A systematic review of the effect of Tranexamic acid in knee and hip arthroplasty Christine Schutz Research Coordinator Wakefield Orthopaedic Clinic.
Overview Background to how TX works The studies of TX acid in Orthopaedics Results of retrospective study at WOC Blood management in elective THR and TKR surgery. Conclusions re dose of tranexamic acid. Where to from here?
Disclosures No conflict of interest Thank you to ANZONA Thank you to Surgeons at WOC
National Joint Registry Australia. Annual report 2012. Hip Arthroplasty Increasing 4% per year in Australia 37,849 in 2012.
Knee Arthroplasty 2012 48,385
Indications for Joint replacement Pain : severity at rest, distance walking commonly due to Osteoarthritis. Function : Need for a cane, Climbing stairs, Daily living Examination: ROM, Joint stability, other. Radiographic. Joint space limited.
Tranexamic Acid Inhibits fibrinolysis by blocking lysine-binding site of plasminogen to fibrin Reduces blood loss and need for Blood transfusions
TX ACID Mechanism of Action. Tranexamic acid also know as CYKLOKAPRON in Aust. Given as IV, intra articular, oral, spray., Topical. Found to reduce blood loss in trauma and elective surgery reducing transfusion rates by a third. Is a synthetic lysine derivative that stops the breakdown of fibrin by inhibiting activation of plasminogen. Has a 2 hour half life. Excreted mainly via kidneys.
Contraindications for TX use Previous History of DVT Sensitivity to Tranexamic acid Visual problems colour disturbances Poor renal function. COMMON SIDE EFFECTS: Nausea Vomiting and Diarrhoea Dizziness Hypotension Rash (allergic reaction) Over dosage rare.
CRASH 2 trial (Trauma) Largest trial published
RESULTS CRASH 2 Cause of death TXA Placebo Risk of death P value 10,060 10,067 Bleeding 489 574 0.85 (0.76 0.96) 0.0077 Thrombosis 33 48 0.69 (0.44 1.07) 0.096 Organ failure 209 233 0.90 (0.75 1.08) 0.25 Head injury 603 621 0.97 (0.87 1.08) 0.60 Other 129 137 0.94 (0.74 1.20) 0.63 Any death 1463 1613 0.91 (0.85 0 97) 0 0035
There was no increase in thrombosis Placebo allocated (10,067) TXA allocated (10,060) Risk ratio (95% CI) DVT 40 (0.40%) 41 (0.41%) PE 72 (0.69%) 71 (0.70%) MI 35 (0.35%) 55 (0.52%) Stroke 57 (0.56%) 66 (0.65%) Any 168 (1.63%) 201 (1.95%).6.7.8.9 1 1.1 1.2 TXA better TXA worse
Tranexamic acid dose Same for hips and knees. 15mg/kg initial dose IV Follow 6 8 hrs post surgery
CYKLOKAPRON Solution for Injection IV 500mg ampoules in 5ml Water 1000mg ampoules in 10ml Water Tablets available in 500mg (bottle of 100 tabs)
Use in Total Knee Arthroplasty meta analysis 16 randomised placebo controlled studies 11 = efficacy (reduced blood loss) Mean age = 65-77 years N= 365 tranx patients N= 390 controls Cemented and non cemented prosthesis used. Post LMWH Overall dose 10-30mg/kg efficacy shown
Knee arthroplasty
Topical v Intra articular for TKA Antapur et al Bone and joint (2012) Study Number= 99 pts Randomized to 3 sub groups Doses 1.5, placebo and 3gm. Results: No difference in rate of transfusion between the 1.5g group and placebo The TX group of 3 g = 0 transfusion. 2 out of 99 pts had PE in the 1.5 g group.
Meta analysis of TKA trials Cochrane Bone, joint and Trauma J Bone Joint Surg Br 2011 Dec 93 (12 ) 1577-85 19 Randomized controlled trials. Reduction in allogenic blood transfusion 16% (95% CI : )9-0.26 Total blood loss 460 mls Concluded that TX was effective and safe for use in TKA and reduced blood loss. Tx does not increase prevalence of DVT or PE.
Timing of Administration of TXA 10-15 minutes before tourniquet released, repeat q 6-8 hrs for first day Nielsen, Ugeskr Laeger 2002 One injection pre-op, one on release of tourniquet Tanaka, JBJS (Br) 2001 Just prior to tourniquet release and 3 hrs later Good, BJA 2003 Oral TX study Repat (50TKA) 25 acid/25 placebo in progress
Dose studies Andreau study (71 TKA ) Looked at 2 dose schedules. IV Dose 1. Given IV in theatre 15mg/kg. Dose 2 Given 3 hours post surgery 15mg/kg. Group 1 Showed no Transfusion required in TX group. Group 2 (control) 37 % requiring Transfusion in non TX group.(autologous blood) Tourniquet times 86-92 mins
Arthroplasty Hip and Knee with DVT prophylaxis. Review presented by Blake et al July 2012 Low risk of Thromboembolic Complications N = 2246 primary THA and TKA Dose TX = 1 g IV beginning and at closure. Results: rate of DVT similar across groups p = 0.61 Aspirin alone Warfarin LMWH
Dose studies some concerns Lack of information regarding DVT prophylaxis and use of TX acid. 1 st Dose of commencement of injectable LMWH post operatively unclear. Variable dose regimes Multiple confounding variables
Imai et al J of Arthroplasty V 27 2012 BLOOD LOSS FOCUS. HIP N= 107 patients. Randomized to 5 groups (Dose and Timing) Found most effective dose for reduction of blood loss for hip arthroplasty 1g TXA given prior to surgery and 6 hrs post. Limited data on risks of DVT
TX in hip arthroplasty Limited dose selected studies 6 studies included in meta analysis No studies that used the dose of 60mg/kg. Same dosing is used as for knees. Should be given as slow intravenous infusion Loading dose 50mg/min 1g in 100ml can give at 5ml/min
TXA and DVT General consensus. No increased DVTs with TXA Nielsen, Ugeskr Laeger 2002 Tanaka, JBJS (Br) 2001 Good, BJA 2003 Yang J Bone and Joint 2012 TGA report: For every 100 pts knee arthroplasty 6 patients at risk of DVT in TX group.
Meta analysis re blood loss Hiipala et al Transfusion risk reduced by 64% Dutch 10 yr Study (Slappendal) 80% less transfusion 40% less infection Decreased morbidity Reduced hospital duration No increase in Thromboembolic events.
Trend Of DVT In TX reports. Recent FDA reports. May 2013 1505 people reported side effects of TX acid. (Gastro type effects) 31 ie (2.06% ) with DVT Most DVT occurred in < 1 month (88.24%) 1-6 months DVT occurred in 11.76 %
Retrospective study at WOC Review of 354 records Hip (151) Knee (203) 61 m 86m 90 f 117 f
RESULTS OF REVIEW WOC HIPs 12 27 24 88 TX Blood and TX Transfusion No TX no Tf
RESULTS OF REVIEW WOC Knees Knees 203 TX 54 Blood and TX 39 5 105 Transfusio n No TX no TF
Adverse events for hip and knees Hypotension (29 H) (17 K) Pulmonary embolism (3 H) Rash (6) Confusion (5)
Clinical Perspective Blood management protocol Preoperative: Get sound history of bleeding v clotting Cease supplements eg fish oils etc. Cease NSAIDs antiplatelet meds and aspirin 7-10 days before surgery. Discontinue warfarin 5 days prior check INR Check for preoperative anaemia. Consider iron therapy if <100 ug/l
Clinical Perspective Blood management protocol Perioperative management Revising the transfusion trigger to 8Hbg or below has been shown to be safe. Maintain normothermia Surgeon preference re tourniquet and drain. TX given by anaesthetist 15mg/kg before tourniquet release and 2 nd dose surgeon pref.
Post operative Clinical Perspective Blood management protocol. Maintain normothermia Limb elevation Withhold thromboprophylaxis until surgical haemostasis (ie 6-8 hrs) Check Hg status transfusion trigger post 8 hr surgery.(<8hgb)
Conclusions TX Acid reduces mortality in bleeding trauma patients. Reduces bleeding generally by 25-30% and leads to decreased transfusion rates. TX acid Preoperatively in Total Knee Replacement does not increase incidence of DVT and PE Best dose : how, timing, and dose???? Preoperative anaemia, intraoperative blood loss and post operative care can be influenced by blood management protocols. Audit regularly TX administration. Dose studies needed
References Blake et al Clinical orthopaedic Research July 2012 Alvarez J et al Transfusion 2008 48: 519-525 Benoni C Acta othopaedics Scand 2001 72: 442-448 Naudi Douglas Ralley Clinical Orthopaedics and related research July 2010 V 468 pg 1905 Product Information Cyklokapron p 1-27. Imai et al Arthroplasty 2012
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