Warfarin is a very important drug often applied after cardiac surgery. The proper use of this drug is extremely closely related to whether the treatment of the disease achieves its ultimate goal (prolonging life expectancy and improving quality of life). In the following, common questions about anticoagulation therapy with warfarin are answered one by one in layman’s terms, as concisely as possible, based on my own knowledge and experience. What is warfarin? In the 1920s, livestock farmers in North America noticed that some of their animals were coming down with a bleeding disorder. The disease seemed to be epidemic in nature, and the affected livestock would die from bleeding more than a small trauma or from internal bleeding. It was later discovered that the disease was related to the presence of moldy clover in the green feed consumed by the animals, and in 1929, it was discovered that the hemorrhaging was due to a dysfunction of the enzyme prothrombin. In 1940, people will be this substance purification, test its chemical structure and synthetic, named coumarin (Coumarin). Coumarin’s molecular structure is similar to vitamin K, it can compete with vitamin K, interfering with the latter’s role in the synthesis of coagulation factors in the liver. 1948, people began to use this type of drug as a rodenticide. 1948, Warfarin (Warfarin, chemical name benzylacetone coumarin, for coumarin derivatives) to be artificially synthesized. The drug was approved for human use by the U.S. Federal Food and Drug Administration in 1954. In 1953, Soviet leader Stalin died of an illness. Based on the hemorrhagic symptoms that preceded his death, U.S. intelligence agencies believe that Beria and Khrushchev may have poisoned Stalin with warfarin. Pure warfarin is a white, odorless powder that is well suited for poisoning. it was also used as an anticoagulant for U.S. President Dwight D. Eisenhower, who suffered an acute myocardial infarction in 1955. Why Warfarin Anticoagulation? Warfarin has an anticoagulant effect, so it is used to prevent the formation of blood clots in the body. Under normal conditions, blood flows smoothly and continuously through the heart and blood vessels. Everywhere the blood touches, it is covered by a layer of endothelial cells, so there is no direct contact between the blood and extravascular tissues, no direct contact between the blood and foreign objects, and no obstruction or stagnation of blood flow. When any of these three “absences” occurs, the coagulation process is activated and a thrombus is formed. After cardiovascular surgery, direct contact of a foreign body with the blood, trauma, exposure of tissues without endothelial cell coverage to the vascular or cardiac chambers, localized slowing or even stagnation of blood flow due to atrial fibrillation or ventricular wall tumors, can lead to thrombus formation in the heart or blood vessels. In addition, a hypercoagulable state of the blood due to physical causes or surgical stimuli can also lead to thrombosis. Currently, the most common conditions requiring warfarin therapy are: implanted mechanical valves in the heart, atrial fibrillation, deep vein thrombosis, pulmonary embolism, implantation of an artificial blood vessel in the venous system (e.g., total vena cava-pulmonary anastomosis), implantation of an artificial blood vessel in the peripheral arteries, myocardial infarction combined with a giant ventricular wall aneurysm with the possibility of intra-ventricular thrombosis, and the antiphospholipid antibody syndrome. In Fuwai Hospital, the most frequent application of warfarin is in patients after valve surgery. Patients with persistent atrial fibrillation. Anticoagulation with aspirin alone is not as effective as the use of warfarin. Warfarin anticoagulation should be used if the patient also has a prosthetic heart valve, whether bioprosthetic or not. How can the intensity of warfarin therapy be checked? The history of warfarin shows that its anticoagulant therapy is a double-edged sword; used well, it can effectively prevent thrombosis, used poorly, either a thrombus still forms or it triggers fatal bleeding. The strength of warfarin’s anticoagulation can be tested, and this indicator is known as the prothrombin time (PT). There are 3 ways to report PT in the laboratory: Prothrombin Time in seconds; Prothrombin Time Activity Percentage (PTA) in percentage; and International Normalized Ratio (INR). The INR is now used as a reference for anticoagulation to prevent thrombosis after cardiac surgery, and it eliminates differences in the activity of different batches of test reagents. This test is not complicated and is one of the basic clinical tests in hospitals, and should be available in any hospital where surgery can be performed. As to whether the test value is accurate, it is not easy to evaluate. Generally speaking, the more this test is performed in a hospital every day, the more standardized the laboratory technician’s operation should be, the more experience he has, and the smaller the error of the test value will be. There is no need to fast before drawing blood for this test, and eating has no effect on the results. What is the right anticoagulation value for me? This is a question asked by almost all patients taking warfarin. The answer: it varies from person to person. There is only one criterion for anticoagulation therapy, which is to minimize the risk of bleeding while ensuring that thrombosis does not occur. The likelihood of thrombosis varies from patient to patient. The likelihood of thrombosis is greater in patients with mechanical prosthetic heart valves than in patients with simple atrial fibrillation without valve disease; the incidence of thrombosis is higher in the mitral position than in the aortic position. The degree of anticoagulation in the event of thrombosis and bleeding may also be different in different patients. Compared with whites and blacks, Asians are less prone to thrombosis at lower levels of anticoagulation and more prone to bleeding at slightly higher levels of anticoagulation. Therefore, the appropriate anticoagulation value depends first and foremost on who is being treated with anticoagulation. The American Heart Association, in its guidelines for the surgical treatment of valvular disease, recommends that the INR be maintained at 2.0-3.0 for patients with a bileaflet or Medtronic-Hall tilting disk valve in the aortic valve position, and 2.5-3.5 for patients with other tilting disk or ball-and-socket valves (older valves that have long been out of use domestically), and 2.5-3.5 for patients with all mitral valves, regardless of the type of valve. All patients with mechanical valves in the mitral position should have an INR of 2.5-3.5, regardless of the type of valve. Patients with mechanical valves in the aortic position who have high risk factors, such as a history of thrombosis, atrial fibrillation, hypercoagulability, or left ventricular dysfunction, should also have an INR of 2.5-3.5. The domestic situation is different. Doctors have found that when the above criteria are used, patients have a high incidence of bleeding complications, while the incidence of thrombosis does not increase when the criteria are slightly lower than the above criteria; bleeding is more common than thrombosis among the complications of anticoagulation therapy in the Chinese. Japanese and Taiwanese physicians have also found a significantly higher incidence of bleeding in their patients (of the same ethnicity as the Chinese) when anticoagulation is performed according to the American Heart Association’s recommended values. Based on my personal knowledge and experience, my recommendations for warfarin anticoagulation in cardiac surgery-related patients are as follows: except for patients from ethnic minorities in Xinjiang (e.g., Kazakhs, Uyghurs, etc.) who have distinctly white characteristics, Chinese with prosthetic mechanical valves should keep their INRs at 1.8-2.3 for simple aortic valves, and at 1.8-2.3 for pure mitral valves or aortic plus mitral valves. If there is a tricuspid prosthetic valve, the INR should be 2.0-2.5. For patients with a bioprosthetic valve but atrial fibrillation or simple atrial fibrillation without valvular disease, the INR should be 1.8-2.3. Patients without atrial fibrillation who have a bioprosthetic valve or a valvuloplasty ring implanted in the mitral or tricuspid position and who have to be treated with anticoagulant therapy with warfarin for six months after the operation should have an INR of 1.8-2.3. For patients undergoing total caval-pulmonary anastomosis, warfarin anticoagulation should be performed in the first three months after surgery, and the INR should be maintained at 1.8-2.3. For ethnic minority, white, and black patients in Xinjiang, the anticoagulation criteria should be based on the relevant guidelines of the American Heart Association. Currently there are such foreign websites that can help patients calculate the dose of warfarin. Of course, it relies on a large number of statistics from Europe and the United States, and the calculated results are based on their anticoagulation strength, which is not adapted to us Chinese. However, from this online calculator, you can see which factors should be taken into account in the calculation of warfarin dosage, and how much weight should be given to each factor. We should have something similar for the Chinese ourselves, but we don’t have it yet. These are things that we medical professionals should strive to do. How should patients administer their own anticoagulation therapy? Patients who need warfarin anticoagulation therapy should start taking warfarin orally as soon as the endotracheal tube is removed from the trachea after surgery and they can drink water, with the first dose of 5-6 mg. From then on until discharge from the hospital, the patient’s blood will be drawn every day during the recovery period to check the INR, and the doctor will adjust the dosage of warfarin according to the results of each day’s examination in order to reach the expected anticoagulant intensity as early as possible and to bring the patient’s warfarin dosage up to a relatively stable level before the patient is discharged from the hospital. a relatively stable level. The INR value and daily warfarin dose at this stage are recorded on an anticoagulation therapy record sheet. This record sheet will be given to the patient at the time of discharge and will serve as an important reference for future anticoagulation therapy. So, don’t forget to take this record sheet when you are discharged from the hospital. Once discharged from the hospital, the patient will need to start taking his/her own medication based on the dose of warfarin he/she took a day or two before discharge. We recommend that patients take their medication every day at a fixed time in the evening. This has two advantages. One is that when you go to the hospital to check the INR in the morning, it may be noon when you get the results, and if you have any questions, you may have to consult with the doctor, and it may be in the afternoon when you finally decide to take the dose. If you take the medicine in the morning or in the morning, the dosage is not appropriate, but you have already taken it and can only adjust it the next day, which is inconvenient. Secondly, if you take the medicine at a fixed time, you will get used to it in the long run and will not miss the dose. When you are in the hospital, you check your INR every day. when you are discharged from the hospital, the ward doctor will give the patient 3 labs. These 3 labs are to facilitate the patient’s postoperative review. The patient can also go to the hospital’s summary clinic for labs. After discharge, laboratory tests are usually done once every 2-3 days. The same anticoagulation record sheet that was in place at the time of discharge should come into play at this time. The patient should record the daily dose of warfarin and the results of each INR on that anticoagulation chart. If the INR value is in the appropriate range, the current dose is maintained, and if it is out of range, the medication needs to be adjusted. Typically, warfarin is increased or decreased in ¼ tablet increments, and the need to increase or decrease by ½ or 1 tablet per day is rare. A very important dosage adjustment tip is to note trends in the INR. If lab values continue to rise or fall, the dose should be adjusted even though it is still within the range needed. If the INR value is greater than 3.0, the medication must be stopped that day and the assay continued the next day. A rule of thumb for labs is that if the INR value is far from the target value, it must be tested daily on subsequent days until your INR lab value is in the required anticoagulant strength. It is important to emphasize that the “normal range” (usually 0.8-1.2) on the labs are the values for a normal population without anticoagulant medication, not the normal values after medication. The strength of anticoagulation that should be achieved after taking the drug (I have made it very clear above) is the “normal value” for patients taking the drug. After the foreign patients are discharged from the hospital, they live near the hospital for about one week, usually after three laboratory tests, the INR value is stabilized, the dose of warfarin is more or less fixed, the anticoagulant treatment and the method of blood test are basically mastered, and there is no need to consult with the operation or ward doctors, so it is safe to go back to their hometowns. After returning home, weekly laboratory tests are generally required. If, after one month, the laboratory values are stable and the warfarin dose does not need to change much, the laboratory tests can be performed every two weeks. If the INR value and warfarin dose remain stable after extending the interval between lab tests, then the test can be done once a month. We seriously recommend monthly testing and strongly criticize patients who test only once every six months or even once a year. That would be irresponsible for life, no matter who that life belongs to. There are currently three types of commercial warfarin on the domestic market. The most widely used is domestic warfarin, white sugar-coated tablets, each 2.5 mg. Its advantages are stable source, low price (80 tablets per box, 20 yuan), the disadvantage is that the accurate division of the difficulty, the drug are once a little poor. The second type is Warfarin, which is imported from Orion, Finland. This brand is available in a variety of dosage forms, with the blue 3 mg tablets currently sold on the Chinese market. The advantages of this drug are that it can be easily and accurately divided, and the homogeneity of the drug is good. The disadvantages are that it is from an unstable source, unavailable in many cities in China, and is slightly more expensive ($50 per box of 100 tablets). The third type is Coumadin (Coumadin) produced in the United States. The advantage of this drug is that there are 9 dosage forms from 1 mg to 10 mg per tablet, with different colors, which makes it easy to distinguish and adjust the dosage. The disadvantage is that it is expensive and rarely available in China. If a patient is taking a particular type of warfarin, it is best not to change it easily. Changing medications may result in a major change in anticoagulation strength, and clinical complications due to changing medications are not uncommon. If a change is necessary, the INR should be tested daily for one to two weeks after the change until the test value is within the therapeutic range and the warfarin dose is stable. What if I miss a dose of warfarin? It does not matter. Simply take the missed dose of warfarin the next day along with your regular dose for that day. Of course, if the dose is missed for several days, it must be treated as a restart of the drug after discontinuation, and in addition to appropriately increasing the dose for the previous days, it is most important to review the INR immediately and daily for several days thereafter until the INR is in the appropriate range. In fact, buy a divided box labeled Monday through Sunday, divide the week’s worth of warfarin, and check the previous day’s box for leftovers when you take your medication each day, so you won’t miss a dose. What if I have a warfarin overdose? Warfarin overdose symptoms are a variety of bleeding manifestations. Symptoms of bleeding, such as bleeding from a wound that won’t stop, vomiting blood, tarry stools, muscle hematomas, bruising under the skin, hemiparesis, or coma should be treated immediately, regardless of the INR value. Managing a warfarin overdose is a matter for the doctor, and all the patient or family member has to do is inform the doctor of the purpose of the patient’s warfarin therapy and recent medication. In general, if the INR is below 4.0, and if there is no bleeding, it is sufficient to stop the medication and test the INR daily. Also, intravenous vitamin K1 can neutralize the anticoagulant effect of warfarin. It is important to remember that the higher the dose of vitamin K1 used, the more vitamin K1 is stored in the patient’s body and the more difficult it will be to achieve therapeutic intensity with another anticoagulation, which the patient will need after the bleeding is controlled. It is generally recommended that the dose of vitamin K1 not exceed 10 mg.