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Names of the Authors:

1) Dr. Pankaj Patni  

2) Dr. Rahul Khanna

3) Dr. Sunil Dewangan

4) Dr. Bharat Mody


Welcare Hospital, Vadodara, Gujarat

Corresponding Author:

Name: Dr. Pankaj Patni

Address: Welcare Hospital

                101/103, Aakashganga Complex, Near Vanijya Bhavan, Above Pizza Hut, 

                Racecourse Circle, Vadodara – 390 007 (Gujarat)

Phone Number: 09879222881


Total Number of pages: 10 

Total Number of photographs: Nil

Source of support: Nil

Presentation at a meeting 

                          Organization: Indian Society for Hip and Knee Surgery (ISHKS)

                          Place: Ahmedabad, Gujarat

Conflicting Interest: Nil




Background: Various measures have been developed to minimize blood loss in Total knee replacement (TKR) surgeries, which includes use of tourniquet, antifibrinolytic agent and cemented prosthesis. Our study analyses the efficacy of Tranexamic Acid (TA) to reduce blood loss by comparing difference in hemoglobin (Hb %), hematocrit (HCT) value and the drain output. A perfectly matched group was created by selecting patient’s one limb as study and the other limb as control group.

Methods: 60 patients undergoing primary sequential bilateral TKR at an interval of one day were enrolled. A dose of TA of 10 mg/kg of body weight or equivalent volume of normal saline (NS) was infused towards the end of surgery, 15 minutes prior to deflation of the tourniquet for either limb. The same dose was repeated after three hours of the primary dose. The two groups were compared for differences in post- operative 24 hrs blood losses.

Results: The groups had similar characteristics. Mean blood loss as calculated from drain collection was 210 +/- 99.10 ml (milliliter), mean difference in Hb% (post operative Hb% - pre operative Hb%) was 0.53 +/- 1.27 gm% and mean difference in HCT (post operative – pre operative) was 1.3 +/- 3.591% for the limb side receiving TA. For the limb side receiving NS the values for drain was 342 +/- 151.42, Hb% difference was -0.95+/-1.02 gm% and HCT difference was -2.39 +/- 2.895%. All the difference between the TA and the NS group was significant on statistical analysis.

Conclusion: Considering the same patients different limb in study and control group eliminates patient related confounding factors and provides a more precise and controlled comparison. Use of TA decreases blood loss up to 38.5% within 24 hrs of TKR. Routine use of TA as a therapeutic prophylactic measure to conserve blood is definitely recommended. Level of Evidence: Level I Study (therapeutic studies – investigating the results of treatment)

J.Orthopaedics 2012;9(1)e13


Antifibrinolytic agent, Tranexamic Acid, Total Knee Replacement, Post-operative blood loss.



Total knee replacement (TKR) surgery is associated with considerable intra-operative and post-operative blood loss. Plugging of the femoral canal, use of cemented prosthesis along with pneumatic tourniquet has been advocated as a routine to minimize per-operative blood loss [1-3]. Though tourniquet provides a dry surgical field, the surgical act itself and the use of tourniquet enhances coagulability and local fibrinolytic activity in the limb subsequently leading to substantial blood loss, especially in the initial post-operative hours [4]. Tranexamic acid (TA), an anti-fibrinolytic agent has been reported to reduce this fibrinolytic activity and thus finally reduces blood loss in the immediate post-operative phase [5-8].

TA a synthetic amino acid is an anti-fibrinolytic agent, which acts by competitively blocking the lysine binding site of plasminogen, plasmin and tissue plasminogen activator, preventing their bonding with fibrin [8]. As a result plasminogen is not activated to plasmin leading to overall inhibition of fibrinolytic activities, finally reducing post-operative blood loss.

Despite clinical studies proving the efficacy of TA in reducing blood loss, its use as a standard protocol is limited. None of the previous studies have been able to standardize the research in term of study and control group. To our knowledge, no study has addressed effect of TA on blood loss in same patient using one limb as study and another limb as control. We have conducted a study to evaluate the efficacy of TA in reducing post-operative blood loss by examining the difference in post-operative hemoglobin (Hb %), hematocrit value (HCT) and drain output. Though similar to previous studies, we tried to standardize our study by creating a perfectly matched group by selecting patients undergoing sequential bilateral TKR at an interval of one day. Same patient’s one knee was taken as a study group and the opposite knee was considered as a control. This helped in excluding the possible patient confounding factors and thus creating an ideal and perfectly matched study.


After approval of study protocol by local research authority and ethical committee, 60 patients who were scheduled to undergo a sequential primary bilateral total knee arthroplasty during November 2010 to July 2011, were enrolled into a prospective, randomized, double blinded, controlled study. Written informed consent was obtained from all the patients. Inclusion criteria were patients with osteoarthritis or rheumatoid arthritis requiring bilateral TKR with normal coagulation profile.

Exclusion criteria were patients undergoing unilateral TKR, patients with renal dysfunction or previous history of renal disorder, history of bleeding disorder and patients on warfarin. All the patients were requested to stop NSAIDS one week prior to surgery.

All the surgeries were performed by a single surgeon in a sequential manner (at an interval of one day) on all the patients. Randomization regarding which of the limb being operated would receive TA was done by the anesthetist. This result of the side receiving TA was not known to the operating surgeon or the investigating team till the results was formulated. Anesthetist was otherwise not involved in the study. Thus, either of the two limbs of the same patient served as study group, while the contra-lateral limb provided the control group. This provided a perfectly matched group in terms of patients characteristic.

All patients received intravenous antibiotic coverage in the peri-operative period, which included oxazolidinone (linezolid), cefoperazone – sulbactum, metronidazole and amikacin. Patients were induced with spinal anesthesia using bupivacaine and adrenaline. All the surgeries were performed in blood less field using pneumatic tourniquet. Tourniquet was inflated to twice the systolic pressure (nearly 300 – 400 mm of Hg) after draining the limb by elevation and ex-sanguination by elastic rubber bandage. At the end of the surgery, tourniquet was deflated and any major bleeding was controlled by diathermy before the wound closure. The PFC Sigma (Warshow, Indiana), total knee prosthesis was used in all patients and implantation done using cement (CMW 1 with gentamicin) for all cases. Plugging of the femoral canal was done using bone plug in all the cases. One intra-articular drain (12 gauges) was used for each TKR and connected to the drain reservoir. The drains were routinely removed at 24 hours. To avoid inter-observer variability, drain collection was measured and recorded by a designated single orthopedic surgeon. Two units of packed cell volume (PCV) were given routinely for each TKR. The first unit was started intraoperatively while the second unit was given post operatively after the first unit was over.

A dose of TA of 10 mg/kg of body weight or equivalent volume of NS was infused by the anesthetist 15 minutes prior to deflation of the tourniquet for either limb as per schedule. The same dose was repeated after three hours. The records of the side receiving TA was kept by the anesthetist and known to the investigating team only when the results were formulated. Blood investigation on the day of admission (Day 1 of admission) includes hemoglobin (Hb %), hematocrit (HCT), beside routine pre-operative blood test including the coagulation profile for each patient. These levels were considered as pre operative measure for the first surgery, which was performed the following day (Day 2 of admission). The Hb% and HCT value were repeated on the second post-operative day (Day 3 of admission) after the removal of the drain. These values acted as post-operative measurement for the first TKR and pre operative level for the opposite TKR. The subsequent limb was operated on the third day (Day 4 of admission) from the first one. Again the values were repeated on the following day (Day 5 of admission) after removal of the drain. These values provided the post-operative measure for the second operated side.


Paired t test was used for quantitative analysis of the data using graph pad software. In the text, data are presented as mean +/- standard deviation (SD) and p values of less than 0.05 was considered significant.


We have analyzed 60 patients undergoing bilateral sequential total knee replacement for the effect of TA on post-operative blood loss. The values were analyzed in terms of drain collection at the end of 24 hours of surgery, Hb% and HCT differences (post operative values – pre operative values).

There was no difference in individual patient’s demographic profile and pre-operative haemostatic status, as the same patient’s either limb was taken in two groups thus making it an ideal and perfectly matched groups. Mean age of the patients was 67 +/- 8.79 years (range 52- 86 years). Male to female ratio was 4:11. Majority of the patients included were of osteoarthritis (OA) and ratio with rheumatoid patients (RA) was 13:2. All the patients underwent bilateral sequential total knee replacement at an interval of one day.

Factors describing time and technical aspects of the surgical procedure were similar for both the groups (Table 1). Mean external blood loss as calculated from drain collection at 24 hours post-operatively between the TA (210 +/- 99.10 ml) and the NS (342 +/- 151.42 ml) group was significant (p < 0.001). The mean difference between the post operative and preoperative Hb% and HCT values for both the groups was significant (p<0.001) (Table 2).




TA GROUP (n=60)

NS GROUP (n=60)

Duration of surgery (min)

68.5 ( 57– 83)

71.5 (56 – 85)

Tourniquet time (min)

47 (25 – 35)

51 (25 – 35)

All the values are mean values with range

TA = Tranexamic acid; NS = Normal Saline



TA GROUP (n=60)

NS GROUP(n=60)

Drain collection (in ml)

210 +/- 99.10

342 +/- 151.42

Hb% difference (in gm %)

0.53 +/- 1.27 

-0.95 +/- 1.02 

HCT difference 

1.3 +/- 3.591 %

-2.387 +/- 2.895 %

All the values are mean values +/- S.D.

The Hb% and HCT difference = post operative value – pre operative value

There were no wound complications like superficial or deep infection. None of the patient in either group had clinical suspicion of any thrombo-embolic event as assessed clinically until 6 wks follow-up of period.



Total knee replacement surgeries can be associated with around 600 - 1500 ml of blood loss [1,9] . Various studies have been conducted to evaluate the effect of surgical and non-surgical techniques in reducing blood loss during TKR [1-3]. Similarly therapeutic interventions like using TA have shown to decrease blood loss by up to 45% when used in TKR [5-8,10]. However all these studies have used separate patients for creating the study and control group, which leaves a margin of error in the two compared group with respect to patient characteristics.

We have conducted this study to evaluate the efficacy of TA in total knee arthroplasty. However in designing our study, we tried to control and reduce the patient confounding factors by keeping the limbs of same patient as study and control groups, thus making the two groups perfectly matched in respect to demographic profile and haemostatic status, this we were able to achieve by performing a bilateral sequential total knee arthroplasty in the same patient. In line with the previous studies it’s proven that TA significantly reduces post-operative blood loss and was evident in our study by a 38.5% difference in drain volume collection between the two groups in 24 hrs. Further there is a statistically significant difference in total blood loss as evident by the hemoglobin and hematocrit values of the two compared groups.

TA has no effect on blood loss during surgery as anti-fibrinolytic agents are not expected to have any major influence on primary hemostasis and coagulation [5]. An initial dose of 10-15 mg/kg of TA given prior to deflation of tourquinet and additional same dose 3 hrs later is sufficient to achieve maximum clinical impact along with the patient safety. We have evaluated use of TA given during TKR in first post-operative day (24 hrs), as blood sparing effect is most evident in the first 24 hrs post operatively [9].

Variation of surgical technique, plugging of the femoral canal and method of anesthesia could all influence the blood loss in TKR or in any orthopedic procedure [2]. To avoid all these variability all the surgeries in our study was performed by a single surgeon and by using standard anesthesia protocols.

Thrombo-embolism is a dreaded complication in any orthopedic surgery, more of a concern in a joint replacement surgery. There has been no positive correlation between TA administration and increased incidence of thrombosis leading to deep venous thrombosis (DVT) [7,11,12]. In accordance with other studies we were also not able to associate any increased incidence of DVT due to TA.

Blood loss was reduced and therefore transfusion requirement also decreased in the treatment group compared to controls. Current study confirms the beneficial effect of TA in TKR associated blood loss. Short term therapy of 2 doses reduces the blood loss by 38.5%. With fewer transfusions, post-operative hemoglobin concentration drop in the study group was lower than the control group.

Thus, in conclusion, our study suggests that there is a definite correlation between administration of TA and reduction of post-operative blood loss in patients operated for total knee replacement. In view of these findings and previously published literature on the same subject routine use of TA as a therapeutic measure to conserve blood is recommendable. Finally we conclude and reinforce the previous result that use of TA significantly reduces blood loss caused by TKR performed with tourniquet, without increasing the risk of thrombo-embolic complications.


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TABLE 1 Time Factors and Technical Data Associated with total knee replacement surgery.

TABLE 2 Drain collection and Hb% and HCT difference between the two groups.

This is a peer reviewed paper 

Please cite as :

J.Orthopaedics 2012;9(1)e13




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