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Abstract

  1. Top of page
  2. Abstract
  3. Materials and Methods
  4. Results
  5. Discussion
  6. Conflict of Interest
  7. References

Background

Tranexamic acid (TXA) is an antifibrinolytic that reduces blood loss and transfusion rates in total joint arthroplasty. Blood loss and allogenic transfusion rates have not been well studied in patients receiving TXA and undergoing bilateral staged total knee arthroplasty (TKA). The purpose was to evaluate the effect of TXA on blood loss, hemoglobin (Hb) changes, and transfusion in patients undergoing staged bilateral TKA.

Study Design and Methods

The authors compared 51 patients undergoing staged bilateral TKA who received TXA (2 g; subjects) with 70 who did not (controls). There were no significant differences between the groups in terms of demographics or preoperative Hb. For each TKA, 1 g of TXA was administered intravenously 15 minutes before incision and 1 g was administered intravenously at tourniquet release. Blood loss, Hb levels, and transfusions were recorded. Statistical analyses were performed using computer software. Significance was set at 0.05.

Results

Subjects had a significantly lower (p < 0.001) mean (±SD) blood loss (373.8 ± 264.6 mL vs. 871.6 ± 457.7 mL), significantly higher (p < 0.005) Hb levels on Postoperative Days 1 and 2, and a significantly lower (p < 0.001) mean (±SD) number of transfused allogenic blood units (0.60 ± 0.84 units vs. 1.53 ± 1.30 units).

Conclusions

TXA reduces blood loss, improves postoperative Hb, and decreases the allogenic blood transfusion requirements for patients undergoing bilateral staged TKA. TXA is an option for patients choosing bilateral staged TKA to decrease the risks associated with blood transfusion or when autologous blood is not available.

Abbreviations
DVT

deep venous thrombosis

TKA

total knee arthroplasty

TXA

tranexamic acid

Total knee arthroplasty (TKA) has the potential for major blood loss. To decrease perioperative bleeding and transfusions surgeons are not only examining technique, but also considering pharmacologic agents that minimize bleeding through the inhibition of blood clot degradation. Antifibrinolytics function to decrease perioperative blood loss by inhibiting clot degradation. Tranexamic acid (TXA) is an antifibrinolytic that saturates the plasminogen-binding sites to fibrin, thereby inhibiting plasminogen from dissolving the clot. Previous studies have examined the effect of TXA on blood loss and transfusion requirements for unilateral TKA patients.1-4 Dhillon and colleagues[5] evaluated the use of TXA in single-stage, bilateral, simultaneous TKAs and found a reduction in blood loss and decreased blood transfusion requirements. Our purpose was to evaluate the effect of TXA on blood loss, hemoglobin (Hb) changes, and transfusion in patients undergoing bilateral TKA staged 3 days apart.

Materials and Methods

  1. Top of page
  2. Abstract
  3. Materials and Methods
  4. Results
  5. Discussion
  6. Conflict of Interest
  7. References

This retrospective case-control study was approved by our institutional review board.

Patient population

We searched our database for patients undergoing bilateral TKA for osteoarthritis from June 1, 2008, through June 15, 2010, staged 3 days apart. We began to routinely use TXA for TKAs on June 15, 2009. We excluded patients with a history of thromboembolic disease, chronic renal failure, or ophthalmologic disease; those with current anticoagulation therapy; those with an allergy to TXA; and those for whom spinal anesthesia failed or who had a contraindication to spinal anesthesia. Of the 121 eligible patients, the 70 (June 1, 2008, through June 1, 2009) who did not receive TXA formed our control group and the 51 (June 15, 2009, through June 15, 2010) who were given TXA formed our study group. The TXA was administered per our protocol: for each TKA, 1 g of TXA in 50 mL of normal saline intravenously approximately 15 minutes before incision and 1 g of TXA in 50 mL of normal saline intravenously when the tourniquet was deflated. Patient demographic data were collected and preoperative Hb levels were recorded before the first surgery. There were no significant differences between the two groups in patient demographics (age, body mass index, sex) and preoperative characteristics (preoperative Hb and hematocrit (Hct; Table 1).

Table 1. Demographic and preoperative characteristics*
CharacteristicControl group (n = 70)Study group (n = 51)p value
  1. * Data are reported as mean (±SD) or number (%).

Age (years)67.2 (±10.1)69.8 (±8.1)0.134
Body mass index (kg/m2)31.2 (±5.6)30.8 (±5.5)0.705
Women45 (64.3)36 (70.6)0.467
Hb (g/dL)13.5 (±1.3)13.7 (±1.4)0.399
Hct (%)40.0 (±3.7)40.5 (±3.6)0.419

Operative and postoperative procedures

All arthroplasties were for osteoarthritis and were performed by the senior author via a medial trivector surgical approach. Tourniquets were used for all patients. A cemented, cruciate-retaining prosthesis (P.F.C. Sigma, DePuy Orthopaedics, Inc., Warsaw, IN) was used for each TKA. A cement plug was used to block the femoral medullary cavity at the time of femoral component insertion. Two medium hemovac drains were placed intraarticularly. All patients received periarticular injections containing ketorolac, ropivacaine, epinephrine, and clonidine. Closure was performed after adequate hemostasis, and cryotherapy was used for all postoperative knees.

Data recorded included hemovac drain output (blood loss), postoperative Hb levels, and transfusion requirements. Drain output was recorded each nursing shift, and all drains were removed in the morning of Postoperative Day 1. Postoperative Hb levels were recorded on Postoperative Days 1 and 2 for each surgery. Allogenic blood transfusion in the form of red blood cells was given to any patient after the first surgery with an Hb level of less than 9 g/L or a Hct of less than 27%. After the second surgery, allogenic blood transfusion was given to any patient with an Hb level of less than 8 g/L or an Hct of less than 24%. No patient was found to be hemodynamically unstable or symptomatically anemic with Hb and Hct results above these cutoff levels. Adherence to the Hb and Hct transfusion parameters were maintained for each group.

For deep venous thrombosis (DVT) prophylaxis all patients received 325 mg of aspirin twice daily along with early ambulation, lower extremity compression stockings, and intermittent pneumatic calf compression pumps while in the hospital. Aspirin was continued for a period of 6 weeks. One patient in each group was treated with low-molecular-weight heparin because of aspirin sensitivity. Physical therapy started with two sessions each day on Postoperative Days 1 and 2. The patient underwent the contralateral TKA on Postoperative Day 3, and then physical therapy was resumed for two sessions each day on Postoperative Day 4 (or Postoperative Day 1 for the second TKA) and Postoperative Day 5 (or Postoperative Day 2 for the second TKA). Patients had a single physical therapy session on Postoperative Day 6 (or Postoperative Day 3 for the second TKA) and were then discharged home or to a rehabilitation facility.

Statistical analyses

All data were assessed for normal distribution using the Shapiro-Wilk test. On the basis of this test, parametric statistics were used. Demographic and preoperative characteristics for controls and subjects were compared using the t test for continuous measures and the chi-square test for categorical measures. Similar univariate analyses were conducted for operative characteristics (e.g., mean allogenic blood units transfused). To adjust for the potential influence of preoperative Hb and Hct on the need for blood products perioperatively, linear regression models were constructed to estimate the influence of TXA on dependent measures (e.g., mean total blood units) while adjusting for the influence of these independent measures.

Statistical analyses were performed using computer software (SAS 9.3, SAS Institute, Inc., Cary, NC). Significance was set at 0.05.

Results

  1. Top of page
  2. Abstract
  3. Materials and Methods
  4. Results
  5. Discussion
  6. Conflict of Interest
  7. References

There were significant differences between subjects and controls in terms of blood loss, postoperative Hb levels, and transfusion requirements. Subjects (those receiving TXA) had a significantly lower (p < 0.001) mean (±SD) total drain output than did controls: 373.8 (±264.6) and 871.6 (±457.7) mL, respectively (Table 2). Subjects also had significantly fewer (p < 0.001) mean allogenic blood units transfused: 0.60 (±0.84) and 1.53 (±1.30) units, respectively (Table 2). Significantly fewer (p = 0.003) subjects than controls required an allogenic blood transfusion: 22 of 51 (43%) and 50 of 70 (71%), respectively. Subjects also had significantly higher Hb levels than did controls on Days 1 (11.13 ± 1.22 g/dL vs. 10.49 ± 1.15 g/dL, p = 0.005) and 2 (11.05 ± 1.30 g/dL vs. 10.16 ± 0.95 g/dL, p = 0.002) after the first TKA and also on Days 1 (9.74 ± 1.26 g/dL vs. 8.53 ± 1.00 g/dL, p < 0.001) and 2 (9.90 ± 1.05 g/dL vs. 9.30 ± 0.93 g/dL, p = 0.001) after the second TKA. When adjusting for differences in preoperative Hb levels and Hct, the difference in mean total blood units between subjects and controls was still significant (mean difference, −0.82; SE, 0.19; p < 0.001).

Table 2. Operative characteristics*
CharacteristicControl group (n = 70)Study group (n = 51)p value
  1. * Data are reported as mean (±SD) or number (%).

Total drain output (mL)871.6 (±457.7)373.8 (±264.6)<0.001
Blood transfusion required50 (71.4)22 (43.1)0.003
Amount allogenic blood transfused (units)1.53 (±1.30)0.60 (±0.84)<0.001

Post hoc sample size estimates were calculated. Based on the pooled SD of total blood loss (SD, 615.8), approximately 46 participants would be required per group to detect as significant the observed difference in total blood loss between subjects and controls. Similarly, using the pooled SD of transfused allogenic blood units (SD, 1.10), approximately 42 participants would be required per group to detect as significant the observed difference in transfused allogenic blood units between subjects and controls.

Patient comorbidities were reviewed and Charlson comorbidity score was calculated for each group.[6] No statistical difference was found between groups (p = 0.878).

Postoperative complications (Table 3), Knee Society Scores, and range-of-motion scores (Table 4) were recorded for each group.

Table 3. Postoperative complications
ComplicationControl group (n = 70)Study group (n = 51)
Infection01
Venous thromboembolism10
Reoperation1 (manipulation for arthrofibrosis)1 (revision for acute infection)
Hematoma10
Table 4. Preoperative and postoperative Knee Society Scores and range of motion*
GroupKnee Society ScoresRange of motion (°)
PainFunctionTotalExtensionFlexion
  1. * Data are reported as mean (range).

Control (n = 70)     
Preoperative8.2 (0-20)54.5 (15-70)44.6 (22-60)3.5 (0-15)123.6 (90-135)
Postoperative (6 weeks)44.2 (10-50)72.7 (30-100)88.7 (46-100)2.4 (0-15)114 (70-135)
Study (n = 51)     
Preoperative10.4 (0-30)57.2 (20-70)42 (21-60)4.8 (0-15)121 (50-135)
Postoperative (6 weeks)45.2 (30-50)69.6 (30-100)89.4 (59-100)4.7 (0-20)113.9 (87-138)

Discussion

  1. Top of page
  2. Abstract
  3. Materials and Methods
  4. Results
  5. Discussion
  6. Conflict of Interest
  7. References

Blood loss is expected to be high for bilateral TKA,[7] and the likelihood of a transfusion is higher for patients undergoing bilateral TKA than for those undergoing unilateral TKA. TXA has been proven to reduce blood loss1-4 and transfusion rates1-4 for TKA. Our study examined the effectiveness of TXA on reducing blood loss and reducing the transfusion rates for patients undergoing bilateral TKAs staged 3 days apart.

Our results confirm previously published studies of single TKAs with TXA showing a reduction in blood loss, higher postoperative Hb levels, and a decrease in the transfusion rate1-4 compared with no use of TXA. However, in addition, our study of patients undergoing bilateral TKAs has also shown that patients receiving TXA for each surgery had a significant decrease in total drain output compared with those who did not receive TXA.

Our study had some limitations. First, it was not a randomized, blinded study and the numbers were limited. However, even with our sample size, we were able to show significant differences in drain output, postoperative Hb levels, and transfusion rates. A larger, multicenter, randomized, blinded study would provide a better level of evidence but, because bilateral staged TKA is not very common, it may take several more years to complete a larger study. Although our sample size is limited, our data help support the use of TXA for bilateral TKA.

Second, our dosing of TXA was not weight based. Per our protocol, for ease of administration and because each vial is a 1-g dose, we used a dose of 1 g of TXA at the start of the case and 1 g when the tourniquet was deflated. Other studies have evaluated the dose of TXA and found that 10 mg/kg[8] or 20 mg/kg[9] TXA are effective doses. Although our dose resulted in a decrease in drain output and transfusion rate, our study may not be comparable with other studies that base TXA dosing on patient weight.

Third, we did not routinely perform venous ultrasonography, venogram, or lung perfusion scan to rule out DVT or pulmonary embolism. Therefore, it is possible that we missed a subclinical DVT or pulmonary embolism in these patients. We recognize that a much larger sample size would be required to determine any increased risk of DVT or pulmonary embolism with this protocol. We also do not have documentation of patient compliance with DVT prophylaxis (325 mg of aspirin twice a day). Nevertheless, symptomatic DVTs were not increased in our study group, which is consistent with findings in earlier studies.4,10-12 There was no adverse reaction to the TXA that we could identify. Whether TXA would increase thromboembolic events in patients with preexisting conditions has not been established. Our study excluded patients with existing conditions such as hypercoagulable states or a history of DVT.

Fourth, we did not attempt to calculate total blood loss by incorporating intraoperative blood loss estimates. We compared only postoperative blood loss through the hemovac drain output. Also, we did not standardize the exact timing of drain removal. All drains were routinely pulled on the morning of Postoperative Day 1, when there had been less than 100 mL of output per 8-hour shift, but we did not standardize the exact number of hours. However, all drains remained for at least 20 hours, with no drain remaining in place for more than 28 hours. Although the exact number of hours was not standardized, the protocol was the same for both groups, and we still found a significant decrease in drain output for patients who received TXA. The decreases in blood loss and transfusion rate also correlate with findings in previous studies.1-4

A relative strength of our study is that we evaluated the use of TXA in patients having bilateral staged TKAs. Previous studies evaluating the effectiveness of TXA have focused on single TKAs[13] or bilateral concurrent TKAs.[5, 8, 14] Dhillon and colleagues[5] found that TXA administered to patients undergoing single-stage bilateral TKAs reduced blood loss and decreased allogenic blood transfusion requirements, findings similar to ours. MacGillivray and coworkers[8] evaluated different TXA dosing regimens for patients undergoing concurrent bilateral TKAs and found that a lower dose of TXA (10 mg/kg) was sufficient to provide a lower allogenic blood transfusion requirement when used in combination with an autologous blood transfusion strategy. Our study did not use an autologous reinfusion strategy, our dosing of TXA was not weight based, and we staged our TKAs apart by 3 days; however, similar to MacGillivray and colleagues,[8] we also showed a decrease in allogenic blood transfusion requirement for patients undergoing bilateral TKAs. In a double-blind study, Kakar and colleagues[14] found decreased drain output and transfusion rates when patients were given TXA for unilateral or bilateral TKAs.

In conclusion, we have shown that TXA reduces postoperative drain output, reduces postoperative transfusion requirements, and increases postoperative Hb for patients undergoing bilateral TKAs staged 3 days apart.

Conflict of Interest

  1. Top of page
  2. Abstract
  3. Materials and Methods
  4. Results
  5. Discussion
  6. Conflict of Interest
  7. References

The authors did not receive any funding or grants in support of their research for or preparation of this work. The authors declare no conflict of interest.

References

  1. Top of page
  2. Abstract
  3. Materials and Methods
  4. Results
  5. Discussion
  6. Conflict of Interest
  7. References
  • 1
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    Ralley FE, Berta D, Binns V, Howard J, Naudie DD. One intraoperative dose of tranexamic acid for patients having primary hip or knee arthroplasty. Clin Orthop Relat Res 2010;468:1905-1911.
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    Kakar PN, Gupta N, Govil P, Shah V. Efficacy and safety of tranexamic acid in control of bleeding following TKR: a randomized clinical trial. Indian J Anaesth 2009;53:667-671.