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Breast: Original Articles

Intravenous Tranexamic Acid in Implant-Based Breast Reconstruction Safely Reduces Hematoma without Thromboembolic Events

Weissler, Jason M. M.D.; Banuelos, Joseph M.D.; Jacobson, Steven R. M.D.; Manrique, Oscar J. M.D.; Nguyen, Minh-Doan T. M.D., Ph.D.; Harless, Christin A. M.D.; Tran, Nho V. M.D.; Martinez-Jorge, Jorys M.D.

Author Information
Plastic and Reconstructive Surgery: August 2020 - Volume 146 - Issue 2 - p 238-245
doi: 10.1097/PRS.0000000000006967
  • Free
  • Discussion
  • Patient Safety CME

Abstract

Over the past several decades, the number of breast reconstructions performed has continued to experience steady growth.1 In parallel, reconstructive techniques have greatly evolved, affording patients and surgeons improved oncologic outcomes, reduced adverse events, and increased patient satisfaction.2 Nonetheless, despite the advances in alloplastic breast reconstruction techniques, the tenets of reconstructing a natural appearing breast remain unchanged, and minimization of complications remains paramount.

As the most predominant form of breast reconstruction in the United States, implant-based breast reconstruction offers predictable and reliable surgical outcomes.3 However, complications such as postoperative hematoma following immediate breast reconstruction occur at a consistently reported rate between 1 and 7 percent, despite efforts to achieve meticulous hemostasis.4–6 Although the risk of postoperative bleeding is inherent in all surgical subspecialties, development of a hematoma following mastectomy and implant reconstruction has both acute and potentially long-term consequences on the outcome of the overall reconstruction, such as unplanned surgery and capsular contracture.7,8 As such, minimization of operative blood loss remains a principal consideration in breast reconstruction, and vigilance when obtaining hemostasis is imperative to minimize patient morbidity.4,7,8

The well-recognized sequelae of both intraoperative blood loss and need for blood transfusions have contributed to the introduction of various pharmacologic agents that have been demonstrated to further mitigate surgical bleeding risk. Among the available agents, antifibrinolytic medications have increasingly gained recognition in plastic surgery as dependable adjuncts capable of minimizing blood loss and transfusion requirements in procedures such as cranial vault reconstruction, facial aesthetics, and body contouring procedures.9–11

Tranexamic acid has emerged as a valuable pharmacologic adjunct capable of minimizing intraoperative blood loss.8–18 It functions by competitively inhibiting the conversion of plasminogen to plasmin, thus, preventing the degradation of fibrin clots by plasmin. Furthermore, tranexamic acid blocks plasmin-induced platelet activation, thereby preserving platelets for clot formation.9–11 Despite its beneficial antifibrinolytic properties, cost-effectiveness, and proven efficacy and safety across many surgical specialties, tranexamic acid has not yet been widely integrated into plastic surgery practice. As such, its role remains ill-defined despite the growing body of literature supporting its use.9–13,19

With an evolving and more comprehensive understanding of the role of antifibrinolytic agents in plastic surgery, further contribution to the expanding body of literature is imperative. To date, the use of tranexamic acid in alloplastic breast reconstruction has not yet been investigated. In this study, the authors aim to investigate the efficacy and safety profile of intravenous tranexamic acid in the setting of immediate implant-based breast reconstruction.

PATIENTS AND METHODS

After approval by our institutional review board, a retrospective electronic chart review was performed for consecutive patients who underwent immediate two-stage implant-based breast reconstruction at a single institution from January of 2015 to December of 2016. In an effort to decrease the risk of confounding bias, only adult women (older than 18 years) who underwent either skin-sparing or nipple-sparing mastectomy and immediate two-stage implant-based breast reconstruction with at least 1 month of follow-up were included. Patients were excluded if there was a documented history of coagulopathy or bleeding disorder, were chronically anticoagulated, or were taking antiplatelet drugs. Demographics and surgical characteristics of the patients were extracted, and included age, body mass index, comorbidities (diabetes and hypertension), history of neoadjuvant chemotherapy, history of breast radiation therapy, type of mastectomy (skin-sparing or nipple-sparing), indication for mastectomy (prophylactic or therapeutic), location of tissue expander (prepectoral or subpectoral), and use of acellular dermal matrix (AlloDerm; LifeCell Corp., Branchburg, N.J.).

All patients undergoing the first stage of implant-based breast reconstruction with tissue expander placement were reviewed. At the time of the first stage of reconstruction, intraoperative assessment of mastectomy flap perfusion was performed in all cases, and if there were concerns with mastectomy flap viability, the reconstruction was delayed. In cases in which reconstruction was delayed secondary to mastectomy flap viability concerns, the patients were excluded from review. All first-stage reconstructions involved placement of textured tissue expanders that were either partially wrapped with fenestrated acellular dermal matrix along the inferior portion of the device or completely wrapped. Placement of the expander in either the prepectoral or subpectoral plane was based on surgeon preference.

With regard to patient selection and indications for treatment with tranexamic acid, all consecutive patients of one author (S.R.J.) were treated between January of 2015 and December of 2016. As part of a practice change, all consecutive patients undergoing first-stage implant-based reconstruction received 1000 mg of intravenous tranexamic acid before mastectomy incision and 1000 mg at the conclusion of the reconstruction. Patients with a history of coagulopathy, thromboembolic events, or adverse reactions to tranexamic acid were not treated. As such, within the treatment group, patients were not selectively treated with tranexamic acid, and all consecutive patients in the treatment group were treated with the medication. The remaining patients who did not receive tranexamic acid underwent reconstruction by all plastic surgery faculty surgeons who specialize in breast reconstruction.

At least one surgical drain was routinely placed in the mastectomy pocket, and all drains were maintained on bulb suction until the daily output was less than 30 ml over 2 consecutive days, at which time they were removed. All patients were admitted for overnight observation and were kept on deep vein thrombosis prophylaxis medications postoperatively with either 5000 mg of heparin three times daily or low-molecular-weight heparin (40 mg Lovenox; Sanofi-Aventis, Paris, France) injections. According to protocol, sequential compression devices were maintained both intraoperatively and postoperatively until discharge.

Our primary outcome measure was hematoma occurrence mandating intervention, defined as operative evacuation, ultrasound-guided percutaneous aspiration, or noninvasive management with external compression garments. Secondary outcomes included seroma and adverse events of tranexamic acid, such as thromboembolic events, including deep vein thrombosis, pulmonary embolism, or cerebrovascular events. The incidence of the primary and secondary outcomes among all patients who either did or did not receive intravenous tranexamic acid at the time of surgery was analyzed. Notably, given the potential for confounding variables, the authors controlled for surgical variables, including type of mastectomy (skin-sparing or nipple-sparing) and location of tissue expander placement (prepectoral or subpectoral), in addition to variables including age and hypertension.

Comparison of categorical data was reported with the Fisher’s exact test; for continuous data, the Mann-Whitney-Wilcoxon test was used, providing median and interquartile ranges. Multivariate logistic regression models were performed to study the impact of intravenously delivered tranexamic acid after adjusting for possible confounders. The area under the receiving operating characteristic curve was calculated for this model. Results with a value of p < 0.05 were considered significant. Statistical analysis was performed using JMP Pro 14 software (SAS Institute, Inc., Cary, N.C.).

RESULTS

A total of 868 consecutive first-stage breast reconstructions among 499 women were included in this study. A total of 116 patients received intravenous tranexamic acid, accounting for 217 reconstructions, whereas 383 patients (651 reconstructions) did not receive tranexamic acid. Characteristics of the patients and comorbidities were similar between the two groups. In addition, mastectomy indication, use of acellular dermal matrix, and history of neoadjuvant radiation therapy and chemotherapy were also similar among the groups. However, patients in the tranexamic acid group underwent more skin-sparing mastectomies (93.1 percent) than patients in the group who did not receive tranexamic acid (82.1 percent; p < 0.001), and more prepectoral reconstructions (98.2 percent) than the patients who did not receive tranexamic acid (71.3 percent; p < 0.001). The type of mastectomy performed (skin-sparing or nipple-sparing) and the location of tissue expander placement (prepectoral or subpectoral) segregated by surgeon are illustrated in Figures 1 and 2, respectively. None of the preoperatively planned nipple-sparing mastectomies were converted to skin-sparing based on concerns for mastectomy flap viability in any cases. General characteristics of both groups are summarized in Table 1.

Table 1. - Characteristics of the Groups
Characteristic TXA Group (%) Control Group (%) p
No. of reconstructions 217 651
Age, yr 0.543
 Median 51 50
 IQR 43–57 42–58
BMI, kg/m2
 Median 26.1 25.6
 IQR 22.7–29.3 22.5–29.8 0.959
Comorbidities
 HTN 55 (25.4) 155 (23.8) 0.647
 DM 15 (6.9) 46 (7.1) 0.938
Neoadjuvant radiation therapy 7 (3.2) 24 (3.7) 0.751
Neoadjuvant chemotherapy 66 (30.4) 177 (27.2) 0.359
Mastectomy
 Nipple-sparing 15 (6.9) 117 (17.9)
 Skin-sparing 202 (93.1) 534 (82.1) <0.001
Indication
 Prophylactic 26 (11.9) 91 (13.9)
 Curative 191 (88.1) 560 (86.1) 0.455
TE location
 Prepectoral 213 (98.2) 464 (71.3)
 Subpectoral 4 (1.8) 187 (28.7) <0.001
ADM use 212 (97.7) 620 (95.2) 0.116
TXA, tranexamic acid; IQR, interquartile range; BMI, body mass index; HTN, hypertension; DM, diabetes mellitus; TE, tissue expander; ADM, acellular dermal matrix.

Fig. 1.
Fig. 1.:
Type of mastectomy performed, segregated by surgeon. SSM, skin-sparing mastectomy; NSM, nipple-sparing mastectomy.
Fig. 2.
Fig. 2.:
Location of tissue expander placement, segregated by surgeon.

Collectively, postoperative hematoma was identified in 20 individual patients within the first week following their reconstruction and before drain removal (Table 2). The mean time to hematoma diagnosis was 3 days (1 to 7 days). Given the discrepancy between the incision patterns and surgical exposure for both skin- and nipple-sparing mastectomies, the risk of hematoma may differ between mastectomy types. Because the impact of mastectomy type on hematoma risk remains understudied between skin-sparing and nipple-sparing mastectomies, this was addressed by controlling for type of mastectomy pattern (nipple-sparing or skin-sparing). Likewise, placement of the tissue expander in a subpectoral plane could increase the hematoma risk, although there are mixed data supporting this. As such, the location of tissue expander placement (prepectoral or subpectoral) was also controlled for in our analysis to account for potential discrepancies.

Table 2. - Primary and Secondary Outcomes of the Groups
Outcomes TXA Group (%) Control Group (%) p
Hematoma 1 (0.46) 19 (2.92) 0.018
Seroma 5 (2.3) 28 (4.3) 0.093
Adverse events 0 (0) 0 (0) N/A
TXA, tranexamic acid; N/A, not applicable.

After controlling for these variables, and for age and history of hypertension, in the reconstructions where tranexamic acid was used, there were significantly fewer hematomas [n = 1 (0.46 percent)] when compared to reconstructions where tranexamic acid was not used [n = 19 (2.9 percent); p = 0.018]. The area under the receiving operating characteristic curve for this model was 0.782. In addition, the rate of seroma in the tranexamic acid group was lower [n = 5 (2.3 percent)] than in the group that did not receive tranexamic acid [n = 28 (4.3 percent)], although this was not statistically significant (p = 0.093). During the study period, none of the patients experienced adverse effects of intravenous tranexamic acid, including thromboembolic phenomena (Table 2). Patients were followed for a median of 18.4 months (range, 11.1 to 24.2 months) postoperatively.

Among the 20 patients who developed a hematoma, 16 required operative intervention for hematoma evacuation, whereas the four patients who did not have surgical intervention all underwent ultrasound evaluation of the breast, and in one case an ultrasound-guided aspiration was performed by our interventional radiology colleagues. The decision to proceed with the aforementioned interventions was left to the clinical discretion of the primary plastic surgeon. Patients who developed a hematoma were admitted to the hospital for observation, and in all cases, the tissue expander reconstruction was salvaged.

Furthermore, simple regression analysis of factors associated with postoperative hematoma demonstrated that demographics, comorbidities, mastectomy indication, type of mastectomy, location of tissue expander placement, and acellular dermal matrix use were similar between the patients who developed hematomas and those who did not (Table 3). However, certain differences were identified. Patients who developed a hematoma were older (median, 59 years; interquartile range, 50 to 67 years), compared to patients who did not develop a hematoma (median, 50 years; interquartile range, 43 to 58 years; p = 0.002). Multivariate analysis further demonstrated that for every 1-year increase in age, the odds of developing a hematoma increased by 4.9 percent (OR, 1.049; 95 percent CI, 1.00 to 1.09; p = 0.040). In addition, patients who presented with a hematoma were more likely to have hypertension than patients who did not develop a hematoma (60 percent versus 23.4 percent; p < 0.001). Hypertension conferred a 3.17 higher risk of developing a hematoma, compared to patients without hypertension (95 percent CI, 1.16 to 8.68; p = 0.023) (Table 4).

Table 3. - Simple Regression Analysis for Hematoma
Hematoma (%) No Hematoma (%) p
No. of reconstructions 20 848
Age, yr 0.002
 Median 59 50
 IQR 50–67 43–58
BMI, kg/m2 0.504
 Median 25.5 25.8
 IQR 23.4–31.5 22.5–29.6
Comorbidities
 HTN 12 (60) 198 (23.4) <0.001
 DM 3 (15) 58 (6.8) 0.158
History of radiation therapy 1 (5) 30 (3.5) 0.727
Neoadjuvant chemotherapy 2 (10) 241 (28.4) 0.069
Mastectomy
 Nipple-sparing 4 (20) 128 (15.1)
 Skin-sparing 16 (80) 720 (84.9) 0.545
Indication
 Prophylactic 2 (10) 115 (13.6)
 Curative 18 (90) 733 (86.4) 0.644
TE location
 Prepectoral 13 (65) 664 (78.3)
 Subpectoral 7 (35) 184 (21.7) 0.156
ADM use 20 (100) 812 (95.8) 0.346
BMI, body mass index; HTN, hypertension; DM, diabetes mellitus; TE, tissue expander; ADM, acellular dermal matrix.

Table 4. - Multivariate Regression Analysis of Risk Factors for Hematoma
Variable OR 95% CI p
Age, per 1 yr* 1.049 1.000–1.099 0.040
HTN 3.167 1.158–8.679 0.023
HTN, hypertension.
*Represents per 1-year increase in age.

DISCUSSION

This study evaluated the effect of intravenous tranexamic acid in reducing the risk of hematoma among patients undergoing immediate implant-based breast reconstruction. Our study demonstrated a significant decrease in the rate of postoperative hematoma in patients who received intravenous tranexamic acid when compared with similar patients who did not receive this medication. No adverse events secondary to the administration of tranexamic acid were observed, corroborating the well-studied safety profile of this medication.

The clinical application of tranexamic acid has been thoroughly investigated in the fields of cardiac, orthopedic, gynecologic, oncologic breast, and trauma surgery.13–15 Recently, the unique pharmacologic properties of antifibrinolytic medications have fostered a paradigm change in the clinical practice of plastic surgeons who perform craniomaxillofacial procedures and aesthetic surgery, as demonstrated by the recent surge in publications on its use.9–13,19 The compelling conclusions drawn from the existing body of literature demonstrate the extensive therapeutic index, acceptable safety profile, and underappreciated value offered to plastic surgeons.

As surgical outcomes are under closer scrutiny, surgeons have increasingly become more vigilant with regard to recognizing both the acute and long-term sequelae of perioperative bleeding.9,10 Beyond obtaining meticulous surgical hemostasis, pharmacologic adjuncts, such as tranexamic acid, have been used to preemptively address anticipated blood loss and possibly curtail the potentially harmful downstream effects of allogenic transfusions or hematoma-related complications.

Although first introduced in the 1960s as a treatment for gynecologic bleeding and hereditary bleeding disorders, the use of tranexamic acid has recently gained greater recognition in several surgical specialities.10,13–15 Within plastic surgery, tranexamic acid has been demonstrated to significantly decrease perioperative blood loss and blood transfusion requirements in the fields of craniofacial and orthognathic surgery.8,9,11,13 In addition, the use of tranexamic acid has also been demonstrated to reduce drain fluid production following procedures such as reduction mammaplasty, neck dissections, and oncologic breast tumor resection.13,14,16,17,19,20 Furthermore, intravenous, topical, and oral administrations of tranexamic acid have been shown to minimize bleeding-related complications, edema, and ecchymosis in facial aesthetic procedures, such as rhinoplasty and rhytidectomy.8,9,11 Rohrich and Cho have also reported observational data on the clinical value of tranexamic acid in blepharoplasty, abdominoplasty, breast augmentation, and noninvasive facial rejuvenation procedures, such as filler injections and neuromodulator injections, with dramatic improvement in surgical field dryness and decreased bruising and swelling.9

Multiple studies endorse the use of tranexamic acid within plastic surgery, underscoring a unique opportunity for plastic surgeons to intervene intraoperatively to mitigate the risks of perioperative bleeding. Despite the potential clinical impact in plastic surgery, universal acceptance and widespread use have yet to occur, especially in breast reconstruction, perhaps in part because of unfamiliarity and misconceptions regarding its efficacy or concern over perceived untoward side effects, such as thromboembolic events.9,10,13 Moreover, it is also likely that plastic surgeons are more familiar with the use of tranexamic acid in other surgical fields, such as cardiac, trauma, and orthopedic surgery, where blood loss or transfusion requirements are perceived to be greater than in certain plastic surgery procedures. The lack of published data from procedures with relatively minimal blood loss translates into surgeons using alternative topical hemostatic agents, such as fibrin glues and absorbable cellulose polymers, as a means of minimizing drain output, swelling, and bruising.9

Is it evident that tranexamic acid is an effective and safe adjunct for minimizing perioperative blood loss for various plastic surgery procedures, as validated by the supportive high-level evidence.9–11,13,16,19 In an effort to expand the scope of tranexamic acid’s pharmacologic value and to contribute to the growing body of evidence, the authors of this study investigated the use of tranexamic acid in implant-based breast reconstruction. In doing so, it was hypothesized that the intravenous use of tranexamic acid would improve clinical outcomes in the breast reconstruction patient population by reducing perioperative blood loss, especially postoperative hematoma.

Although the risk of postoperative bleeding is inherent in all surgical subspecialties, hematoma in the setting of implant-based breast reconstruction carries unique consequences that could negatively impact overall reconstructive success.6,7 Interestingly, the risk of postoperative hematoma after mastectomy with immediate reconstruction has previously not been demonstrated to be affected by any measurable factors, including antiplatelet and anticoagulation medication use.4 However, on multivariate analysis, our study demonstrated that increasing age and hypertension both independently increased the risk for developing hematoma following implant-based breast reconstruction.

Our study corroborates previously published findings in other plastic surgery procedures, and supports the notion that tranexamic acid significantly minimizes the risk of hematoma. However, this study is the first to evaluate the use of tranexamic acid in patients undergoing implant-based breast reconstruction. The authors demonstrate that intravenous tranexamic acid reduces the incidence of postoperative hematoma for patients undergoing immediate alloplastic implant-based breast reconstruction following mastectomy. Although the results of our study are promising, it is important to note that the authors recognize that the role of tranexamic acid is simply a valuable adjuvant modality to reduce perioperative bleeding, and that no pharmacologic agent supersedes meticulous surgical technique.

Although an in-depth discussion of pharmacologic and dosing considerations is beyond the scope of this article, it is important to recognize that tranexamic acid has safely been used across a wide range of dosages and delivery modalities.9,16,20,21 Although available and effective in oral and topical formulations, intravenous administration has been the most commonly studied. However, there has been increasing support for its use as a topical hemostatic agent with equivalent efficacy, acceptable safety profile, and minimized systemic exposure in procedures such as rhytidectomy, rhinoplasty, liposuction, and reduction mammaplasty.9–11 As such, the authors are also currently investigating the role of topical tranexamic acid in reducing hematoma risk in patients undergoing implant-based breast reconstruction.

With regard to the perceived barriers to widespread integration of tranexamic acid into plastic surgery practice, it is worth acknowledging the previously reported acceptable safety profile of tranexamic acid.8,9,19,22 Although antifibrinolytic therapy has yet to gain unanimous acceptance amid uncertainties regarding perceived thrombotic risks, the efficacy and safety of these drugs have repeatedly been demonstrated in several retrospective and prospective studies.10,18,22,23 Moreover, in the only study on the use of tranexamic acid in lower extremity free flap reconstruction, Valerio et al. verified that intravenous tranexamic acid does not increase the risk for thromboembolic events, and did not influence overall flap complications in lower extremity reconstruction patients.19 Similar findings were further substantiated in a recent publication by Lardi et al. analyzing 98 free tissue transfers for breast reconstruction, which demonstrated that administration of up to 3 g of intravenous tranexamic acid did not increase thrombosis rate, although the difference was not statistically significant.24

Although this is a large study comparing consecutive patients, there are certain recognizable limitations. Its retrospective single-institution design comes with an inherent potential for selection bias. However, despite the benefits of tranexamic acid in several plastic surgery procedures, this study is the first to report its use in patients undergoing implant-based breast reconstruction. Although no thromboembolic events secondary to the administration of tranexamic acid were observed, to more scientifically investigate thromboembolic risk, further larger-scale prospective randomized studies with standardized methods of drug administration and dosages are warranted. Furthermore, attributable in part to the limited body of Level I and II evidence within plastic surgery, the use of tranexamic acid has not been widely integrated into the management of patients undergoing implant-based breast reconstruction. To further elucidate our understanding of its clinical role in breast reconstruction, prospective, randomized, placebo-controlled trials of tranexamic acid are imperative.

CONCLUSIONS

As the role of tranexamic acid in plastic surgery increases, there remains a recognizable gap in the literature with regard to its impact on breast reconstruction. Whereas randomized prospective trials repeatedly support the use of tranexamic acid as an adjunct for reducing hematoma risk, this study represents the first portrayal of its clinical efficacy in implant-based breast reconstruction, demonstrating that its use safely reduces hematoma risk. Overall, this study reflects a potential paradigm shift and should encourage plastic surgeons to consider integration of tranexamic acid into clinical practice.

ACKNOWLEDGMENT

The authors thank Nathan R. Foster, M.S., for his help with the statistical analysis.

REFERENCES

1. American Society of Plastic Surgeons. 2018 national plastic surgery statistics. Available at: https://www.plasticsurgery.org/documents/News/Statistics/2018/plastic-surgery-statistics-report-2018.pdf. Accessed May 2, 2019.
2. Ter Louw RP, Nahabedian MY. Prepectoral breast reconstruction. Plast Reconstr Surg. 2017;140(Advances in Breast Reconstruction):51S–59S.
3. Frey JD, Salibian AA, Karp NS, Choi M. Implant-based breast reconstruction: Hot topics, controversies, and new directions. Plast Reconstr Surg. 2019;143:404e–416e.
4. Seth AK, Hirsch EM, Kim JY, et al. Hematoma after mastectomy with immediate reconstruction: An analysis of risk factors in 883 patients. Ann Plast Surg. 2013;71:20–23.
5. Collins JB, Verheyden CN. Incidence of breast hematoma after placement of breast prostheses. Plast Reconstr Surg. 2012;129:413e–420e.
6. Manrique OJ, Banuelos J, Abu-Ghname A, et al. Surgical outcomes of prepectoral versus subpectoral implant-based breast reconstruction in young women. Plast Reconstr Surg Glob Open 2019;7:e2119.
7. Calobrace MB, Stevens WG, Capizzi PJ, Cohen R, Godinez T, Beckstrand M. Risk factor analysis for capsular contracture: A 10-year Sientra study using round, smooth, and textured implants for breast augmentation. Plast Reconstr Surg. 2018;141(Sientra Shaped and Round Cohesive Gel Implants):20S–28S.
8. Bachour Y, Bargon CA, de Blok CJM, Ket JCF, Ritt MJPF, Niessen FB. Risk factors for developing capsular contracture in women after breast implant surgery: A systematic review of the literature. J Plast Reconstr Aesthet Surg. 2018;71:e29–e48.
9. Rohrich RJ, Cho MJ. The role of tranexamic acid in plastic surgery: Review and technical considerations. Plast Reconstr Surg. 2018;141:507–515.
10. Brown S, Yao A, Taub PJ. Antifibrinolytic agents in plastic surgery: Current practices and future directions. Plast Reconstr Surg. 2018;141:937e–949e.
11. Cansancao AL, Condé-Green A, David JA, Cansancao B, Vidigal RA. Use of tranexamic acid to reduce blood loss in liposuction. Plast Reconstr Surg. 2018;141:1132–1135.
12. Guerriero C, Cairns J, Perel P, Shakur H, Roberts I; CRASH 2 trial collaborators. Cost-effectiveness analysis of administering tranexamic acid to bleeding trauma patients using evidence from the CRASH-2 trial. PLoS One 2011;6:e18987.
13. Murphy GR, Glass GE, Jain A. The efficacy and safety of tranexamic acid in cranio-maxillofacial and plastic surgery. J Craniofac Surg. 2016;27:374–379.
14. Dai Z, Chu H, Wang S, Liang Y. The effect of tranexamic acid to reduce blood loss and transfusion on off-pump coronary artery bypass surgery: A systematic review and cumulative meta-analysis. J Clin Anesth. 2018;44:23–31.
15. El-Menyar A, Sathian B, Asim M, Latifi R, Al-Thani H. Efficacy of prehospital administration of tranexamic acid in trauma patients: A meta-analysis of the randomized controlled trials. Am J Emerg Med. 2018;36:1079–1087.
16. Ausen K, Fossmark R, Spigset O, Pleym H. Randomized clinical trial of topical tranexamic acid after reduction mammoplasty. Br J Surg. 2015;102:1348–1353.
17. Oertli D, Laffer U, Haberthuer F, Kreuter U, Harder F. Perioperative and postoperative tranexamic acid reduces the local wound complication rate after surgery for breast cancer. Br J Surg. 1994;81:856–859.
18. Coffey A, Pittmam J, Halbrook H, Fehrenbacher J, Beckman D, Hormuth D. The use of tranexamic acid to reduce postoperative bleeding following cardiac surgery: A double-blind randomized trial. Am Surg. 1995;61:566–568.
19. Valerio IL, Campbell P, Sabino J, et al. TXA in combat casualty care: Does it adversely affect extremity reconstruction and flap thrombosis rates? Mil Med. 2015;180(Suppl):24–28.
20. Ker K, Edwards P, Perel P, Shakur H, Roberts I. Effect of tranexamic acid on surgical bleeding: Systematic review and cumulative meta-analysis. BMJ 2012;344:e3054.
21. Sakallioğlu Ö, Polat C, Soylu E, Düzer S, Orhan İ, Akyiğit A. The efficacy of tranexamic acid and corticosteroid on edema and ecchymosis in septorhinoplasty. Ann Plast Surg. 2015;74:392–396.
22. Benoni G, Fredin H. Fibrinolytic inhibition with tranexamic acid reduces blood loss and blood transfusion after knee arthroplasty: A prospective, randomised, double-blind study of 86 patients. J Bone Joint Surg Br. 1996;78:434–440.
23. Lindoff C, Rybo G, Astedt B. Treatment with tranexamic acid during pregnancy, and the risk of thrombo-embolic complications. Thromb Haemost. 1993;70:238–240.
24. Lardi AM, Dreier K, Junge K, Farhadi J. The use of tranexamic acid in microsurgery: Is it safe? Gland Surg. 2018;7(Suppl 1):S59–S63.
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