SPECIAL TOPIC

Antifibrinolytic Agents in Plastic Surgery:

Current Practices and Future Directions
Stav Brown, B.S.
Amy Yao, B.S.
Peter J. Taub, M.D.
Tel Aviv, Israel; and New York, N.Y.
Background: Prevention of blood loss is a chief consideration in plastic and
reconstructive surgery. The antifibrinolytic drugs tranexamic acid and ε-
aminocaproic acid have emerged as promising agents to reduce both periop-
erative blood loss and transfusion requirements. However, published reports in
the plastic surgery literature are lacking. The authors sought to summarize the
current knowledge of the use of antifibrinolytics in plastic surgery by reviewing
the existing literature for clinical outcomes and recommendations.
Methods: A systematic review of the PubMed, Cochrane, and Google Scholar
databases was conducted for publications examining the use of antifibrinolytics
in plastic surgery. Studies were abstracted for procedure type, antifibrinolytic
dose, time and mode of administration, blood loss, transfusion requirements,
and complications.
Results: Thirty-three studies were deemed eligible for inclusion, comprising a
total of 1823 patients undergoing plastic surgical procedures with tranexamic
acid (n = 1328) and/or ε-aminocaproic acid (n = 495).
Conclusions: Tranexamic acid and ε-aminocaproic acid are widely used to
reduce blood loss and transfusion requirements in craniofacial and orthog-
nathic surgery, without an increased risk of adverse events. Intravenous ad-
ministration is most commonly used, although topical formulations show
similar efficacy with a reduced systemic distribution. Tranexamic acid has also
emerged as a promising agent in aesthetic surgery and burn care, due to its fa-
vorable safety profile and role in reducing blood loss, achieving an improved
surgical field, and reducing edema and ecchymosis. Further investigation of
these agents in the fields of burn care, aesthetic surgery, and microsurgery
is warranted to standardize protocols for clinical use.  (Plast. Reconstr. Surg.
141: 937e, 2018.)

A
chieving hemostasis is essential to sur-
gery. Patients undergoing major surgery
are often at risk for significant blood loss,
which may necessitate transfusion of blood prod-
ucts. Although blood products are largely safe
when used judiciously, transfusions are not with-
out risks, including infection, hemolytic reactions,
and immunologic complications.1 The primary
prevention of significant intraoperative blood loss
is therefore of critical interest to plastic surgeons.
In light of the well-known risks associated
with the use of blood products, antifibrinolytics
have emerged as increasingly popular agents to
reduce perioperative blood loss and the need for
From the Sackler School of Medicine at Tel Aviv University;
and the Division of Plastic and Reconstructive Surgery,
Icahn School of Medicine at Mount Sinai.
Received for publication October 2, 2017; accepted December
6, 2017.
Copyright © 2018 by the American Society of Plastic Surgeons
DOI: 10.1097/PRS.0000000000004421
transfusion. The antifibrinolytic agents tranexamic
acid, ε-aminocaproic acid, and aprotinin are drugs
that prevent hyperfibrinolysis and improve clot sta-
bility. Tranexamic acid and ε-aminocaproic acid
act on the lysine-binding sites of plasminogen by
reversibly inhibiting tissue plasminogen activa-
tors, thus blocking the formation of plasmin and
preventing lysis of fibrin polymers.2–4 Aprotinin
acts by means of inhibition of trypsin and related
proteolytic enzymes, thereby slowing the rate of
Disclosure: None of the authors has a financial in-
terest in any of the products, devices, or drugs men-
tioned in this article.
By reading this article, you are entitled to claim
one (1) hour of Category 2 Patient Safety Credit.
ASPS members can claim this credit by logging
in to PlasticSurgery.org Dashboard, clicking
“Submit CME,” and completing the form.

www.PRSJournal.com 937e
Copyright © 2018 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
 Plastic and Reconstructive Surgery • June 2018

fibrinolysis. However, aprotinin was removed from
the American market in 2008 because of the docu-
mented increased risk of major complications.5
Multiple systematic reviews and meta-analyses
have demonstrated the efficacy of tranexamic acid
and ε-aminocaproic acid in cardiac surgery,6,7 total
joint arthroplasty,8–10 and major spine surgery.11 Pro-
phylactic use of tranexamic acid or ε-aminocaproic
acid in these settings has been shown to signifi-
cantly reduce intraoperative bleeding and the need
for subsequent transfusion, without an increased
risk of renal failure or thromboembolic events,
including myocardial infarction, stroke, deep vein
thrombosis, or pulmonary embolism.3,8 Early use of
tranexamic acid significantly reduced all-cause mor-
tality in bleeding trauma patients.12 Moreover, both
tranexamic acid and ε-aminocaproic acid have been
shown to be cost-effective in both trauma and surgi-
cal settings, not only reducing direct hospital costs
(drug and blood products) but also decreasing many
subsequent costs by decreasing length of stay and the
incidence of complications.13 However, the use of
tranexamic acid and ε-aminocaproic acid in plastic
surgical procedures has not been as well described.14
Current reports of tranexamic acid and
ε-aminocaproic acid in plastic surgery are so
far limited to pediatric craniofacial cases. Stud-
ies of antifibrinolytics in aesthetic surgery, burn
care, and reconstructive procedures are lacking,
despite the high incidence of transfusions in
these procedures. Moreover, there are compara-
tively few studies of the use of ε-aminocaproic acid
in plastic surgery. The present systematic review
aims to summarize current knowledge and pro-
vide clinical recommendations regarding the effi-
cacy and safety of antifibrinolytic agents in plastic
surgical procedures. The indications, mecha-
nism of action, pharmacodynamics and kinetics,
and point of action of the antifibrinolytic agents
reviewed are summarized in Table 1 and Figure 1.
PATIENTS AND METHODS
Literature Search Strategy
Two independent investigators conducted a
literature search of the PubMed, Cochrane, and
Google Scholar databases since their inception
for relevant clinical studies. All databases were
queried using the following headings and key-
word terms: “TXA,” “tranexamic acid,” “EACA,”
“6-aminocaproic acid,” “aminocaproic acid,”
“antifibrinolytics,” “antifibrinolytic agents,” “plas-
tic surgery,” “craniofacial surgery,” “orthognathic
surgery,” “aesthetic surgery,” “burns,” “microsur-
gery,” and “reconstructive surgery.”

Table 1.  Mechanism of Action and Pharmacodynamics of the Antifibrinolytic Agents Tranexamic Acid and
ε-Aminocaproic Acid
TXA EACA
Mechanism of action Competitive inhibition of plasminogen activa- Competitive inhibition of plasminogen activa-
tion; antiplasmin activity* tion; antiplasmin activity
Bioavailability, % 34
Terminal half-life, hr 3.1 2
Elimination 95% renal excretion as unchanged drug 65% renal excretion as unchanged drug
Administration By mouth or injection By mouth or injection
Clinical indications Treat or prevent excessive blood loss from Treatment of acute bleeding caused by
major trauma, postpartum bleeding, surgery, elevated fibrinolytic activity
tooth removal, nosebleeds, and heavy menses
Drug interactions No studies of interactions between TXA and No studies of interactions between EACA and
other drugs have been conducted other drugs have been conducted
Contraindications Acquired defective color vision†, subarachnoid Active intravascular clotting
hemorrhage, active intravascular clotting,
hypersensitivity to tranexamic acid
Main adverse effects Headaches, back pain, nasal sinus problem, Edema, headache, malaise
abdominal pain, diarrhea, fatigue, anemia
Recommended dosages Intravenous: 16 to 20 ml injection in 250 ml
of diluent during the first hour;
then 4 ml/hr in 50 ml of diluent
Oral: 5000 mg during first hour, then
1000 mg/hr
 Normal renal function 10 mg/kg 3–4 times daily
 Cr 1.36 to 2.83  mg/dl 10 mg/kg twice daily
 Cr 2.83 to 5.66  mg/dl 10 mg/kg once daily, or 10 mg/kg every 48 hr
 Cr >5.66  mg/dl 5 mg/kg every 24 hr
TXA, tranexamic acid; EACA, ε-aminocaproic acid; Cr, creatinine.
*At high concentrations.
†This prohibits the measurement of visual abnormalities, a known sign of toxicity.

938e
Copyright © 2018 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
 Volume 141, Number 6 • Antifibrinolytic Agents
Fig. 1. Tranexamic acid and ε-aminocaproic acid points of action. HMWK, high-molecular-weight kininogen.
Study Selection
Inclusion criteria included the following: ran-
domized and nonrandomized controlled trials, ret-
rospective cohort studies, and case reports and series
of the use of the antifibrinolytic agents in plastic sur-
gery in the fields of craniofacial surgery, orthognathic
surgery, aesthetic surgery, burn care, and reconstruc-
tive microsurgery. Titles and abstracts were reviewed
for the following exclusion criteria: (1) absence
of discussion of one or more of the antifibrinolytic
agents (tranexamic acid and ε-aminocaproic acid);
(2) absence of index plastic surgery procedures;
(3) nonhuman studies; and (4) studies not written
in English. After redundant titles were removed, full-
text review was performed for publications that met
these criteria. Reference lists of relevant criteria were
searched to identify additional studies. The date of
the last search was September 1, 2017.
Data Collection
Procedure types, dose regimen, and time
and mode of administration for each study were
recorded. Outcome data collected included blood
Copyright © 2018 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
loss, transfusion requirements, adverse events,
complications, and clinical recommendations.
Additional factors such as duration of surgery,
hospital length of stay, drain output, surgeon sat-
isfaction of the surgical field, and drop in hemo-
globin were recorded when available.
RESULTS
Fifteen randomized controlled trials, one
nonrandomized controlled trial, 14 retrospec-
tive cohort studies, one case series, and two case
reports describing the use of antifibrinolytic agents
in plastic surgery from 2003 to 2017 were fully
reviewed. A total of 1823 patients undergoing sur-
gical procedures with tranexamic acid (n = 1328)
and ε-aminocaproic acid (n = 495) were identified.
Tranexamic Acid
Twenty-eight articles on the use of tranexamic
acid in plastic surgery were identified (Tables 2
and 3); 21 articles discussed the use of intrave-
nously administered tranexamic acid, two articles
939e
 Table 2.  Tranexamic Acid in Plastic Surgery

940e
Study Group
(Total AF-Associ-
Subspecialty and Study Sample Surgery Administration Mode, Main Outcomes Significant ated Com-
Reference Design Size) Type Time, and Dosage Measured Outcomes* p plications
Craniofacial
surgery
 Kurnik et  al., RCS 35 (114) CVR IV, intraoperative and TTR pRBCs: 428 ± 213 ml (44.3 ± 22 ml/kg) <0.0001 None
2017 postoperative vs. 264 ± 110 ml (28.0 ± 11 ml/kg) (38%)
LD: 10 mg/kg ITR 366 ± 208 ml (39.1 ± 22 ml/kg) vs. 264 ± 0.0013
IR: 5 mg/kg/hr for 110 ml (28.0 ± 11 ml/kg) (27.8%)
24 hr PTR 0, IQR 0–151 ml (0, IQR 0–0 ml/kg) <0.0001
vs. 0, IQR 0–14.9 ml (0, IQR 0–0 ml/kg)
IOB 34.8 ± 26 ml/kg vs. 25.9 ± 11 ml/kg 0.0143
Postoperative Hb NS
Postoperative Hct NS
LOS NS
SD NS
 Hansen et  al., RCS 16 (25) CVR IV, intraoperative TR NS None
2017 LD: 10 mg/kg Postoperative ERCV 223.4 ml vs. 332.7 ml 0.017
IR: 5 mg/kg/hr Hb 8.8 vs. 10.6 g/dl 0.009
Hb drop 2.5 ml/kg vs. 1.1 ml/kg 0.035
DO (24 hr) 17.2 ml/kg vs. 11.0 ml/kg
 Goobie et  al., RCS 591 (1638) CVR IV, intraoperative Seizures 1 DVT
2017 LD: 50 mg/kg (IQR, 2 seizures
10–50 mg/kg)
IR: 5 mg/kg/hr (IQR,
5–5 mg/kg/hr)
 Arantes et  al., RCT 66 (136) CP IV, intraoperative IOB NS None
2017 LD: 10 mg/kg
IR: 1 mg/kg/hr
 Crantford RCS 17 (37) CVR IV, intraoperative IOB 9.4 ml/kg vs. 21.1 ml/kg (55%) 0.0001 None
et al., 2015 LD: 20 mg/kg TR 12.8 ml/kg vs. 31.3 ml/kg (59%) <0.0001
IR: 10 mg/kg/hr Hct drop NS
SD NS
 Durga et  al., RCT 33 (65) CP IV, preoperative SF 0.003 None
2015 10 mg/kg Surgeon satisfaction 0.008
 Engel et  al., RCS 17 (33) CVR IV, intraoperative IOB 158.8 ml vs. 198.5 ml (20%) 0.0001 None
2015 LD: 10 mg/kg TR pRBCs: 252.2 ml vs. 280.0 ml (9.8%) 0.0001
IR: 5 mg/kg/hr SD NS
 Martin et  al., RCS 69 (187) CVR IV, intraoperative IOB 26  ml/kg vs. 36  ml/kg (27.8%)  <0.001 None
2016 LD: 50 mg/kg TR Cell saver: 6 ml/kg vs. 10  ml/kg (40%) 0.001
IR: 5 mg/kg/hr pRBCs: 32  ml/kg vs. 42  ml/kg (23.8%) 0.001
Plasma: 0% vs. 24% (100%)  <0.001
Cryo: 0% vs. 16% (100%)  <0.001
Platelets: 0% vs. 7.6% (100%) 0.03
LOS 4 days (IQR, 3–4 days) vs. 4 days 0.001
(IQR, 4–5 days)
DO 181 ml vs. 311 ml (41.8%)  <0.001
Postoperative Hct NS

(Continued )
Plastic and Reconstructive Surgery • June 2018

Copyright © 2018 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
 Table 2.  (Continued)
Study Group
(Total AF-Associ-
Subspecialty and Study Sample Surgery Administration Mode, Main Outcomes Significant ated Com-
Reference Design Size) Type Time, and Dosage Measured Outcomes* p plications
 Dadure et  al., RCT 19 (39) CVR IV, intraoperative TR pRBCs intraoperatively: 11 ml/kg vs. <0.05 None
2011 LD: 15 mg/kg 1.6 ml/kg (85.5%) (1 hema-
IR: 10 mg/kg/hr toma)
pRBCs total: 16.6–7.2 ml/kg (56.6%) <0.05
% Children requiring blood transfusion <0.05
(intraoperatively): 2 (10.5%) vs. 9 (45%)
Total: 7 (37%) vs. 14 (70%) <0.05
IOB NS
Surgeon satisfaction NS
 Goobie et  al., RCT 23 (43) CVR IV, intraoperative TBL 65 ml/kg vs. 119 ml/kg (45%) <0.001 None
2011 LD: 50 mg/kg IOB 62 ml/kg vs. 101 ml/kg (38%) 0.008
IR: 5 mg/kg/hr POB 3 ml/kg vs. 12 (72%) ml/kg < 0.001
TR 33 ml/ kg vs. 56 ml/ kg (32%) 0.006
Exposure of patients to transfused blood: 1 <0.001
unit vs. 3 units (67%)
 Maugans RCS 26 (56) CVR IV, intraoperative IOB 9.62 ml/ kg vs. 15.94 ml/kg (39.6%) 0.0231 None
et al., 2011 LD: 50 mg/kg TR 10.76 ml/ kg vs. 19.43 ml/kg (44.6%) 0.0723
IR: 5 mg/kg/hr
Orthognathic
surgery
 Eftekharian RCT 28 (56) Bimaxillary Topical irrigations, IOB 575.00 ± 286.0 ml vs. 817.85 ± 261.3 ml <0.05 None
Volume 141, Number 6 • Antifibrinolytic Agents

et al., 2015 osteotomy intraoperative (29.7%)

1 mg/ml solution SD 3.94 ± 0.61 hr vs. 4.17 ± 0.98 hr (5.5%) <0.05
 Christabel RCT 25 (49) Le Fort I IV, preoperative TBL 405.83 ± 72.27 ml vs. 220.96 ± 78.196 ml 0.0001 None
et al., 2014 osteotomy (45.6%)
10 mg/kg Postoperative Hb% 9.86 ± 1.445 mg/dl vs. 10.72 ± 0.005
1.381 mg/dl (8%)
Hb% drop 2.50 ± 0.894 mg/dl vs. 1.89 ± 0.005
0.504 mg/dl (24.4%)
Postoperative Hct 29.66 ± 4.41% vs. 32.73 ± 4.19% (9.37%) 0.016
Hct drop 7.31 ± 2.553 vs. 5.21 ± 2.090 (28.72%) 0.003
SD 77.91 ± 16.740 min vs. 57.60 ± 0.0001
14.868 min (26%)
SF assessment 0.0001
 Sankar et  al., RCT 25 (50) Mixed IV, intraoperative IOB 166.1 ± 65.49 ml vs. 256.4 ± 77.80 ml (35.2%) <0.001 None
2012 osteotomy LD: 10 mg/kg SF <0.001
IR: 1 mg/kg/hr TR NS
SD NS
 Karimi et  al., RCT 16 (32) Bimaxillary IV, preoperative IOB 585.9 ± 21.3 ml vs. 790 ± 32.4 ml (25.8%) 0.008 None
2012 osteotomy 20 mg/kg TR NS
 Kaewpradub RCT 20 (40) Bimaxillary Topical irrigations, IOB NS None
et al., 2011 osteotomy intraoperative TR NS
0.05% solution
(500 mg, 10 ml)
in 1 liter (Continued )

941e
Copyright © 2018 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
 Table 2.  (Continued)

942e
Study Group
(Total AF-Associ-
Subspecialty and Study Sample Surgery Administration Mode, Main Outcomes Significant ated Com-
Reference Design Size) Type Time, and Dosage Measured Outcomes* p plications
 Choi et  al., RCT 32 (61) Bimaxillary IV, preoperative IOB 428.0 ± 233.3 ml vs. 643.8 ± <0.05 None
2009 osteotomy 20 mg/kg 430.0 ml (33.5%)
TBL 878.6 ± 577.7 ml vs. 1257.2 ± <0.05
LOS 817.8 ml (30.1%) NS
TR NS
 Zellin et  al., RCS 15 (30) Le Fort I IV, intraoperative1 g IOB 740 ± 410 ml vs. 400 ± 210 ml (46%) 0.02 None
2004 osteotomy (+0.3 μg/kg SC TR NS
desmopressin)
Burn care
 Domínguez RCS 52 (107) Burns IV, intraoperative TR pRBC units: 1.6 vs. 2.6 0.017 None
et al., 2017
 Tang et  al., Case 1 (1) Débridement Topical, None None None
2012 report and grafting intraoperative
 Jennes et  al., RCT 14 (27) Tangential IV, preoperative IOB 1.03 ml/cm2 vs. 1.62 ml/cm2 (26.4%) 0.09 None
2003 burns 20 mg/kg
excision
Aesthetic
surgery
 Ghavimi RCT 24 (50) Rhinoplasty IV, preoperative IOB 254.34 ± 55.4 ml vs. 213.29 ± 56.87 ml (16%) 0.013 None
et al., 2017 10 mg/kg Preoperative and NS None
postoperative Hb
Preoperative and 279.2 ± 60.39 ml vs. 247.06 ± 42.7 ml 0.035
postoperative Hct (11.4%)
Eyelid edema 0.03
Periorbital 0.04
ecchymosis
Surgeon satisfaction 0.03
 Eftekharian RCT 25 (50) Rhinoplasty Oral, preoperative TBL 144.6 ± 60.28 ml vs. 199.6 ± 73.05 ml (27.6%) < 0.05
and 2 × 500 mg
Rajabzadeh, SD 2.60 ± 0.53 hr vs. 2.99 ± 0.59 hr 0.017
2016 SF satisfaction 0.001
 Butz and Case 57 (57) Rhytidectomy Topical (soaked Edema, ecchymosis, N/A None
Geldner, series pledgets placed return to social
2016 under skin flap), activity
intraoperative, dose
N/A
 Cansanção nRCT 10 (20) Liposuction IV, preoperative and Hct reduction N/A None
et al., 2015 postoperative LD
(30 min preopera- Blood volume in the 37.7 ± 15.5 ml vs. 59.9 ± 25.1 ml (37%)
tively):10 mg/kg aspirate
plus 10 mg/kg at Volume of blood per 8.8 ± 2.0 ml/liter vs. 20.1 ± 7.6 ml/liter
the end of surgery liter of aspirate (43.8%)

(Continued )
Plastic and Reconstructive Surgery • June 2018

Copyright © 2018 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
 Volume 141, Number 6 • Antifibrinolytic Agents

discussed its oral use, and five articles discussed its

red blood cells; ITR, intraoperative transfusion requirements; PTR, postoperative transfusion requirements; IQR, interquartile range; IOB, intraoperative bleeding; Hb, hemoglobin; Hct,
hematocrit; LOS, length of stay; SD, surgery duration; NS, nonsignificant; TR, transfusion requirement; ERCV, estimated red cell volume; DO, drain output; DVT, deep vein thrombosis; RCT,
randomized controlled trial; CP, cleft palate; Hct, hematocrit; SF, surgical field, TBL, total blood loss; POB, postoperative bleeding; N/A, not available; nRCT, nonrandomized controlled trial.
AF, antifibrinolytic; RCS, retrospective cohort study; CVR, cranial vault reconstruction; IV, intravenous; LD, loading dose; IR, infusion rate; TTR, total transfusion requirements; pRBCs, packed
ated Com-
AF-Associ-

plications
topical use.

None
None
None
Craniofacial Surgery
Regarding craniofacial surgery, four random-
ized controlled trials and seven retrospective cohort

0.017
<0.05

<0.05

NS
studies involving 912 patients who received intra-
p

venous tranexamic acid in craniofacial surgery

procedures were analyzed.15–25 Surgical procedures
included cranial vault reconstructions and cleft
palate operations. Preoperative intravenous load-
12.9 ± 47 ml vs. 22.0 ± 100 ml (42%)

ing doses ranged from 10 to 50 mg/kg, and the

infusion rate ranged from 1 to 10 mg/kg/hour.
The majority of studies reviewed observed a statis-
tically significant reduction in both intraoperative
Outcomes*
Significant

bleeding and transfusion requirements with intra-

venous tranexamic acid administration.17,19,20,22,24
N/A
68 ± 21 ml (48.8%)

Intraoperative bleeding reduction ranged from

20 (p = 0.0001)19 to 55 percent (p < 0.0001),17 and
transfusion reduction ranged from 10 (p = 0.0001)19
133 ± 63

to 86 percent (p < 0.05).21 Other statistically signifi-

cant outcomes included improved surgical field,18
surgeon satisfaction,18 reduced length of stay,20
reduced drain output,20,25 higher postoperative
periorbital edema
Main Outcomes

hemoglobin,25 lower hemoglobin drop,25 higher

complications,
Flap failure, flap
Measured

postoperative estimated red blood cell volume,25

Postoperative
Postoperative

ecchymosis

and reduced total22 and postoperative blood loss.22

Pain scores

VTE rate

However, Arantes et al. and Dadure et al.,

studying cleft lip and palate surgery16 and cranial
IOB

DO

vault reconstruction,21 respectively, did not find a

Administration Mode,

significant difference in intraoperative bleeding

tively), 1 g every 8 hr
Time, and Dosage

1 g (2 hr preopera-

Topical, intraopera-
plus postoperative

and transfusion requirements. Few complications

Oral, preoperative

IV, preoperative,

were associated with tranexamic acid in the litera-

mammaplasty (25 mg/ml)

ture. One deep vein thrombosis and two seizure

tive, 20 ml

100 free flaps dose N/A

for 5 days

events were described with the intraoperative

use of tranexamic acid in craniofacial surgery.15
However, the incidences of both thromboembolic
events and seizures were not significantly differ-
ent from those of the control group. No further
septorhino-
Surgery

reduction

73 pedicles,

adverse events such as allergic reactions or ana-

Type

Bilateral

phylaxis related to the use of tranexamic acid were

plasty
Open

reported. No hematoma events were reported in

any of the articles reviewed.
Study Group

19 (173)

Orthognathic Surgery
Sample

28 (56)
25 (50)
(Total

Size)

Regarding orthognathic surgery, six ran-

domized controlled trials and one retrospective
cohort study of the use of tranexamic acid were
Design

identified, involving 161 cases.26–32 Surgical pro-

Subspecialty and Study

RCT
RCT

RCS
Table 2.  (Continued)

cedures included bimaxillary osteotomies and

standardized Le Fort I osteotomies. Preoperative
 Valerio et  al.,
et al., 2015

intravenous doses ranged from 10 to 20 mg/kg.

 Ausen et  al.,
 Sakalliogllu

Microsurgery

Only one study used an additional infusion rate

Reference

2015
2015

of 1 mg/kg/hour.28 Five studies27–29,31,32 demon-

strated a statistically significant decrease in intra-
operative bleeding ranging from 26 (p = 0.008)29

943e
Copyright © 2018 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
 Plastic and Reconstructive Surgery • June 2018

Table 3.  Articles with Statistically Significant Outcomes versus Articles with Non–Statistically Significant
Outcomes
Transfusion Requirements
Blood Loss Reduction Reduction Drain Output Reduction
No. of No. of No. of No. of No. of No. of
Articles with Articles with Articles with Articles with Articles with Articles with
Statistically Non–Statistically Statistically Non–Statistically Statistically Non–Statistically
Significant Significant Significant Significant Significant Significant
Outcomes Outcomes Outcomes Outcomes Outcomes Outcomes
Craniofacial surgery
 TXA 6 2 7 1 2 0
 EACA 2 1 3 0 1 0
Orthognathic surgery
 TXA 6 1 0 5 N/A N/A
Burn care
 TXA 1 0 1 0 N/A N/A
Aesthetic surgery
 TXA 4 0 N/A N/A 1 0
TXA, tranexamic acid; EACA, ε-aminocaproic acid.

to 45 percent (p = 0.02)32 when tranexamic acid
was given intravenously. However, none of these
studies found a significant difference in transfu-
sion reduction with the use of tranexamic acid.
Topical use of tranexamic acid had mixed
results in the literature. Eftekharian et al.26
reported a significant intraoperative bleeding
reduction (29 percent; p < 0.05) with the use of
topical 1% tranexamic acid solution. In contrast,
Kaewpradub et al.30 did not find a significant
difference in intraoperative bleeding and trans-
fusion reduction with the use of 0.05% topical
tranexamic acid solution.
Other statistically significant outcomes
included improved surgical field,27,28 higher
postoperative hemoglobin percentage,27,29 lower
hemoglobin percentage drop,27 higher postopera-
tive hematocrit,27 lower hematocrit drop, shorter
surgery duration,27 reduced drain output,26 and
reduced total blood loss.27,31 No thromboembolic
events or other systemic complications related to
the use of tranexamic acid in orthognathic sur-
gery were reported. No hematoma events were
reported in any of the articles reviewed.
Burn Care
Regarding burn care, one randomized con-
trolled trial, one retrospective cohort study, and
one case report describing 67 total cases were
identified in burn surgery.33–35 Surgical proce-
dures included débridement, skin grafting, and
tangential burn excision. Administration proto-
cols included preoperative and intraoperative use
of 20 mg/kg intravenous tranexamic acid, and
topical solutions.
Domínguez et al.33 described the use of
intravenous tranexamic acid in 52 burn patients
undergoing primary wound excision. The use
of tranexamic acid exhibited an absolute risk
reduction in the need for transfusion during sur-
gery of 24.2 percent. Jennes et al.35 conducted
a preliminary randomized controlled trial on
the effect of a single 20-mg/kg tranexamic acid
bolus on blood loss in 27 tangential burn exci-
sions. The study demonstrated a reduction in
calculated blood loss in the tranexamic acid
group, although the significance of this finding
was dependent on the calculation method used.
Topical tranexamic acid use in burn surgery
was also supported for use in tangential burn
débridement.34 No thromboembolic events or
other systemic complications related to the use
of tranexamic acid in burn care were reported.
No hematoma events were reported in any of the
articles reviewed.
Aesthetic Surgery
Six randomized controlled trials and one case
series describing 263 total cases were identified in
the area of aesthetic surgery.36–40 Surgical proce-
dures included rhinoplasty, rhytidectomy, liposuc-
tion, and reduction mammaplasty. Administrative
protocols included oral, topical, and intravenous
dosing.36 Sakalliogllu et al.39 described the use of
1 g of oral tranexamic acid before rhinoplasty.
Sakalliogllu et al. used an additional 1 g every 8
hours postoperatively. Both trials reported a sta-
tistically significant reduction in total blood loss
and intraoperative bleeding, respectively (27.6
percent, p < 0.05; 48.8 percent, p < 0.05). Notably,
tranexamic acid was superior to steroid treatment
in the prevention of bleeding.39
Ghavimi et al.41 reported that administration
of 10 ml/kg tranexamic acid had a significant

944e
Copyright © 2018 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
 Volume 141, Number 6 • Antifibrinolytic Agents

effect in decreasing the intraoperative bleeding Microsurgery

rate, eyelid edema, and periorbital ecchymosis in
rhinoplasty, with minimal side effects. Butz and
Geldner37 described a similar therapeutic effect
of topical tranexamic acid on reducing eyelid
edema and periorbital ecchymosis and acceler-
ating return to social activity in 57 rhytidectomy
cases, with only one hematoma reported. Cansan-
ção et al.38 used a preoperative and postoperative
loading dose of 10 mg/kg of tranexamic acid in
liposuction and reported a significant 37 percent
reduction in intraoperative bleeding and a 43.8
percent reduction in the volume of aspirated
blood. A 25-mg/ml topical tranexamic acid solu-
tion was also associated with a 39 percent reduc-
tion in drainage volume in the setting of bilateral
reduction mammaplasty.40
Other significant outcomes in aesthetic sur-
gery included improved surgical field36 and
shorter surgery duration.36 No thromboembolic
events or other systemic complications related to
the use of tranexamic acid were reported.
Regarding microsurgery, one retrospective
cohort study described 19 trauma patients who
received tranexamic acid before undergoing
reconstructive procedures.42 One hundred sev-
enty-three extremity flap procedures were per-
formed (100 pedicled flaps and 73 free flaps),
with no documented venous thromboembolisms
in patients who received tranexamic acid.43 Total
flap complications did not differ significantly
between patients that received tranexamic acid
versus those that did not. This is the only study to
date on the use of tranexamic acid in microsurgery
and its influence on flap-related complications.
ε-Aminocaproic Acid
Five articles described the use of intravenous
ε-aminocaproic acid in plastic surgery (Tables 3
and 4). No articles describing alternate routes of
administration were identified. Regarding cra-
niofacial surgery, four retrospective cohort stud-
ies and one case report involving 495 patients

Table 4.  ε-Aminocaproic Acid in Craniofacial Surgery

Study Group
(Total Administration Main
Study Sample Surgery Mode, Time, Outcome Significant AF-Associated
Reference Design Size) Type and Dose Measures Outcomes* p Complications
Thompson RCS 14 (45) CVR IV, preoperative, Drain use (% of 21.4% vs. 0.037 None
et al., 2017 intraoperative patients) 55.2%
LD: 50 mg/kg IOB (when 0.005
(preoperatively) controlling
IR: 25 mg/kg/hr for SD)
TR (when 0.010
controlling
for SD)
Mean discharge Hb NS
Goobie et al., RCS 383 (1638) CVR IV, intraoperative Seizures None 4 seizures
2017 LD: 100 mg/kg (IQR,
97–100 mg/kg)
IR: 33 mg/kg/hr (IQR,
20–40 mg/kg/hr
Hsu et al., RCS 66 (152) CVR IV, intraoperative IOB 82 ± 43 vs. 0.01
2016 LD: 100 mg/kg 106 ± 63 ml
IR: 40, 30, 20 mg/kg/hr (22.6%)
(age depending) Blood donor 2 (IQR, 1–2) 0.02 None
exposures vs. 2 (IQR,
1–3)
DO (24 hr) 28 ml/kg vs. 0.001
37 ml/kg
(24.3%)
Reddy et al., Case 2 (2) CVR IV, preoperative, None None None
2016 report intraoperative
LD (preoperative):
100 mg/kg
IR: 40 mg/kg/hr
Oppenheimer RCS 30 (148) CVR IV, intraoperative TR 25.5 ml/kg vs. 0.0001 None
et al., 2014 (dose, N/A) 53.3 ml/
IOB kg (52.1%) NS
AF, antifibrinolytic; RCS, retrospective cohort study; CVR, cranial vault reconstruction; IV, intravenous; LD, loading dose; IR, infusion rate; IOB,
intraoperative bleeding; SD, surgery duration; TR, transfusion requirement; Hb, hemoglobin; NS, not significant; IQR, interquartile range;
DO, drain output; N/A, not available.

945e
Copyright © 2018 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.

assessed intravenous ε-aminocaproic acid given
during cranial vault reconstruction surgery.15,43–46
Doses ranged from 50 to 100 mg/kg for a load-
ing dose with a 20-mg/kg/hour infusion rate.
Thompson et al.43 and Hsu et al.44 reported a sta-
tistically significant reduction in intraoperative
bleeding and transfusion requirements with intra-
venous administration of ε-aminocaproic acid. In
contrast, Oppenheimer et al.46 demonstrated a
significant reduction in transfusion requirements
(52.1 percent; p < 0.0001), although they did not
find a decrease in intraoperative bleeding. Other
significant outcomes included reduced drain out-
put (24.3 percent; p = 0.001).44
Four cases of seizures were reported with the
use of ε-aminocaproic acid.15 No thromboembolic
events or other systemic complications related
to the use of ε-aminocaproic acid were reported.
No hematoma events were reported in any of the
articles reviewed. No studies were reported on
patients undergoing orthognathic surgery, aes-
thetic surgery, burn care procedures, or microsur-
gery procedures on ε-aminocaproic acid.
DISCUSSION
The present study represents the largest sys-
tematic review on the use of antifibrinolytic
agents in plastic and reconstructive surgery. Stud-
ies on the use of intravenous, oral, and topical
tranexamic acid and ε-aminocaproic acid in the
fields of craniofacial surgery, orthognathic sur-
gery, aesthetic surgery, burn care, and microsur-
gery were analyzed. The main objective was to
explore the efficacy and safety profiles of antifi-
brinolytics within plastic surgery, to assess current
practices and protocols provided for clinical use.
Craniofacial Surgery
Regarding craniofacial surgery, antifibrinolyt-
ics have been reported to significantly decrease
blood loss and transfusion requirements in pedi-
atric cranial vault reconstruction surgery.17,43
Although the risk of thrombotic events is the
main concern regarding the use of antifibrinolyt-
ics, their efficacy has been repeatedly described
in both prospective trials16,18,21,22 and retrospec-
tive studies15,17,19,20,23 when used intraoperatively in
open craniosynostosis surgery.
Despite their demonstrated efficacy, the clini-
cal use of antifibrinolytics in craniofacial surgery
remains complicated by the challenge of decreas-
ing blood loss while minimizing the risk of adverse
events.15,47 However, our review observed that
946e
Copyright © 2018 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
Plastic and Reconstructive Surgery • June 2018
seizures were rare in the field of craniofacial sur-
gery.15 Only one case of postoperative deep vein
thrombosis following tranexamic acid adminis-
tration was reported in this review.15 It is unclear
whether there is a causal association between
tranexamic acid exposure and the risk of deep
vein thrombosis.15
Overall, tranexamic acid and ε-aminocaproic
acid both appear to possess sizable benefits and
an appropriately low incidence of adverse effects
when used in pediatric craniofacial surgery. Anti-
fibrinolytics are currently administered in 72
percent of craniofacial reconstructions and 50 per-
cent of cranial vault reconstructions, according to
the Pediatric Craniofacial Surgery Perioperative
Registry database.15 Tranexamic acid (72 percent)
was used more frequently than ε-aminocaproic
acid (28 percent). Fifty-seven percent of the cen-
ters not routinely using antifibrinolytics cited con-
cerns over adverse effects as the main factor.
This review summarizes the various protocols for
tranexamic acid and ε-aminocaproic acid administra-
tion in craniofacial surgery. We observed a notable
gap between clinical use and pharmacologic recom-
mendations. Clinically, a tranexamic acid dosing
regimen of a 5-mg/kg loading dose and a 5-mg/kg/
hour infusion, or a 15-mg/kg load with a 10-mg/kg/
hour infusion, were reported to be the most clinically
used dosage.48,49 However, pharmacokinetic models
recommend a 10-mg/kg loading dose followed by a
5-mg/kg/hour infusion.50 ε-Aminocaproic acid clini-
cal use better correlates with pharmacologic recom-
mendations of a loading dose of 100 mg/kg and a
maintenance dose of 40 mg/kg/hour.51
Orthognathic Surgery
Orthognathic surgery has been associated
with significant perioperative blood loss and need
for blood transfusions.3,32 Concerns regarding the
possible systemic effects of intravenous adminis-
tration have led to the development of various
topical application forms of tranexamic acid,
which result in 70 percent lower systemic absorp-
tion.52 These topical formulations are assumed to
be more target-directed and reasonably effective
in reducing perioperative bleeding.53
However, the use of topical tranexamic acid
has been met with mixed reviews.26,30 Discrep-
ancies may be explained by the differences in
methods used to estimate blood loss and the vari-
able dose of tranexamic acid solution used. This
emphasizes the importance of establishing clear
guidelines for the use of topical tranexamic acid
in orthognathic surgery, and universal algorithms
for blood loss evaluation. The reported influence
 Volume 141, Number 6 • Antifibrinolytic Agents
of tranexamic acid administration on postopera-
tive hemoglobin levels in orthognathic surgery
also varies.26,29,31,54
Burn Care
Studies of antifibrinolytics in the setting of
burn care, although limited, yielded largely posi-
tive results.33–35 However, further research is war-
ranted to determine tranexamic acid’s effect on
graft take, and its most optimum route of admin-
istration in burn care.
Aesthetic Surgery
The use of antifibrinolytics has recently
expanded to the field of aesthetic surgery.
Tranexamic acid administration has been
described in rhinoplasties,36,39,41 face lifts,37 lipo-
suction,38 and reduction mammaplasties40 to
decrease intraoperative bleeding and improve
visibility in the surgical field. Tranexamic acid is
the most popular antifibrinolytic used in aesthetic
surgery.41 It is likely that tranexamic acid may
have definitive benefit when used in rhinoplasty,
with positive effects such as intraoperative bleed-
ing reduction, improved visibility of the surgical
field, and reduced postoperative eyelid edema
and periorbital ecchymosis. Such advantages
would be enormously beneficial for these tech-
nically precise procedures. Tranexamic acid may
be considered as a useful substitute for steroids
in rhinoplasty and thus eliminate the deleterious
and well-described side effects of systemic steroid
use.41 Intravenous tranexamic acid substantially
decreased blood loss in liposuction,38 and topi-
cal tranexamic acid decreased drain output when
used in reduction mammaplasty.40
Microsurgery
No trials were identified that specifically stud-
ied the use of antifibrinolytics in microsurgery.
However, Valerio et al.42 explored the association
between tranexamic acid use in combat casualty
care and microsurgical complications in patients
undergoing free tissue transfer for extremity recon-
struction. No venous thromboembolism events
were reported in patients who received tranexamic
acid, and total flap complications did not differ sig-
nificantly between those that received tranexamic
acid versus those that did not. No data clearly sup-
port the use of antifibrinolytics in microsurgery.
Limitations
This review possesses a number of limitations.
First, the heterogeneity of the included studies
Copyright © 2018 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
limits the conclusions that can be drawn in the
aggregate. Second, the lack of consistency in dos-
age, vehicle of administration, and measured out-
comes precludes the development of substantial
quantitative conclusions. However, this review is
the first to summarize the use of antifibrinolytics
in plastic surgery, and provides a broad view of
their utility for use in the various plastic surgery
subspecialties, and a contemporary appraisal of
current administration protocols, outcomes, and
complications.
One of the goals of the present review was
to emphasize the efficacy and well-documented
safety profile of antifibrinolytics, to assuage widely
held concerns about related adverse effects. The
authors believe that there is room for investiga-
tion in this area, and encourage burn care pro-
viders and aesthetic surgeons to report their
tranexamic acid use in practice to establish guide-
lines for optimum administration. In addition,
further studies with a larger sample size, standard-
ized measurements of blood loss, and clear hema-
toma rates reports are required to confirm the
safety and efficacy of topical tranexamic acid in
orthognathic surgery.
CONCLUSIONS
The present review summarizes the litera-
ture addressing the use of antifibrinolytics within
plastic surgery. Antifibrinolytics are consistently
reported to significantly decrease intraoperative
and postoperative blood loss and blood transfu-
sion requirements in the fields of craniofacial and
orthognathic surgery. Intravenous administration
was most commonly studied; however, topical for-
mulations are similarly efficacious and reduce the
systemic effects of the agents. Tranexamic acid
has also emerged as a promising agent in aes-
thetic surgery and burn care procedures, because
of its favorable safety profile and role in reducing
blood loss, achieving an improved surgical field
and surgical precision, and reducing edema and
ecchymosis. Further investigation of the use of
tranexamic acid and ε-aminocaproic acid in the
fields of burn care, aesthetic surgery, and micro-
surgery is warranted to standardize protocols for
clinical use.
Stav Brown, B.S.
Sackler School of Medicine
Tel Aviv University
35 Klatskin Street
Tel Aviv, Israel 69978
brown.stav@gmail.com
947e

REFERENCES
1. Goodnough LT, Brecher ME, Kanter MH, AuBuchon JP.
Transfusion medicine: First of two parts. Blood transfusion.
N Engl J Med. 1999;340:438–447.
2. White N, Marcus R, Dover S, et al. Predictors of blood loss
in fronto-orbital advancement and remodeling. J Craniofac
Surg. 2009;20:378–381.
3. McCormack PL. Tranexamic acid: A review of its use in the
treatment of hyperfibrinolysis. Drugs 2012;72:585–617.
4. Verstraete M. Clinical application of inhibitors of fibrinoly-
sis. Drugs 1985;29:236–261.
5. Markin JM. Lessons learned in antifibrinolytic therapy: the
BART Trial. Semin Cardiothorac Vasc Anesth. 2009;13:127-131.
6. Henry DA, Carless PA, Moxey AJ, et al. Anti-fibrinolytic use
for minimising perioperative allogeneic blood transfusion.
Cochrane Database Syst Rev. 2007;1:CD001886.
7. Schouten ES, van de Pol AC, Schouten AN, Turner NM,
Jansen NJ, Bollen CW. The effect of aprotinin, tranexamic
acid, and aminocaproic acid on blood loss and use of blood
products in major pediatric surgery: A meta-analysis. Pediatr
Crit Care Med. 2009;10:182–190.
8. Huang F, Wu D, Ma G, Yin Z, Wang Q. The use of tranexamic
acid to reduce blood loss and transfusion in major orthope-
dic surgery: A meta-analysis. J Surg Res. 2014;186:318–327.
9. Poeran J, Rasul R, Suzuki S, et al. Tranexamic acid use and
postoperative outcomes in patients undergoing total hip or
knee arthroplasty in the United States: Retrospective analysis
of effectiveness and safety. BMJ 2014;349:g4829.
10. Kim TK, Chang CB, Koh IJ. Practical issues for the use of
tranexamic acid in total knee arthroplasty: A systematic
review. Knee Surg Sports Traumatol Arthrosc. 2014;22:1849–1858.
11. Elgafy H, Bransford RJ, McGuire RA, Dettori JR, Fischer D.
Blood loss in major spine surgery: Are there effective mea-
sures to decrease massive hemorrhage in major spine fusion
surgery? Spine (Phila Pa 1976) 2010;35(Suppl):S47–S56.
12. CRASH-2 Collaborators; Shakur H, Roberts I, et al. Effects
of tranexamic acid on death, vascular occlusive events, and
blood transfusion in trauma patients with significant haem-
orrhage (CRASH-2): A randomised, placebo-controlled trial.
Lancet 2010;376:23–32.
13. Guerriero C, Cairns J, Perel P, Shakur H, Roberts I; CRASH 2
trial collaborators. Cost-effectiveness analysis of administer-
ing tranexamic acid to bleeding trauma patients using evi-
dence from the CRASH-2 trial. PLoS One 2011;6:e18987.
14. 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.
15. Goobie SM, Cladis FP, Glover CD, et al.; the Pediatric
Craniofacial Collaborative Group. Safety of antifibrinolyt-
ics in cranial vault reconstructive surgery: A report from the
pediatric craniofacial collaborative group. Paediatr Anaesth.
2017;27:271–281.
16. Arantes GC, Pereira RMR, de Melo DB, Alonso N, Duarte
MDCMB. Effectiveness of tranexamic acid for reducing
intraoperative bleeding in palatoplasties: A randomized clin-
ical trial. J Craniomaxillofac Surg. 2017;45:642–648.
17. Crantford JC, Wood BC, Claiborne JR, et al. Evaluating the safety
and efficacy of tranexamic acid administration in pediatric cra-
nial vault reconstruction. J Craniofac Surg. 2015;26:104–107.
18. Durga P, Raavula P, Gurajala I, et al. Evaluation of the effi-
cacy of tranexamic acid on the surgical field in primary cleft
palate surgery on children: A prospective, randomized clini-
cal study. Cleft Palate Craniofac J. 2015;52:e183–e187.
948e
Copyright © 2018 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
Plastic and Reconstructive Surgery • June 2018
19. Engel M, Bodem JP, Busch CJ, et al. The value of tranexamic
acid during fronto-orbital advancement in isolated metopic
craniosynostosis. J Craniomaxillofac Surg. 2015;43:1239–1243.
20. Martin DT, Gries H, Esmonde N, et al. Implementation of
a tranexamic acid protocol to reduce blood loss during cra-
nial vault remodeling for craniosynostosis. J Craniofac Surg.
2016;27:1527–1531.
21. Dadure C, Sauter M, Bringuier S, et al. Intraoperative
tranexamic acid reduces blood transfusion in children
undergoing craniosynostosis surgery: A randomized double-
blind study. Anesthesiology 2011;114:856–861.
22. Goobie SM, Meier PM, Pereira LM, et al. Efficacy of
tranexamic acid in pediatric craniosynostosis surgery:
A double-blind, placebo-controlled trial. Anesthesiology
2011;114:862–871.
23. Maugans TA, Martin D, Taylor J, Salisbury S, Istaphanous G.
Comparative analysis of tranexamic acid use in minimally
invasive versus open craniosynostosis procedures. J Craniofac
Surg. 2011;22:1772–1778.
24. Kurnik NM, Pflibsen LR, Bristol RE, Singh DJ. Tranexamic
acid reduces blood loss in craniosynostosis surgery. J Craniofac
Surg. 2017;28:1325–1329.
25. Hansen JK, Lydick AM, Wyatt MM, Andrews BT. Reducing
postoperative bleeding after craniosynostosis repair utiliz-
ing a low-dose tranexamic acid infusion protocol. J Craniofac
Surg. 2017;28:1255–1259.
26. Eftekharian H, Vahedi R, Karagah T, Tabrizi R. Effect of
tranexamic acid irrigation on perioperative blood loss dur-
ing orthognathic surgery: A double-blind, randomized con-
trolled clinical trial. J Oral Maxillofac Surg. 2015;73:129–133.
27. Christabel A, Muthusekhar MR, Narayanan V, et al. Effectiveness
of tranexamic acid on intraoperative blood loss in isolated Le
Fort I osteotomies: A prospective, triple blinded randomized
clinical trial. J Craniomaxillofac Surg. 2014;42:1221–1224.
28. Sankar D, Krishnan R, Veerabahu M, Vikraman B. Evaluation
of the efficacy of tranexamic acid on blood loss in orthogna-
thic surgery: A prospective, randomized clinical study. Int J
Oral Maxillofac Surg. 2012;41:713–717.
29. Karimi A, Mohammadi SS, Hasheminasab M. Efficacy of
tranexamic acid on blood loss during bimaxilary osteotomy:
A randomized double blind clinical trial. Saudi J Anaesth.
2012;6:41–45.
30. Kaewpradub P, Apipan B, Rummasak D. Does tranexamic
acid in an irrigating fluid reduce intraoperative blood loss in
orthognathic surgery? A double-blind, randomized clinical
trial. J Oral Maxillofac Surg. 2011;69:e186–e189.
31. Choi WS, Irwin MG, Samman N. The effect of tranexamic
acid on blood loss during orthognathic surgery: A random-
ized controlled trial. J Oral Maxillofac Surg. 2009;67:125–133.
32. Zellin G, Rasmusson L, Pålsson J, Kahnberg KE. Evaluation
of hemorrhage depressors on blood loss during orthogna-
thic surgery: A retrospective study. J Oral Maxillofac Surg.
2004;62:662–666.
33. Domínguez A, Alsina E, Landín L, García-Miguel JF, Casado
C, Gilsanz F. Transfusion requirements in burn patients
undergoing primary wound excision: Effect of tranexamic
acid. Minerva Anestesiol. 2017;83:353–360.
34. Tang YM, Chapman TW, Brooks P. Use of tranexamic acid to
reduce bleeding in burns surgery. J Plast Reconstr Aesthet Surg.
2012;65:684–686.
35. Jennes S, Degrave E, Despiegeleer X, Grenez O. Effect of
tranexamic acid on blood loss in burn surgery: A preliminary
study. J Burn Care Rehabil. 2003;24:S59.
36. Eftekharian HR, Rajabzadeh Z. The efficacy of preoperative
oral tranexamic acid on intraoperative bleeding during rhi-
noplasty. J Craniofac Surg. 2016;27:97–100.
 Volume 141, Number 6 • Antifibrinolytic Agents
37. Butz DR, Geldner PD. The use of tranexamic acid in rhytid-
ectomy patients. Plast Reconstr Surg Glob Open 2016;4:e716.
38. Cansanção AL, Cansanção AJ, Cansanção BP, Vidigal RA.
Effect of tranexamic acid in bleeding control in liposuction.
Plast Reconstr Surg. 2015;136(Suppl):80.
39. 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.
40. Ausen K, Fossmark R, Spigset O, Pleym H. Randomized clini-
cal trial of topical tranexamic acid after reduction mammo-
plasty. Br J Surg. 2015;102:1348–1353.
41.
Ghavimi MA, Taheri Talesh K, Ghoreishizadeh A,
Chavoshzadeh MA, Zarandi A. Efficacy of tranexamic acid
on side effects of rhinoplasty: A randomized double-blind
study. J Craniomaxillofac Surg. 2017;45:897–902.
42. Valerio IL, Campbell P, Sabino J, et al. TXA in combat casu-
alty care: Does it adversely affect extremity reconstruction
and flap thrombosis rates? Mil Med. 2015;180(Suppl):24–28.
43. Thompson ME, Saadeh C, Watkins P, Nagy L, Demke J.
Blood loss and transfusion requirements with epsilon-amino-
caproic acid use during cranial vault reconstruction surgery.
J Clin Anesth. 2017;36:153–157.
44. Hsu G, Taylor JA, Fiadjoe JE, et al. Aminocaproic acid admin-
istration is associated with reduced perioperative blood
loss and transfusion in pediatric craniofacial surgery. Acta
Anaesthesiol Scand. 2016;60:158–165.
45. Reddy SK, Swink JM, Rogers GF, Myseros JS, Keating RF,
Santos DN. Transfusion-free calvarial vault reconstruction
using multimodal blood conservation strategies in two pedi-
atric Jehovah’s Witness patients with craniosynostosis. A A
Case Rep. 2016;7:33–36.
Copyright © 2018 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
46. Oppenheimer AJ, Ranganathan K, Levi B, et al. Minimizing
transfusions in primary cranial vault remodeling: The role of
aminocaproic acid. J Craniofac Surg. 2014;25:82–86.
47. White N, Bayliss S, Moore D. Systematic review of interven-
tions for minimizing perioperative blood transfusion for sur-
gery for craniosynostosis. J Craniofac Surg. 2015;26:26–36.
48. Lecker I, Wang DS, Whissell PD, Avramescu S, Mazer CD,
Orser BA. Tranexamic acid-associated seizures: Causes and
treatment. Ann Neurol. 2016;79:18–26.
49. Martin K, Knorr J, Breuer T, et al. Seizures after open heart
surgery: Comparison of ε-aminocaproic acid and tranexamic
acid. J Cardiothorac Vasc Anesth. 2011;25:20–25.
50. Goobie SM, Meier PM, Sethna NF, et al. Population phar-
macokinetics of tranexamic acid in paediatric patients
undergoing craniosynostosis surgery. Clin Pharmacokinet.
2013;52:267–276.
51. Stricker PA, Zuppa AF, Fiadjoe JE, et al. Population phar-
macokinetics of epsilon-aminocaproic acid in infants under-
going craniofacial reconstruction surgery. Br J Anaesth.
2013;110:788–799.
52. Wong J, Abrishami A, El Beheiry H, et al. Topical application
of tranexamic acid reduces postoperative blood loss in total
knee arthroplasty: A randomized, controlled trial. J Bone Joint
Surg Am. 2010;92:2503–2513.
53. Khalil PN, Ismail M, Kalmar P, von Knobelsdorff G, Marx G.
Activation of fibrinolysis in the pericardial cavity after cardio-
pulmonary bypass. Thromb Haemost. 2004;92:568–574.
54. Song G, Yang P, Hu J, Zhu S, Li Y, Wang Q. The effect of
tranexamic acid on blood loss in orthognathic surgery: A
meta-analysis of randomized controlled trials. Oral Surg Oral
Med Oral Pathol Oral Radiol. 2013;115:595–600.
949e