Long-term Warfarin Use Research Articles

Individualised strategy of warfarin treatment for deep vein thromboembolism – case reports

Individualised strategy of warfarin treatment for deep vein thromboembolism – case reports

New Options in Anticoagulation for Atrial Fibrillation

The presence of atrial fibrillation significantly increases the risk and burden of thromboembolic stroke.1 Warfarin is the reference standard treatment for the primary prevention of embolic stroke during atrial fibrillation.2 However, the long-term use of warfarin has its limitations. Although guidelines suggest a target international normalized ratio (INR) of 2.5 (range, 2.0 to 3.0) for this indication,2 only about 60% of patients have an INR within the recommended range at a given time in usual clinical practice. This is the reason that is most often given for the search for other oral antithrombotic agents that could be simpler to manage . . .

Anticoagulant-induced intramural intestinal hemorrhage

Background Long-term use of warfarin can provide benefits in the treatment of many diseases, but adverse bleeding events are unpreventable because of a narrow therapeutic range. Objective The aim of this retrospective chart review with data abstraction was to investigate the clinical presentations of intestinal intramural hemorrhage in emergency department (ED) patients. Methods We reviewed the cases of 17 patients with acute abdominal pain in our ED. Medical records including demographic data and results of abdominal computed tomography were retrospectively reviewed and analyzed. Results The mean ± SD age of the reviewed patients was 77.7 ± 8.5 years (range, 60-93 years). The mean ± SD duration from onset of symptoms to ED visit was 2.5 ± 1.3 days (range, 1-5 days). All patients had abdominal pain, and 64.7% had nausea/vomiting. A total of 64.7% of patients had peritoneal signs. The jejunum was most commonly involved (88.2% of all cases). The maximal mean ± SD wall thickening of the bowel was 14.1 ± 4.4 mm (range, 7.4-26.7 mm), and the estimated mean ± SD length was 35.6 ± 24.4 cm (range, 9-105 cm). The mean ± SD prothrombin time and activated partial thromboplastin time were prolonged to 86.5 ± 26.9 and 116.2 ± 43.1 seconds, respectively. All patients received medical treatment and survived. At the last follow-up (mean, 27.4 months), none of the patients had recurrence of intestinal intramural hemorrhage or intestinal obstruction. Conclusion Prolonged prothrombin time and drug history can indicate the possibility of intramural intestinal hemorrhage, and abdominal computed tomography may help to exclude surgical diseases and prevent unnecessary surgery.

Upper Gastrointestinal Tract Hemorrhage, Warfarin, and Urinary Tract Antibiotics

Hemorrhage is a well-known side effect of long-term warfarin use in older patients. Interactions between warfarin and certain other drugs can increase

Warfarinized Patients with Proximal Femoral Fractures: Survey of UK Clinical Practice.

In an aging population, anticoagulation in patients with musculoskeletal injuries is increasingly prevalent. The North American literature indicates an absence of consensus concerning the most appropriate management for this group. We aim to test the hypothesis that there is a lack of consensus in the UK regarding the perioperative management of patients with hip fractures on long-term warfarin therapy. A representative group of 400 consultant orthopedic surgeons was surveyed by postal questionnaire regarding their policy on the reversal of anticoagulation in warfarinized patients with hip fractures. The consultants contacted were selected to represent a geographical spread throughout the UK. There were 159 respondents (40% response rate), of which 79% (126) had a trauma commitment. 95 (75%) of these had a protocol for the reversal of anticoagulation prior to surgery. The commonest method used was to simply withhold warfarin and wait (70%). Other methods included FFP (16%), and low-dose (23%) and high-dose (14%) vitamin K. Some respondents used more than onemethod. Although nearly all respondents preferred an INR < 2.0 prior to surgery, 55% preferred an INR < 1.5. Hip fracture in the presence of long-term warfarin use is associated with significantly increased morbidity. This problem is likely to increase. Our results demonstrate variation in approach throughout the UK with regard to warfarin reversal and the acceptable INR at which to operate in this group of patients. We propose that low-dose vitamin K is considered more widely as a safe and effective method of warfarin reversal in this group.

Warfarin-induced impairment of cortical bone material quality and compensatory adaptation of cortical bone structure to mechanical stimuli

Long-term warfarin use has been reported to increase fracture risk of rib and vertebra but not hip in elderly patients, but the mechanisms remain unknown. We hypothesized that warfarin would impair bone material quality but could not weaken bone strength under conditions with higher mechanical stimuli. To test this hypothesis, rats were randomized to vehicle or warfarin group at 4 weeks of age and subsequently weight matched into a sedentary or jumping exercise group at 12 weeks of age. At 6 months of age, osteocalcin content, bone mineral density (BMD), mineral size, material properties, morphological parameters, and biomechanical properties of cortical bones were evaluated. In order to seek evidence for a common mechanism of action, effects of nucleation rate of mineral crystals on their rigidity were also investigated using computer simulation. In humeral cortical bones, warfarin did not change BMD, but markedly decreased osteocalcin content, diminished mineral size, and impaired material hardness. Consistent with these results, our computer-simulation model showed that osteocalcin-induced delay of mineral crystal nucleation decreased mineral formation rate, increased mean and distribution of mineral sizes, and strengthened mineral rigidity. In tibial cortical bones, warfarin decreased material ultimate stress; however, under jumping exercise, warfarin increased cross-sectional total and bone areas of these tibiae and completely maintained their biomechanical properties including work to failure. Collectively, our findings suggest that long-term warfarin therapy weakens rib and vertebra by impairing cortical bone material quality due to a marked decrease in osteocalcin content but could not reduce hip strength through compensatory adaptation of cortical bone structure to higher mechanical stimuli.

Long-term warfarin use could reduce the risk of prostate cancer

Long-term warfarin use could reduce the risk of prostate cancer

Risk of Osteoporotic Fracture in Elderly Patients Taking Warfarin

Vitamin K allows for gamma-carboxylation of glutamyl residues, a conversion that activates clotting factors and bone proteins. Vitamin K antagonists such as warfarin inhibit this process. Our goal was to quantify the association between warfarin and osteoporotic fractures in patients with atrial fibrillation. This was a retrospective cohort study of Medicare beneficiaries with atrial fibrillation who were hospitalized between March 1998 and April 1999 in all 50 US states. The study outcome was osteoporotic fractures, identified by an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for a fracture of the hip, spine, or wrist. Compared with 7587 patients who were not prescribed warfarin, the adjusted odds ratio (OR) of fracture was 1.25 (95% confidence interval [CI], 1.06-1.48) in 4461 patients prescribed long-term warfarin therapy (> or = 1 year). The association between osteoporotic fracture and long-term warfarin use was significant in men (OR, 1.63; 95% CI, 1.26-2.10) but nonsignificant in women (OR, 1.05; 95% CI, 0.88-1.26). In 1833 patients prescribed warfarin for less than a year, the risk of osteoporotic fracture was not increased significantly (OR, 1.03). Odds ratios (95% CIs) of independent predictors of osteoporotic fractures were as follows: increasing age, 1.63 (1.47-1.80) per decade; high fall risk, 1.78 (1.42-2.21); hyperthyroidism, 1.77 (1.16-2.70); neuropsychiatric disease, 1.51 (1.28-1.78); and alcoholism, 1.50 (1.01-2.24). Factors with a reduced OR (95% CI) included African American race, 0.30 (0.18-0.51); male sex, 0.54 (0.46-0.62); and use of beta-adrenergic antagonists, 0.84 (0.70-1.00). Long-term use of warfarin was associated with osteoporotic fractures, at least in men with atrial fibrillation. Beta-adrenergic antagonists may protect against osteoporotic fractures.

Variability in long-term warfarin use after new onset atrial fibrillation: Results of the FRACTAL registry

Background: Warfarin has a well established role in the prevention of stroke in patients with atrial fibrillation (AF). Previous studies have found variability in the impact of stroke risk factors on warfarin use. There is a paucity of data regarding factors impacting continued long-term use of warfarin after new onset AF.

Stroke in the Very Elderly

To the Editor: Atrial fibrillation (AF) is the most common, potent, and independent risk factor for ischemic stroke,1 the incidence of which increases with age.2 To determine the influence of advanced age on anticoagulation therapy in elderly patients with AF, a retrospective cohort study of all patients admitted in our department (from 1995 to 2003) was conducted. These patients were >90 years of age and had had an acute stroke. The following parameters were analyzed: age, sex, cardiovascular risk factors and their treatment, and outcome. Among the 404 patients experiencing acute stroke, 39 (9.65%) were >90 years old (average age 91.73±2.34), and 82% were females. Four patients had cognitive impairment (Alzheimer disease) whose quality of life was average for their age. Major risk factors for stroke were AF (64%), hypertension (51%), and diabetes mellitus (7%). Smoking habits, before stroke or transient ischemic attack (TIA), had not …

Warfarin Versus Low-Molecular-Weight Heparin Therapy in Cancer Patients

The association between cancer and venous thromboembolism (VTE) is well established. Importantly, VTE is a significant cause of mortality in cancer patients. Although long-term warfarin (Coumadin(trade mark); Bristol-Myers Squibb; New York, NY) therapy is the mainstay of treatment for cancer patients with VTE, there are many practical problems with its use in this population. In particular, achieving therapeutic drug levels is difficult in cancer patients due to the increased risk of drug interactions, malnutrition, vomiting, and liver dysfunction in these patients. Moreover, cancer patients are at an increased risk of adverse effects of warfarin therapy. In contrast, low-molecular-weight heparins (LMWHs) are associated with a lower risk of adverse events compared with warfarin in patients with cancer. These agents also offer practical advantages compared with warfarin, including more predictable anticoagulant effects and ease of administration in addition to possible antineoplastic effects. Several LMWHs have demonstrated superior efficacy to warfarin in the secondary prevention of VTE. In particular, the LMWH, dalteparin (Fragmin; Pfizer; New York, NY), has recently been shown to have superior efficacy to warfarin in a large trial of patients with cancer and VTE without increasing the risk of bleeding. A randomized trial of dalteparin has also shown improved response rates and survival in patients with small cell lung cancer. In view of the availability of more effective and reliable alternatives to warfarin therapy in cancer patients, it is appropriate to reassess the role of warfarin therapy in patients with cancer and VTE. Further evaluation of the LMWHs for effects on cancer outcome is indicated.

Dementia in subjects with atrial fibrillation: hemostatic function and the role of anticoagulation

Atrial fibrillation (AF) is associated with cognitive impairment and dementia, perhaps through encouraging a prothrombotic state and cardioembolism. We wished to test the hypotheses that hemostatic function is altered in subjects with AF who develop dementia, and that long-term warfarin anticoagulation is protective against this complication. Recruitment was from an observational cohort study of AF. Baseline assessment included measurement of plasma fibrinogen, fibrin D-dimer, prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complexes (TAT), von Willebrand factor and tissue plasminogen activator. We assessed cognitive function after 3 years' follow-up using the 13-item modified Telephone Interview for Cognitive Status (TICSm) and the short form of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Of the 218 subjects assessed, 145 (66%) were prescribed warfarin. Forty-nine (22%) met TICSm/IQCODE criteria for dementia. D-dimer, F1+2 and TAT levels were higher in AF subjects with dementia compared with those without (medians 81 vs. 60 ng mL(-1), P = 0.008; 0.76 vs. 0.49 nmol L(-1), P = 0.006; and 1.78 vs. 1.44 microg L(-1), P = 0.003, respectively). These associations became of borderline statistical significance following adjustment for age. Logistic regression showed a trend towards warfarin use being independently associated with reduced prevalence of dementia (odds ratio 0.52, P = 0.08). We found evidence of increased thrombin generation and fibrin turnover in subjects with AF and dementia compared with those without dementia. Long-term warfarin use may be protective against the development of dementia in subjects with AF.

Choosing antithrombotic therapy for elderly patients with atrial fibrillation who are at risk for falls.

To determine whether the risk of falling (with a possible increased chance of subdural hematoma) should influence the choice of antithrombotic therapy in elderly patients with atrial fibrillation. A Markov decision analytic model was used to determine the preferred treatment strategy (no antithrombotic therapy, long-term aspirin use, or long-term warfarin use) for patients with atrial fibrillation who are 65 years of age and older, are at risk for falling, and have no other contraindications to antithrombotic therapy. Input data were obtained by systematic review of MEDLINE. Outcomes were expressed as quality-adjusted life-years. For patients with average risks of stroke and falling, warfarin therapy was associated with 12.90 quality-adjusted life-years per patient; aspirin therapy, 11.17 quality-adjusted life-years; and no antithrombotic therapy, 10.15 quality-adjusted life-years. Sensitivity analysis demonstrated that, regardless of the patients' age or baseline risk of stroke, the risk of falling was not an important factor in determining their optimal antithrombotic therapy. For elderly patients with atrial fibrillation, the choice of optimal therapy to prevent stroke depends on many clinical factors, especially their baseline risk of stroke. However, patients' propensity to fall is not an important factor in this decision.

4-07-53 Intracerebral hemorrhage associated with long-term use of warfarin in chinese patients

4-07-53 Intracerebral hemorrhage associated with long-term use of warfarin in chinese patients

Effect of adsorbed oxygen upon thermal activation-deactivation of platinum black

Long-term use of warfarin can provide benefits in the treatment of many diseases, but adverse bleeding events are unpreventable because of a narrow therapeutic range.The aim of this retrospective chart review with data abstraction was to investigate the clinical presentations of intestinal intramural hemorrhage in emergency department (ED) patients.We reviewed the cases of 17 patients with acute abdominal pain in our ED. Medical records including demographic data and results of abdominal computed tomography were retrospectively reviewed and analyzed.The mean ± SD age of the reviewed patients was 77.7 ± 8.5 years (range, 60-93 years). The mean ± SD duration from onset of symptoms to ED visit was 2.5 ± 1.3 days (range, 1-5 days). All patients had abdominal pain, and 64.7% had nausea/vomiting. A total of 64.7% of patients had peritoneal signs. The jejunum was most commonly involved (88.2% of all cases). The maximal mean ± SD wall thickening of the bowel was 14.1 ± 4.4 mm (range, 7.4-26.7 mm), and the estimated mean ± SD length was 35.6 ± 24.4 cm (range, 9-105 cm). The mean ± SD prothrombin time and activated partial thromboplastin time were prolonged to 86.5 ± 26.9 and 116.2 ± 43.1 seconds, respectively. All patients received medical treatment and survived. At the last follow-up (mean, 27.4 months), none of the patients had recurrence of intestinal intramural hemorrhage or intestinal obstruction.Prolonged prothrombin time and drug history can indicate the possibility of intramural intestinal hemorrhage, and abdominal computed tomography may help to exclude surgical diseases and prevent unnecessary surgery.

EPR spectra and magnetic susceptibility of aluminochromate catalysts

Long-term use of warfarin can provide benefits in the treatment of many diseases, but adverse bleeding events are unpreventable because of a narrow therapeutic range.The aim of this retrospective chart review with data abstraction was to investigate the clinical presentations of intestinal intramural hemorrhage in emergency department (ED) patients.We reviewed the cases of 17 patients with acute abdominal pain in our ED. Medical records including demographic data and results of abdominal computed tomography were retrospectively reviewed and analyzed.The mean ± SD age of the reviewed patients was 77.7 ± 8.5 years (range, 60-93 years). The mean ± SD duration from onset of symptoms to ED visit was 2.5 ± 1.3 days (range, 1-5 days). All patients had abdominal pain, and 64.7% had nausea/vomiting. A total of 64.7% of patients had peritoneal signs. The jejunum was most commonly involved (88.2% of all cases). The maximal mean ± SD wall thickening of the bowel was 14.1 ± 4.4 mm (range, 7.4-26.7 mm), and the estimated mean ± SD length was 35.6 ± 24.4 cm (range, 9-105 cm). The mean ± SD prothrombin time and activated partial thromboplastin time were prolonged to 86.5 ± 26.9 and 116.2 ± 43.1 seconds, respectively. All patients received medical treatment and survived. At the last follow-up (mean, 27.4 months), none of the patients had recurrence of intestinal intramural hemorrhage or intestinal obstruction.Prolonged prothrombin time and drug history can indicate the possibility of intramural intestinal hemorrhage, and abdominal computed tomography may help to exclude surgical diseases and prevent unnecessary surgery.