Blood Loss Reduction After Total Knee Arthroplasty. A Comparison Between Topical Tranexamic Acid and Platelet Rich Plasma: Controlled Clinical Trial
Phase: PHASE3
Conditions: Osteoarthritis
Sponsor: Universidad Autonoma de Nuevo Leon

 
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Blood Loss Reduction After Total Knee Arthroplasty. Comparison Topical 
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Tranexamic Acid vs Platelet Rich Plasma 
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NCT02650856 
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Document Date: October 21, 2019  
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Date of Study Closure: April 26 2017 
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Statistical analysis Plan  
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The sample size was calculated using the following characteristics: 90% power and a 
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critical p value of 0.05 for a decrease in the transfusion rate of 100% based on a previous 
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report and on the assumption that may abate transfusion requirements.[21] This resulted 
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in a total of 40 patients. Central tendency and dispersion measures were calculated for 
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the numerical variables, and frequencies and percentages were calculated for the 
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categorical variables. The Kolmogorov-Smirnov test was performed to test the normal 
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distribution of all numerical variables. In the case of parametric numerical variables, 
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Student’s t-tests, one-way ANOVA, and multiple comparisons ANOVA were performed for 
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related and independent samples. For non-parametric numerical variables, Mann-Whitney 
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U, Wilcoxon, and Kruskal Wallis tests were performed. The Bonferroni sequential 
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correction test was performed in the post hoc analyses. Statistical significance was set at a 
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value of p < 0.05. The SPSS version 20.0 (IBM, Armonk, NY) statistical package for 
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Windows 7 was used for the statistical analysis. 
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Brief Summary 
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The investigators will include patients who will be schedule for total knee  
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arthroplasty with a diagnosis of osteoarthritis. The patients will be divided in two 
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groups. In both groups a verbal and clear detailed information will be given on the 
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intraoperative approach. The first group will receive topical tranexamic acid and the 
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second group topical platelet rich plasma; both in the surgical site. Both groups will 
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be assessed before and after the intervention with laboratory results (hemoglobin, 
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hematocrit levels) and drainage drain. 
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Detailed Description: 
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Total knee replacement (TKR) surgery is one the most common orthopaedic 
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procedure in the world. Morbility in perioperative TKR is associated to: blood loss, 
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pain, infection, wound complications, stiffness and thrombotic events. Blood loss 
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and transfusion have been associated to increased hospital stay, costs, morbility 
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and mortality of the patient. Indications for blood transfusions are now limited and it 
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is well known that is not a free risk procedure. Complications such as; ABO 
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incompatibility, viral transmission, hemolysis, immunosuppression and wound 
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infection have been reported. 
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Literature reports have reported blood loss in TKR ranging from 300ml to 1 liter, 
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and transfusion rate varying from 10-38%. In diminishing hospital cost Moskal J. et 
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al reported 53.90% of savings and a 100% reduction in working hours of the 
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hospital staff using topical tranexamic acid in TKR. Tranexamic acid is an 
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antifibrinolytic agent that acts inhibiting the plasminogen, stabilizing the blood clot; 
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it is used to stop surgical or traumatic bleeding like in the CRASH-2 trial, 
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demonstrating its efficiency in the polytraumatized patients. Tranexamic acid has 
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been used in the last years for blood loss with good results. Due to its systemic 
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effects and past medical history of myocardial infarction, stents and previous 
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thromboembolic events its intravenous use is limited. In this study the investigators 
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will use topical tranexamic acid and its use has been proven in clinical trials as 
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secure strategy por blood loss reduction in TKR, without excluding patients with 
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previous thromboembolic events. 
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Platelet rich plasma (PRP) is an orthobiologic that has played an important role 
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over the past decade in different areas like; spinal fusion, ACL reconstruction, 
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osteoarthrosis and tendinopathies. The use of platelet rich plasma (PRP) in 
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orthopaedics is overrated and true indications for its use and cost benefit are still 
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unclear. Retrospective studies like Pace T et al in 268 patients did not 
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demonstrated differences in hospital stay, Postoperative hemoglobin levels, range 
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of motion with the use PRP in TKR. Morishita M. Et al in a clinical trial of 40 
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patients, using intralesional PRP didn´t show any benefits for blood loss reduction 
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in TKR, but good clinical results were observed in clinical scores like KOOS and 
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VAS compared to the control group. Other studies have demonstrated the efficacy 
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of topical PRP in blood loss reduction in TKR. 
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Due to its high platelet concentration and growth factors contained in the alfa 
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granules; it is used as an hemostatic, analgesic and antiseptic agent in TKR. 
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There is a variety of blood loss prevention strategies for TKR and this strategies 
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can be divided in preoperative, intraoperative or postoperative. The aim of this 
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study is to compare the use of topical tranexamic acid versus topical platelet rich 
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plasma. 
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An Insall knee approach, parapatellar medial will be used in all the patients. After 
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the final cuts of the femoral, tibial and patellar and before placing the final 
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cemented components the experimental intervention of the study will begin. 
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Group 1. A dosis of 2 gr of tranexamic acid (1000mg/10mL X-GEN 
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pharmaceuticals inc.) is diluted in 80mL of physiologic solution and will be divided 
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in two applications: 
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First application: 40mL of the solution previously prepared is applied over the 
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surgical site and it will be left for five minutes then drained out completely by 
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suction. 
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Second application: The rest of 40mL of solution previously prepared is applied 
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after placing the final TKR cemented components (femoral, tibial and patellar), over 
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the surgical site and leaving it there without draining it by suction. 
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Group 2. In the preoperative room with previous premedication, a total of 55cc of 
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total venous blood is obtained from the forearm (cubital o basilic veins). The blood 
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is carried on 12 steriles tubes using sodium citrate at 3.8% as anticoagulant (BD, 
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Vacutainer; Becton, Dickinson and Company, NJ). Blood samples are then 
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transported to the Bank of Tissue (Banco de hueso Dr. José E. Gonzalez) where 
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by centrifugation at 1800 rpm for 10 minutes (HeraeusMegafuge 1.0R; 
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ThermoElectronCorporation) the separation of the 3 layers (White, yellow and red). 
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The superior layer rich in plasma will be collected in 50 microliters polypropylene 
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tubes (Corning,NY). A final volumen of 16 ml of platelet rich plasma is obtained 
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and will transferred to airtight tubes (BD Vacutainer; Becton, Dickinson and 
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Company, NJ). The manipulation of the blood samples is made on laminar flow 
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cabin biosecurity class II (Logic 3440801; Labconco, KC). The platelet rich plasma 
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will be activated with calcium gluconate at 10% (Pisa Farmacéutica, Jalisco, 
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México) before using it is placed in the surgical site topically. The PRP simple will 
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be divided in two applications, initiating the intervention after the final cuts of the 
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TKR components (like the tranexamic acid group). 
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First application: 8 mL of PRP are applied over the surgical site and are left for five 
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minutes then drained out completely by suction. 
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Second application: The rest of the 8 mL are applied over the surgical site after 
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placing the final TKR cemented components (femoral, tibial and patellar), over the 
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surgical site and leaving it without draining. 
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Then a primary closure of the wound is performed (capsule, fascia, subcutaneous 
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tissue and skin) in both groups. A close drainage (Drenovac, NEdren S de R.L. de 
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C.V.) is left intraarticular and fixed to the skin. The drainage will be clamped for 2 
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hours and removed at the 48 hours of the surgery. Thromboprophylaxis (low 
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weight heparin) will be initiated after 6 hours of the end of the surgery. In the 
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postoperative follow up, any patient with hemoglobin levels less than 9mg/dl with 
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anemic syndrome will be transfused. 
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