Heart valve disease is a common and frequent disease in China, with patients receiving inpatient surgery for rheumatic heart valve disease accounting for approximately 30% of our cardiac surgical patient population. Heart valve replacement surgery has been, is, and will continue to be the primary treatment for patients with heart valve disease for some time in the foreseeable future. Currently, the majority of patients with heart valve disease treated clinically in China are still predominantly young and middle-aged, and therefore the majority of prosthetic heart valves placed are mechanical valves. To prevent thrombosis and possible thromboembolic complications, patients with mechanical heart valves require lifelong anticoagulation therapy. Patients with bioprosthetic valves also require anticoagulation for at least 3 to 6 months. The choice of anticoagulant drugs is coumarin (warfarin) antiplatelet agents (aspirin, pentoxifylline, etc.) heparin/low-molecular heparin thrombin inhibitors (similartan) Warfarin has been used for more than 60 years in the anticoagulation of patients after cardiac mechanical valve replacement, and its safety and effectiveness have been unanimously accepted by clinicians. Warfarin is a VIT-K antagonist that prevents the reduction of inactive oxidized VIT-K to active reduced VIT-K by inhibiting hepatic cyclo-oxidative reductase, which prevents VIT-K-dependent activation of coagulation factors II, VII, IX, and X, resulting in anticoagulant effects. Pharmacokinetics of warfarin Warfarin is bound to albumin in plasma with a half-life of 36-42h and a bioavailability of 100%. Metabolism: It is mainly metabolized by hepatic P450, only <2% is excreted into the urine as a prototype, and no dose adjustment is required in patients with renal insufficiency. The anticoagulant response to warfarin is stronger in 60 year olds than (PT/INR) demonstrated and should be reduced appropriately. The dose-response relationship for warfarin is highly variable and is influenced by many factors (e.g., genetics, medications, diet, disease status, etc.). Pharmacokinetics of warfarin The anticoagulant effect of warfarin needs to wait until the original VIT-K-dependent coagulation factors (II, VII, IX, X) are depleted in the body. The anticoagulant effect of warfarin occurs within 24 h after oral administration and peaks at 72-96 h. After discontinuation of the drug, the anticoagulant effect is reduced as new clotting factors become available. After discontinuation, coagulation gradually returns to a normal state as new active coagulation factors are synthesized. Warfarin dosing regimen is usually administered on the first or second postoperative day. Saturated dosing method: 5mg/day x 3 days, measure INR, change maintenance dose. Maintenance dosing method: 2.5mg/day x 3 days, measure INR and adjust dosage. Warfarin anticoagulation monitoring and standard PT: Prothrombin Time (PTR) is the most commonly used monitoring index for anticoagulation therapy, which can reflect the reduction of four VIT-K-dependent coagulation factors, but its accurate letter can be affected to varying degrees by reagents, methods, technology and other factors. PTR (Prothrombin Time Ratio) Prothrombin time ratio = patient PT value/normal control PT value. INR (International normalize ratio) International normalize ratio: INR standard model was adopted in 1982 and its formula is: INR=(PTR)ISI=(patient PT value/normal control PT value) ISIISI:International sensitivity index (International sensitivity index):Calibration of prothrombin reagent activity INR can chip away at the influence of reagent activity instability and is currently the preferred monitoring index. Anticoagulation strength after valve replacementAnticoagulation strength target value:1.8-2.5Biological valveAnticoagulation strength target value: 1.5-2.0Mechanical valve: Aortic valve replacement target value: 1.8-2.3Micuspid valve replacement target value: 1.8-2.5Tricuspid valve replacement target value: 2.0-2.5Bicuspid valve replacement target value: 1.8-2.5There is no uniform anticoagulation strength standard in China, and different hospitals may use different anticoagulation standards, but the trend is to use low-intensity anticoagulation. INR check frequency Generally, INR should be checked 2-3 days after starting to take warfarin, and monitored every 2-3 days. After the anticoagulation intensity is controlled within the above criteria and stabilized, it can be changed to weekly monitoring. After one month, it can be changed to once a month. After six months, it can be changed to every 2-3 months. Due to the influence of diet, drugs, alcohol, poor compliance and other factors, warfarin dose response can sometimes be significant, so patients should be followed up regularly and at intervals that are not too long. Effects of drugs - Enhanced anticoagulation Warfarin has a high plasma protein binding rate, and when combined with other plasma protein binding drugs, competitive binding increases the concentration of unbound warfarin. For example, chloral hydrate. Warfarin is metabolically inactivated by hepatic drug enzymes, and when combined with hepatic drug enzyme inhibitors, such as amiodarone, metronidazole, cimetidine, omeprazole, etc. Effects of drugs - reduced anticoagulant effect Warfarin is metabolically inactivated by hepatic drug enzymes, when combined with hepatic drug enzyme inducers, such as barbiturates, rifampin, etc. When combined with drugs that enhance the synthesis of anticoagulant factors, such as VIT-K, estrogens, oral contraceptives, or drugs that affect the absorption of VIT-K, such as cauleenamide. The effect of food on anticoagulation VIT-K intake and absorption in food affects the efficacy of warfarin, leading to a weakening of the anticoagulant effect. When the systemic condition improves and liver function is restored, it is often necessary to increase the dosage of the drug, especially if VIT-K-rich foods are eaten regularly, such as cauliflower, cabbage, carrots, egg yolk, and pork liver. Other foods may reduce the anticoagulant effect of warfarin, for example: garlic, mango, grapefruit, etc. However, after the anticoagulant dose adjustment phase, the effect of diet on anticoagulation is not important in normal lifestyle habits. Strategy: Patients taking oral warfarin do not have to change their diet, but should avoid alcohol abuse or prolonged monotonous consumption of a VIT-K-rich food. The effect of disease on anticoagulation Biliary obstruction, acute viral hepatitis, hyperthyroidism, and infectious hyperthermia can reduce the absorption of VIT-K and enhance the anticoagulant effect of warfarin. Diarrhea and vomiting can affect the absorption of the drug and weaken the anticoagulant effect of warfarin. In congestive heart failure, hepatic synthesis of VIT-K-dependent coagulation factors is reduced and sensitivity to oral anticoagulants is increased, and the dose should be reduced. Patients with myocardial infarction and pulmonary embolism have low tolerance to oral anticoagulants, and prothrombin time can be prolonged quickly. Influence of geography and race The maintenance dose of warfarin varies greatly among patients of different geographic regions and races. The daily maintenance dose of (2.5±0.6) mg for mainland Chinese is similar to that of Hong Kong (2.0-3.0) mg and Iran (3.8±1.0) mg, and significantly lower than that of South Africa (4.0-6.0) mg and North America (mean 8.78 mg). The reason for this difference is unclear and may be related to differences in dietary structure and organismal metabolic function of patients from different geographical and ethnic groups. The effect of age study showed no significant correlation between gender and weight and warfarin dose and PT/INR in the treatment range. The difference in warfarin dose between age groups was significant (P < 0.05), with patients under 35 years of age requiring approximately one times the warfarin dose as patients over 75 years of age. The warfarin dose required by the elderly was lower than that required by the young. The reason for this may be related to the decrease in hepatic metabolism and synthetic function with age, and does not exclude the influence of factors such as changes in coagulation factors or enzyme activity. Early manifestations of excessive anticoagulation may include skin petechiae, purpura, gum bleeding, epistaxis, prolonged wound bleeding, and excessive menstruation. Bleeding can occur at any site, especially in the urinary and digestive tracts. Intestinal wall hematomas can cause subacute intestinal obstruction and are also seen subdurally and intracranially. Any puncture can cause a hematoma, and in severe cases local pressure symptoms are evident. Uncommon adverse effects include nausea, vomiting, diarrhea, pruritic rash, allergic reactions and skin necrosis. Bilateral breast necrosis, microangiopathy or hemolytic anemia, and widespread skin gangrene have even been reported with large oral doses; they are particularly dangerous with large primary doses. How to deal with anticoagulation overdose INR > 4 has an increased risk, INR > 5 has a dramatically increased risk 2001 American Cardiothoracic Surgery: INR < 5, no clinically significant bleeding, no need for rapid reversal of INR, can be reduced or discontinued once, and applied in small doses until the target is reached. In patients with INR 5-9, no bleeding and high risk of bleeding tendency, can stop 1-2 times and start taking the drug in small doses after reaching the standard, if the patient has a high risk of bleeding, can stop once and take VIT-K1 (1-2.5mg) orally at the same time, if you cannot take it orally, inject 0.5-1mg by sedation. INR>9, no clinically significant bleeding, take VIT-K1 3-5mg orally; with severe bleeding or INR> In case of severe bleeding or INR > 20, 10mg can be given orally, and transfusion of fresh plasma and prothrombin concentrate can be considered. In the presence of life-threatening bleeding, in addition to 10 mg of VIT-K1 by sedation, replace the treatment with prothrombin concentrate. The situation in China differs somewhat from that in the United States and requires the specialist to make the appropriate decision based on the patient’s reality. Intravenous injection is fast-acting, but attention should be paid to allergic reactions, and the efficacy of subcutaneous injection is unpredictable. Oral administration is convenient and safe, with clear efficacy.