Use of Tranexamic acid is a cost effective method in preventing blood loss during and after total knee replacement
© Sepah et al; licensee BioMed Central Ltd. 2011
Received: 13 October 2010
Accepted: 21 May 2011
Published: 21 May 2011
Background & Purpose
Allogenic blood transfusion in elective orthopaedic surgery is best avoided owing to its associated risks. Total knee replacement often requires blood transfusion, more so when bilateral surgery is performed. Many strategies are currently being employed to reduce the amount of peri-operative allogenic transfusions. Anti-fibrinolytic compounds such as aminocaproic acid and tranexamic acid have been used systemically in perioperative settings with promising results. This study aimed to evaluate the effectiveness of tranexamic acid in reducing allogenic blood transfusion in total knee replacement surgery.
This was a retrospective cohort study conducted on patients undergoing total knee replacement during the time period November 2005 to November 2008. Study population was 99 patients, of which 70 underwent unilateral and 29 bilateral knee replacement. Forty-seven patients with 62 (49.5%) knees (group-I) had received tranexamic acid (by surgeon preference) while the remaining fifty-two patients with 66 (51.5%) knees (group-II) had did not received any tranexamic acid either pre- or post-operatively.
The mean drop in the post-operative haemoglobin concentration in Group-II for unilateral and bilateral cases was 1.79 gm/dl and 2.21 gm/dl, with a mean post-operative drainage of 1828 ml (unilateral) and 2695 ml (bilateral). In comparison, the mean drop in the post-op haemoglobin in Group-I was 1.49 gm/dl (unilateral) and 1.94 gm/dl (bilateral), with a mean drainage of 826 ml (unilateral) and 1288 ml (bilateral) (p-value < 0.001).
Tranexamic acid is effective in reducing post-operative drainage and requirement of blood transfusion after knee replacement.
Total knee replacement is a frequently done procedure in modern day practice of any Orthopedics unit. Limiting blood loss both postoperatively and intra-operatively presents a challenge to the surgeon. Postoperatively, blood continues to ooze from the cut ends of bone, the open intra-medullary canal and the raw, dissected soft tissues. This can amount to significant bleeding with figures ranging from 600 - 1500 ml [1–7]. As this procedure is performed under tourniquet control, there is an associated increase in localized fibrinolysis, which contributes to two events. Firstly, it decreases the risk of venous thromboembolism and secondly it may aggravate post-operative haemorrhage [8–10]. The problem of excessive blood loss is further highlighted in cases of simultaneous bilateral total knee replacement where blood loss is usually twice that of a unilateral knee replacement and the number of allogenic blood units transfused can be as high as three to four per person [11, 12]. Risks associated with allogenic blood transfusion are numerous and well documented. Of these the most important are blood borne infections, immunological reactions and cost incurred in producing a unit of red cells [13–15].
■ The aim of this study was to determine: if the use of tranexamic acid reduces perioperative blood loss and need for allogenic blood transfusion in patients undergoing total knee replacement
■ Any untoward effects with the use of this drug in our population
Materials and methods
All patients having undergone total knee replacement at our hospital between November 2005 to November 2008 were included in the study sample.
A total of 99 patients with 128 knee joints were included in the study. Patients from Group I received one gram of IV tranexamic acid before inflation of the tourniquet and 1 g after deflation of tourniquet. Sixty-six patients (66.4%) underwent unilateral and 23 patients (24.6%) had bilateral procedures.
All patients with no known bleeding disorders who under-went TKR were included in our study. All patients were given routine DVT prophylaxis with Injection Enoxaparin 40 mg subcutaneous once a day. Anaesthesia was standardized and all patients received epidural anaesthesia according to standard practice. Patients receiving chronic anticoagulants were excluded from the study. Haemoglobin was measured preoperatively, one hour postoperatively and at 72 hours postoperatively. The same surgical team performed all procedures and the same implant (IB-II - Zimmer, Warsaw, IN) was used in all patients. Patellar replacement was performed in all cases and all components were cemented.
Postoperative Hb is < 7 mg/dl in patients with no coronary heart disease, or < 9 mg/dl in patients who have coronary heart disease
Physiological signs of inadequate oxygenation such as hemodynamic instability or symptoms of myocardial ischemia occur
Drainage of more than 1 liter of blood in the first 24 hours
47 patients with 32 (68%) undergoing a unilateral and 15 (32%) undergoing simultaneous bilateral total knee replacement had received tranexamic acid and these were labelled as Group-I. Data form Group-I was collected retrospectively by chart review and then compared with that of Group-II which was a historical control group. Group-II underwent the same procedure of either a unilateral or simultaneous bilateral total knee replacements, but did not receive tranexamic acid and also did not undergo any other procedure to reduce post-operative bleeding. Patients in both groups were age and disease-matched. There were 52 patients in Group-II with 38 (76%) undergoing a unilateral and 14 (24%) undergoing a simultaneous bilateral knee replacement procedure.
Student t-test was used to compare the means via SPSS 13.
Summary of results
Mean Post-Operative Drainage
Mean Drop in Post-Operative HB
Mean number of Packed Cells Transfused
Number of Patients requiring Transfusion
Group-I (N = 47)
Group-II (N = 52)
Different methods of blood conservation and their complications.
Alternatives used to avoid allogenic blood transfusions and their disadvantages
Preoperative Blood Donation (PAD)
• Cardiac, Vasovagal (Risk Factors: Younger Age, Lower weight, 1 St time donation) 
• 12 times increase in Anginal and Vasovagal complications (Risk Factor: 1 st time donation) 
• Not Cost Effective in Orthopaedic Procedures (More expensive to produce one unit of autologous blood, Cost also incurred in disposal of more than half of the blood discarded which is not used)
Acute Normovolemic Hemodilution (ANH)
Not effective in Orthopedic Procedures (data termed inconclusive) 
Perioperative red cell salvage (PCS)
Cost effectiveness of the postoperative blood collection devices was challenged (1 st six hour collection would cost 31-35 million dollars) 
Deliberate Hypotension DH)
Recombinant Human Erythropoietin (RHE)
Routine use not justified due to high cost 
• Low dose not effective in orthopedic procedure 
• Evidence has been published to suggest an increase in renal events in patients given aprotinin when compared to those where tranexamic acid was used 
Tranexamic acid, by way of its anti-fibrinolytic action, prevents clot breakdown and a consequent re-bleed. Our results demonstrate significant reduction in blood loss with the use of tranexamic acid. Other studies have also had similar results [20, 22]. A meta analysis which looked at double blinded randomized controlled trial also found that tranexamic acid was useful in reducing blood loss in major orthopedic procedures .
No adverse effects were seen in our population with the use of tranexamic acid. Although side effects have been reported in other large scale studies but none of them were serious enough to warrant disuse of the drug [25, 26].
In South Asia, apart from poverty, low literacy, social factors that result in the inability of women to negotiate safe sex, intravenous drug use and unsafe transfusion is regarded as one of the most important factors that influence transmission of infection [27, 28]. High frequency of viremia due to transfusion-transmitted virus was observed in most of the study populations from third world countries, with values ranging from 16 percent in Pakistan to 83 percent in Gambia 
A large scale study  in Pakistan has shown that the screening coverage on the average has been 77.42% for HIV and 86.84% for HBV. The prevalence of HIV is 0.001% and of HBV is 2.259% . The probability of receiving an infective unit P(R) per 10000 donations is 0.023 for HIV and 29.72 for HBV. The probability of transmitting infection P (I) per 10000 donations is 0.021 for HIV and 26.75 for HBV. The spreading index for both viral infections combined is 26.75 per 10000 donations. Although 80% of joint replacement procedures take place in the United States and Europe, South Asia is not far behind with an estimated 40-50 thousand joint replacement procedures already done yearly in India alone . Number of knees replaced annually in Pakistan is estimated to be 1500-2000 .
The cost of one unit of red cells is estimated 120 pounds  in Britain while it costs 19.20 British Pounds in Pakistan . The regimen of tranexamic acid that was administered in our study population costs 3.75 Pounds. These figures reflect that if one is able to decrease the requirement of blood by even one unit per patient the cumulative effect will be a decrease of burden on the health care system. Countries where individuals pay for their own health care and there is no third party plan (health insurance companies) involved can benefit from adopting such cost effective measures.
Although we conducted a retrospective analysis of a relatively small number patients and the possibility of the results being affected by recall bias due to historical controls cannot be ruled out it does provide the basis for conducting larger scale prospective randomized studies in order to determine the efficacy of tranxemic acid in reducing perioperative blood loss.
We believe that the use of tranexamic acid in TKR surgery is a low cost option in reducing the requirement of allogenic blood transfusion.
- Cushner FD, F R: Blood loss in total knee arthroplasty. Clin Orth. 1991, 269: 98-101.
- Fragen RJ, S S, Wixson R: Effect of Ketorolac tromethamine on bleeding and requirements for analgesia after total knee arthroplasty. J Bone Joint Surg(Am). 1995, 77: 998-1002.
- Bukart BC, B R, Rorabeck CH: The efficacy of tourniquet release in blood conservation after total knee replacement. Clin Orth. 1994, 299: 147-52.
- Karnezis TA, S S, Wixson RL, Reilly P: The hemostatic effects of desmopressin on patients who had total joint arthroplasty. J Bone Joint Surg(Am). 1994, 76: 1545-50.
- Mylod AG, F M, Muser DE, Parsons JR: Perioperative blood loss associated with total knee arthroplasty. J Bone Joint Surg(Am). 1990, 72: 1010-2.
- Fauno P, S O, Rehnberg V: Prophylaxis for the preventiopn of venous thromboembolism after total knee arthroplasty. J Bone Joint Surg(Am). 1994, 76: 1814-8.
- Goodnough LT, V D, Marcus RE: The relationship between hematocrit, blood lost and blood transfused in total knee replacement. Am J Knee Surg. 1995, 8: 83-7.PubMed
- Klenerman L, M I, Chakrabarti R: Changes in the hemostatic system after application of a tourniquet. Lancet. 1977, I: 970-2.View Article
- Benoni G, C A, Petersson C, Fredin H: Does Tranexamic Acid reduces blood loss after total knee arthroplasty?. Am J Knee Surg. 1995, 8: 88-92.PubMed
- Petaja J, M P, Myllyla G, Vahtera E: Fibrinolysis after application of a pnematic tourniquet. Acta Chir Scand. 1987, 153: 647-51.PubMed
- Martin JW, W L, Milliano MT, Reedy ME: Post operative blood Retrieval and transfusion in cementless total knee arthroplasty. J Arthroplasty. 1992, 7: 205-10. 10.1016/0883-5403(92)90019-M.View ArticlePubMed
- Lane GJ, H W, Shah S, Rothman RH, Booth RE, Engh K, Smith P: Simultaneous bilateral versus unilateral total knee replacement arthroplasty. Outcomes Analysis. Clin Orthop. 1997, 345: 106-12.View ArticlePubMed
- Nozoe Tadahiro, M M, Saeki Hiroshi, Ohga Takefumi, Keizo Sugimachi: Significance of allogenic blood transfusion on decreased survival in patients with esophageal carcinoma. Cancer. 2001, 92 (7): 1913-18. 10.1002/1097-0142(20011001)92:7<1913::AID-CNCR1709>3.0.CO;2-8.View ArticlePubMed
- Brian McClelland MC: Appropriateness and safety of blood transfusion. BMJ. 2005, 330: 104-105. 10.1136/bmj.330.7483.104.PubMed CentralView ArticlePubMed
- Spanh DR, C M: Eliminating blood transfusions. New aspects and perspectives. Anesthesiology. 2000, 93: 242-55. 10.1097/00000542-200007000-00035.View Article
- P O, H : Antifibrinolytic therapy with Cyklopropan in connection with prostatectomy: a double blind study. Scand J Urol Nephrol. 1969, 3: 177-82. 10.3109/00365596909135401.View Article
- Dunn CJ, G K: Tranexamic Acid: a review of its use in surgery and other indications. Drugs. 1999, 57: 1005-32. 10.2165/00003495-199957060-00017.View ArticlePubMed
- Bekasssy Z, A B: Treatment with fibrinolytic inhibitor tranexamic acid: risk for thrombosis?. Acta Obstet Gynecol Scand. 1990, 69: 353-4. 10.3109/00016349009036161.View Article
- Kataros D, P M, Snow NJ, Woodland DD, Van Bergan : Tranexamic Acid reduces postbypass blood loss: a double blinded, prospective, randomised study of 210 patients. Ann Thorac Surg. 1996, 61: 1131-5. 10.1016/0003-4975(96)00022-7.View Article
- Hiippala ST, S L, Wennerstrand MI, Arvela JV, Niemel a HM, M antyl a SK, Kuisma RP, Ylinen JE: Tranexamic Acid radically reduces blood loss and transfusions associated with total knee arthroplasty. Anesth Analg. 1997, 84: 839-44.PubMed
- Hiippala S, S L, Wennerstrand M: Tranexamic Acid (Cyklopropan) reduces perioperative blood loss associated with total knee arthroplasty. Br J Anesth. 1995, 74: 534-7. 10.1093/bja/74.5.534.View Article
- Benoni G, G H: Fibrinolytic inhibition with tranexamic acid reduces blood loss and blood transfusion after knee arthroplasty: A prospective, randomized, double blind study of 86 patients. J Bone Joint Surg Br. 1996, 78: 434-440.PubMed
- Rosenblatt MA: Strategies for minimizing the use of allogeneic blood during orthopedic surgery. Mt Sinai J Med. 2002, 69 (1-2): 83-7.PubMed
- Zufferey Paul, F M, Laporte Silvy, Decousus Herve', Mismetti Patrick, Auboyer Christian, Charles Marc Samama, Molliex Serge: Do Antifibrinolytics Reduce Allogeneic Blood Transfusion in Orthopedic Surgery?. Anesthesiology. 2006, 105: 1034-46. 10.1097/00000542-200611000-00026.View ArticlePubMed
- Ip , P P: Tranexamic acid-associated necrosis and intralesional thrombosis of uterine leiomyomas: a clinicopathologic study of 147 cases emphasizing the importance of drug-induced necrosis and early infarcts in leiomyomas. Am J Surg Pathol. 2007, 31 (8): 1215-24. 10.1097/PAS.0b013e318032125e.View ArticlePubMed
- Sethna NF: Tranexamic acid reduces intraoperative blood loss in pediatric patients undergoing scoliosis surgery. Anesthesiology. 2005, 102 (4): 727-32. 10.1097/00000542-200504000-00006.View ArticlePubMed
- Chrishantha Abeysenaa HJdS: HIV in South Asia. Medicine. 2005, 33 (6): 42-43. 10.1383/medc.188.8.131.52005.View Article
- Ali S, T W, Khan A: Viral hepatitis in children. 1998, AFIP Rawalpindi, Pakistan
- Linda E, Prescott PS: Global Distribution of Transfusion-Transmitted Virus. NEJM. 1998, 339 (11): 776-777. 10.1056/NEJM199809103391118.View Article
- Mahfooz ur Rahman AGN, Lodhi Y: Transfusion transmitted HIV & HBV infections in Punjab, Pakista. Pakistan Journal of Medical Sciences. 2002, 18 (1): 18-25.
- Mukherjee Rupali T: India to be largest market for knee, hip replacements., in The Times of India. 2007
- Sons Fa: Number of total knee implants supplied to Pakitan. 2007, Karachi
- Aga Khan University Hospital Karachi, Pakistan. Price list. http://www.aku.edu/AKUH/Patient_Visitor/page6.shtml
- Gandini G: Preoperative autologous blood donation by 1073 elderly patients undergoing elective surgery: a safe and effective practice. Transfusion. 1999, 39 (2): 174-8. 10.1046/j.1537-2995.1999.39299154732.x.View ArticlePubMed
- Trouern-Trend JJ: A case-controlled multicenter study of vasovagal reactions in blood donors: influence of sex, age, donation status, weight, blood pressure, and pulse. Transfusion. 1999, 39 (3): 316-20. 10.1046/j.1537-2995.1999.39399219291.x.View ArticlePubMed
- Forgie MA: Preoperative autologous donation decreases allogeneic transfusion but increases exposure to all red blood cell transfusion: results of a meta-analysis. International Study of Perioperative Transfusion (ISPOT) Investigators. Arch Intern Med. 1998, 158 (6): 610-6. 10.1001/archinte.158.6.610.View ArticlePubMed
- Sculco TP, Gallina J: Blood management experience: relationship between autologous blood donation and transfusion in orthopedic surgery. Orthopedics. 1999, 22 (Suppl 1): s129-34.PubMed
- Etchason J: The cost effectiveness of preoperative autologous blood donations. N Engl J Med. 1995, 332 (11): 719-24. 10.1056/NEJM199503163321106.View ArticlePubMed
- Bryson GL, Laupacis A, Wells GA: Does acute normovolemic hemodilution reduce perioperative allogeneic transfusion? A meta-analysis. The International Study of Perioperative Transfusion. Anesth Analg. 1998, 86 (1): 9-15.PubMed
- Umlas J: Red cell loss following orthopedic surgery: the case against postoperative blood salvage. Transfusion. 1994, 34 (5): 402-6. 10.1046/j.1537-2995.1994.34594249051.x.View ArticlePubMed
- Lee AG: Ischemic optic neuropathy following lumbar spine surgery. Case report. J Neurosurg. 1995, 83 (2): 348-9. 10.3171/jns.1995.83.2.0348.View ArticlePubMed
- Stevens WR: Ophthalmic complications after spinal surgery. Spine (Phila Pa 1976). 1997, 22 (12): 1319-24. 10.1097/00007632-199706150-00008.View Article
- James ML, Keifer JC: Posterior optic nerve ischemic neuropathy in the setting of phenoxybenzamine therapy after uneventful spinal fusion. J Neurosurg Anesthesiol. 2011, 23 (2): 169-70. 10.1097/ANA.0b013e31820396d6.View ArticlePubMed
- Coyle D: Economic analysis of erythropoietin use in orthopaedic surgery. Transfus Med. 1999, 9 (1): 21-30. 10.1046/j.1365-3148.1999.009001021.x.View ArticlePubMed
- Kasper SM: A retrospective study of the effects of small-dose aprotinin on blood loss and transfusion needs during total hip arthroplasty. Eur J Anaesthesiol. 1998, 15 (6): 669-75. 10.1097/00003643-199811000-00008.View ArticlePubMed
- Royston D, van Haaften N, De Vooght P: Aprotinin; friend or foe? A review of recent medical literature. Eur J Anaesthesiol. 2007, 24 (1): 6-14.View ArticlePubMed
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