Atrial Fibrillation Anticoagulation: Warfarin Four Questions and Four Answers

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Warfarin is an effective drug for the prevention and treatment of atrial fibrillation stroke.Warfarin has become the standard treatment for valvular atrial fibrillation, rheumatic mitral valve stenosis, mechanical valve replacement, biological valve replacement within 3 months or mitral valve repair with AFFor antithrombotic therapy, warfarin should be selected.Warfarin can also be used in patients with nonvalvular atrial fibrillation with anticoagulant indications.How to determine the dose of warfarin?The best anticoagulant strength of warfarin is INR 2.0 ~ 3.0, at this time the risk of bleeding and thromboembolism is the lowest.The best results were achieved when INR was within 60% of the treatment time (TTR).During the treatment with warfarin, the INR should be monitored regularly and the warfarin dose adjusted accordingly.1. Initial dosage It is recommended that the initial dosage for Chinese is 1 ~ 3 mg, which can reach the target range in 2 ~ 4 weeks.In some patients, such as the elderly, patients with impaired liver function, patients at high risk of congestive heart failure, and bleeding, the initial dose can be appropriately reduced.If rapid anticoagulation is required, give unfractionated heparin or low-molecular-weight heparin and warfarin for more than 5 days. Warfarin will be given on the first or second day of heparin administration. When the INR reaches the target range, the generalHeparin or low molecular weight heparin.In the Chinese Atrial Fibrillation Antithrombotic Study, the mean maintenance dose of warfarin was 3 mg.To reduce excessive anticoagulation, loading doses are generally not recommended.Depending on the dose of warfarin, anticoagulation began to appear 2 to 7 days after oral administration.2. When the initial dose of the dose adjustment is not within 1 week, the dose can be adjusted according to the original dose of 5% ~ 20% and the INR can be monitored continuously (every 3 ~ 5 d) until it reaches the target value (INR 2.0 ~ 3.0)..If the INR has been stable, occasionally fluctuates, and the amplitude does not exceed 0.5 above and below the target range of the INR, you do not need to adjust the dose, and review the INR as appropriate and pay attention to the cause.If the two INRs are outside the target range, the dose should be adjusted.Can increase or decrease the original dose of 5% to 20%, pay attention to strengthen monitoring after adjusting the dose.When the dose adjustment of warfarin is small, the method of calculating the weekly dose can be adopted, which is more accurate than adjusting the daily dose.How to monitor when using warfarin?Due to the metabolic characteristics and pharmacological effects of warfarin itself, its application is more complicated, and many factors also affect the anticoagulant effect of warfarin. Therefore, it is necessary to closely monitor the coagulation index and repeatedly adjust the dose.1. Monitoring indicators Prothrombin time (PT) is the most commonly used indicator for monitoring the anticoagulant strength of warfarin.PT reflects the degree of inhibition of prothrombin, factor VII, and factor X.INR is calculated from the PT measured by different laboratories after being adjusted by the international sensitivity index (ISI) of thromboplastin.INR can make coagulation indicators measured in different laboratories comparable.2. Frequency of monitoring Inpatients take warfarin for 2 to 3 days and start monitoring INR daily or every other day until the INR reaches the treatment target and is maintained for at least 2 days.Thereafter, the stability of the INR results is monitored once a few days to one week, which can be extended according to the situation, and stable patients can be monitored once every 4 weeks after discharge.Outpatients should be monitored from a few days to once a week before the dose is stable. Once the INR is stable, they can be monitored every 4 weeks.If dose adjustment is required, the monitoring frequency described above should be repeated until the INR stabilizes again.The frequency of treatment monitoring should be based on the patient’s bleeding risk and medical conditions.Warfarin clearance is reduced in elderly patients, and other diseases or medications are frequently used. Monitoring should be strengthened.In combination with drugs or other diseases that may affect the effect of warfarin, the frequency of surveillance should be increased and the warfarin dose adjusted as appropriate.The frequency of INR monitoring in patients taking long-term warfarin is affected by patient compliance, co-morbidity, co-administration, diet adjustment, and stability of anticoagulant response.What should I do about abnormally elevated INR and / or bleeding?The following factors affect the INR value: accuracy of INR detection methods, changes in vitamin K intake, absorption and metabolism changes of warfarin, changes in vitamin K-dependent coagulation factor synthesis and metabolism, changes in other drug treatments, warfarinThe compliance of Lin taking medicine.When the INR is beyond the scope of treatment, we should look for the above factors, and take different methods according to the degree of increase and the risk of bleeding.The risk of bleeding in patients taking warfarin is related to anticoagulation intensity, anticoagulation management, and stability of INR; bleeding risk factors related to patients such as previous bleeding history, age, tumors, liver and kidney dysfunction, stroke history, alcoholismConcomitant use, especially antiplatelet drugs and non-steroidal anti-inflammatory drugs.1. INR 3.0 ~ 4.5, no bleeding complications due to lower dose warfarin (5% to 20%) or stop taking 1, 1 ~ 2 d after review INR.When the INR returns to within the target value, adjust the warfarin dose and restart treatment.Or strengthen the monitoring of whether INR can return to the treatment level, while looking for factors that may increase INR.2. INR 4.5 ~ 10.0, no bleeding complications deactivated warfarin, intramuscular injection of vitamin K1 (1.0 ~ 2.5 mg), 6 ~ 12 h after review INR.After INR <3, treatment was restarted with a small dose of warfarin.3. INR≥10.0, no bleeding complications deactivated warfarin, intramuscular injection of vitamin K1 (5 mg), 6 ~ 12 h after review INR.After INR <3, treatment was restarted with a small dose of warfarin.In patients with high risk factors for bleeding, infusion of fresh frozen plasma, prothrombin concentrate, or recombinant factor VIIa may be considered.4. Severe bleeding, regardless of the level to disable INR warfarin, intramuscular injection of vitamin K1 (5 mg), infusion of fresh frozen plasma, prothrombin concentrates or recombinant clotting factor VIIa, INR monitored at any time.The need for warfarin therapy needs to be re-evaluated when the condition is stable.5. For minor bleeding, there is no need to immediately stop or reduce the dose when the INR is within the target range. The cause should be found and monitoring should be strengthened.In addition to bleeding, warfarin has rare adverse reactions.Such as acute thrombosis, including skin necrosis and limb gangrene, usually appear on the 3rd to 8th days of medication, which may be related to protein C and protein S deficiency.Further warfarin also interfere with the synthesis of bone proteins, leading to osteoporosis and vascular calcification.Which drugs or foods affect the pharmacokinetics of warfarin?Warfarin absorption, pharmacokinetics and pharmacodynamics affected by genetic and environmental factors, including drugs and diet.Significantly enhance the anticoagulant effect of warfarin drugs: amiodarone, phenylbutazone, sulfinpyrazone, and metronidazole suladimethoxypyrimidine like.Drugs that slightly enhance the anticoagulant effect of warfarin: cimetidine and omeprazole.Drugs that reduce the anticoagulant effect of warfarin: barbiturate, rifampicin, carbamazepine.Drugs that increase the risk of bleeding: Taken at the same time as non-steroidal anti-inflammatory drugs, certain antibiotics, and antiplatelet drugs, increasing the risk of bleeding.Long-term drinking can increase warfarin clearance, but drinking large amounts of wine has almost no effect on patients' coagulation function.Some traditional Chinese medicines (such as salvia, ginseng, angelica, ginkgo, etc.) or food (such as grape sleeve, mango, garlic, ginger, onion, kelp, cauliflower, kale, carrot, etc.) can also enhance or weaken the anticoagulant effect of warfarin.The above content is only authorized by for exclusive use, please do not reprint without authorization of the copyright party..


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