Abstract： Background:Total knee arthroplasty (TKA) is the most frequently performed procedure in treating advanced knee osteoarthritis.Excessive perioperative blood loss can sometimes lead to postoperative anemia.Tranexamic acid (TXA) is a potent fibrinolysis inhibitor which has been extensively used at the surgical incision and closure to lower overall blood loss in adult reconstruction surgery.Our previous study suggested that about two-thirds of the total blood loss (TBL) came from hidden blood loss (HBL) on postoperative days 1 and 2.The role of reducing HBL with TXA administration in postoperative TKA patients is unknown.The current study was designed to evaluate the efficiency and safety of supplemental intravenous (Ⅳ) TXA in further reducing HBL after primary TKA.Methods:A prospective pilot study was conducted at a single institution on 43 consecutive patients who underwent unilateral TKA from September 2014 to February 2015.All patients were given 1 g of Ⅳ TXA 10-15 min before operation and another 1 g of Ⅳ TXA at the time of wound closure on the day of surgery.On postoperative days 1 and 2,the supplemental group (n =21) was given additional 1 g of TXA intravenously twice a day,whereas the control group (n =22) received an equal volume of saline.Drain output,hemoglobin (Hb),and hematocrit (HCT) were recorded preoperatively and 5 consecutive days postoperatively in both groups.HBL was calculated with the Gross formula.Pre-and post-operative lower extremity Doppler venous ultrasound was performed in all patients to detect deep vein thrombosis (DVT).The indexes were compared using the Mann-Whitney test,whereas the results of Hb and HCT were analyzed by repeated-measures analysis of variance.The difference was considered statistically significant if P ＜ 0.05.Results:The demographics and surgical characteristics of the two groups were comparable.Supplemental group had higher Hb level on postoperative days 1-5 compared to the control;however,the difference was not significant (F =2.732,P =0.106).The HCT of the supplemental group was significantly higher than that of the control group on postoperative day 5 (F =5.254,P =0.027).No significant difference was found in drainage volume and TBL,but the HBL was reduced in the supplemental group (supplemental 133.1 [71.8,287.3]ml and control 296.0 [185.3,421.4] ml,Z =2.478,P =0.013,median [interquartile range]).There was one DVT in the control group and none in the supplemental group.All patients were followed at 1 year after surgery,and no further complications were reported.Conclusion:Based on the current study,additional doses of Ⅳ TXA could potentially further reduce HBL after primary TKA without increasing the risk of venous thromboembolism.