| | Factor | How it affects |
| | Age | Conventional risk factors, comorbidities, and malignant disease in elderly adults increase the risk of bleeding and VTE [41]. In younger patients, DOACs were associated with lower bleeding risk compared with warfarin but there were no statistically significant differences in >75 years [30]. |
| | Gender | Factors proposed to explain the increased thromboembolic risk in women: increased hypertension, renal dysfunction, hyperthyroidism, increased hypercoagulability, cardiovascular remodeling, and estrogen hormone replacement therapy, as well as specific gender influences on the quality of the anticoagulant treatment (i.e., lower quality of warfarin anticoagulation in females with AF, which requires higher rates of anticoagulation prescription that increases the risk of bleeding [42]. |
| | Food interactions | Warfarin is affected by a wide range of targets in blood hemostasis, including inhibition of COX, the presence of coumarins and other substances, or high amounts of vitamin K. Herbs with the greatest potential to interact with warfarin include ginseng, garlic, ginkgo, St. John’s wort, and ginger, but even menthol cough drops may reduce the INR [43]. |
| | Drug-drug interactions | Some examples of medication affecting VKAs:
(a) Drugs, including ciprofloxacin, cotrimoxazole, cephalosporins, fluconazole, and metronidazole, can increase the warfarin effect.
(b) Several cardiovascular drugs can potentiate the metabolism of warfarin and increase the INR, including aspirin, amiodarone, antihyperlipidemic agents, and statins, such as fluvastatin, lovastatin, and simvastatin.
(c) Analgesics, including phenybutazone, piroxicam, acetaminophen, and NSAIDs, can increase the anticoagulation effects.
(d) Central nervous system drugs, such as antidepressants, citalopram, fluoxetine, paroxetine, and tricyclics antidepressant can increase the INR and the risk of bleeding.
(e) Alcohol is a risk factor with concomitant liver disease.
(f) Gastrointestinal drugs, such as cimetidine and omeprazole, can increase the INR [44].
Some examples of medication affecting DOACs:
(a) Dabigatran interacts with antacids, which decrease the effect of dabigratan;
(b) Antiarrhythmic agents, such as amiodarone, verapamil, quinidine, as well as antiplatelet agents, LMWH, and nonsteroidal anti-inflammatory drugs (NSAIDs), increase the anticoagulant effects [40].
(c) Rivaroxaban interacts with antiacids, antifungical medications, such as itraconazole, voriconazole, and posaconazole, antiplatelet agents, NSAIDs, such as naproxen, and LMWH among others increasing the anticoagulant effects [40]. |
| | Renal impairments | In mild renal insufficiency (eGFR: 50–79 mL/min), the major bleeding risk was lower with any DOACs than with warfarin. In moderate renal insufficiency (eGFR: 30–49 mL/min), the risk was higher, with rates of major bleeding of 6.8% versus 4.8% in patients with mild insufficiency and a trend toward less major bleeding with the DOACs [41]. |
| | Exercise | A study carried out on three patients taking warfarin showed an inverse relationship with increased physical activity and decreased INR. Thus, it may be possible that an increase in physical activity puts patients at greater risk of thromboembolism [45–47].
Ryan et al.’s study showed that taking aspirin before running 60 minutes increased both the intestinal and gastroduodenal permeability of aspirin compared with taking a placebo and running or placebo plus rest but not aspirin plus rest. Nevertheless, the clinical significance of this study is highly questionable [48].
In a study by Sawrymowicz et al., 20 healthy patients took an oral dose of aspirin 1 g and then walked on a treadmill at 4.8 km/h for 20 minutes per half hour for 3 hours. Blood samples taken during the exercise did not show changes in plasma concentration, clearance, or half-life compared with a 3-hour rest [49]. |
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