Joints Use of tranexamic acid in total knee arthroplasty FraNCeSCO Marra 2, FeDerICa rOSSO 1, MatteO BruZZONe 1, DaVIDe eDOarDO BONaSIa 1, FeDerICO DettONI 1, rOBertO rOSSI 1 1 aO Ordine Mauriziano, Department of Orthopaedics and traumatology, turin, Italy 2 university of Study of turin, Italy Abstract were found between the groups, with the exception of a significantly lower maximum hemoglobin loss in the Purpose: different strategies have been developed to combined versus the iV group (p=0.02). there were no reduce blood loss in total knee arthroplasty (tKA). differences between the groups in the amount of the efficacy of both systemic and local tranexamic blood in the drain or the rate of transfusions. acid (tXA) administration is demonstrated in the lite - Conclusions: the data from this preliminary study, as rature. the aim of the present study was to compare well as data from the literature, confirm that tXA administration is safe and effective in reducing total the efficacy of systemic, local and combined (systemic + local) administration of tXA in reducing blood loss blood loss in tKA, and no administration protocol after tKA. seems to be superior to the others. Methods: we enrolled all patients submitted to a pri - Level of evidence: Level ii, prospective comparative mary tKA in our department between november study. 2014 and August 2015. they were divided into three groups corresponding to the method of tXA admini - Keywords: tranexamic acid, knee, arthroplasty, bleed - stration used: intravenous (iV), intra-articular (iA), ing, blood loss. and a combination of the two. Demographic data, as well as preoperative hemoglobin and platelet levels, were collected. the primary outcome was the maxi - Introduction mum hemoglobin loss, while the secondary outcomes were the amount of blood in the drain (cc/hour) and Perioperative bleeding remains one of the main con - the rate of transfusions; postoperative pain was also cerns in elective total knee arthroplasty (tKA), with assessed. student’s t-test or a χ2 test was used to eval - blood loss ranging between 800 ml and 1800 ml (1-3). uate between-group differences, using p<0.05 as the Fibrinolysis induced by surgical trauma, which may be cut-off for statistically significant differences. increased by using a tourniquet, reduces the risk of Results: the sample comprised 34 patients: iV, 10 venous thromboembolism, but at the same time favors cases; iA, 15 cases, and combined (iV + iA), 9 cases. postoperative blood loss (4, 5). Different methods to the average age of the patients was 71.1 +6.4 years. reduce perioperative blood loss have been studied, no significant differences in the outcome measures such as perioperative blood donation, perioperative red cell salvage, deliberate hypotension, and use of recom - binant human erythropoietin. Furthermore, periopera - Corresponding Author: tive transfusions add to the costs of the treatment and Federica Rosso, MD Ao Mauriziano Umberto i, Department of orthopaedics the risks (of infection, allergic reaction and disease and traumatology transmission, for example) to the patient (6, 7). Largo turati 62, 10128 turin, italy in recent years, pharmacological approaches have E-mail: [email protected] become more popular. As hyperfibrinolysis is consid - 202 Joints 2016;4(4):202-213 tranexamic acid in tKa Joints ered the major cause of postoperative bleeding after iodine solution (3 g of topical tXA in povidone- tKA surgery, antifibrinolytic drugs have been pro - iodine solution) (24). posed, including aprotin, aminocaproic acid, and the aim of the present study was to compare the effi - tranexamic acid (tXA). cacy of systemic, local and combined administration tXA is a fibrinolysis inhibitor, which prevents clot of tXA in reducing blood loss after tKA. the lysis by blocking the proteolytic activity of plasmino - hypothesis of the study was that there is no significant gen activators (8). since the first report by Benoni et difference between the three treatment protocols. al. (9), different studies have been published on the efficacy of tXA in reducing perioperative blood loss in total joint arthroplasty. Methods theoretically, intravenous (iV) administration of tXA increases the risk of thrombotic events. All the patients who underwent a primary tKA in our Furthermore, some cases of allergic reaction to tXA department between november 2014 and August have also been reported. For these reasons, some 2015 were enrolled in this study. they were divided Authors consider tXA contraindicated in patients into three groups, corresponding to the tXA admin - with a history of allergy, arterial or venous thrombo - istration protocol used: group 1, iV: 10 mg/kg of sis, an intrinsic risk of thrombosis or thromboem - tXA in 50 ml of saline solution administered over a bolism, acute renal failure, subarachnoid hemorrhage, time of 10 minutes during induction and 3 hours later; or a history of epilepsy (10). other studies have group 2, iA: washing with 2 g of tXA in 20 ml of demonstrated that the supposed increased risk of sterile saline for 2 minutes after placement of the final thrombotic events can be avoided by the usual post - components; and group 3, a combination of the two operative prophylactic regimens against deep vein methods (iV+iA). Patients with contraindications to thrombosis (DVt), such as aspirin, warfarin, low-mol - iV administration (a medical history of DVt or pul - ecular-weight heparin (LMWH) (11-14), and even fac - monary thromboembolism, acute myocardial infarc - tor Xa inhibitor (15). tion, heart failure, heart valve stenosis, ischemic Different Authors have proposed topical iA adminis - stroke, coagulopathy, allergy to tXA, severe liver or tration of tXA before wound closure in order to kidney disease) were included in the iA protocol. All reduce the possible complications related to the risk of the patients received a dose of LMWH 12 hours thrombotic events (3, 16, 17). Another route for local before surgery, and LMWH treatment was continued administration is through the drain, with or without postoperatively for 30 days. drain clamping (18). some studies also showed the All the surgeries were performed using a standard efficacy of orally administered tXA in patients under - medial parapatellar approach, with cemented compo - going primary tKA compared with controls (19, 20). nents and using a tourniquet during the cementation in the literature, there is considerable variability in the phase. in all the patients an iA drain (without suction) timing of administration (which may be preoperative, was subsequently positioned and kept in place for 24 intraoperative or postoperative, or a combination of hours. Postoperatively the knee was positioned in 50° these), as well as in the amount of tXA administered. to 70° of flexion for 6 hours (25, 26). Knee mobiliza - Reported iV tXA doses range from 10 to 20 mg/kg tion and weight bearing were allowed between day one although, in several studies, a 1 g dose (ranging from and day two postoperatively. Continuous passive 500 mg to 3 g) was used as standard. in continuous motion was started on postoperative day one. infusion, doses range from 2 mg/kg/h for 20 hours to Demographic data, as well as preoperative hemoglo - 10 mg/kg/h for 3 hours. iV tXA has been used as bin and platelet levels, were collected. Patients were single dose bolus or as continuous infusion (for 2-3 interviewed about their pain preoperatively, the day hours) (21-23). after surgery, and on the fifth postoperative day. the For topical administration, doses of tXA range from numeric pain rating scale (nRs) was used for this pur - 250 mg to 3 g, diluted in 75 to 250 ml of saline solu - pose. Maximum hemoglobin loss (calculated as the tion. tXA has also been shown to be effective admin - difference between the preoperative and lowest post - istered with other topical medications, like povidone- operative hemoglobin level) was taken as the primary Joints 2016;4(4):202-213 203 Joints F. Marra et al. outcome measure for evaluating the efficacy of tXA. group. the rate of blood transfusions was: 10% (1 the secondary outcomes were the amount of blood case) in the iV group, 40% (6 cases) in the iA group in the drain (cc/hour) and the rate of transfusions. and 22.2% (2 cases) in the combined group. there the hemoglobin cut-off value for transfusion was 8 were no statistically significant differences in these g/dl in symptomatic patients. However, patients with secondary outcomes (blood in drain and transfusion cardiac disease could also undergo transfusion also rate) between the three groups ( Tab. 1 ). the average even in the presence of high hemoglobin levels. preoperative nRs score was statistically higher in the Complications, such as postoperative fever (>38.5°), combined group (p=0.03) compared to the iV group, bruising, wound dehiscence, hematoma, DVt, throm - but it was similar to the score recorded in the iA botic events and infections were recorded. group. However, there were no differences in nRs student’s t-test or a χ2 test was used to evaluate the dif - score on the first or fifth postoperative day between ferences between the groups, using p<0.05 as the cut- the iV and the combined group. the only significant off for statistically significant differences. difference in nRs values was found on the fifth post - operative day, when comparing the iA vs combined groups (p=0.006) ( Tab. 1 ). Results no complications occurred in any of the included patients. in particular, no DVt or other thrombotic the study population comprised 34 patients with a events were detected. mean age of 71.1 years (sD 6.45; range 59-83), and a mean BMi of 29.17 kg/m 2 (sD 4.82, range 16.8 to 38.9); 58.8% (20 cases) were women and 41.2% (14 Discussion cases) were men.