Study End Points
Since the study was designed to evaluate clinically relevant recurrent thromboembolic events, no surveillance for asymptomatic thrombosis was undertaken. Rather, at each visit, clinical events that had occurred since the previous visit were evaluated. All end points were reviewed by a committee of physicians who were unaware of treatment-group assignments. The end point of recurrent deep venous thrombosis was considered to be confirmed if there was a positive venographic study, Doppler compression ultrasonography, or MRI. Events documented by clinical diagnosis alone were not considered to be confirmed. The end point of pulmonary embolism was considered to be confirmed if there was a positive angiogram, a ventilation–perfusion scan that showed at least two segmental defects without ventilation defects, or clear evidence of thrombosis documented by CT or MRI of the chest. In cases of deep venous thrombosis or pulmonary embolism in which the recurrent event occurred in the same leg or lung field as the index event, documentation demonstrating a clear difference between the two events was required. Major hemorrhage was defined as any bleeding episode that led to hospitalization or transfusion.
As an index of net clinical benefit, we defined an a priori composite end point of recurrent venous thromboembolism, major hemorrhage, and death from any cause. New stroke events were also monitored and classified as hemorrhagic or thromboembolic on the basis of clinical records and CT or MRI. So that no event would be counted twice, hemorrhagic strokes were counted as major hemorrhages in analyses of the composite end point.
Genetic Analyses
Blood samples obtained on enrollment underwent DNA extraction and were evaluated in a central laboratory for factor V Leiden and the G20210A prothrombin polymorphism. Genetic data were not made available to the clinical sites or to the end-points committee.
Monitoring of the Trial
The National Heart, Lung, and Blood Institute appointed an independent data and safety monitoring committee that monitored the primary end point of recurrent venous thromboembolism at an overall alpha level of 0.05 using the O'Brien–Fleming spending function according to the method of Lan and DeMets.15 Unblinded reviews occurred at least annually or when an additional 20 percent of the expected information was available. At the fourth review (involving approximately 40 percent of the expected information), the committee voted on December 4, 2002, to stop the trial because there was strong evidence of efficacy and the monitoring boundary specified by the Lan–DeMets procedure had been crossed.
Statistical Analysis
For comparisons between treatment groups in the distributions of continuous variables, Wilcoxon rank-sum tests were used; for comparisons of categorical variables, chi-square tests were used. The primary analysis was an intention-to-treat comparison, with a two-sided log-rank test, of the two treatment groups in terms of the time to the first confirmed recurrent venous thromboembolism after randomization. The Kaplan–Meier method was used to estimate the probability of recurrence over time in each treatment group. Estimation of the number of patients who would need to be treated to prevent one recurrent event was based on the rates at three years. We used the proportional-hazards model for estimation of the relative hazard of recurrent events associated with low-intensity warfarin treatment and obtained confidence intervals from this model. The hypothesis of a varying effect of treatment over time was tested in a proportional-hazards model that included a term for the interaction between the treatment group and time. The same methods were used for tests and estimates of the effect of treatment on the composite end point.
The primary prespecified subgroup analysis evaluated the effect of treatment separately in patients with and without either factor V Leiden or the G20210A prothrombin mutation. The hypothesis that the effect of treatment would vary according to genotype was tested by means of a proportional-hazards model that included a term for the interaction between treatment group and the presence or absence of either factor V Leiden or the G20210A prothrombin mutation. The same methods were also used for other comparisons within subgroups.
Results
Patients, Therapy, and Evaluations of the INR
Between July 6, 1998, and December 4, 2002, 578 patients entered the 28-day run-in phase. At the time of the early termination of the trial, 13 patients were still in the 28-day run-in phase, and 508 patients had undergone randomization — 253 assigned to placebo and 255 assigned to low-intensity warfarin. The remaining 57 participants did not complete or were not eligible for the trial at the end of the 28-day run-in. The median duration of full-dose anticoagulation therapy before enrollment was 6.5 months. Clinical characteristics and the frequency of known risk factors were similar in the two treatment groups (Table 1Table 1
Base-Line Characteristics of the Study Participants.).The mean duration of follow-up after randomization was 2.1 years, with a maximal duration of treatment of 4.3 years. The median INR of patients in the placebo group was 1.0 (interquartile range, 1.0 to 1.1), whereas the median INR in the warfarin group was 1.7 (interquartile range, 1.4 to 2.0). This difference was maintained throughout the study period (Figure 1Figure 1
Distribution of International Normalized Ratio (INR) Levels at the Bimonthly Follow-up Visits, According to Randomized Treatment Assignment.). In the warfarin group, the median dose of warfarin was 4 mg (interquartile range, 3 to 6), with a range of 0.5 to 10.0 mg daily.Recurrent Venous Thromboembolism
In total, there were 51 confirmed recurrences of venous thrombosis after randomization. Of these, 39 involved deep venous thrombosis only, and 12 were associated with pulmonary embolism. Eighty-six percent of all recurrent events were idiopathic, and 14 percent were associated with a new diagnosis of cancer, recent surgery, or trauma.
Of the 253 patients assigned to placebo, 37 had confirmed recurrent venous thromboembolism (7.2 per 100 person-years), as compared with 14 of the 255 patients assigned to low-intensity warfarin (2.6 per 100 person-years) — a risk reduction of 64 percent (hazard ratio, 0.36 [95 percent confidence interval, 0.19 to 0.67]; P<0.001) (Table 2Table 2
Major Study End Points According to Treatment Group.). The cumulative risk of recurrent venous thromboembolism is shown in Figure 2Figure 2Cumulative Risk of the Primary Study End Point of Recurrent Venous Thromboembolism (Panel A) and of the Composite Study End Point of Recurrent Venous Thromboembolism, Major Hemorrhage, or Death from Any Cause (Panel B).. Low-intensity warfarin therapy had similar efficacy in the prevention of early and late recurrent events. On the basis of these rates, 10 patients would need to be treated for three years to prevent one recurrent event.Of 77 patients with either factor V Leiden or the prothrombin mutation who were assigned to placebo, 14 had recurrent events (8.6 events per 100 person-years), as compared with 3 of 66 such patients who were assigned to low-intensity warfarin (2.2 events per 100 person-years) (Table 3Table 3
Rates and Hazard Ratios for Recurrent Venous Thromboembolism in Clinically Important Subgroups, According to Treatment-Group Assignment.). This 75 percent reduction in risk among those with inherited thrombophilias (hazard ratio, 0.25 [95 percent confidence interval, 0.07 to 0.87]) was not significantly different from the 58 percent risk reduction among those without factor V Leiden or the prothrombin mutation (hazard ratio, 0.42 [95 percent confidence interval, 0.20 to 0.86]; P for interaction = 0.51).Risk reductions were of similar magnitude in the other subgroups we evaluated (Table 3). Among women, low-intensity warfarin therapy was associated with an 80 percent reduction in the risk of recurrent venous thromboembolism (hazard ratio, 0.20 [95 percent confidence interval, 0.06 to 0.67]), and a 53 percent reduction was observed among men (hazard ratio, 0.47 [95 percent confidence interval, 0.23 to 0.96]; P for interaction = 0.23). We observed no significant interactions between the magnitude of the reduction in risk and categories of age, time since randomization, time since cessation of full-dose warfarin therapy, or number of previous venous thromboembolic events.
Bleeding Episodes
In the placebo group, two patients had bleeding episodes necessitating hospitalization (0.4 per 100 person-years), and in the warfarin group, five patients had such episodes (0.9 per 100 person-years) — a nonsignificant difference (P=0.25). Of the major bleeding episodes in the warfarin group, three involved gastrointestinal bleeding, one a hematoma in the leg, and one hematuria associated with the removal of a renal calculus. Only one major hemorrhage necessitated the transfusion of packed red cells; this hemorrhage occurred in a patient in the warfarin group who was receiving full-dose warfarin at the time of the hemorrhage. A total of 34 patients in the placebo group and 60 patients in the warfarin group reported minor bleeding or bruising (hazard ratio, 1.92 [95 percent confidence interval, 1.26 to 2.93]).
Death, Stroke, and Other End Points
Eight deaths occurred in the placebo group, and four in the warfarin group (P=0.26). Two deaths were due to fatal pulmonary embolism, and one death was due to fatal hemorrhagic stroke; all three of these were in the placebo group.
There were two confirmed strokes in the placebo group and one in the warfarin group. As noted above, one stroke was hemorrhagic and occurred in a patient assigned to placebo. This patient was initially hospitalized for a thromboembolic stroke that became hemorrhagic after the initiation of treatment with heparin and clopidogrel. There were 13 diagnoses of cancer during follow-up: 9 in the placebo group and 4 in the warfarin group (P=0.18).
The rate of the composite end point (recurrent venous thromboembolism, major hemorrhage [including hemorrhagic stroke], or death from any cause) was reduced by 48 percent in the warfarin group (hazard ratio, 0.52 [95 percent confidence interval, 0.31 to 0.87]; P=0.01) (Table 2 and Figure 2).
Per-Protocol and As-Treated Analyses
The study drug was discontinued before the completion of follow-up in 56 patients in the placebo group and 64 patients in the warfarin group (P=0.43). The primary reasons for discontinuation were refusal of treatment by the patient, minor bruising, the development of other medical conditions, or a new indication for anticoagulation therapy. Discontinuation of treatment for each of these reasons, including minor bleeding, occurred with equal frequency in the placebo group and the warfarin group.
Fifteen patients had a recurrent venous thromboembolism after cessation of treatment with the assigned study drug. Of these, eight were in the placebo group and seven were in the warfarin group. Thus, among patients who were documented to be receiving the assigned study drug at the time of the recurrent event, the risk reduction associated with low-intensity warfarin therapy was 76 percent (hazard ratio, 0.24 [95 percent confidence interval, 0.10 to 0.54]).
No patients with recurrent events who had stopped taking the study drug were receiving another form of anticoagulation therapy at the time of the recurrent event. Thus, according to an analysis of the subgroup that was using long-term anticoagulation therapy at the time of the recurrent event, there was an 81 percent reduction in risk in the warfarin group (hazard ratio, 0.19 [95 percent confidence interval, 0.09 to 0.43]).
Discussion
This randomized, double-blind, placebo-controlled trial demonstrates that long-term, low-intensity warfarin therapy given with a target INR of 1.5 to 2.0 results in a large and significant reduction in the risk of recurrent venous thrombosis. This benefit was seen in all the subgroups we evaluated and was achieved with little evidence of any increase in the risk of major hemorrhage or stroke, despite the infrequent monitoring of anticoagulation therapy. Thus, long-term, low-intensity warfarin therapy can be readily implemented in clinical practice.
Previous studies have demonstrated that short-term use of full-dose warfarin is highly effective after a first episode of venous thrombosis, and on the basis of evidence from randomized trials, usual care typically includes full-dose warfarin therapy for up to 12 months.1-4 Two completed trials show that the use of full-dose warfarin for longer than one year continues to provide efficacy, in comparison with placebo, in preventing recurrent events,2,3 and preliminary data from one trial suggest that there is a greater reduction in the rate of recurrent thrombosis with full-dose warfarin than with low-dose warfarin.16 However, in the two published trials, rates of major bleeding episodes were high during extended therapy with full-dose warfarin — an observation that supports the widespread concern regarding the net clinical benefit of long-term warfarin therapy with a target INR of 2.0 to 3.0.7-9 One trial comparing an oral thrombin inhibitor with placebo for the prevention of recurrent venous thromboembolism has also recently been described.17 Direct comparisons will be needed in order to determine whether any of these approaches is truly superior to the others for long-term management.
Our study also addressed the question of whether low-intensity warfarin therapy had differential effects among those with and without inherited thrombophilias such as factor V Leiden and the G20210A prothrombin polymorphism, each of which is known to increase the risk of a first venous thrombosis.18-23 Whether these genetic disorders are associated with an increased risk of recurrent venous thromboembolism remains controversial.24-29 In our study, patients with factor V Leiden or the G20210A prothrombin polymorphism were not at substantially increased risk of recurrent events as compared with patients without these disorders. Moreover, the relative benefit of low-intensity warfarin therapy in preventing recurrent events was not significantly affected by the patient's genetic status. Thus, it is uncertain whether screening for either of these polymorphisms had important clinical consequences, either in terms of prognosis or in terms of differential therapeutic response. Since our study excluded patients with known antiphospholipid-antibody syndrome, the efficacy of low-intensity warfarin therapy among such patients remains uncertain.
Long-term, low-intensity warfarin therapy is a highly effective method of preventing recurrent venous thromboembolism. Our data reinforce the importance of investigating agents that might be clinically useful but whose status as generic drugs provides little financial incentive for investigation by the pharmaceutical industry.
Supported by grants (HL-57951 and HL-58036) from the National Heart, Lung, and Blood Institute. Study drug and placebo were supplied without fee by Bristol-Myers Squibb. Dr. Ridker receives additional research support from the Leducq Foundation and the Doris Duke Charitable Foundation.
Dr. Ridker reports having received grant support from Bristol-Myers Squibb, AstraZeneca, and Roche Diagnostics, Dr. Goldhaber consulting fees from Aventis and Pharmacia and grant support from Aventis and AstraZeneca, Drs. Cushman and Moll grant support from AstraZeneca, Dr. Kessler consulting and lecture fees from Aventis, Dr. Paulson lecture fees from Aventis, Dr. Bounameaux consulting fees from Aventis and AstraZeneca and lecture fees from Aventis, and Dr. Glynn consulting fees from AstraZeneca and grant support from Bristol-Myers Squibb.
This article was published at www.nejm.org on February 24, 2003.
Source Information
From the Center for Cardiovascular Disease Prevention and the Divisions of Preventive Medicine and Cardiology, Brigham and Women's Hospital and Harvard Medical School, Boston (P.MR., S.Z.G., E.D., R.J.G.); the National Institutes of Health, Bethesda, Md. (Y.R.); Washington University, St. Louis (C.S.E., J.P.M.); the Cleveland Clinic Foundation, Cleveland (S.R.D.); the University of Vermont, Burlington (M.C.); the University of North Carolina, Chapel Hill (S.M.); Georgetown University Medical Center, Washington, D.C. (C.M.K.); LDS Hospital, Salt Lake City (C.G.E.); Altru Research Clinic, Grand Forks, N.D. (R.P.); St. Boniface General Hospital, Winnipeg, Man., Canada (T.W.); Beth Israel Deaconess Medical Center, Boston (K.A.B.); Midwest Pulmonary Consultants, Kansas City, Mo. (B.A.S.); and the University Hospitals of Geneva, Geneva (H.B.).
Address reprint requests to Dr. Ridker at the Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, 900 Commonwealth Ave. E., Boston, MA 02215, or at pridker@partners.org.
The Prevention of Recurrent Venous Thromboembolism (PREVENT) Investigators are listed in Appendix 1.
Appendix
Appendix 1
The following persons participated in the Prevention of Recurrent Venous Thromboembolism (PREVENT) Study. Chair: P.M. Ridker (Brigham and Women's Hospital, Boston); Data Coordinating Center: R.J. Glynn (Director), E.M. Danielson, D. Bates, W. Christen, P. DeFonce, W. Griffin, F. Jackson, A. Murray, K. Taylor, K. Johnson, K. McKenna, J. Pierre, B. Holman, F. Dessources, P. Quinn, T. Laurinaitis, J. MacFadyen (Brigham and Women's Hospital, Boston); Laboratory Coordinating Center: C. Eby (Co-Director), J.P. Miletich (Co-Director), R. Porche-Sorbet (Washington University, St. Louis); Clinical Coordinating Center: S.Z. Goldhaber (Director), R.B. Morrison, R.C. MacDougall, R.M. Morrison (Brigham and Women's Hospital, Boston); Independent Data and Safety Monitoring Board: G. Lamas (Chair), K. Bailey, B. Gersh, E. Pellegrino, M. Rick, D. Vaughan; Scientific Project Officer: Y. Rosenberg (National Heart, Lung, and Blood Institute).
Study sites and investigators (numbers in parentheses are the numbers of patients who underwent randomization): Brigham and Women's Hospital, Boston — S.Z. Goldhaber, R.B. Morrison, R.C. MacDougall, R.M. Morrison (119); Cleveland Clinic Foundation, Cleveland — S.R. Deitcher, J. Olin, S. Sulzer, T. Clark (32); University of Vermont and Fletcher Allen Health Care, Burlington — M. Cushman, R. Cohen (27); University of North Carolina, Chapel Hill — S. Moll, S. Jones (27); Georgetown University Medical Center, Washington, D.C. — C.M. Kessler, A. Lee (18); LDS Hospital, Salt Lake City — C.G. Elliott, N. Kitterman (16); Henry Ford Hospital, Detroit — S. Jafri, N. Wulbrecht (14); Beth Israel Deaconess Medical Center, Boston — K. Bauer, M. Mahony (13); Altru Research Clinic, Grand Forks, N.D. — R. Paulson, D. Vold (13); St. Boniface General Hospital, Winnipeg, Man., Canada — T. Wong, S. Erickson-Nesmith (13); University Hospitals of Geneva, Geneva — H. Bounameaux, S. de Lucia, I. Chagnon (12); Midwest Pulmonary Consultants, Kansas City, Mo. — B. Schwartz, R. Thackery, N. Gates (12); Hôtel Dieu de Montréal, Montreal — P. Nguyen, S. Paris, B. LeCours (11); Morristown Memorial Hospital, Morristown, N.J. — M. Oliver, K. Hodapp (11); Northwest Oncology and Hematology, Elk Grove Village, Ill. — G. Grad, B. Bank, J. Rindels, C. Leano (10); University of Nebraska Medical Center, Omaha — W. Haire, D. O'Grady, J. Schneider (10); Fairview University Medical Center, Minneapolis — N. Key, B. Christie (10); Jewish General Hospital, Montreal — M. Blostein, C. Strulovitch (8); Asheville Cardiology Associates, Asheville, N.C. — J. Usedom, D. Oskins (8); Washington University Medical Center, St. Louis — C. Eby, V. Lee, S. Heuerman (7); Vanderbilt University, Nashville — D. Kerins, B. Roberts (7); University of California–Davis, Sacramento — R. White, E. Castro, E. Riddle, M. Ingram (7); University of Massachusetts, Worcester — R.C. Becker, C. Emery (6); Scott and White Memorial Hospital, Temple, Tex. — L. Wong, S. Dent (6); Oklahoma Veterans Affairs Medical Center, Oklahoma City — P. Comp, D. Havarda (5); Research Institute of Kansas, Wichita — J.P. Galichia, L. Terry, S. Waldren (5); University of California–San Francisco, San Francisco — J. Hambleton, J. Roth (5); Foothills Hospital, Calgary, Alta., Canada — G. Pineo, R. Hull, J. Sheldon (5); Lahey Clinic, Burlington, Mass. — N. Tsapatsaris, G. Woodhead, M. Mann (5); Denver Veterans Affairs Medical Center, Denver — C. Welsh, T. Schoch, J. Goldsmith (5); Syracuse Veterans Affairs Medical Center, Syracuse, N.Y. — T. Anthony, J. Walters (4); Evanston Hospital, Evanston, Ill. — J. Caprini, M.L. Maher, K. Medica, S. Rabbitt (4); Akron General Medical Center, Akron, Ohio — J. Finocchio, K. Keaton (4); Group Health Centre, Sault Ste. Marie, Ont., Canada — H. Lee, S. McLean, K. Barban (4); Presbyterian Medical Center, Philadelphia — E. Mohler, E. Medenilla, M. Wolfe, A. deLemos (4); University of Michigan–Ann Arbor, Ann Arbor — M. Rubenfire, S. McDevitt, S. Housholder (4); Cardiza Foundation Hemophilia Center, Philadelphia — J.E. Siegel (4); McGuire Veterans Affairs Medical Center, Richmond, Va. — B. Bradley (3); Boston Veterans Affairs Medical Center, Boston — M. Brophy, C. Reilly (3); Bronx Lebanon Hospital Center, Bronx, N.Y. — E. Brown, A. Valeria, L. Rodriguez (3); Hot Springs Medical Center, Hot Springs, S.D. — A. Kumar, J. Pekron, J. Wagner (3); Saint Louis University Health Sciences Center, St. Louis — J. Richart, J. Jones (3); Geisinger Medical Center, Danville, Pa. — V. Weber, C. Fellin, J. Sim (3); Kansas City Veterans Affairs Medical Center, Kansas City, Mo. — M. Graham, D. Sutton (2); Rhode Island Hospital, Providence — A. Kestin (2); North Idaho Cancer Center, Coeur d'Alene — H. Tezcan, S. Herbst (2); University of Alabama, Birmingham — M. Waldrum, T. Meadows (2); Harvard Vanguard Medical Associates, Boston — W. Carlson, M. Welch-Costantino (1); Wisconsin Heart and Vascular, Milwaukee — J. Gosset, J. Nonnweiler (1); Fort Meade Medical Center, Fort Meade, S.D. — A. Kumar, K. Green (1); Duke University Medical Center, Durham, N.C. — V. Tapson, A. Krichman (1); Toronto General Hospital, Toronto — E. Yeo, S. Boross-Harmer (1).
Appendix 2: Regimen Used during the Bimonthly Follow-up Visits for the Titration of the Warfarin Dose
If the international normalized ratio (INR) <1.3 (on blinded measurement), increase current dose by 2 mg per day and repeat blinded measurement of INR in one week.
If INR ≥1.3 and <1.5, increase current dose by 1 mg per day and repeat measurement of INR in eight weeks.
If INR ≥1.5 and ≤2.0, maintain current dose and repeat measurement of INR in eight weeks.
If INR >2.0 and ≤3.0, decrease current dose by 1 mg per day and repeat measurement of INR in eight weeks.
If INR >3.0 and ≤4.0, decrease current dose by 2 mg per day and repeat measurement of INR in one week.
If INR >4.0, stop study drug for three days and repeat measurement of INR. If INR remains >4.0, discontinue therapy. If INR ≤4.0 on repeated measurement, decrease current dose by 2 mg per day and repeat measurement of INR in one week.
- References
References
1
Schulman S ,Rhedin A-S ,Lindmarker P , et al. A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. N Engl J Med 1995;332:1661-1665
Full Text | Web of Science | Medline2
Schulman S ,Granqvist S ,Holmstrom M , et al. The duration of oral anticoagulant therapy after a second episode of venous thromboembolism. N Engl J Med 1997;336:393-398
Full Text | Web of Science | Medline3
Kearon C ,Gent M ,Hirsh J , et al. A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. N Engl J Med 1999;340:901-907[Erratum, N Engl J Med 1999;341:298.]
Full Text | Web of Science | Medline4
Agnelli G ,Prandoni P ,Santamaria MG , et al. Three months versus one year of oral anticoagulant therapy for idiopathic deep venous thrombosis. N Engl J Med 2001;345:165-169
Full Text | Web of Science | Medline5
Prandoni P ,Lensing AW ,Cogo A , et al. The long-term clinical course of acute deep venous thrombosis. Ann Intern Med 1996;125:1-7
Web of Science | Medline6
Hirsh J . The optimal duration of anticoagulant therapy for venous thrombosis. N Engl J Med 1995;332:1710-1711
Full Text | Web of Science | Medline7
Fihn SD ,Callahan CM ,Martin DC ,McDonell MB ,Henikoff JG ,White RH . The risk for and severity of bleeding complications in elderly patients treated with warfarin. Ann Intern Med 1996;124:970-979
Web of Science | Medline8
Beyth RJ ,Quinn LM ,Landefeld CS . Prospective evaluation of an index for predicting the risk of major bleeding in outpatients treated with warfarin. Am J Med 1998;105:91-99
CrossRef | Web of Science | Medline9
McMahan DA ,Smith DM ,Carey MA ,Zhou XH . Risk of major hemorrhage for outpatients treated with warfarin. J Gen Intern Med 1998;13:311-316
CrossRef | Web of Science | Medline10
Poller I ,MacCallum PK ,Thomson JM ,Kerns W . Reduction of factor VII coagulant activity (VIIC), a risk factor for ischaemic heart disease, by fixed dose warfarin: a double blind crossover study. Br Heart J 1990;63:231-233
CrossRef | Web of Science | Medline11
Millenson MM ,Bauer KA ,Kistler JP ,Barzegar S ,Tulin L ,Rosenberg RD . Monitoring “mini-intensity“ anticoagulation with warfarin: comparison of the prothrombin time using a sensitive thromboplastin with prothrombin fragment F1+2 levels. Blood 1992;79:2034-2038
Web of Science | Medline12
Bern MM ,Lokich JJ ,Wallach SR , et al. Very low doses of warfarin can prevent thrombosis in central venous catheters: a randomized prospective trial. Ann Intern Med 1990;112:423-428
Web of Science | Medline13
Levine M ,Hirsh J ,Gent M , et al. Double-blind randomised trial of a very-low-dose warfarin for prevention of thromboembolism in stage IV breast cancer. Lancet 1994;343:886-889
CrossRef | Web of Science | Medline14
Ridker PM . Long-term, low-dose warfarin among venous thrombosis patients with and without factor V Leiden mutation: rationale and design for the Prevention of Recurrent Venous Thromboembolism (PREVENT) trial. Vasc Med 1998;3:67-73
Medline15
Lan KKG ,DeMets DL . Discrete sequential boundaries for clinical trials. Biometrika 1983;70:659-663
CrossRef | Web of Science16
Kearon C ,Ginsberg JS ,Kovacs M , et al. Low-intensity (INR 1.5-1.9) versus conventional-intensity (INR 2.0-3.0) anticoagulation for extended treatment of unprovoked VTE: a randomized double blind trial. Blood 2002;100:150a-150a abstract.
Web of Science17
Eriksson H ,Wahlander K ,Lundstrom T ,Clason SB ,Schulman S . Extended secondary prevention with the oral direct thrombin inhibitor ximelagatran for 18 months after 6 months of anticoagulation in patients with venous thromboembolism: a randomized, placebo-controlled trial. Blood 2002;100:81a-81a abstract.
Web of Science18
Bertina RM ,Koeleman BPC ,Koster T , et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994;369:64-67
CrossRef | Web of Science | Medline19
Svensson PJ ,Dahlback B . Resistance to activated protein C as a basis for venous thrombosis. N Engl J Med 1994;330:517-522
Full Text | Web of Science | Medline20
Ridker PM ,Hennekens CH ,Lindpaintner K ,Stampfer MJ ,Eisenberg PR ,Miletich JP . Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke, and venous thrombosis in apparently healthy men. N Engl J Med 1995;332:912-917
Full Text | Web of Science | Medline21
Poort SR ,Rosendaal FR ,Reitsma PH ,Bertina RM . A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 1996;88:3698-3703
Web of Science | Medline22
Price D ,Ridker PM . Factor V Leiden mutation and the risk for thromboembolic disease: a clinical perspective. Ann Intern Med 1997;127:895-903
Web of Science | Medline23
Hillarp A ,Zoller B ,Svensson PJ ,Dahlback B . The 20210 A allele of the prothrombin gene is a common risk factor among Swedish outpatients with verified deep venous thrombosis. Thromb Haemost 1997;78:990-992
Web of Science | Medline24
Ridker PM ,Miletich JP ,Stampfer MJ ,Goldhaber SZ ,Lindpaintner K ,Hennekens CH . Factor V Leiden and risks of recurrent idiopathic venous thromboembolism. Circulation 1995;92:2800-2802
Web of Science | Medline25
Simioni P ,Prandoni P ,Lensing AWA , et al. The risk of recurrent venous thromboembolism in patients with an Arg506→Gln mutation in the gene for factor V (factor V Leiden). N Engl J Med 1997;336:399-403
Full Text | Web of Science | Medline26
Miles JS ,Miletich JP ,Goldhaber SZ ,Hennekens CH ,Ridker PM . G20210A mutation in the prothrombin gene and the risk of recurrent venous thromboembolism. J Am Coll Cardiol 2001;37:215-218
CrossRef | Web of Science | Medline27
Eichinger S ,Pabinger I ,Stumpflen A , et al. The risk of recurrent venous thromboembolism in patients with and without factor V Leiden. Thromb Haemost 1997;77:624-628
Web of Science | Medline28
Lindmarker P ,Schulman S ,Sten-Linder M , et al. The risk of recurrent venous thromboembolism in carriers and non-carriers of the G1691A allele in the coagulation factor V gene and the G20210A allele in the prothrombin gene. Thromb Haemost 1999;81:684-689
Web of Science | Medline29
De Stefano V ,Martinelli I ,Mannucci PM , et al. The risk of recurrent deep venous thrombosis among heterozygous carriers of both factor V Leiden and the G20210A prothrombin mutation. N Engl J Med 1999;341:801-806
Full Text | Web of Science | Medline
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Full Text2
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CrossRef6
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CrossRef10
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CrossRef11
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CrossRef12
Jeffrey I. Weitz. 2012. Pulmonary Embolism. , 596-603.
CrossRef13
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CrossRef14
E. Noel Savina, F. Couturaud. (2011) Durée optimale du traitement anticoagulant au décours d’une maladie veineuse thrombo-embolique. Journal des Maladies Vasculaires 36, S28-S32
CrossRef15
J. A. Heit, B. D. Lahr, T. M. Petterson, K. R. Bailey, A. A. Ashrani, L. J. Melton. (2011) Heparin and warfarin anticoagulation intensity as predictors of recurrence after deep vein thrombosis or pulmonary embolism: a population-based cohort study. Blood 118:18, 4992-4999
CrossRef16
S.M. Schellong. (2011) Therapie der Beinvenenthrombose und der Lungenembolie. Der Internist 52:11, 1284-1291
CrossRef17
Faisal Aziz, Mary Corder, Jaclyn Wolffe, Anthony J. Comerota. (2011) Anticoagulation monitoring by an anticoagulation service is more cost-effective than routine physician care. Journal of Vascular Surgery 54:5, 1404-1407
CrossRef18
F. Couturaud. (2011) Durée optimale du traitement anticoagulant au décours d’une embolie pulmonaire. Revue des Maladies Respiratoires
CrossRef19
James A. Airoldi. 2011. Venous thromboembolism and anticoagulation. , 215-226.
CrossRef20
Shannon M. Bates. (2011) Pregnancy-Associated Venous Thromboembolism: Prevention and Treatment. Seminars in Hematology 48:4, 271-284
CrossRef21
Julia A.M. Anderson, Jeffrey I. Weitz. (2011) Hypercoagulable States. Critical Care Clinics 27:4, 933-952
CrossRef22
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CrossRef23
Juan Francisco Sanchez Muñoz-Torrero, Henri Bounameaux, José María Pedrajas, Alicia Lorenzo, Silvino Rubio, Clive Kearon, Luís Hernández, Manuel Monreal. (2011) Effects of age on the risk of dying from pulmonary embolism or bleeding during treatment of deep vein thrombosis. Journal of Vascular Surgery
CrossRef24
B. Fuentes, J. Gállego, A. Gil-Nuñez, A. Morales, F. Purroy, J. Roquer, T. Segura, J. Tejada, A. Lago, E. Díez-Tejedor. (2011) Guía para el tratamiento preventivo del ictus isquémico y AIT (II). Recomendaciones según subtipo etiológico. Neurología
CrossRef25
David Keeling, Trevor Baglin, Campbell Tait, Henry Watson, David Perry, Caroline Baglin, Steve Kitchen, Michael Makris, . (2011) Guidelines on oral anticoagulation with warfarin - fourth edition. British Journal of Haematology 154:3, 311-324
CrossRef26
Deborah A. Lewis, Gregg J. Stashenko, Olga M. Akay, Lulit I. Price, Kouros Owzar, Geoffrey S. Ginsburg, Jen-Tsan Chi, Thomas L. Ortel. (2011) Whole blood gene expression analyses in patients with single versus recurrent venous thromboembolism. Thrombosis Research
CrossRef27
G. LE GAL, M. CARRIER, M. J. KOVACS, M. T. BETANCOURT, S. R. KAHN, P. S. WELLS, D. A. ANDERSON, I. CHAGNON, S. SOLYMOSS, M. CROWTHER, M. RIGHINI, A. DELLUC, R. H. WHITE, L. VICKARS, M. RODGER. (2011) Residual vein obstruction as a predictor for recurrent thromboembolic events after a first unprovoked episode: data from the REVERSE cohort study. Journal of Thrombosis and Haemostasis 9:6, 1126-1132
CrossRef28
M. CARRIER, M. A. RODGER, P. S. WELLS, M. RIGHINI, G. LE GAL. (2011) Residual vein obstruction to predict the risk of recurrent venous thromboembolism in patients with deep vein thrombosis: a systematic review and meta-analysis. Journal of Thrombosis and Haemostasis 9:6, 1119-1125
CrossRef29
Francisco Buitrago Ramírez, José Antonio Morales Gabardino, Javier Alejandre Carmona. (2011) Tratamiento y prevención secundaria del tromboembolismo. FMC - Formación Médica Continuada en Atención Primaria 18:6, 366-378
CrossRef30
Charles V. Pollack. (2011) Advanced Management of Acute Iliofemoral Deep Venous Thrombosis: Emergency Department and Beyond. Annals of Emergency Medicine 57:6, 590-599
CrossRef31
E J Do, P Lenzini, C S Eby, A R Bass, G A McMillin, S M Stevens, S C Woller, R C Pendleton, J L Anderson, P Proctor, R M Nunley, V Davila-Roman, B F Gage. (2011) Genetics informatics trial (GIFT) of warfarin to prevent deep vein thrombosis (DVT): rationale and study design. The Pharmacogenomics Journal
CrossRef32
A. Janoly-Duménil, C. Bourne, K. Loiseau, J. Luauté, P.-O. Sancho, S. Ciancia, F. Caillet, D. Boisson, C. Rioufol, M.M. Plauchu, G. Rode, S. Jacquin-Courtois. (2011) Oral anticoagulant treatment – Evaluating the knowledge of patients admitted in physical medicine and rehabilitation units. Annals of Physical and Rehabilitation Medicine 54:3, 172-180
CrossRef33
Sameh M. Hakim. (2011) Warfarin for Refractory Chronic Cluster Headache: A Randomized Pilot Study. Headache: The Journal of Head and Face Pain 51:5, 713-725
CrossRef34
Sylvia Elisabeth Reitter, Thomas Waldhoer, Michaela Mayerhofer, Ernst Eigenbauer, Cihan Ay, Paul Alexander Kyrle, Ingrid Pabinger. (2011) Long-term survival of patients with a history of venous thromboembolism. Annals of Hematology 90:5, 585-594
CrossRef35
Clive Kearon. (2011) Extended anticoagulation for unprovoked venous thromboembolism: a majority of patients should be treated. Journal of Thrombosis and Thrombolysis 31:3, 295-300
CrossRef36
Richard J. Friedman, Sylvia Haas. (2011) Strengths and Limitations of Standards of Care to Guide the Orthopedic Surgeon in VTE Prevention. Orthopedics 34:2, 121-128
CrossRef37
Piazza, Gregory, Goldhaber, Samuel Z., . (2011) Chronic Thromboembolic Pulmonary Hypertension. New England Journal of Medicine 364:4, 351-360
Full Text38
JCS Joint Working Group. (2011) Guidelines for the Diagnosis, Treatment and Prevention of Pulmonary Thromboembolism and Deep Vein Thrombosis (JCS 2009). Circulation Journal 75:5, 1258-1281
CrossRef39
Iraklis Tsangaris, Georgios Tsaknis, Argirios Tsantes, Petros Kopterides, Apostolos Armaganidis. (2011) Life-threatening aortic thrombosis in a trauma patient homozygous for factor V Leiden mutation: Case report. Thrombosis Journal 9:1, 8
CrossRef40
Russell D. Hull, Graham F. Pineo. 2011. Pulmonary Embolism. , 418-427.
CrossRef41
Hylek, Elaine M., . (2010) Therapeutic Potential of Oral Factor Xa Inhibitors. New England Journal of Medicine 363:26, 2559-2561
Full Text42
K. A. Bauer. (2010) Duration of Anticoagulation: Applying the Guidelines and Beyond. Hematology 2010:1, 210-215
CrossRef43
Julia A.M. Anderson, Jeffrey I. Weitz. (2010) Hypercoagulable States. Clinics in Chest Medicine 31:4, 659-673
CrossRef44
Paul Alexander Kyrle, Frits R Rosendaal, Sabine Eichinger. (2010) Risk assessment for recurrent venous thrombosis. The Lancet 376:9757, 2032-2039
CrossRef45
Clive Kearon. (2010) Long-term Anticoagulation for Venous Thromboembolism: Duration of Treatment and Management of Warfarin Therapy. Clinics in Chest Medicine 31:4, 719-730
CrossRef46
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CrossRef47
John R. Spurzem, Stephen A. Geraci. (2010) Outpatient Management of Patients following Pulmonary Embolism. The American Journal of Medicine 123:11, 987-990
CrossRef48
Joann M. Lohr, Angela N. Fellner. (2010) Isolated Calf Vein Thrombosis Should Be Treated With Anticoagulation. Disease-a-Month 56:10, 590-600
CrossRef49
L. LINKINS, M. O’DONNELL, J. A. JULIAN, C. KEARON. (2010) Intracranial and fatal bleeding according to indication for long-term oral anticoagulant therapy. Journal of Thrombosis and Haemostasis 8:10, 2201-2207
CrossRef50
Andrea T. East, Thomas W. Wakefield. (2010) What is the Optimal Duration of Treatment for DVT? An Update on Evidence-Based Medicine of Treatment for DVT. Seminars in Vascular Surgery 23:3, 182-191
CrossRef51
H. Bounameaux. (2010) Contemporary management of pulmonary embolism: the answers to ten questions. Journal of Internal Medicine 268:3, 218-231
CrossRef52
R.B. Zotz, A. Gerhardt, C. Sucker. (2010) Tiefe Venenthrombose bei junger Frau mit heterozygoter Faktor-V-Leiden-Mutation. Gefässchirurgie 15:5, 340-344
CrossRef53
Agnelli, Giancarlo, Becattini, Cecilia, . (2010) Acute Pulmonary Embolism. New England Journal of Medicine 363:3, 266-274
Full Text54
Brian M. Kelly, Brian M. Yoder, Chi-Tsai Tang, Thomas W. Wakefield. (2010) Venous Thromboembolic Events in the Rehabilitation Setting. PM&R 2:7, 647-663
CrossRef55
Paul D. Stein, Fadi Matta. (2010) Acute Pulmonary Embolism. Current Problems in Cardiology 35:7, 314-376
CrossRef56
M. Rodger, M. Carrier, E. Gandara, G. Le Gal. (2010) Unprovoked Venous Thromboembolism: Short term or Indefinite Anticoagulation? Balancing Long-Term Risk and Benefit. Blood Reviews 24:4-5, 171-178
CrossRef57
Andrew D. Johnson, Anupama Bhimavarapu, Emelia J. Benjamin, Caroline Fox, Daniel Levy, Gail P. Jarvik, Christopher J. OʼDonnell. (2010) CLIA-tested genetic variants on commercial SNP arrays: potential for incidental findings in genome-wide association studies. Genetics in Medicine1
CrossRef58
D Voora, D C Koboldt, C R King, P A Lenzini, C S Eby, R Porche-Sorbet, E Deych, M Crankshaw, P E Milligan, H L McLeod, S R Patel, L H Cavallari, P M Ridker, G R Grice, R D Miller, B F Gage. (2010) A Polymorphism in the VKORC1 Regulator Calumenin Predicts Higher Warfarin Dose Requirements in African Americans. Clinical Pharmacology & Therapeutics 87:4, 445-451
CrossRef59
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CrossRef60
Aaron B. Holley, Christopher S. King, Jeffrey L. Jackson, Lisa K. Moores. (2010) Different Finite Durations of Anticoagulation and Outcomes following Idiopathic Venous Thromboembolism: A Meta-Analysis. Thrombosis 2010, 1-9
CrossRef61
Howard A. Liebman, Ilene C. Weitz. 2010. Hypercoagulable States. , 588-598.
CrossRef62
Roberto F. Machado, Mark T. Gladwin. 2010. Pulmonary Complications of Hematologic Disease. , 1999-2021.
CrossRef63
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CrossRef64
B. Giannakopoulos, S. A. Krilis. (2009) How I treat the antiphospholipid syndrome. Blood 114:10, 2020-2030
CrossRef65
W. M. Lijfering, N. J. G. M. Veeger, S. Middeldorp, K. Hamulyak, M. H. Prins, H. R. Buller, J. van der Meer. (2009) A lower risk of recurrent venous thrombosis in women compared with men is explained by sex-specific risk factors at time of first venous thrombosis in thrombophilic families. Blood 114:10, 2031-2036
CrossRef66
Suhail Allaqaband, Romas Kirvaitis, Fuad Jan, Tanvir Bajwa. (2009) Endovascular Treatment of Peripheral Vascular Disease. Current Problems in Cardiology 34:9, 359-476
CrossRef67
L.-C. Linke. (2009) Therapie der postoperativen Thrombose. Der Orthopäde 38:9, 812-817
CrossRef68
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CrossRef69
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CrossRef70
C. KEARON. (2009) Balancing risks and benefits of extended anticoagulant therapy for idiopathic venous thrombosis. Journal of Thrombosis and Haemostasis 7, 296-300
CrossRef71
U. Zeymer, J. Senges, R. Zahn. (2009) Antithrombotische Therapie bei Patienten mit Indikation zur oralen Antikoagulation und koronarer Stentimplantation. Clinical Research in Cardiology Supplements 4:S2, 150-153
CrossRef72
Robert Y.L. Zee, Vadim Bubes, Sanjay Shrivastava, Paul M Ridker, Robert J. Glynn. (2009) Genetic risk factors in recurrent venous thromboembolism: A multilocus, population-based, prospective approach. Clinica Chimica Acta 402:1-2, 189-192
CrossRef73
M. CUSHMAN. (2009) A new indication for statins to prevent venous thromboembolism? Not yet. Journal of Thrombosis and Haemostasis 7:4, 511-513
CrossRef74
Sergio Siragusa, Domenica Caramazza, Alessandra Malato. (2009) How should we determine length of anticoagulation after proximal deep vein thrombosis of the lower limbs?. British Journal of Haematology 144:6, 832-837
CrossRef75
Isaac E. Hall, Martin S. Andersen, Harlan M. Krumholz, Cary P. Gross. (2009) Predictors of Venous Thromboembolism in Patients with Advanced Common Solid Cancers. Journal of Cancer Epidemiology 2009, 1-9
CrossRef76
Jeffrey I. Weitz. (2009) Unanswered questions in venous thromboembolism. Thrombosis Research 123, S2-S10
CrossRef77
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CrossRef78
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CrossRef79
Thomas W. Wakefield, Joseph Caprini, Anthony J. Comerota. (2008) Thromboembolic Diseases. Current Problems in Surgery 45:12, 844-899
CrossRef80
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CrossRef81
C. Kearon, J. A. Julian, M. J. Kovacs, D. R. Anderson, P. Wells, B. MacKinnon, J. I. Weitz, M. A. Crowther, S. Dolan, A. G. Turpie, W. Geerts, S. Solymoss, P. van Nguyen, C. Demers, S. R. Kahn, J. Kassis, M. Rodger, J. Hambleton, M. Gent, J. S. Ginsberg, . (2008) Influence of thrombophilia on risk of recurrent venous thromboembolism while on warfarin: results from a randomized trial. Blood 112:12, 4432-4436
CrossRef82
David Garcia. (2008) Duration of anticoagulant therapy for patients with venous thromboembolism. Thrombosis Research 123, S62-S64
CrossRef83
Fernando Uresandi, Gemma Iruin, Beatriz Gómez, Amaia Uresandi. (2008) Seguimiento de la tromboembolia pulmonar. Medicina Clínica 131, 54-59
CrossRef84
N. Sarafoff, G. Ndrepepa, J. Mehilli, K. Dörrler, S. Schulz, R. Iijima, R. Byrne, A. Schömig, A. Kastrati. (2008) Aspirin and clopidogrel with or without phenprocoumon after drug eluting coronary stent placement in patients on chronic oral anticoagulation. Journal of Internal Medicine 264:5, 472-480
CrossRef85
Joseph A. Caprini. (2008) The Future of Medical Therapy for Venous Thromboemboli. The American Journal of Medicine 121:11, S10-S19
CrossRef86
Geno J. Merli. (2008) Treatment of Venous Thromboembolism. The American Journal of Medicine 121:11, S2-S9
CrossRef87
Timothy K. Liem, Thomas G. DeLoughery. (2008) First Episode and Recurrent Venous Thromboembolism: Who is Identifiably at Risk?. Seminars in Vascular Surgery 21:3, 132-138
CrossRef88
Marta Spreafico, Corrado Lodigiani, Y van Leeuwen, Denise Pizzotti, Lidia L Rota, FR Rosendaal, Pier M Mannucci, Flora Peyvandi. (2008) Effects of CYP2C9 and VKORC1 on INR variations and dose requirements during initial phase of anticoagulant therapy. Pharmacogenomics 9:9, 1237-1250
CrossRef89
Gilles Pernod, José Labarère, Jacqueline Yver, Bernadette Satger, Benoit Allenet, Touffek Berremili, Michèle Fontaine, Guy Franco, Jean Luc Bosson. (2008) EDUC’AVK: Reduction of Oral Anticoagulant-related Adverse Events After Patient Education: A Prospective Multicenter Open Randomized Study. Journal of General Internal Medicine 23:9, 1441-1446
CrossRef90
BF Gage, C Eby, JA Johnson, E Deych, MJ Rieder, PM Ridker, PE Milligan, G Grice, P Lenzini, AE Rettie, CL Aquilante, L Grosso, S Marsh, T Langaee, LE Farnett, D Voora, DL Veenstra, RJ Glynn, A Barrett, HL McLeod. (2008) Use of Pharmacogenetic and Clinical Factors to Predict the Therapeutic Dose of Warfarin. Clinical Pharmacology & Therapeutics 84:3, 326-331
CrossRef91
Susan I. O’Shea, Murat O. Arcasoy, Gregory Samsa, Sandra E. Cummings, Elizabeth H. Thames, Richard S. Surwit, Thomas L. Ortel. (2008) Direct-to-patient expert system and home INR monitoring improves control of oral anticoagulation. Journal of Thrombosis and Thrombolysis 26:1, 14-21
CrossRef92
Chenrong Huang, Jian Yang, Yonghong Du, Liyan Miao. (2008) Measurement of free concentrations of highly protein-bound warfarin in plasma by ultra performance liquid chromatography–tandem mass spectrometry and its correlation with the international normalized ratio. Clinica Chimica Acta 393:2, 85-89
CrossRef93
Jesús Javier Castellanos Monedero, María Luisa Legaz Huidobro, María Ángeles Galindo Andugar, Álvaro Rodríguez Pérez, José María Mantrana del Valle. (2008) Isquemia intestinal de repetición por el factor VIII. Gastroenterología y Hepatología 31:6, 347-348
CrossRef94
Zohreh Rahimi, Asad Vaisi-Raygani, Hadi Mozafari, Hadi Kharrazi, Mansour Rezaei, Ronald L. Nagel. (2008) Prevalence of factor V Leiden (G1691A) and prothrombin (G20210A) among Kurdish population from Western Iran. Journal of Thrombosis and Thrombolysis 25:3, 280-283
CrossRef95
Job Harenberg, Ingrid Jörg, Yvonne Vukojevic, Gerd Mikus, Christel Weiss. (2008) Anticoagulant effects of Idraparinux after termination of therapy for prevention of recurrent venous thromboembolism: observations from the van Gogh trials. European Journal of Clinical Pharmacology 64:6, 555-563
CrossRef96
M. Levi, G. K. Hovingh, S. C. Cannegieter, M. Vermeulen, H. R. Buller, F. R. Rosendaal. (2008) Bleeding in patients receiving vitamin K antagonists who would have been excluded from trials on which the indication for anticoagulation was based. Blood 111:9, 4471-4476
CrossRef97
, A. Torbicki, A. Perrier, S. Konstantinides, G. Agnelli, N. Galie, P. Pruszczyk, F. Bengel, A. J.B. Brady, D. Ferreira, U. Janssens, W. Klepetko, E. Mayer, M. Remy-Jardin, J.-P. Bassand, , A. Vahanian, J. Camm, R. De Caterina, V. Dean, K. Dickstein, G. Filippatos, C. Funck-Brentano, I. Hellemans, S. D. Kristensen, K. McGregor, U. Sechtem, S. Silber, M. Tendera, P. Widimsky, J. L. Zamorano, , J.-L. Zamorano, F. Andreotti, M. Ascherman, G. Athanassopoulos, J. De Sutter, D. Fitzmaurice, T. Forster, M. Heras, G. Jondeau, K. Kjeldsen, J. Knuuti, I. Lang, M. Lenzen, J. Lopez-Sendon, P. Nihoyannopoulos, L. Perez Isla, U. Schwehr, L. Torraca, J.-L. Vachiery. (2008) Guidelines on the diagnosis and management of acute pulmonary embolism: The Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). European Heart Journal 29:18, 2276-2315
CrossRef98
Lawrence J Lesko, Brian F Gage. (2008) Couma-Gen: implications for future randomized trials of pharmacogenetic-based warfarin therapy. Personalized Medicine 5:2, 163-168
CrossRef99
Amir K. Jaffer. (2008) Managing anticoagulant related coagulopathy. Journal of Thrombosis and Thrombolysis 25:1, 85-90
CrossRef100
Richard A. Marlar, Sanam Husain. (2008) The enigmas of the lupus anticoagulant: Mechanisms, diagnosis, and management. Current Rheumatology Reports 10:1, 74-80
CrossRef101
Giancarlo Agnelli, Cecilia Becattini. (2008) Treatment of DVT: how long is enough and how do you predict recurrence. Journal of Thrombosis and Thrombolysis 25:1, 37-44
CrossRef102
Waldemar E. Wysokinski, Izabela Gosk-Bierska, Eddie L. Greene, Diane Grill, Heather Wiste, Robert D. McBane. (2008) Clinical Characteristics and Long-term Follow-up of Patients With Renal Vein Thrombosis. American Journal of Kidney Diseases 51:2, 224-232
CrossRef103
Cynthia L. Leibson, Tanya M. Petterson, Kent R. Bailey, L. Joseph Melton, John A. Heit. (2008) Risk Factors for Venous Thromboembolism in Nursing Home Residents. Mayo Clinic Proceedings 83:2, 151-157
CrossRef104
Cynthia L. Leibson, Tanya M. Petterson, Kent R. Bailey, L. Joseph Melton, John A. Heit. (2008) Risk Factors for Venous Thromboembolism in Nursing Home Residents. Mayo Clinic Proceedings 83:2, 151-157
CrossRef105
(2008) CrossRef Listing of Deleted DOIs. CrossRef Listing of Deleted DOIs
CrossRef106
H. Bounameaux, A. Perrier. (2008) Duration of Anticoagulation Therapy for Venous Thromboembolism. Hematology 2008:1, 252-258
CrossRef107
Steven R. Deitcher. 2008. Diagnosis, Treatment, and Prevention of Cancer-Related Venous Thrombosis. , 693-715.
CrossRef108
T. Housten-Harris. (2007) The nurse specialist and practical issues in the care of pulmonary arterial hypertension patients. International Journal of Clinical Practice 61, 10-18
CrossRef109
C. KEARON. (2007) Indefinite anticoagulation after a first episode of unprovoked venous thromboembolism: yes. Journal of Thrombosis and Haemostasis 5:12, 2330-2335
CrossRef110
Liyan Miao, Jian Yang, Chenrong Huang, Zhenya Shen. (2007) Contribution of age, body weight, and CYP2C9 and VKORC1 genotype to the anticoagulant response to warfarin: proposal for a new dosing regimen in Chinese patients. European Journal of Clinical Pharmacology 63:12, 1135-1141
CrossRef111
Melvyn Rubenfire, Melike Bayram, Zachary Hector-Word. (2007) Pulmonary Hypertension in the Critical Care Setting: Classification, Pathophysiology, Diagnosis, and Management. Critical Care Clinics 23:4, 801-834
CrossRef112
The van Gogh Investigators. (2007) Extended Prophylaxis of Venous Thromboembolism with Idraparinux. New England Journal of Medicine 357:11, 1105-1112
Full Text113
Elizabeth Varga. (2007) Inherited Thrombophilia: Key Points for Genetic Counseling. Journal of Genetic Counseling 16:3, 261-277
CrossRef114
Andrew F Shorr, William L Jackson, Brendan M Weiss, Lisa K Moores. (2007) Low-molecular weight heparin for deep vein thrombosis prophylaxis in hospitalized medical patients: results from a cost-effectiveness analysis. Blood Coagulation & Fibrinolysis 18:4, 309-316
CrossRef115
Cary P. Gross, Deron H. Galusha, Harlan M. Krumholz. (2007) The Impact of Venous Thromboembolism on Risk of Death or Hemorrhage in Older Cancer Patients. Journal of General Internal Medicine 22:3, 321-326
CrossRef116
(2007) d-Dimer and Duration of Anticoagulation. New England Journal of Medicine 356:4, 421-423
Full Text117
Takafumi TAMURA, Takayuki TERASAWA, Yutaka MIZUNO, Michitaka OKAMOTO, Masahide SATO. (2007) TWO CASES OF BOWEL NECROSIS CAUSED BY PRIMARY THROMBOSIS OF THE SUPERIOR MESENTERIC VEIN. Nihon Rinsho Geka Gakkai Zasshi (Journal of Japan Surgical Association) 68:3, 617-622
CrossRef118
Matthew T. Rondina, Robert C. Pendleton, Michelle Wheeler, George M. Rodgers. (2007) The treatment of venous thromboembolism in special populations. Thrombosis Research 119:4, 391-402
CrossRef119
Frederick R. Rickles, Mark Levine. 2007. Thrombosis and Cancer. , 389-403.
CrossRef120
Samuel Z. Goldhaber. 2007. Deep Vein Thrombosis and Pulmonary Embolism. , 245-256.
CrossRef121
John A. Heit. 2007. Thrombophilia: Clinical and Laboratory Assessment and Management. , 211-244.
CrossRef122
Gregory Piazza, Samuel Z. Goldhaber. (2006) Venous Thromboembolism Guidebook. Critical Pathways in Cardiology: A Journal of Evidence-Based Medicine 5:4, 211-227
CrossRef123
2006. Venous Thromboembolism. .
CrossRef124
M. CUSHMAN, R. J. GLYNN, S. Z. GOLDHABER, S. MOLL, K. A. BAUER, S. DEITCHER, S. SHRIVASTAVA, P. M. RIDKER. (2006) Hormonal factors and risk of recurrent venous thrombosis: the Prevention of Recurrent Venous Thromboembolism trial. Journal of Thrombosis and Haemostasis 4:10, 2199-2203
CrossRef125
Michael B. Streiff, Jodi B. Segal, Leonardo J. Tamariz, Mollie W. Jenckes, Dennis T. Bolger, John Eng, Jerry A. Krishnan, Eric B. Bass. (2006) Duration of vitamin K antagonist therapy for venous thromboembolism: A systematic review of the literature. American Journal of Hematology 81:9, 684-691
CrossRef126
L. YOUNG, P. OCKELFORD, D. MILNE, V. ROLFE-VYSON, S. MCKELVIE, P. HARPER. (2006) Post-treatment residual thrombus increases the risk of recurrent deep vein thrombosis and mortality. Journal of Thrombosis and Haemostasis 4:9, 1919-1924
CrossRef127
Simon McRae, Huyen Tran, Sam Schulman, Jeff Ginsberg, Clive Kearon. (2006) Effect of patient's sex on risk of recurrent venous thromboembolism: a meta-analysis. The Lancet 368:9533, 371-378
CrossRef128
Philippe de Moerloose, Charles Marc Samama, Serge Motte. (2006) Management of venous thromboembolism. Canadian Journal of Anesthesia/Journal canadien d'anesthésie 53:S2, S80-S88
CrossRef129
P. W. KAMPHUISEN. (2006) Can anticoagulant treatment be tailored with biomarkers in patients with venous thromboembolism?. Journal of Thrombosis and Haemostasis 4:6, 1206-1207
CrossRef130
S. SHRIVASTAVA, P. M. RIDKER, R. J. GLYNN, S. Z. GOLDHABER, S. MOLL, H. BOUNAMEAUX, K. A. BAUER, C. M. KESSLER, M. CUSHMAN. (2006) D-dimer, factor VIII coagulant activity, low-intensity warfarin and the risk of recurrent venous thromboembolism. Journal of Thrombosis and Haemostasis 4:6, 1208-1214
CrossRef131
Val??rie Gras-Champel, Annelise Voyer, Nicolas Guillaume, C??line Lematte, Bertrand Roussel, Charlotte Machu-Prestaux, Michel Andr??jak, Jean-Jacques Lefr??re. (2006) Quality Evaluation of the Management of Oral Anticoagulation Therapy (OAT): The Awareness of Treating Physicians and the Education of Patients Needs to Be Improved. American Journal of Therapeutics 13:3, 223-228
CrossRef132
Gordon D. O. Lowe. (2006) Can haematological tests predict cardiovascular risk? The 2005 Kettle Lecture*. British Journal of Haematology 133:3, 232-250
CrossRef133
Jane Pruemer. (2006) Treatment of Cancer-Associated Thrombosis: Distinguishing Among Antithrombotic Agents. Seminars in Oncology 33, 26-39
CrossRef134
Karin Wahlander, Henry Eriksson, Torbjorn Lundstrom, Solveig Billing Clason, Ulrika Wall, Per Nystrom, Peter Wessman, Sam Schulman, . (2006) Risk of recurrent venous thromboembolism or bleeding in relation to thrombophilic risk factors in patients receiving ximelagatran or placebo for long-term secondary prevention of venous thromboembolism. British Journal of Haematology 133:1, 68-77
CrossRef135
S. A. BROWN, L. M. ALEDORT, C. A. LEE. (2006) Current issues facing coagulationists - meeting report1. Haemophilia 12:2, 115-123
CrossRef136
Chris Gardiner, Karen Williams, Ian Longair, Ian J. Mackie, Samuel J. Machin, Hannah Cohen. (2006) A randomised control trial of patient self-management of oral anticoagulation compared with patient self-testing. British Journal of Haematology 132:5, 598-603
CrossRef137
Job Harenberg, Ingrid Jörg, Christel Weiss. (2006) Incidence of recurrent venous thromboembolism of patients after termination of treatment with ximelagatran. European Journal of Clinical Pharmacology 62:3, 173-177
CrossRef138
Jeffrey I. Weitz. (2006) Changing Paradigms in the Management of Venous Thromboembolism. The American Heart Hospital Journal 4:2, 135-141
CrossRef139
McDonald K. Horne, Donna Jo McCloskey. (2006) Factor V Leiden as a Common Genetic Risk Factor for Venous Thromboembolism. Journal of Nursing Scholarship 38:1, 19-25
CrossRef140
V. M. Maqueda, V. Thijs. (2006) Risk of thromboembolism after cerebral venous thrombosis. European Journal of Neurology 13:3, 302-305
CrossRef141
Brian F. Gage, Yan Yan, Paul E. Milligan, Amy D. Waterman, Robert Culverhouse, Michael W. Rich, Martha J. Radford. (2006) Clinical classification schemes for predicting hemorrhage: Results from the National Registry of Atrial Fibrillation (NRAF). American Heart Journal 151:3, 713-719
CrossRef142
Samuel Z. Goldhaber. (2006) Low Intensity Warfarin Anticoagulation is Safe and Effective as a Long-Term Venous Thromboembolism Prevention Strategy. Journal of Thrombosis and Thrombolysis 21:1, 51-52
CrossRef143
T. P. Baglin, D. M. Keeling, H. G. Watson, . (2006) Guidelines on oral anticoagulation (warfarin): third edition - 2005 update. British Journal of Haematology 132:3, 277-285
CrossRef144
W. Blättler, H.-E. Gerlach. (2006) Diagnostik und Therapie der Rezidivthrombose. Gefässchirurgie 11:1, 28-32
CrossRef145
B. Weingessel, S. Richter-Müksch, S. Sacu, U. Schmidt-Erfurth, P. V. Vécsei-Marlovits. (2006) Sinnhaftigkeit der Fundusbegutachtung vor Marcoumarisierung. Spektrum der Augenheilkunde 20:1, 23-28
CrossRef146
Jack Ansell. (2006) Point—Counter Point: Low Intensity vs Standard Intensity Oral Anticoagulation for Long-Term Prevention of Venous Thromboembolism Recurrence. Journal of Thrombosis and Thrombolysis 21:1, 49-49
CrossRef147
Michael J Kovacs. (2006) The Standard is Still the Standard or Why an INR of 2–3 is Still the Optimal Intensity for Secondary Prevention of Venous Thromboembolism. Journal of Thrombosis and Thrombolysis 21:1, 53-56
CrossRef148
Mariana M. Bonduel. (2006) Oral anticoagulation therapy in children. Thrombosis Research 118:1, 85-94
CrossRef149
Anders Odén, Martin Fahlén, Robert G. Hart. (2006) Optimal INR for prevention of stroke and death in atrial fibrillation: a critical appraisal. Thrombosis Research 117:5, 493-499
CrossRef150
H. DECOUSUS, A. LEIZOROVICZ. (2006) Superficial thrombophlebitis of the legs: still a lot to learn. Reply to a rebuttal. Journal of Thrombosis and Haemostasis 4:1, 290-290
CrossRef151
George A Makar, Gregory G Ginsberg. (2006) Therapy Insight: approaching endoscopy in anticoagulated patients. Nature Clinical Practice Gastroenterology & Hepatology 3:1, 43-52
CrossRef152
Massimo Franchini, Dino Veneri, Gian Luca Salvagno, Franco Manzato, Giuseppe Lippi. (2006) Inherited Thrombophilia. Critical Reviews in Clinical Laboratory Sciences 43:3, 249-290
CrossRef153
G MONETA. (2006) Predictive Value of D-Dimer Test for Recurrent Venous Thromboembolism After Anticoagulation Withdrawal in Subjects With a Previous Idiopathic Event and in Carriers of Congenital ThrombophiliaPalareti G, Legnani C, Cosmi B, et al (Univ Hosp S Orsola-Malpighi, Bologna, Italy; Univ of Ferrara, Italy) Circulation 108:313–318, 2003§. Yearbook of Vascular Surgery 2006, 361-362
CrossRef154
Christian M. Schambeck. (2005) Fibrinolysis – new perspectives Fibrinolysis-neue Perspektiven. LaboratoriumsMedizin 29:6, 397-397
CrossRef155
J. Weil, H. Schunkert. (2005) Antikoagulation zur Sekundärprävention. Der Internist 46:12, 1310-1317
CrossRef156
Marc Meysman, Patrick Haentjens. (2005) Pulmonary embolism: Current treatment options. Current Treatment Options in Cardiovascular Medicine 7:6, 483-490
CrossRef157
Ramón Lecumberri, Jesús Feliu, Eduardo Rocha. (2005) Nuevas estrategias en la prevención secundaria de la recurrencia de la tromboembolia venosa. Medicina Clínica 125:19, 748-755
CrossRef158
, , , , , , , , , , , , , , , , . (2005) Interdisziplinäre S2-Leitlinie. Diagnostik und Therapie der Bein- und Beckenvenenthrombose und der Lungenembolie. Intensivmedizin und Notfallmedizin 42:7, 552-565
CrossRef159
Julio César Rojas, Bernardo Aguilar, Emma Rodríguez-Maldonado, María Teresa Collados. (2005) Pharmacogenetics of oral anticoagulants. Blood Coagulation & Fibrinolysis 16:6, 389-398
CrossRef160
H. R. BULLER, M. SOHNE, S. MIDDELDORP. (2005) Treatment of venous thromboembolism. Journal of Thrombosis and Haemostasis 3:8, 1554-1560
CrossRef161
Paula G. Rychlik, Karol S. Henry, Henry I. Bussey. (2005) Duration of Treatment of Deep Vein Thrombosis: Time for a New Approach?. Pharmacotherapy 25:8, 1112-1115
CrossRef162
Geno Merli. (2005) Anticoagulants in the treatment of deep vein thrombosis. The American Journal of Medicine 118:8, 13-20
CrossRef163
Clive Kearon, Michael J Kovacs, Jim A Julian. (2005) Deep vein thrombosis. The Lancet 366:9480, 118
CrossRef164
Robert Mohapatra, Maichi Tran, Joel M. Gore, Frederick A. Spencer. (2005) A review of the oral direct thrombin inhibitor ximelagatran. American Heart Journal 150:1, 19-26
CrossRef165
Drahomir Aujesky, Kenneth J. Smith, Mark S. Roberts. (2005) Oral anticoagulation strategies after a first idiopathic venous thromboembolic event. The American Journal of Medicine 118:6, 625-635
CrossRef166
Christy Locke, Susan L. Ravnan, Rajul Patel, James A. Uchizono. (2005) Reduction in Warfarin Adverse Events Requiring Patient Hospitalization After Implementation of a Pharmacist-Managed Anticoagulation Service. Pharmacotherapy 25:5, 685-689
CrossRef167
J. H. S. You, F. W. H. Chan, R. S. M. Wong, G. Cheng. (2005) Is INR between 2.0 and 3.0 the optimal level for Chinese patients on warfarin therapy for moderate-intensity anticoagulation?. British Journal of Clinical Pharmacology 59:5, 582-587
CrossRef168
Peter Rosenberger, Stanton K. Shernan, James D. Rawn, Joseph Scott, Holger K. Eltzschig. (2005) Critical Role of Inferior Vena Caval Filter Placement After Pulmonary Embolectomy. Journal of Cardiac Surgery 20:3, 289-290
CrossRef169
José Ramón Paño Pardo, María del Carmen Fernández Capitán, Mónica López Rodríguez, Mariam Amer López. (2005) Epidemiología de las tromboembolias pulmonares asintomáticas en los pacientes con cáncer. Medicina Clínica 124:12, 477-478
CrossRef170
Steven R. Kayser. (2005) Practical Challenges in the Management of Oral Anticoagulation. Progress in Cardiovascular Nursing 20:2, 80-85
CrossRef171
Paul A Kyrle, Sabine Eichinger. (2005) Deep vein thrombosis. The Lancet 365:9465, 1163-1174
CrossRef172
Deepak Goyal, Anirban Choudhury, Gregory YH Lip. (2005) Thrombotic complications and thromboprophylaxis in breast and gynaecological malignancies. Current Opinion in Obstetrics and Gynecology 17:1, 13???20
CrossRef173
Graham F. Pineo, Russell D. Hull. (2005) Vitamin K Antagonists and Direct Thrombin Inhibitors: Present and Future. Hematology/Oncology Clinics of North America 19:1, 69-85
CrossRef174
Nic J. G. M. Veeger, Margriet Piersma-Wichers, Jan G. P. Tijssen, Hans L. Hillege, Jan Meer. (2005) Individual time within target range in patients treated with vitamin K antagonists: main determinant of quality of anticoagulation and predictor of clinical outcome. a retrospective study of 2300 consecutive patients with venous thromboembolism. British Journal of Haematology 128:4, 513-519
CrossRef175
Paolo Prandoni. (2005) Emerging strategies for treatment of venous thromboembolism. Expert Opinion on Emerging Drugs 10:1, 87-94
CrossRef176
Masataka Ikeda, Mitsugu Sekimoto, Shuji Takiguchi, Masaru Kubota, Masakazu Ikenaga, Hirofumi Yamamoto, Yoshiyuki Fujiwara, Masayuki Ohue, Takushi Yasuda, Hiroshi Imamura, Masayuki Tatsuta, Masahiko Yano, Hiroshi Furukawa, Morito Monden. (2005) High Incidence of Thrombosis of the Portal Venous System After Laparoscopic Splenectomy. Annals of Surgery 241:2, 208-216
CrossRef177
R. D. McBane, C. L. Felty, M. L. Hartgers, R. Chaudhry, L. K. Beyer, P. J. Santrach. (2005) Importance of Device Evaluation for Point-of-Care Prothrombin Time International Normalized Ratio Testing Programs. Mayo Clinic Proceedings 80:2, 181-186
CrossRef178
Elizabeth Blanchard, Jack Ansell. (2005) Extended Anticoagulation Therapy for the Primary and Secondary Prevention of Venous Thromboembolism. Drugs 65:3, 303-311
CrossRef179
Chris Gardiner, Karen Williams, Ian J. Mackie, Samuel J. Machin, Hannah Cohen. (2005) Patient self-testing is a reliable and acceptable alternative to laboratory INR monitoring. British Journal of Haematology 128:2, 242-247
CrossRef180
Giancarlo Agnelli. (2005) Current Issues in Anticoagulation. Pathophysiology of Haemostasis and Thrombosis 34:1, 2-9
CrossRef181
Carsten N. Gutt, Traian Oniu, Frédéric Wolkener, Ari Mehrabi, Shilu Mistry, Markus W. Büchler. (2005) Prophylaxis and treatment of deep vein thrombosis in general surgery. The American Journal of Surgery 189:1, 14-22
CrossRef182
V. Vicente García, M.L. Lozano Almela. (2005) Trombosis venosa profunda: consideraciones terapéuticas. Revista Clínica Española 205:1, 1-2
CrossRef183
Sam Schulman. (2005) The Role of Ximelagatran in the Treatment of Venous Thromboembolism. Pathophysiology of Haemostasis and Thrombosis 34:1, 18-24
CrossRef184
Valter Lubrano, Franca Cocci, Debora Battaglia, Angela Papa, Paolo Marraccini, Gian Carlo Zucchelli. (2005) Usefulness of high-sensitivity IL-6 measurement for clinical characterization of patients with coronary artery disease. Journal of Clinical Laboratory Analysis 19:3, 110-114
CrossRef185
Margaret O???Byrne. (2004) Post-Thrombotic Syndrome After Orthopaedic Surgery. Techniques in Orthopaedics 19:4, 347-357
CrossRef186
H. WHITE, S. MURIN. (2004) Is the current classification of venous thromboembolism acceptable? No. Journal of Thrombosis and Haemostasis 2:12, 2262-2263
CrossRef187
R. M. Bauersachs. (2004) Therapie der Beinvenenthrombose. Der Internist 45:12, 1345-1355
CrossRef188
Mary Ann Knovich, Glenn J. Lesser. (2004) The management of thromboembolic disease in patients with central nervous system malignancies. Current Treatment Options in Oncology 5:6, 511-517
CrossRef189
Darlene J. Elias. (2004) Pulmonary Embolism in Orthopaedic Patients: Diagnosis and Treatment. Techniques in Orthopaedics 19:4, 317-326
CrossRef190
M.P. Sánchez Antón, J. Feliu Sánchez, R. Lecumberri Villamediana, E. Rocha Hernando. (2004) Mujer de 51 años con sospecha de trombosis venosa profunda. Medicine - Programa de Formación Médica Continuada Acreditado 9:22, 1447-1449
CrossRef191
Toni L. Ripley, Dawn E. Havrda, Steve Blevins, Daniel Culkin. (2004) Early Evaluation of Hematuria in a Patient Receiving Anticoagulant Therapy and Detection of Malignancy. Pharmacotherapy 24:11, 1638-1640
CrossRef192
R. Lecumberri Villamediana, M.P. Sánchez Antón, J. Feliú Sánchez, E. Rocha Hernando. (2004) Trombofilia venosa. Clasificación, implicaciones clínicas y terapéuticas. Medicine - Programa de Formación Médica Continuada Acreditado 9:22, 1393-1400
CrossRef193
Anthony J. Busti, Henry I. Bussey. (2004) The Role of Oral Direct Thrombin Inhibitors in the Treatment of Venous Thromboembolism. Pharmacotherapy 24:10 Part 2, 184S-189S
CrossRef194
David Bergqvist. (2004) Bleeding profiles of anticoagulants, including the novel oral direct thrombin inhibitor ximelagatran: definitions, incidence and management. European Journal of Haematology 73:4, 227-242
CrossRef195
Kenneth A. Bauer. (2004) Low intensity warfarin: is it clinically useful in venous thromboembolism management?. British Journal of Haematology 127:2, 155-158
CrossRef196
S STONE, T MORRIS. (2004) Pulmonary embolism and pregnancy. Critical Care Clinics 20:4, 661-677
CrossRef197
Karen Heskett. (2004) Clinical Trials. Journal of Consumer Health On the Internet 8:3, 35-52
CrossRef198
Wylie Burke. (2004) GENETIC TESTING IN PRIMARY CARE. Annual Review of Genomics and Human Genetics 5:1, 1-14
CrossRef199
V. De Stefano. (2004) Inherited thrombophilia and life-time risk of venous thromboembolism: is the burden reducible?. Journal of Thrombosis and Haemostasis 2:9, 1522-1525
CrossRef200
G. Le Gal, H. Bounameaux. (2004) d-Dimer testing to predict recurrence risk in venous thromboembolism: looking for a useful threshold: a rebuttal. Journal of Thrombosis and Haemostasis 2:9, 1670-1672
CrossRef201
J. A. Kline, A. M. Mitchell, C. Kabrhel, P. B. Richman, D. M. Courtney. (2004) Clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism. Journal of Thrombosis and Haemostasis 2:8, 1247-1255
CrossRef202
Joseph L. Blackshear. (2004) Closure of patent foramen ovale in cryptogenic stroke. Journal of the American College of Cardiology 44:4, 759-761
CrossRef203
Bates, Shannon M., Ginsberg, Jeffrey S., . (2004) Treatment of Deep-Vein Thrombosis. New England Journal of Medicine 351:3, 268-277
Full Text204
H. C. Whinna, E. B. Lesesky, D. M. Monroe, K. A. High, P. J. Larson, F. C. Church. (2004) Role of the
-carboxyglutamic acid domain of activated factor X in the presence of calcium during inhibition by antithrombin-heparin. Journal of Thrombosis and Haemostasis 2:7, 1127-1134
CrossRef205
P. M. Ridker. (2004) Long-term low-dose warfarin use is effective in the prevention of recurrent venous thromboembolism: yes. Journal of Thrombosis and Haemostasis 2:7, 1034-1037
CrossRef206
M. J. Kovacs. (2004) Long-term low-dose warfarin use is effective in the prevention of recurrent venous thromboembolism: no. Journal of Thrombosis and Haemostasis 2:7, 1041-1043
CrossRef207
G. Agnelli. (2004) Long-term low-dose warfarin use is effective in the prevention of recurrent venous thromboembolism: no. Journal of Thrombosis and Haemostasis 2:7, 1038-1040
CrossRef208
Elliott, C. Gregory, Rubin, Lewis J., . (2004) Mars or Venus — Is Sex a Risk Factor for Recurrent Venous Thromboembolism?. New England Journal of Medicine 350:25, 2614-2616
Full Text209
L. Poller. (2004) International Normalized Ratios (INR): the first 20 years. Journal of Thrombosis and Haemostasis 2:6, 849-860
CrossRef210
Cabot, Richard C.Harris, Nancy Lee, Shepard, Jo-Anne O., Ebeling, Sally H.Ellender, Stacey M.Peters, Christine C., Goldhaber, Samuel Z., Nadel, Eric S., King, Mary Etta, Sharma, Amita, . (2004) Case 17-2004. New England Journal of Medicine 350:22, 2281-2290
Full Text211
Daniel Farray, Teresa L Carman, Bernardo B Fernandez. (2004) The treatment and prevention of deep vein thrombosis in the preoperative management of patients who have neurologic diseases. Neurologic Clinics 22:2, 423-439
CrossRef212
Arina J ten Cate-Hoek, Martin H Prins. (2004) Appropriate level and length of postthrombotic warfarin treatment: an evaluation of recent developments. Current Opinion in Hematology 11:3, 182-186
CrossRef213
Edwin G Bovill, Mark Fung, Mary Cushman. (2004) Vitamin K and oral anticoagulation: thought for food. The American Journal of Medicine 116:10, 711-713
CrossRef214
Samuel Z Goldhaber. (2004) Pulmonary embolism. The Lancet 363:9417, 1295-1305
CrossRef215
Craig M Kessler. (2004) Antidotes to haemorrhage: recombinant factor VIIa. Best Practice & Research Clinical Haematology 17:1, 183-197
CrossRef216
Richard L Mueller. (2004) First-generation agents: aspirin, heparin and coumarins. Best Practice & Research Clinical Haematology 17:1, 23-53
CrossRef217
(2004) Ximelagatran for Secondary Prevention of Venous Thromboembolism. New England Journal of Medicine 350:6, 618-619
Full Text218
P Léger, D Barcat, C Boccalon, J Guilloux, H Boccalon. (2004) Thromboses veineuses des membres inférieurs et de la veine cave inférieure. EMC - Cardiologie-Angéiologie 1:1, 80-96
CrossRef219
Henry Eriksson. (2004) Treatment of Venous Thromboembolism and Long-Term Prevention of Recurrence. Drugs 64:Supplement 1, 37-46
CrossRef220
Eli V. Gelfand, Gregory Piazza, Samuel Z. Goldhaber. (2003) Venous Thromboembolism Guidebook, Fourth Edition. Critical Pathways in Cardiology: A Journal of Evidence-Based Medicine 2:4, 247-265
CrossRef221
Candice K Silversides, John T Granton, Eli Konen, Michelle A Hart, Gary D Webb, Judith Therrien. (2003) Pulmonary thrombosis in adults with Eisenmenger syndrome. Journal of the American College of Cardiology 42:11, 1982-1987
CrossRef222
(2003) Low-Intensity versus Conventional-Intensity Warfarin for Prevention of Recurrent Venous Thromboembolism. New England Journal of Medicine 349:22, 2164-2167
Full Text223
Marc Ruivard, Christine Berger, Abdellaziz Achaibi, Claude Campagne, Pierre Philippe. (2003) Physician Compliance with Outpatient Oral Anticoagulant Guidelines in Auvergne, France. Journal of General Internal Medicine 18:11, 903-907
CrossRef224
Robert A. S. Roubey. (2003) New approaches to prevention of thrombosis in the antiphospholipid syndrome: Hopes, trials, and tribulations. Arthritis & Rheumatism 48:11, 3004-3008
CrossRef225
DOUGLAS S. SCHERR, W. REID PITTS. (2003) The Nonsteroidal Effects of Diethylstilbestrol: The Rationale for Androgen Deprivation Therapy Without Estrogen Deprivation in the Treatment of Prostate Cancer. The Journal of Urology 170:5, 1703-1708
CrossRef226
Schulman, Sam, Wåhlander, Karin, Lundström, Torbjörn, Clason, Solveig Billing, Eriksson, Henry, . (2003) Secondary Prevention of Venous Thromboembolism with the Oral Direct Thrombin Inhibitor Ximelagatran. New England Journal of Medicine 349:18, 1713-1721
Full Text227
(2003) Scientific surgery. British Journal of Surgery 90:10, 1310-1310
CrossRef228
D. Gustafsson. (2003) Oral direct thrombin inhibitors in clinical development. Journal of Internal Medicine 254:4, 322-334
CrossRef229
Michelle Petri. (2003) Evidence-based management of thrombosis in the antiphospholipid antibody syndrome. Current Rheumatology Reports 5:5, 370-373
CrossRef230
Joel G. Ray. (2003) Dyslipidemia, statins, and venous thromboembolism: a potential risk factor and a potential treatment. Current Opinion in Pulmonary Medicine 9:5, 378-384
CrossRef231
Kearon, Clive, Ginsberg, Jeffrey S., Kovacs, Michael J., Anderson, David R., Wells, Philip, Julian, Jim A., MacKinnon, Betsy, Weitz, Jeffrey I., Crowther, Mark A., Dolan, Sean, Turpie, Alexander G., Geerts, William, Solymoss, Susan, van Nguyen, Paul, Demers, Christine, Kahn, Susan R., Kassis, Jeannine, Rodger, Marc, Hambleton, Julie, Gent, Michael, . (2003) Comparison of Low-Intensity Warfarin Therapy with Conventional-Intensity Warfarin Therapy for Long-Term Prevention of Recurrent Venous Thromboembolism. New England Journal of Medicine 349:7, 631-639
Full Text232
Büller, Harry R., Prins, Martin H., . (2003) Secondary Prophylaxis with Warfarin for Venous Thromboembolism. New England Journal of Medicine 349:7, 702-704
Full Text233
Schulman, Sam, . (2003) Care of Patients Receiving Long-Term Anticoagulant Therapy. New England Journal of Medicine 349:7, 675-683
Full Text234
. (2003) Langer maar minder antistollen?. Medisch-Farmaceutische Mededelingen 41:8, 232-232
CrossRef235
(2003) Low-Intensity Warfarin Therapy for the Prevention of Recurrent Venous Thromboembolism. New England Journal of Medicine 349:4, 398-400
Full Text236
K. A. Bauer. (2003) Management of thrombophilia. Journal of Thrombosis and Haemostasis 1:7, 1429-1434
CrossRef237
S. Schulman. (2003) Unresolved issues in anticoagulant therapy. Journal of Thrombosis and Haemostasis 1:7, 1464-1470
CrossRef238
Schafer, Andrew I., . (2003) Warfarin for Venous Thromboembolism — Walking the Dosing Tightrope. New England Journal of Medicine 348:15, 1478-1480
Full Text239
Cecilia Becattini, Giancarlo Agnelli. (2003) Duration of Anticoagulant Treatment after VenousThromboembolism. Pathophysiology of Haemostasis and Thrombosis 33:5-6, 354-357
CrossRef240
Philip C Comp. (2003) Treatment and management of acute venous thromboembolic disease. Thrombosis Research 111:1-2, 3-8
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