n Commonly used anticoagulants n Anticoagulation after valve surgery n Anticoagulation after coronary surgery n Anticoagulation for atrial fibrillation after cardiac surgery n Summary Arterial and venous thrombosis and thromboembolism are not uncommon after cardiac surgery, and rational anticoagulation is important. They are addressed in the post-valvular surgery, perioperative period of coronary artery bypass graft surgery, as well as in the management of atrial fibrillation and deep vein thrombosis. Commonly used anticoagulants】 The process of thrombosis includes three stages: platelet adhesion, aggregation and release, coagulation system activation and fibrin formation. For these three stages, antithrombotic drugs are divided into antiplatelet drugs, anticoagulant drugs and thrombolytic drugs. The first two are mainly used to prevent the formation of arterial and venous thrombosis, while the latter is used for the dissolution of thrombus. Anticoagulant drugs are divided into three categories: 1, indirect inhibitors of thrombin, including common heparin (UFH) and low molecular heparin (LMWH); 2, direct inhibitors of thrombin, leucovorin; 3, vitamin K antagonists, such as coumarin-based anticoagulants. Antiplatelet agents are divided into four categories: 1) drugs that inhibit platelet arachidonic acid metabolism, such as cyclooxygenase inhibitors aspirin, benzosulfone, etc.; 2) drugs that increase intraplatelet cAMP, such as pansentin, prostacyclin, prostaglandin E1, etc.; 3) drugs that specifically inhibit platelet activation by ADP, such as ticlopidine, clopidogrel; 4) platelet membrane fibrinogen receptor antagonists. Here we mainly introduce several commonly used after cardiac surgery. Heparin is a sulfated glycosaminoglycan, and the molecular weight of heparin is 3000~30000D, with an average of 15000D. The anticoagulant effect of heparin is mainly mediated by antithrombin III. Antithrombin III is an inhibitor of serine hydrolase, which can form a complex with serine as the active center of coagulation factors (thrombin, Xa, Ⅺa, Ⅻa, Ⅸa), thus causing these coagulation factors to lose their enzymatic activity. The mechanism of anticoagulant action of heparin is to accelerate the formation of antithrombin III-thrombin complex, which can increase the rate of antithrombin III-thrombin complex formation by 1000 times, and also increase the reaction rate of antithrombin III and thrombin by 4-15 times. Heparin is a mixture of components with different molecular weights and different affinities for antithrombin III. Its anticoagulant activity center is mainly in the low molecular weight (3000-5000D) fragment, which has a high affinity part for antithrombin III, and the rest of the fragment has a weak anticoagulant effect at therapeutic concentrations. Heparin is not secreted in breast milk and does not pass through the placenta, so it does not affect fetal coagulation and can be used in pregnant women. It also does not pass through the plasma membrane (pleura, peritoneum and meninges), so local application added to peritoneal dialysis fluid causes little systemic effect. Most of heparin can be metabolized in the liver by heparinase to the less active uroheparin (uroheparin). Heparin sensitivity is increased in patients with severe liver and kidney damage. Thrombocytopenia is a common adverse reaction, usually occurring on days 10 to 15 after heparin therapy, and can occur several hours after heparin administration in patients who have been on heparin before. Thrombocytopenia is reversible and recovers approximately 4 days after discontinuation of the drug, and the mechanism is an immune response. Heparin overdose can cause bleeding, and fisetin neutralizes heparin and binds to it to form an inactive insoluble complex. Therefore, bleeding caused by primary heparin increase or heparin overdose of medical origin can be treated with this drug. II. Low molecular heparin Low molecular heparin (LMWH) can be derived from ordinary heparin by chemical cleavage into short polysaccharide chains, or can be prepared simultaneously during heparin production. Like regular heparin, these molecules are still a heterogeneous mixture of sulfated polysaccharides, yet have a smaller average molecular weight (4000-5000 D on average) and a narrower distribution range. The mechanism of anticoagulant action of LMWH is the same as that of heparin, which produces anticoagulant effect through the specific pentosan sequence in the molecule binding to the lysine residue in antithrombin III and accelerating the inactivation of coagulation factors by antithrombin III. Compared with heparin, LMWH has the following characteristics: 1) strong anti-Xa effect and weak anti-thrombin IIa effect. 2) long duration of action because LMWH is less negatively charged than heparin, has low affinity for plasma proteins, does not bind to endothelium and is not cleared by reticulocytes. 3) low impact on platelet function and does not cause a decrease in platelet count. 4) stronger pro-fibrinolytic effect, but less risk of bleeding. (5) The drug is more completely absorbed by subcutaneous injection, with a bioavailability of 90% and a half-life of 2-6 hours, and is excreted from the urine via the kidney. LMWH has the anticoagulant effect of common heparin without some side effects of heparin, and can be injected subcutaneously without special hematological tests, so it is more convenient to use and can be used for outpatients. Coumarins Coumarin anticoagulants are a class of vitamin K antagonists, the most representative of which is Warfarin. The main sublimation structure of vitamin K is menaquinone, which is involved in the carboxylation of the N-terminal glutamate side chains of these factors during the biosynthesis of vitamin K-dependent coagulation factors, while the N-terminal r-carboxyglutamate residues of the factors bind to Ca2+ to promote blood clotting. The pharmacological effect of coumarin-based anticoagulants is mainly to inhibit the mutual transformation of cyclic dithiothreitol and oxidized dithiothreitol, thus hindering the utilization of vitamin K by vitamin K-dependent coagulation factors and inhibiting the biosynthesis of prothrombinogen, factor VII, factor IX and factor X. As a result, it causes prolongation of prothrombin time. Vitamin K antagonism waits until these factors are depleted to a certain extent in the body before it can exert its anticoagulant effect. After starting treatment with oral anticoagulants, it is necessary to wait 12-24 hours before the drug effect appears, and it usually takes 36-48 hours to reach the peak of anticoagulant effect. (Table 1) Table 1 Oral anticoagulants start and peak time of action Start of action (h) Peak of action After stopping the drug, prothrombin returns to normal New anticoagulation Faster than bicoumarin 24~48 48~72h Warfarin 12~18 24~72 5~6 days Bicoumarin 12~24 24~72 4 days or so New bicoumarin 12 24~48 48~72h IV. Aspirin Aspirin can make cyclic oxidase activity partially inactivated, preventing arachidonic acid from generating PGG2 and PGH2 and reducing TXA2 synthesis. High-dose aspirin can inhibit vascular endothelial cell cyclooxygenase and reduce peroxide synthesis within prostaglandins, thus reducing PGI2 synthesized by vascular endothelial cells. In contrast, PGI2 inhibits platelet adhesion and aggregation on the surface of the vessel wall and has an antithrombotic function. Small doses of aspirin only inhibit the production of platelet TXA2 and do not affect the synthesis of PGI2 in the vessel wall. Aspirin is rapidly and completely absorbed after oral administration. Most of it is absorbed in the small intestine and a small portion in the stomach. Plasma concentration peaks in 1 to 2 hours. After absorption, it is rapidly hydrolyzed to salicylic acid. The plasma half-life is 15-20 minutes and the plasma protein binding rate is 41%. Salicylic acid is the main metabolite of aspirin, which is slowly metabolized in the body, with high plasma concentration and maintenance time of up to 2~3 hours. The suitable dose of aspirin is 100~500mg/d. Aspirin has an irreversible inhibitory effect on TXA2-induced platelet aggregation, and the antiplatelet effect of a single oral dose of aspirin can last for 5~7 days, which is roughly comparable to the survival period of platelets. Therefore, the drug needs to be stopped for at least 5 days before coronary artery bypass grafting. The main adverse effect of aspirin is irritation of the gastric mucosa and is contraindicated in people with peptic ulcers. Gastrointestinal symptoms may be reduced by taking it as an enteric solvent, extended-release, aqueous solvent, or with a meal. Occasionally, it has been seen to cause allergic reactions such as playing smooth muscle spasm and rash. Aspirin is currently the most commonly used antiplatelet drug, in acute coronary syndrome, secondary prevention of myocardial infarction, PCI and coronary artery bypass grafting perioperative period have achieved positive efficacy. V. Ticlopidine Ticlopidine is a thienopyridine compound, a class of ADP receptor antagonist, which has a specific and strong inhibitory effect on ADP-induced platelet aggregation in both phase I and phase II, and is irreversible. After oral administration, about 80% is rapidly absorbed, and the absorption rate can be increased by 20% after meals. The protein binding rate is 98%. It is biotransformed in the liver and has at least 20 metabolites, none of which have anti-platelet activity in vitro. After a single oral dose of 250 mg of ticlopidine, the peak time of blood concentration is 2 hours, and the half-life is 8-12 hours. The antiplatelet effect occurs after 2-4 days of continuous dosing (250mg twice daily), with the strongest effect after 8-11 days and stable blood concentration after 14-21 days. 60% is excreted from the kidney and 23% is excreted from the biliary tract and feces. The effect can be maintained for several days after discontinuation of the drug (equivalent to the survival period of platelets). Severe side effects are neutropenia (2.4-4%) and thrombotic thrombocytopenic purpura (rare). Several trials have demonstrated that ticlopidine is at least as effective as aspirin in the treatment of acute coronary syndromes and in the secondary prevention of myocardial infarction, and ticlopidine has been successfully used after coronary artery bypass grafting to reduce the rate of obstruction of venous bridge vessels. However, due to its serious adverse effects, it has been replaced by the faster-acting, more potent, and safer clopidogrel. The chemical structure of clopidogrel is similar to that of ticlopidine, a thienopyridine compound that belongs to a new generation of ADP receptor antagonists. Compared with ticlopidine, clopidogrel has faster onset of action, stronger effect, and better safety and tolerability, and was first marketed in the United States in 1998 under the trade name of Plavix and in China in August 2001. It has now replaced ticlopidine. Clopidogrel selectively and irreversibly binds to platelet surface adenylate cyclase-coupled ADP receptors through its active metabolite (SR26334), thereby preventing ADP-mediated platelet aggregation and release of particulate matter, and inhibiting ADP-induced fibrinogen binding to activated platelet membrane glycoprotein IIb/IIIa. The antiplatelet effect of clopidogrel is dose-dependent. Oral clopidogrel is rapidly absorbed and is unaffected by food or acid suppressants. After absorption, it is rapidly metabolized mainly in the liver to the active product SR26334. SR26334 has a peak time of 1 hour. >The drug concentration and effective drug concentration of SR26334 increase proportionally to the dose of clopidogrel from 50 to 150 mg. The platelet inhibitory effect of clopidogrel 75 mg orally daily reaches steady state in 3-7 days, and the average inhibition level is maintained at 40-60%. The elimination half-life of the major metabolites in plasma is 8 hours, and platelet function and bleeding practices generally return gradually to baseline within 5 days after discontinuation of the drug. Clopidogrel and its metabolites are excreted in the urine and feces, each accounting for 50% of the total. Gastrointestinal adverse effects of clopidogrel are significantly lower than those of aspirin, and hematologic adverse effects are similar to those of aspirin. Anticoagulation after valve surgery] The contact between blood and the surface material of the prosthetic valve and the nonphysiological hemodynamic properties of the valve site initiate the coagulation response of the body, leading to the formation of fibrin network and platelet clots and the formation of prosthetic valve thrombosis. Prosthetic valve thrombosis can cause both valve dysfunction and serious complications due to embolism from thrombus dislodgement; therefore, both mechanical and biological valves require anticoagulation after surgery. Mechanical valves require lifelong anticoagulation, while biological valves should generally be anticoagulated for a short period of time. 1, anticoagulation methods 1, anticoagulation program mainly has the following three programs: 1) a single use of coumarin oral anticoagulation, this method is simple and easy to use, is currently the most used at home and abroad, its Chinese law is the most commonly used program. (2) Heparin and coumarins cross-combination program, that is, early 3-5 days after surgery, first intravenous injection of heparin, so that the APTT reached 55-70 seconds, while starting oral warfarin, when the effect of warfarin reached the anticoagulation requirements, stop heparin, continue warfarin treatment. 3) The regimen of antiplatelet agents in combination with coumarins is recommended by the ACC/AHA 2006 guidelines for the treatment of heart valve disease, with aspirin (75-100 mg/d) + Warfarin anticoagulation regimen for those with mechanical valve replacement and/or the presence of high-risk factors, and with aspirin + Warfarin anticoagulation for three months for those with biological valves and no high-risk factors, followed by aspirin alone for more than one year. There is controversy over the latter two regimens. Most domestic scholars do not advocate the combination of warfarin + aspirin or warfarin + heparin, believing that the combination does not reduce the incidence of embolism but increases the risk of bleeding. However, the author believes that the latter two anticoagulant regimens are still of high clinical value in patients with valve surgery combined with high risk factors for thromboembolism (atrial fibrillation, large left atrium, history of thromboembolism, left ventricular insufficiency, and hypercoagulable state). The following is an overview of the use of oral anticoagulant Warfarin. 2. Anticoagulant usage Warfarin is administered in maintenance doses and saturated doses. The maintenance dose method refers to a small dose of 2.5mg of Warfarin daily starting 1-2 days after surgery, and adjusting the dose after 2-3 days according to the test results; the saturation dose method refers to the first dose of 5-7.5mg/d starting 1-2 days after surgery for 2-3 days, and then starting the maintenance dose and adjusting the dose according to the test results. Both methods can reach the therapeutic range in about 5 days, but the saturation dosing method is prone to anticoagulation overload, and the maintenance dosing method is safer. 3. Anticoagulation strength monitoring of Warfarin The therapeutic dose of Warfarin is very close to the toxic dose, so it is necessary to monitor the anticoagulation strength and adjust the dose according to the test results. In the past, the index of anticoagulation strength monitoring was prothrombin time (PT), which was required to reach 1.5-2.0 times of the normal control value. However, because of the different sources of prothrombin in the reagents used for testing in each country or region, and the different sensitivity to the activity of vitamin k-dependent coagulation factors, it was not reliable to use PT as the standard for anticoagulation strength monitoring. In 1982, WHO proposed to replace the prothrombin time (PT) with the international normalized ratio (INR), which is a calibration of the activity of different prothrombin reagents with the International Sensitivity Index (ISI). The INR is the result of indexing the prothrombin time ratio (PTR) with the ISI value and is the standardized prothrombin time. In the United States, the anticoagulation intensity was INR 3.0 to 4.5 until 1992, when it was changed to INR 2.5 to 3.5 due to massive bleeding events, and the ACC/AHA 2006 guidelines recommend an anticoagulation intensity of INR 2.0 to 3.0 after mechanical AVR and bioprosthetic flap surgery and INR 2.5 to 3.5 after mechanical MVR, in addition to the presence of high-risk factors (atrial fibrillation In general, the anticoagulation intensity standard in foreign countries has a tendency to decrease. Currently, the most commonly used anticoagulation intensity in China is INR 2.0 to 3.0, which was developed based on the characteristics of the Oriental population with reference to foreign standards. Since there have been no reports of studies on bulk anticoagulation therapy based on INR, it has not been possible to propose a truly suitable anticoagulation intensity standard for INR that fits the characteristics of our patients. In recent years, most domestic reports have pointed out that the incidence of anticoagulation-related bleeding after mechanical flap surgery is significantly higher than that of thromboembolism, thus proposing lower intensity anticoagulation standards. The authors recommend a lower intensity anticoagulation range (AVR INR 1.8-2.3, MVR, DVR INR 2.0-2.5) for anticoagulation intensity after mechanical valve replacement in China, which can satisfactorily prevent thromboembolism while reducing anticoagulation-related bleeding. Anticoagulation intensity monitoring should be started from the second day of drug administration, and the adjustment period generally takes 1~2 weeks, measured once in 1~2 days, and can be measured once a week after the adjustment period and once a month after discharge, and can be changed to once every 3 months if the measured value is stable for 2~3 consecutive times. 4.Adjustment of anticoagulant dose The adjustment of oral anticoagulant dose is mainly in the early postoperative weeks. Some patients who have been taking oral Warfarin for a long time need to adjust the dose because the INR results measured several times are outside the target range. Dose adjustment of Warfarin should be based on the degree of INR deviation and the patient’s previous response to dose adjustment, with an increase or decrease of 5-20% being appropriate; too much change may be overkill. Since the INR changes only after a whole number of days of the strip, dose adjustment should not be too frequent. 1) Insufficient anticoagulation: If INR is lower than the target value, 1/4 or 1/8 of the maintenance dose can be added as appropriate. If significant anticoagulation deficiency occurs continuously, drug factors should be checked, whether the drug has deteriorated, whether there are disturbing factors such as vomiting and diarrhea during the dosing period, and if necessary, change to tablets of different lot numbers or switch to other anticoagulants. (2) Excessive anticoagulation: If INR exceeds 3.0, the maintenance dose should be reduced by 1/4 or 1/8 and INR should be rechecked after 24 hours; if INR exceeds 5.0, Warfarin should be discontinued and the INR should be lowered to the target range before starting from a small dose. Those with signs of bleeding may be given oral vitamin K3, intravenous vitamin K1 or fresh frozen plasma or prothrombin complex. 4, Anticoagulation after bioprosthetic valve replacement and mitral valvuloplasty The incidence of thromboembolism after bioprosthetic valve replacement is low, but still occurs, mainly in the early stages of implantation, when thrombus is easily formed around the suture ring fabric, and three months after surgery, after complete endothelialization of the valve ring, the incidence of thromboembolism is significantly reduced. Therefore, the anticoagulation protocol after bioprosthetic valve replacement is to start with Warfarin anticoagulation in March. In older, bleeding-prone patients, aspirin alone can be used for anticoagulation. The anticoagulation protocol after mitral valvuloplasty with an implanted prosthetic ring is modeled after the management after bioprosthetic valve replacement. The author recommends that the anticoagulation strength after mitral valvuloplasty with biological valve replacement and implantation of an artificial ring in China, using the anticoagulation range INR 1.8 to 2.3. IV. Anticoagulation interference 1. Interference of drugs with the action of coumarins Several common drugs that enhance or diminish the anticoagulant effect of coumarins are shown in Table 2 Table 2 Drugs that interfere with the anticoagulant effect of coumarins Enhanced effect Diminished effect Alcohol Vitamin K Allopurinol Sleeping pills Cimetidine Estrogens Steroids (steroids) Oral contraceptives Anti-inflammatory pain Rifampin Quinidine Salicylates Methotrexate Sulfa Drugs with significant interfering effects, such as vitamin K, should be avoided, and some can be replaced by other drugs. For long-term use, such as oral contraceptives, the coumarin dosage can be adjusted by laboratory testing the INR several times at the beginning of addition and after discontinuation. Short-term increase of a drug, such as cold medicine or broad-spectrum antibiotics, interference is not significant, generally do not need to adjust the coumarin dose. 2, the effect of diet on the role of coumarins normal diet and lifestyle habits of anticoagulant drugs is very little interference. Only need to pay attention to the stage of anticoagulant dose adjustment, because spinach, cabbage, cauliflower, fresh peas and other vegetables and pork liver and other meat rich in vitamin K, can make the prothrombin time shorten, must be appropriate to increase the amount of drugs. 3, other factors Older, poor general condition of patients, high sensitivity to oral anticoagulants, the dose is smaller. In addition, the influence of certain diseases can reduce the absorption of vitamin K, thus increasing the anticoagulant effect of coumarins, such as dysentery, biliary obstruction, acute hepatitis, hyperthyroidism, surgery and serious infection. In congestive heart failure, the liver’s synthesis of coagulation factors is impaired, and sensitivity to oral anticoagulants is increased, often requiring a reduction in dose or even postponement of anticoagulation. V. Anticoagulation complications 1. Bleeding Bleeding is the most common and important complication of anticoagulation therapy in Chinese people, with an incidence of 0.7-10.4% patient-years, which is significantly higher than that in Europe and the United States (1.4-2.4% patient-years). There is no negative correlation between the incidence of bleeding and the incidence of embolism. Bleeding can be divided into general bleeding (subcutaneous bleeding, carnal hematuria, excessive menstrual flow, epistaxis, subconjunctival bleeding, etc.) and severe bleeding (leading to hospitalization, transfusion or death of the patient). Intracranial hemorrhage is the most dangerous complication of anticoagulation therapy, with an incidence of 0.3 to 1% of patient-years and a mortality rate of 60%. Factors associated with bleeding on anticoagulation therapy with Warfarin are: 1) Anticoagulation intensity: The intensity of anticoagulation therapy after heart valve replacement is closely related to the rate of bleeding. In recent years, it has been recognized at home and abroad that high anticoagulation intensity is an important cause of postoperative bleeding, and the intensity of anticoagulation has been reduced to varying degrees; 2) patient factors: people with previous history of gastrointestinal bleeding, bleeding disorders, liver and kidney insufficiency, hypertension, and other vascular diseases are prone to bleeding, and the bleeding rate is significantly higher in people aged ≥70 years; 3) duration of anticoagulation therapy: bleeding is most likely to occur in the early three months of anticoagulation therapy; 4) duration of anticoagulation therapy. 3) Duration of anticoagulation therapy: bleeding is most likely to occur in the early 3 months of anticoagulation; 4) Combination of antiplatelet agents, such as aspirin; 5) Race: the risk of bleeding is significantly higher in non-Caucasians than in Caucasians, and anticoagulation therapy should focus on prevention of bleeding. 2. prosthetic valve thrombosis and thromboembolism The incidence of embolism after mechanical valve surgery is reported to be about 2.0-3.8% patient-years in the European and American literature, whereas it is reported to be lower in China, only 0.3-1.48% patient-years. Factors associated with the occurrence of embolism are: 1) Valve type: Biologic valves have the lowest incidence of thromboembolism, and bileaflet valves with central flow have less chance of forming thrombus than valves with peripheral flow. 2) Site of heart valve replacement: AVR has the lowest rate of embolism (0.17-2.3% patient-years), MVR is about twice as high (1.3-4.0% patient-years), and double valve replacement (DVR) has the lowest rate of embolism. (3) Anticoagulation intensity: Inadequate anticoagulation intensity may lead to embolism. 4) Other factors: Atrial fibrillation, large left atrium and left heart insufficiency are all risk factors for embolism. Second, anticoagulation treatment in several special issues 1, anticoagulation during the treatment of non-cardiac surgery After valve replacement for other reasons need to be made for surgery, anticoagulation and surgery can be handled as follows four types of programs. (1) nonstop anticoagulation: small body surface surgery, the surgical site can be pressurized to stop bleeding, such as clear sutures, thoracic puncture, etc., can be nonstop anticoagulation for surgery. However, deeper sites or procedures that cannot be stopped by local compression should not be performed under anticoagulation. (2) Postponement of anticoagulation: When anticoagulation has not yet been started after valve replacement, and for some reason emergency surgery is required, the start of anticoagulation should be postponed. Because platelets are often significantly reduced in the early postoperative period after extracorporeal circulation surgery; the patient’s diet has not returned to normal, the intake of limited vitamin K, poor liver function and medications can often prolong the prothrombin time, therefore, it is feasible to delay the start of anticoagulation in the early postoperative period due to emergency surgery. Such as tracheotomy, acute renal failure peritoneal dialysis, calf partial necrosis debridement, etc. 3) Discontinue anticoagulation: after valve replacement has begun anticoagulation therapy, and need for emergency surgery, can discontinue anticoagulation, and intravenous injection of vitamin K120mg, about 4~5h recheck prothrombin time, such as has normal or close to normal value, can be operated; can not wait for the patient, then should be immediately after the injection of vitamin K1 surgery to relieve the emergency problem, the operation should be carefully stopped, the prothrombin time should be rechecked at 4 hours after the injection, and the incision should be sutured after waiting for no blood leakage to end the operation. Resume oral anticoagulation 48 hours postoperatively. Cases in which coumarin-based anticoagulation has been discontinued with vitamin K1 may be ineffective against coumarin-based anticoagulation for 1 week or longer, and anticoagulation may be resumed by cross-linking heparin and coumarin-based methods. (4) Suspension of anticoagulation: If elective surgery is required after flap replacement, anticoagulants can be stopped for 2-3 days before surgery, and surgery can be started again 48 hours after surgery after checking that the prothrombin time is close to normal. Cranial surgery must resume anticoagulation therapy 6 weeks after surgery. 2.Anticoagulation therapy for women of childbearing age The anticoagulation therapy for women of childbearing age after flap replacement is usually not significantly different from that of male patients, but differs in special cases such as menstrual flow, oral contraceptives, pregnancy and childbirth. (1) Menstruation In women with normal preoperative menstruation who take anticoagulants after flap replacement, most patients with increased menstrual flow compared to preoperative menstruation may stop taking Warfarin or halve the amount of Warfarin taken from the day before menstruation to the day before menstruation is basically clean. In patients with regular functional uterine bleeding before surgery, postoperative anticoagulation may prolong the menstrual period and increase the menstrual flow. If the bleeding is heavy, vitamin K1 can be injected to stop the bleeding, and if repeated heavy bleeding is required each time to stop the bleeding with drugs, microwave treatment or hysterectomy can be used. (2) Oral contraceptives Most of the contraceptives currently used are composed of estrogen in combination with progestin. Estrogen can reduce the effect of oral anticoagulants and increase the risk of thromboembolism. Therefore, pay attention to check the prothrombin time, adjust the dose of medication in time, after the application of the two types of drugs has formed a regular, there is no need to increase the number of additional laboratory tests. (3) Pregnancy and childbirth Pregnancy can produce two kinds of risks to the mother: first, excessive cardiac load; second, maternal blood is in a hypercoagulable state during pregnancy. Pregnancy is allowed 2 to 3 years after valve replacement due to the significant improvement in hemodynamics and cardiac function after valve replacement. Anticoagulation regimens during pregnancy have been controversial. Coumarins are effective anticoagulants and easy to administer, but can cross the placental barrier into the fetus and have a high teratogenic rate. Heparin has a large molecular weight and does not cross the placenta, but is poorly anticoagulated and inconvenient to use. Previously, the anticoagulation protocol for pregnancy was to use heparin anticoagulation in the first trimester and 2 weeks before delivery, while oral warfarin anticoagulation was given during the rest of pregnancy. However, in clinical practice, this protocol is difficult to operate, and there is no significant difference between the miscarriage rate and the teratogenic rate of anticoagulation with Warfarin alone. The use of a single anticoagulation regimen of low-dose warfarin (<5 mg/d) during pregnancy is safe and reliable. Patients may be terminated during pregnancy due to hypercoagulable state or circulatory overload, usually before the third month of pregnancy. Anticoagulation management at termination of pregnancy is: stop anticoagulation for 2-3 days before surgery, operate after checking for normal prothrombin time, and resume anticoagulation starting 48 hours after surgery. Patients should be hospitalized 1 to 3 weeks before the expected delivery date for observation, and if oral anticoagulants are not discontinued, a cesarean section is appropriate. Check the prothrombin time first, and after the patient's uterine contractions start, inject vitamin K 120mg intramuscularly and recheck it in 3~5 hours, if the prothrombin time is close to the normal level, caesarean section can be done to remove the fetus. Administer vitamin K15mg to the newborn via umbilical vein. breastfeeding should be abandoned because breast milk contains anticoagulants. Restart anticoagulation therapy 48-72 hours after surgery. [Anticoagulation after coronary surgery] The main purpose of antithrombotic therapy after coronary artery bypass graft surgery is to prevent occlusion of the bypass graft vessel. The blockage rate of saphenous vein graft vessels is 10-15% in the first month after surgery, 25% in the first year after surgery, 2-4% new blockage per year between 2 and 5 years, and up to 50% blockage rate in the ten years after surgery. In contrast, the 10-year blockage rate of the left internal mammary artery is about 10%. The pathological changes in the saphenous vein graft vessels are divided into several stages: 1) early stage (first month after surgery), mainly platelet aggregation and thrombosis caused by technical reasons; 2) intermediate stage (January to one year after surgery), which is platelet-mediated intimal hyperplasia and thrombosis, corresponding to the early stage of atherosclerotic plaque formation; 3) late stage (more than one year after surgery), which is progressive within the venous bridge aggravated atherosclerotic lesions. According to the 2004 ACC/AHA treatment guidelines, the anticoagulation regimen in the perioperative period of coronary artery bypass grafting is recommended as follows: 1. Discontinue aspirin and clopidogrel for 5-7 days prior to surgery. Switch to subcutaneous injection of low-molecular heparin and discontinue low-molecular heparin 12 hours prior to surgery. 2.Start antiplatelet therapy as early as possible after surgery (after extubation), and use low-molecular heparin or heparin replacement therapy if extubation is not possible 12 hours after surgery. 3, Aspirin alone can be used for anticoagulation after coronary artery bypass surgery under conventional extracorporeal circulation, while aspirin combined with clopidogrel regimen is recommended for anticoagulation after non-extracorporeal circulation coronary artery bypass surgery. The dose of antiplatelet agents: aspirin 100 mg/d, clopidogrel 300 mg on the first day and 75 mg/d thereafter. patients are advised to take aspirin for life and clopidogrel for six months. 4. In the presence of the following high-risk factors in the postoperative period, heparin anticoagulation should be added early in the postoperative period: 1) blood hypercoagulation state; 2) coronary artery endarterectomy patients; 3) extensive coronary artery lesions, distal anastomosis own vessel inner diameter <1.0 mm, incomplete recanalization; 4) intraoperative vessel anastomosis is not satisfactory. [Anticoagulation therapy for atrial fibrillation after cardiac surgery] Atrial fibrillation is the most common arrhythmia after cardiac surgery, and the incidence is related to the type of surgery. The incidence of atrial fibrillation after CABG is 20-30%, but the incidence of atrial fibrillation in combined valve replacement is greatly increased, reaching 57%, and it mostly recovers on its own within 24 hours. Only a minority of patients with precordial disease have atrial fibrillation, which is associated with an enlarged right atrium. A history of preoperative atrial fibrillation, left atrial enlargement, advanced age, poor left heart function, hypomagnesemia and hypokalemia are risk factors for the development of postoperative atrial fibrillation. Atrial fibrillation is an independent risk factor for stroke, with an incidence of stroke of 1.5% for those under 60 years of age, increasing to 23.5% for those 80 to 90 years of age. In August 2006, ACC/AHA/ESC jointly published updated guidelines for the treatment of atrial fibrillation. The new guidelines, based on the 2001 edition, integrate the large-scale clinical trials published in recent years and enrich the thromboembolic therapy as the focus of long-term treatment of atrial fibrillation, and provide a reference for antithrombotic treatment of atrial fibrillation after cardiac surgery. 1, emphasizing the importance of antithrombotic therapy for atrial fibrillation, all patients with atrial fibrillation are recommended to take antithrombotic drugs to prevent thromboembolism, except for isolated atrial fibrillation and with contraindications. 2. Emphasize the importance of deciding the appropriate antithrombotic treatment strategy according to the risk factor stratification criteria for stroke. Risk factors are divided into three classes (Table 3). It is recommended to choose warfarin anticoagulation with one high-risk factor or two intermediate risk factors with an effective anticoagulation intensity of INR 2.0 to 3.0; aspirin or warfarin can be chosen if the patient has only one intermediate risk factor; aspirin anticoagulation can be chosen if the patient has no risk factors for stroke. (Table 4) Table 3 Risk factor analysis for the 2006 edition of the guidelines Risk factors Unproven or weak risk factors Moderate risk factors High risk factors Female Age >= 75 years Prior stroke, TIA, or embolism Age 65-74 years Hypertension Mitral stenosis Coronary heart disease Heart failure Post-valve replacement Thyrotoxicosis Left ventricular ejection fraction <= 35% Diabetes Table 4 Anticoagulation for atrial fibrillation Risk category Treatment recommendation No risk factor Aspirin 81-325 mg/d One moderate risk factor Aspirin 81-325 mg/d or warfarin (INR 2.0-3.0, target 2.5) Any one high risk factor or more than one moderate risk factor Warfarin (INR 2.0-3.0, target 2.5) 3. No clinical alternative to warfarin is currently available There is no new drug that can replace warfarin for anticoagulation of atrial fibrillation. 4.Anti-thrombotic therapy for the conversion of sinus rhythm: 1) elective conversion: atrial fibrillation for more than 48 hours, whether by electric or drug resuscitation, oral anticoagulation therapy (INR 2.0~3.0) is required 3 weeks before and 4 weeks after resuscitation; 2) emergency conversion: atrial fibrillation for more than 48 hours, patients who need emergency resuscitation due to hemodynamic instability should first be given intravenous heparin to make their APTT time reach 1.5 to 2.0 times the normal value, and then defibrillation. This should be followed by oral anticoagulant therapy for 4 weeks. 5.After heart valve replacement combined with atrial fibrillation, anticoagulation therapy should be implemented according to the anticoagulation program of valve replacement. 6. In patients with coronary artery disease combined with atrial fibrillation, the choice of anticoagulation therapy has been a challenge in clinical treatment. Low-intensity anticoagulation and antiplatelet therapy are not superior to antiplatelet therapy alone, while moderate-intensity anticoagulation combined with antiplatelet inevitably increases the risk of bleeding. In the new version of the guidelines, experts recommend that in patients with stable coronary artery disease in combination with atrial fibrillation who are at high risk for embolism, moderate-intensity anticoagulation may be chosen without aspirin, and that adjusted-dose anticoagulation is effective in preventing both ischemic events. However, in patients with AF after PCI or coronary artery bypass grafting, antiplatelet agents are important. Because there is still no direct evidence, the guideline development expert group gave a consensus recommendation for this situation, that warfarin anticoagulation be given along with low-dose aspirin (less than 100 mg per day) and/or clopidogrel (75 mg per day), but this leads to an increased risk of bleeding and requires care to regulate the dose intensity of anticoagulation. Summary】 1. Anticoagulants commonly used after cardiac surgery are: 2. Anticoagulation therapy is required after either mechanical or biological flap surgery. Mechanical valves require lifelong anticoagulation, and biological valves and mitral valvuloplasty should generally be anticoagulated for three months after surgery. 3.A single oral coumarin-based drug, Warfarin, is the most commonly used anticoagulation regimen at home and abroad after valve surgery. There are two types of maintenance dosing method and saturation dosing method. 4.Replace the prothrombin time (PT) with international normalized ratio (INR)