Recently, many patients have asked about anticoagulation after valve replacement, especially about the effects of food and medications on anticoagulation. There is a lot of information about anticoagulation on the Internet, and some of it is very detailed, so I should not write anything else; however, not writing it does not mean that patients understand it, and it does not mean that they do not ask about it, so I think it is better to write something else. For this part, I want to answer some questions in reverse order according to the patient’s degree of concern. 1, first of all, there are so many factors affecting anticoagulation, what should we do? My advice is to respond to all changes with no change. The so-called unchanging is that the dose of warfarin should always be regulated according to the INR value. As we all know, the INR value after valve replacement should be controlled between 1.8 and 2.5, and the drug dose should be increased if it is lower than 1.8 and decreased if it is higher than 2.5. This is our general rule to regulate warfarin. Therefore, when you take the so-called “may affect the anticoagulation of food and drugs” what to do, is to review the INR, according to the results of the decision warfarin dosage. 2. What foods can affect anticoagulation? Foods rich in vitamin K can reduce the anticoagulant effect of warfarin, such as: cabbage, cabbage, capers (ground vegetables), kale, carrots, egg yolk, pig liver, green tea, etc.. Among them, green leafy vegetables have higher vitamin K content, such as: spinach, leek, rape up to 236-436μg/100g, cabbage medium for 89μg/100g, celery stems, radish, cauliflower, cucumber less content of 30-40μg/100g (cucumber skin content is high, should be peeled and eaten), while tomatoes at least only 5μg/100g. In addition, natto contains natto In addition, Bacillus natto, which can produce a large amount of vitamin K in the intestine, makes warfarin anticoagulant effect reduced . There are also foods that reduce the anticoagulant effect of warfarin by other means. Avocados can induce liver-related drug metabolizing enzyme activity and promote warfarin metabolism, while interfering with the absorption of warfarin in the intestine, thus reducing the anticoagulant effect of warfarin. Soy milk and seaweed weaken the anticoagulant effect of warfarin by altering its metabolism and affecting its absorption. Some foods can enhance the anticoagulant effect of warfarin. For example, the combination of garlic and ginger with warfarin can increase the anticoagulant effect of warfarin. Grapefruit contains coumarins, which also inhibit the activity of liver-related drug metabolizing enzymes, reducing the metabolism of warfarin and enhancing its anticoagulant effect. Mango contains vitamins A, C, B1, B6, etc., which can also enhance the anticoagulant effect of warfarin when combined with it. Fish oil enhances the anticoagulant effect of warfarin by inhibiting platelet aggregation and reducing the levels of coagulation-related thromboxane and vitamin K-dependent coagulation factors. Although there are so many foods that affect anticoagulation, however, studies have shown that occasional intake of large amounts of vitamin K-rich foods does not significantly affect the anticoagulant effect of warfarin, and only continuous consumption of large amounts of related foods for more than a week (e.g., eating spinach daily at half a pound per day for more than a week) can significantly reduce the anticoagulant effect of warfarin. Therefore, we can conclude that: 1, related foods can be eaten, but do not consume large amounts every day; 2, forced to consume related foods every day, you need to check the INR diligently and adjust the warfarin dose in a timely manner. 3, which drugs affect anticoagulation? There are many drugs that affect anticoagulation, so let’s name them in general. First of all, there are drugs that can enhance anticoagulation: aspirin, acetaminophen (paracetamol), amiodarone, pautazone, methotrexate, clobetasol (Antomin), tetracycline, sulfonamides, propofol, chloramphenicol, allopurinol, monoamine oxidase inhibitors, metronidazole (methotrexate), fluconazole, miconazole, itraconazole, omeprazole, indomethacin, cimetidine, azithromycin, erythromycin Clarithromycin (metribuzin), doxycycline, cephalosporins, nalidixic acid, ciprofloxacin, norfloxacin, ofloxacin, isoniazid, lodetate, gemfibezil, clobetine, propafenone, liquid paraffin, quinidine, levothyroxine, phenylephrine, salicylates, chlorpromazine, diphenhydramine, streptokinase, urokinase, heparin, etc. Next are drugs that attenuate anticoagulation: acidophilus, cathepsin, ashwagandha, neomycin III, antipyrine, carbamazepine, barbital, pentobarbital, phenobarbital, isopentobarbital, isobutalbital, rifampin, grumet (conduction of sleep energy), meprobamate (anine, sleeper), abortifacient, aluminum thioglycollate, azathioprine, cyclosporine, trazodone, vitamin K, oral contraceptives, estrogen, etc. . Herbs that can enhance the anticoagulant effect include: Danshen, Chuanxiong, safflower, peach kernel, motherwort, turmeric, curcuma, leech, cinnamon, frankincense, yanhuosuo, tulip, tiger scepter, jing sanling, chicken blood vine, red peony, wang bu liu xing, etc. The Chinese medicines that can weaken the anticoagulant effect are: ginseng, American ginseng, Diyu, Phellodendron, Bupleurum, Blood remaining charcoal, Lotus root, Little thistle, Phellodendron, Dragon’s toothwort, Cyperus, Palm, Cyperus, Ramie, White foxglove, Sophora japonica, and Prickly spurge. Although so much has been introduced, the most common concern is: Is it possible to take cold medicine? Cold medicines often contain acetaminophen, which is also known as paracetamol, such as Benadryl and Tylenol contain this ingredient, a large number of prolonged use will have a certain impact on anticoagulation; in addition, the cold itself can also affect anticoagulation by changing the body’s metabolism of warfarin; therefore, cold medicines can be taken in small doses when you have a cold, while paying attention to the impact of drugs on anticoagulation, appropriately increase the INR test The number of INR tests should be increased, and warfarin dosage should be adjusted if necessary. In addition, some of the “tonic” drugs are rich in vitamin K, such as Sun Cun and Silcon, which can reduce the anticoagulant effect, which also deserves our attention. 4.What if the INR test is significantly higher? Currently, the anticoagulation standard recommended for national patients after valve replacement is to maintain an INR value between 1.8 and 2.5. When the INR is greater than 2.5, adjustments can be made according to the specific value. Three methods of adjustment include: discontinuation of warfarin, or administration of vitamin K1, or transfusion of fresh plasma and concentrated prothrombin preparations. INR values can generally decrease significantly after 4 to 5 days of discontinuing warfarin. And the administration of vitamin K1 can cause a significant decrease in INR values within 24 hours. In general, the risk of bleeding increases only when the INR value is greater than 4, and increases significantly when the INR value is greater than 5. Even with excessively prolonged INR values, the absolute risk of bleeding remains low, so many physicians often manage patients with INR values as high as 5 to 10 by discontinuing warfarin unless the patient has high risk qualities for bleeding or already has symptoms of bleeding. Therefore, for patients with INR values greater than 2.5 and less than 3, it is important not to have any nervousness and to adjust the drug dose appropriately by stopping the drug once and rechecking the INR value every other day. However, patients with high INR values should also be treated seriously. The following is a reproduction of the anticoagulation guidelines published by the American College of Chest Physicians (ACCP) for the management of increased INR. (1) Warfarin may be reduced or discontinued when the INR is outside the therapeutic range but less than 5 and the patient is not bleeding from a clinically significant site or undergoing surgery that would require rapid reversal of the INR value. It should be given again at a lower dose when the INR is close to the desired range. (2) If the INR value is between 5 and 9, the patient is not bleeding, and there are no risk factors for bleeding, warfarin can be discontinued for 1 to 2 days and then re-given at a smaller dose when the INR value falls into the therapeutic range. For patients at higher risk of bleeding give oral vitamin K1 (1 to 2.5 mg) and discontinue warfarin. (3) For emergency surgery or tooth extraction requiring rapid reversal of INR values and expecting INR values to decrease within 24 hours, oral vitamin K1 2 to 5 mg may be given, with an additional 1 to 2 mg of vitamin K1 if INR values remain high after 24 hours. (4) If INR values are greater than 9 but not associated with clinically significant bleeding, oral vitamin K13 to 5 mg and expect the INR value to decrease within 24-48 hours, closely monitor the INR value and repeat oral vitamin K1 if necessary. (5) If rapid reversal of anticoagulation is required because of severe bleeding or warfarin overdose (INR >20), 10 mg of vitamin K1 should be given slowly intravenously and supplemented with fresh plasma or prothrombin complex concentrate, depending on the urgency of the situation. Additional doses of vitamin K1 may be administered every 12 hours if necessary. (6) In the event of life-threatening bleeding or severe warfarin overdose, replacement therapy with prothrombin complex concentrate is necessary, with slow intravenous administration of 10 mg of vitamin K1 as supplemental therapy, which may be repeated depending on the INR value. If warfarin is to be reapplied after administration of high doses of vitamin K1, heparin should be given until the effect of vitamin K1 is reversed and the patient regains warfarin sensitivity. 5. What if bleeding occurs during anticoagulation? Depending on the degree of bleeding, patients can be divided into minor and major bleeding. For minor bleeding, such as oral (gum) bleeding, nasal bleeding, subcutaneous bruising or hematoma, subconjunctival bleeding, microscopic or visual hematuria, respiratory bleeding, increased menstruation or black stool, etc., most of the bleeding can be controlled and gradually absorbed after short-term dose reduction or suspension of the drug for one or two times. Such bleeding does not affect the continuation of treatment or lead to serious consequences. In addition, some patients reported that purple spots easily appear on the lower legs of both limbs, which may be related to capillary rupture. I often suggest patients to take a small amount of vitamin C to improve the flexibility of capillary walls, and the efficacy is to be further observed. For major bleeding, such as cerebral hemorrhage or severe visceral bleeding, a hospital visit is required to terminate the anticoagulant effect of warfarin with rapid medication. For bleeding that occurs when the INR value is outside the therapeutic range, warfarin can be reintroduced once the bleeding has stopped or the cause of the bleeding has been corrected. For patients who are at risk of bleeding when the INR value is maintained within the therapeutic range, the INR value should be reduced to between 1.5 and 2.0 so that the anticoagulant effect is diminished but not lost. 6.What if I want to have other surgery after flap replacement? First, the appropriate response is decided according to the size of the surgery. If it is a tooth extraction or superficial surgery on the body surface, the warfarin dose can be appropriately reduced to maintain the INR value at about 1.8 for the surgery. Postoperative attention to moderately increase the compression hemostasis time can avoid bleeding, and if necessary, tranexamic acid or aminoacetic acid can be applied to rinse the mouth to help stop bleeding. In case of larger surgery or emergency surgery, the INR should be lowered to 1.0-1.5 as much as possible at the time of surgery; since the patient is not allowed to have an anticoagulation “vacuum”, it must be supplemented with low molecular heparin or heparin therapy. Warfarin is usually stopped for 4-5 days prior to surgery and low-dose heparin (5000 U subcutaneously) or low-molecular heparin is added until the early morning of the day of surgery. Secondly, resume warfarin dosing from the evening after surgery, while adding low-dose heparin or low-molecular heparin for at least 4-5 days, because it takes 3-7 days for the anticoagulant effect to appear after warfarin is taken orally, and discontinue heparin or low-molecular heparin after reaching the target INR value by monitoring INR. 7, Finally, the anticoagulation mechanism of warfarin is introduced. Warfarin is a bicoumarin derivative that produces an anticoagulant effect by interfering with the conversion cycle between vitamin K and 2 and 3 epoxides of vitamin K. Vitamin K is a cofactor of coagulation factors II, VII, IX and X. It induces the conversion of amino-terminal glutamate carboxylation to γ-carboxyglutamate in vitamin K-dependent proteins, which include coagulation factors II, VII, IX and X. These proteins need to be biologically active through the involvement of vitamin K in their γ-carboxylation. Warfarin reduces coagulation activity by inhibiting the vitamin K conversion loop and inducing the production of hepatic-derived partially decarboxylated proteins. Carboxylation promotes the binding of vitamin K-dependent coagulation factors to the phospholipid surface and therefore accelerates blood clotting. γ-carboxylation requires the involvement of reduced vitamin K (vitamin KH2). By inhibiting the activity of vitamin K epoxide reductase and thus blocking the production of vitamin KH2, bicoumarins inhibit the γ-carboxylation of vitamin K-dependent coagulation factors. In addition, vitamin K antagonists can inhibit the carboxylation of anticoagulant proteins C and S. The anticoagulant effect of bicoumarins can be antagonized by small doses of vitamin K1 (phylloquinone) because vitamin K1 can be reduced by bypass. Large doses of vitamin K1 (usually greater than 5 mg) can resist the effects of warfarin for more than a week because the vitamin K1 that accumulates in the liver can be reduced by vitamin K epoxide reductase via bypass.