Tranexamic acid (TXA) is a synthetic lysine analogue that can reduce the activity of plasmin by competitively inhibiting the binding of plasminogen to fibrin, so as to achieve the effect of inhibiting plasmin reaction and reducing blood loss. In recent years, a number of evidence-based medical studies have confirmed that TXA can effectively reduce the amount of blood lost during the perioperative period of hip and knee arthroplasty, reduce the rate of blood transfusion, and do not increase the risk of postoperative venous thromboembolism.
The antifibrinolytic effect of tranexamic acid is 7-10 times that of aminocaproic acid, which is currently the strongest antifibrinolytic effect of the drug at the same molecular concentration, but it will be affected by the site of action and the dose.
Inhibition of plasminogen activity by TXA:
Plasma 30 min to peak liver or heart 90 min to peak muscles 120 min to peak.
2 Tranexamic acid with joint replacement
Hip and knee replacement surgery often has a lot of bleeding, the amount of blood lost after total knee arthroplasty (TKA) can reach 1000 to 1790 ml, while total hip arthroplasty (THA) blood loss is greater, up to an average of 1944ml, easy to cause anemia, often require allogeneic blood transfusions. However, there are many risks and problems in allogeneic blood transfusion, and anemia in patients also affects postoperative functional exercise and rehabilitation. Therefore, how to safely and effectively reduce bleeding in joint replacement surgery is a key concern for clinicians.
There are a number of ways to reduce intraoperative and postoperative blood loss, among which tranexamic acid (TXA) has greatly improved circulation management in total jointarthroplasty (TJA).
1. TXA has a protective effect on TKA and blood
At present, there is no consensus conclusion that TXA reduces intraoperative bleeding volume of TXA, but the conclusion that TXA can reduce postoperative blood loss after TXA is more consistent.
Hsu et al. randomized 60 subjects into an experimental group versus a blank control group. Patients in the experimental group were given 1 gTXA intravenous infusion before and after surgery, and the control group was given the same dose of normal saline. The intraoperative bleeding volume of the two groups was 441 and 615 mL, respectively, and the difference was statistically significant (P<0.05).
Zhou et al. (19 randomized trials) included a meta-analysis of 1030 participants, and the postoperative blood loss using TXA was significantly reduced compared with the control group, and the difference was statistically significant (P < 0.05).
Claeys et al. found through randomized controlled experiments that preoperative intraoperative intravenous infusion of tranexamic acid 15 mg·kg-1 reduced total bleeding by 237 ml.
Sukeik et al. found through a review of 11 randomized controlled trials that the use of tranexamic acid reduced intraoperative and postoperative blood loss by 104 ml and 172 ml, respectively.
Ralley et al. found in retrospective studies that intravenous infusions of tranexamic acid 20 mg·kg-1 reduced transfusion rates by up to 73%.
Hynes et al. found through a comparison of preoperative and postoperative hemoglobin levels that intravenous infusion of tranexamic acid 20 mg·kg-1 during anesthesia induction significantly reduced the decrease in postoperative hemoglobin levels.
2. Application of tranexamic acid in joint replacement
(1) Tranexamic acid administration mode :
At present, the commonly used routes of administration of tranexamic acid in clinical practice include topical administration and intravenous injection.
Intravenous tranexamic acid is the most commonly administered in total hip replacement, usually with load maintenance methods, i.e., kilogram weight-related or unrelated loads after induction of anesthesia, followed by a maintenance amount of intravenous infusion until the end of surgery or 3 hours after surgery. Topical medication is to apply high-concentration drugs directly to the wound during surgery or at the end of surgery to stop bleeding.
For the medication mode of the two, through clinical research observation, it is found that both can effectively reduce the amount of blood loss during and after surgery, reduce the transfusion rate during and after surgery, and do not increase the incidence of deep vein thrombosis of the lower limbs.
Tmethamic acid in combination with intravenous infusion in the THA and TKA perioperative periods is more effective at reducing bleeding and reducing transfusion rates than intravenous infusion alone or topically. ——"Accelerated Rehabilitation of Hip and Knee Replacement in China: Expert Consensus on Perioperative Management Strategies"
(2) Tranexamic acid dosage :
Although tranexamic acid has been widely used in orthopedic surgery, there is still a lack of corresponding standards for its dosage. It is generally based on the experience of the surgeon. Small doses of medication can not play a good role in hemostasis, while the application of large doses can easily lead to risks such as deep vein embolism.
Recommended dose hip replacement (1) intravenous single administration: 5 to 10 minutes before cutting the skin, tranexamic acid 10 to 50 mg / kg or 1 to 3 g intravenous infusion is completed; (2) intravenous multiple administration: the first dose is the same as a single administration method, and the drug is administered once every 3 to 6 hours after surgery (10 mg/kg or 1 g each time) within 24 h after surgery ;(3) Topical application: tranexamic acid 1 to 3 g topical application; (4) intravenous and local combination: intravenous method and simple intravenous application, combined with the opening before closing the incision 1 ~ Knee arthroplasty of 2 g of tranexamic acid topical application (1) intravenous single administration: 5 to 10 minutes before the skin is cut (without tourniquet) or loose tourniquet, tranexamic acid 20 to 60 mg/kg or 1 to 5 g intravenous infusion is completed; (2) multiple intravenous administration: the first administration is the same as a single administration method, and the administration is given once every 3 to 4 hours (10 mg/kg or 1 g each time) within 24 hours after surgery, and it is recommended not to use a tourniquet in the case of multiple administrations ;(3) Topical application: tranexamic acid ≥ 2 g or concentration ≥20 mg/ml before closing the incision, due to the relatively small amount of knee cavity content, the use of 10% tranexamic acid is recommended; (4) intravenous and local combination application: before the skin is cut (without the use of tourniquets) or before the release of the tourniquet 5 to 10 min, 20 to 60 mg / kg or 1 to 5 g intravenous infusion, after 24 hours after surgery, every interval of 3 to 4 hours to administer once (10 mg / kg or 1 g each), combined to close the incision before 1 ~ 2g topical application.
3 Tranexamic acid and spine surgery
In 2019, the Global Spine Journal published a study on the control of intraoperative and postoperative bleeding by tranexamic acid in lumbar posterior surgery, which discussed the use of tranexamic acid and its clinical effects in more detail.
The researchers concluded that in the control of intraoperative bleeding, preoperative intravenous infusion and local puncture infiltration of tranexamic acid have the same effect (which is also well understood, and the topical use of tranexamic acid before closing the incision has no effect on intraoperative bleeding); however, in the control of postoperative bleeding, the local use of tranexamic acid before closing the incision is more effective and safe and effective; in the three groups of patients who apply tranexamic acid, no significant changes in the main coagulation indicators were found, proving that the effect of tranexamic acid on blood coagulation function is controllable.
Recommended dose (1) intravenous single administration: 15 minutes before cutting the skin, tranexamic acid 15 to 30 mg / kg or 1 ~ 2 g intravenous infusion is completed; (2) intravenous continuous administration maintenance: the first administration is the same as a single dose, intraoperative administration is given 1 to 20 mg / kg · h maintenance; (3) intravenous multiple interval administration: the first administration is the same as a single dose, and the dose is 1 g every 3 to 8 hours after surgery (15 mg/kg or 1 to 2 g each time) ;(4) Topical application: tranexamic acid soaking in the surgical area before the closure of the incision, the dose is 1 g (5) Intravenous and topical combination application: intramethic acid 15 mg/kg intravenous infusion 15 min before cutting the skin, combined with the incision of tranexamic acid 1g local soak for 5 min.
In addition, tranexamic acid has been shown to have a precise and safe and effective hemostatic effect in spinal surgery, and can be used in cervical, thoracic spine, lumbosacral spine surgery, and can also be safely used in spinal tuberculosis surgery.
4 Summary and Outlook
The use of TXA in traumatic orthopedic surgery is increasing, and intravenous or topical application of TXA in hip fracture surgery can achieve good hematoprotection without increasing the risk of thrombotic events. However, compared with the application exploration in the field of hip and knee replacement surgery, there is still insufficient exploration, and there is no consensus on the route, timing and dosage of TXA application, and large samples and prospective studies are still needed. The effect of its application in other traumatic orthopedic surgeries such as pelvic and acetabular fractures still needs further study.