The effects of multiple intravenous tranexamic acid administrations after total knee arthroplasty on fibrinolytic activity and inflammatory response

Abstract

Objective To explore the effects of multiple intravenous tranexamic acid (IV-TXA) administrations after total knee arthroplasty (TKA) on fibrinolytic activity and inflammatory response in an enhanced recovery after surgery (ERAS) program and to assess the efficacy and safety of IV-TXA. Methods One hundred and forty-one severe knee osteoarthritis patients following primary unilateral TKA from January 2016 to April 2017 were investigated retrospectively. The patients were divided into following three groups based on the dosage of IV-TXA after surgery: 40 patients received ≤3 g IV-TXA after surgery (group T1), 50 patients received 4 g (group T2) and the other 51 patients received ≥5 g IV-TXA (group T3). The total blood loss (TBL), hidden blood loss (HBL), transfusion rate, maximum hemoglobin (Hb) drop, the incidence of intramuscular venous thrombosis, deep vein thrombosis (DVT) and pulmonary embolism (PE), fibrinolysis parameters [fibrin(-ogen) degradation products (FDP), D-dimer], and inflammation markers [C-reactive protein (CRP), interleukin-6 (IL-6)] during perioperative period were evaluated. In addition, correlation analyses between the dosage of IV-TXA and fibrinolysis parameters and inflammation markers were conducted. Results The mean TBL, HBL and maximum Hb drop in group T2 (537.16±270.43 ml, 431.36±271.99 ml, 19.68±10.68 g/L) and T3 (541.31±290.00 ml, 439.94±290.71 ml, 20.24±8.48 g/L) were lower than those in group T1 (748.22±394.34 ml, P=0.012, 0.013; 636.47±388.14 ml, P=0.011, 0.015; 25.88±11.77 g/L, P=0.005, 0.010, respectively). No patient needed transfusion in all groups. There was no statistically difference in the incidence of intramuscular venous thrombosis of lower limbs among three groups (P>0.05). No episode of DVT or PE occurred in any group in two weeks after surgery. There were negative correlation between the dosage of IV-TXA and FDP at postoperative day 1 and day 3 (r=-0.191, P=0.025; r=-0.291, P=0.001) and D-dimer on postoperative day 3 (r=-0.176, P=0.048). Moreover, the CRP (r=-0.184, P=0.036) and IL-6 (r=-0.269, P=0.002) level in serum on postoperative day 1 also showed a negative relationship with the dosage of IV-TXA after surgery. Conclusion The multiple IV-TXA (≥4 g) after surgery can further reduce the TBL, HBL and maximum Hb drop following primary TKA in ERAS program without increasing the risk of thrombotic events. Most importantly, the effect of anti-fibrinolysis will be enhanced and may have an anti-inflammatory effect with the dosage of IV-TXA increased. Key words: Tranexamic acid; Arthroplasty, replacement, knee; Fibrinolysis; Inflammation