J Oral Maxillofac Surg

70:e547-e552, 2012

Intraoperative Blood Loss During

Orthognathic Surgery Is Predicted
by Thromboelastography
Daniel E. Madsen, MSc,* Janne Ingerslev, DDS,†
Johannes J. Sidelmann, PhD,‡ Jens J. Thorn, DDS, PhD,§ and
Jørgen Gram, MD, DSc储

Purpose: The aim of this prospective study was to evaluate the predictive value of the viscoelastic
properties of whole blood samples collected preoperatively in relation to intraoperative blood loss in
patients subjected to orthognathic surgery.
Materials and Methods: Forty-one consecutive patients underwent simultaneous mandibular and
maxillary osteotomy. Whole blood samples were collected preoperatively. The intraoperative blood loss
volume was precisely estimated. The viscoelastic properties of whole blood samples were evaluated by
thromboelastography (TEG), a global method that addresses the complex interplay among coagulation
factors, blood platelets, and components of the fibrinolytic system. Blood platelet count, activated partial
thromboplastin time, prothrombin time, plasma fibrinogen concentration, and D-dimer concentration
were determined by routine methods.
Results: Patients were separated into 2 groups according to their intraoperative bleeding volume
(ⱕ400 mL and ⬎400 mL). No significant associations were observed between routine coagulation
tests and intraoperative bleeding volume. The TEG results for the groups were compared. Significant
associations were observed between intraoperative blood loss and the clot formation time, maxi-
mum clot firmness, and ␣ angle, whereas bleeding volume was not related to the fibrinolytic
resistance of the blood clot. An ␣ angle exceeding 67° predicted with 95% certainty a blood loss of
400 mL or less.
Conclusions: We conclude that intraoperative bleeding volume in patients subjected to orthognathic
surgery can be predicted by means of preoperative TEG analysis. TEG results provide optimization of
patient safety and can be used for the evaluation of bleeding risk.
© 2012 American Association of Oral and Maxillofacial Surgeons
J Oral Maxillofac Surg 70:e547-e552, 2012

Orthognathic surgery involves surgical manipulation
of the jaws and facial skeletal structures to correct
congenital or acquired dentofacial abnormalities. The
surgical procedures are performed in anatomic areas
rich in vessels. Intraoperative blood loss can be abun-
dant and may, though rarely, require blood transfu-
sion.1,2 The mean bleeding volume during the surgical
procedure is approximately 400 mL.1
Routine coagulation tests such as blood platelet
count, activated partial thromboplastin time (aPTT),
and prothrombin time (PT) assays, have in general
failed to predict excessive blood loss in different

*Research Fellow, Unit for Thrombosis Research, Institute of
Public Health, University of Southern Denmark, Esbjerg, Denmark.
†Chief Oral and Maxillofacial Surgeon, Department of Oral and
Maxillofacial Surgery, Hospital of South West Denmark, Esbjerg,
Denmark.
‡Associate Professor, Unit for Thrombosis Research, Institute of
Public Health, University of Southern Denmark, Esbjerg, Denmark.
§Chief Oral and Maxillofacial Surgeon, Department of Oral and
Maxillofacial Surgery, Hospital of South West Denmark, Esbjerg,
Denmark.
储Chief Physician, Unit for Thrombosis Research, Institute of Pub-
lic Health, University of Southern Denmark, Esbjerg, Denmark, and
Department of Clinical Biochemistry, Hospital of South West Den-
mark, Esbjerg, Denmark.
Address correspondence and reprint requests to Dr Madsen:
Unit for Thrombosis Research, Institute of Public Health, University
of Southern Denmark, Niels Bohrs Vej 9, 6700 Esbjerg, Denmark;
e-mail: dmadsen@health.sdu.dk
© 2012 American Association of Oral and Maxillofacial Surgeons
0278-2391/12/7010-0$36.00/0
http://dx.doi.org/10.1016/j.joms.2012.06.182

e547
e548
FIGURE 1. An orthognathic surgeon (J.I.) loads a whole blood
sample for analysis in the thromboelastograph. The analysis is
followed in real time on the laptop, where the data are also stored.
Madsen et al. Blood Loss During Orthognathic Surgery. J Oral
Maxillofac Surg 2012.
types of surgery. Blood coagulation and wound heal-
ing, however, involve complex interplay among
coagulation factors, blood platelets, and fibrinolytic
factors. Thus, specific routine coagulation assays
performed preoperatively have limited predictive
value of intraoperative blood loss because they fail
to address the complexity of the blood coagulation
processes.3,4
Thromboelastography (TEG) is a global coagulation
assay measuring the viscoelastic properties of whole
blood as it is induced to clot in a low–shear stress
environment (Fig 1). TEG has the capacity to address
the complex interactions that take place during blood
clotting.5 Several studies have used TEG- and throm-
boelastometry-based methods to analyze the vis-
coelastic properties of patient blood samples during
major surgery. The results of these studies have
shown an association between results obtained by
preoperative TEG and the risk of postoperative bleed-
ing, but so far, no studies have shown an association
between results obtained by preoperative TEG and
intraoperative bleeding.6-12 The objective of this study
was to investigate whether the viscoelastic properties
of blood, as determined by preoperative TEG, were
predictive for intraoperative blood loss in a group of
patients subjected to orthognathic surgery.
Materials and Methods
This prospective clinical study included 41 consec-
utive patients undergoing simultaneous mandibular
and maxillary osteotomy at the Department of Oral
and Maxillofacial Surgery, Hospital of South West
Denmark, Esbjerg. Approval was obtained from the
local ethics committee, and the Helsinki Declaration
was observed. Patients aged under 18 years and pa-
tients with a history of diabetes, connective tissue
BLOOD LOSS DURING ORTHOGNATHIC SURGERY
disorders, or cancer were excluded. Women receiv-
ing hormonal contraceptives or hormonal replace-
ment therapy were also excluded. Intake of omega-3
fatty acids, garlic, ginseng, and Gingko biloba was
discontinued 10 days preoperatively.
All patients were diagnosed with maxillary and/or
mandibular deficiency, excess, or asymmetries, and
the patients underwent a combined orthodontic sur-
gical treatment to improve occlusion, facial balance,
and airways. The patients were preoperatively medi-
cated with nonsteroidal anti-inflammatory drugs and
paracetamol, and 2 hours preoperatively, the patients
received low–molecular weight heparin (Innohep;
Leo Pharma, Ballerup, Denmark), 3,500 international
units, subcutaneously. In addition, thrombosis pro-
phylaxis included compression stockings on the day
of surgery. The patients received controlled hypoten-
sive anesthesia. The arterial blood pressure was mea-
sured invasively, and arterial blood gasses were eval-
uated just before the operation started, after 2 hours,
and at the end of surgery. The patients were placed
with the head above the level of the heart. Local
anesthesia with a vasoconstrictor was given periop-
eratively.
A standardized modified Obwegeser sagittal split
osteotomy was performed bilaterally in the lower jaw
together with a standardized Le Fort I osteotomy.
Unsegmented Le Fort I osteotomy was performed in 4
patients, whereas segmented osteotomy was per-
formed in 37. In addition, 2 patients had a genio-
plasty. Bone transplantation to the osteotomy lines
was necessary in 30 patients. The mean duration of
the surgical procedure was 4 hours. All operations
were performed by 1 of 2 experienced surgeons (J.I.
or J.J.T.).
The intraoperative blood loss was calculated by
deducting the volume of the saline solution used
during surgery from the total volume in the suction
device.
BLOOD SAMPLING AND LABORATORY ASSAYS
Blood samples were collected from fasting pa-
tients preoperatively with the Venoject system
(Terumo Europe, Leuven, Belgium). K2-EDTA–anti-
coagulated whole blood samples were collected in
Venosafe VF-053SDK tubes and used to measure
platelet count on an ADVIA 120 analyzer (Siemens
Healthcare Diagnostics, Bad Nauheim, Germany).
With the use of an automated thromboelastograph
(Roteg; Pentapharm, Munich, Germany), citrate-anti-
coagulated whole blood samples collected in
Venosafe VF-054SBCS07 tubes were subjected to TEG
analysis. Extrinsic activation of clotting was initiated
with Innovin (Dade Behring, Marburg, Germany), and
InTEM (Pentapharm) was used for intrinsic activation
of coagulation. The following TEG parameters were
MADSEN ET AL e549

Table 1. PATIENT DATA AND BLEEDING

All Patients Bleeding ⱕ400 mL Bleeding ⬎400 mL

(N ⫽ 41) (n ⫽ 29) (n ⫽ 12) P Value

Bleeding (median [25%-75%]) (mL) 300 (200-463) 250 (200-300) 575 (500-850) NA
BMI (median [25%-75%]) (m2/kg) 23.8 (22.2-26.9) 24.2 (22.6-27.6) 22.6 (21.6-25.3) ⬎.05
Age (median [25%-75%]) (yr) 22 (20-34) 24 (20-40) 22 (19-23) ⬎.05
Gender: % male 63% 55% 83% ⬎.05
Height (median [25%-75%]) (cm) 181 (171-184) 178 (170-184) 182 (177-187) ⬎.05
Weight (median [25%-75%]) (kg) 80 (72-86) 80 (73-86) 78 (67-83) ⬎.05
NOTE. Patients were separated according to intraoperative bleeding volume. Patients with blood loss above 400 mL were
compared with patients with blood loss below or equal to 400 mL, and the P values were calculated with the Fisher exact
test for gender or with the Mann-Whitney U test.
Abbreviations: BMI, body mass index; NA, not analyzed.
Madsen et al. Blood Loss During Orthognathic Surgery. J Oral Maxillofac Surg 2012.

recorded: clotting time, clot formation time (CFT),
maximum clot firmness (MCF), ␣ angle, and maxi-
mum lysis. Citrate-anticoagulated samples were cen-
trifuged at 4°C at 2,000g for 20 minutes and used to
measure aPTT and fibrinogen concentration by use of
the STA-5 kit (Diagnostica Stago, Asnières-sur-Seine,
France), PT by use of the STA-SPA⫹ kit (Diagnostica
Stago), and D-dimer concentration by use of the STA-
Liatest kit with an STA-R Evolution coagulation ana-
lyzer (Diagnostica Stago).
STATISTICAL METHODS AND DATA ANALYSIS
The results were analyzed with the use of SigmaStat
4 for PC (Aspire Software International, Ashburn, VA).
The Mann-Whitney U test was applied to compare
patient data, routine coagulation values, and TEG pa-
rameters. The correlation between surgical time and
blood loss was studied by use of the Spearman rank
correlation coefficient. Receiver operating character-
istic (ROC) curves were generated by use of IBM SPSS
statistics 19 for PC (IBM, Armonk, NY).
correlation was observed between the 2 parameters
(P ⬎ .05).
The results of the routine coagulation tests in the
bleeding groups are shown in Table 2. Median val-
ues of aPTT, fibrinogen, blood platelet count, PT,
and D-dimer concentration were calculated for
each group. No significant difference between the
2 groups was observed.
The results of the preoperative TEG analyses
showed that CFT (upon extrinsic activation) was sig-
nificantly longer in patients bleeding more than 400
mL than in patients bleeding 400 mL or less. The MCF
(upon extrinsic and intrinsic activation) and the ␣
angle (upon extrinsic activation) were significantly
lower in patients bleeding more than 400 mL than in
patients bleeding 400 mL or less (Table 3).
Patient TEG data were analyzed with regard to the
negative and positive predictive values of intraopera-
tive blood loss of the patients. The TEG parameters

Results
Intraoperative blood loss (mL)

Patients were divided into 2 groups according to

their intraoperative blood loss: 29 patients with blood
loss less than or equal to 400 mL and 12 patients with
blood loss greater than 400 mL. Median bleeding
volumes in the 2 groups were 250 mL and 575 mL,
respectively. No significant differences were ob-
served between the 2 groups with respect to body
mass index, age, height, and weight. Men comprised
83% of the patient group with blood loss above 400
Surgical time (min)
mL compared with 55% in the group with blood loss
of 400 mL or less. Patient data are reported in Table 1. FIGURE 2. Intraoperative blood loss as a function of surgical time.
A circle represents 1 patient; a circle with a line through it, 2
No patients in this study needed blood transfusions patients; a circle with a dot in it, 3 patients; and a square, 4
perioperatively or postoperatively. patients.
The correlation between surgical time and intraop- Madsen et al. Blood Loss During Orthognathic Surgery. J Oral
erative blood loss was analyzed (Fig 2). No significant Maxillofac Surg 2012.
e550 BLOOD LOSS DURING ORTHOGNATHIC SURGERY

Table 2. ROUTINE COAGULATION VALUES

All Patients (N ⫽ 41) Bleeding ⱕ400 mL (n ⫽ 29) Bleeding ⬎400 mL (n ⫽ 12)

(Median [25%-75%]) (Median [25%-75%]) (Median [25%-75%]) P Value

aPTT (ratio) 1.20 (1.10-1.22) 1.20 (1.11-1.22) 1.16 (1.09-1.23) ⬎.05

Fibrinogen (␮mol/L) 7.4 (6.5-8.4) 7.6 (6.7-9.0) 6.7 (6.2-7.5) ⬎.05
TRC (109 cells/mL) 233 (204-270) 236 (221-278) 220 (193-254) ⬎.05
PT (ratio) 1.10 (1.06-1.15) 1.09 (1.03-1.12) 1.13 (1.10-1.20) ⬎.05
D-dimer (mg/L) 0.21 (0.15-0.27) 0.21 (0.15-0.28) 0.22 (0.17-0.25) ⬎.05
NOTE. Patients were separated and compared as described in Table 1. aPTT and PT ratios were calculated as the patient
clotting time divided by mean normal clotting time based on a plasma pool from 20 healthy individuals. Patients with
intraoperative blood loss above 400 mL were compared with patients with blood loss of 400 mL or less, and the P values were
calculated with the Mann-Whitney U test.
Abbreviation: TRC, blood platelet count.
Madsen et al. Blood Loss During Orthognathic Surgery. J Oral Maxillofac Surg 2012.

that displayed significant differences between the
bleeding groups (CFT upon extrinsic activation, MCF
upon extrinsic and intrinsic activation, and ␣ angle
upon extrinsic activation) were used for calculation
of predictive values.
Cutoff values for CFT, MCF, and ␣ angle were set to
130 seconds, 54 seconds, and 67°, respectively. The
negative predictive values were calculated as 0.88 for
CFT, 0.86 and 0.78 for MCF, and 0.95 for ␣ angle,
whereas the positive predictive values ranged from
0.45 to 0.62 (Table 4).
To further assess the ability of the ␣ angle to classify
patients correctly into high or normal bleeding risk
groups, an ROC curve was generated. This curve is
presented in Figure 3, and the area under the curve
was calculated as 0.8.13
Discussion
Intraoperative bleeding associated with orthog-
nathic surgery is usually not a common complication.
However, in some patients bleeding may be abundant
and difficult to control. The patient population is
rather homogeneous regarding age, body mass index,
and health status, and the surgical procedures per-
formed are similar. Despite this, there is a great vari-
ance of the intraoperative blood loss. Several studies
have investigated the correlations between routine

Table 3. THROMBOELASTOGRAPHIC DATA

Base Value (N ⫽ 41) Bleeding ⱕ400 mL (n ⫽ 29) Bleeding ⬎400 mL (n ⫽ 12)

(Median [25%-75%]) (Median [25%-75%]) (Median [25%-75%]) P Value

CT (s)
ex 32 (30-37) 32 (30-37) 33 (31-42) ⬎.05
in 163 (15-171) 163 (142-171) 164 (150-174) ⬎.05
CFT (s)
ex 120 (97-140) 112 (93-131) 139 (130-152) ⬍.001
in 84 (66-92) 72 (63-92) 88 (82-96) ⬎.05
MCF (s)
ex 55 (52-59) 56 (54-60) 52 (49-55) .015
in 58 (56-62) 60 (57-63) 56 (52-58) .012
␣ Angle (°)
ex 67 (65-75) 69 (67-75) 65 (64-67) .005
in 75 (73-77) 76 (73-78) 75 (72-76) ⬎.05
ML (%)
ex 8 (7-11) 8 (7-10) 9 (7-12) ⬎.05
in 8 (6-10) 8 (6-10) 8 (7-11) ⬎.05
NOTE. Patients were separated and compared as described in Table 1. Data from patients with intraoperative blood loss above
400 mL were compared with data from patients with blood loss of 400 mL or less, and the P values were calculated with the
Mann-Whitney U test.
Abbreviations: CT, clotting time; ex, extrinsic activation pathway of TEG analysis; in, intrinsic activation pathway of TEG
analysis; ML, maximum lysis.
Madsen et al. Blood Loss During Orthognathic Surgery. J Oral Maxillofac Surg 2012.
MADSEN ET AL e551

Table 4. PREDICTIVE VALUES OF

tion) above 67° in 19 of 20 cases identified a blood
THROMBOELASTOGRAPHIC DATA loss of 400 mL or less. The overall performance of
the ␣ angle (upon extrinsic activation) to predict
Bleeding Predictive Value blood loss was established by calculation of the
⬎400 mL ⱕ400 mL Negative Positive area under the ROC curve, which showed an ade-
quate predictability of the test with an area under
CFTex 0.88 0.56
ⱖ130 s 9 7 the curve of 0.8. The ␣ angle (upon extrinsic acti-
⬍130 s 3 22 vation) is a measure of the speed of fibrin forma-
MCFex 0.86 0.45 tion, fibrin cross-linking, and clot strengthening,
ⱕ54 s 9 11 and this study suggests that these features are of
⬎54 s 3 18
MCFin
particular importance with respect to intraopera-
0.78 0.56
ⱕ54 s 5 4 tive bleeding tendency among patients subjected to
⬎54 s 7 25 orthognathic surgery. This hypothesis is further
␣ Angleex 0.95 0.62 supported by the observed significant association
ⱕ67° 11 10 between intraoperative blood loss and clot forma-
⬎67° 1 19
tion time, as well as MCF. The fibrinolytic resis-
NOTE. Patients were separated according to blood loss as tance of the clot, in contrast, seems of less impor-
described in Table 1 and grouped according to their TEG tance because we observe no association between
parameters. Negative and positive predictive values were
maximum lysis or D-dimer concentration and intra-
calculated as true negative/all negative and true positive/all
positive, respectively. operative blood loss.
Abbreviations: ex, extrinsic activation pathway of TEG To our knowledge, this study is the first to show a
analysis; in, intrinsic activation pathway of TEG analysis. correlation between TEG parameters obtained before
Madsen et al. Blood Loss During Orthognathic Surgery. J Oral surgery and intraoperative bleeding. Previous studies
Maxillofac Surg 2012. on the usefulness of TEG in the prediction of surgical
bleeding have mostly focused on open heart surgery
and cardiopulmonary bypass. Such procedures often
coagulation test results (eg, aPTT, PT, and D-dimer implicate excessive bleeding, with the need for blood
concentration) and bleeding tendency during various transfusions. Studies have shown that cardiopulmo-
surgical procedures.14,15 Routine coagulation tests nary bypass patients have a 14% risk for excessive
such as aPTT and PT do not take into account the bleeding,17 and it has been shown that intraoperative
complex interactions among coagulation factors and
inhibitors, the fibrin meshwork, and cellular compo-
nents, and clear correlations between routine tests 1.0

and intraoperative bleeding have not been ob-

served.16 TEG methods are used to analyze the vis-
coelastic properties of whole blood samples and do 0.8
take into account the interplay among coagulation
factors and inhibitors, fibrin clot properties, blood
cells, and fibrinolytic factors. Thus, TEG parameters 0.6
contribute with a more complete and comprehensive
Sensitivity

presentation of the clotting process that takes place in

the body16 than routine coagulation assays do.
0.4
A recent review states that the mean intraoperative
bleeding volume during orthognathic surgery is ap-
proximately 400 mL.1 In our study we used an intra-
operative blood loss of 400 mL as the cutoff for 0.2

separation of our study population into low- or high-

risk bleeding groups. Significant differences in 4 of
the TEG parameters were observed between the 2 0.0
0.0 0.2 0.4 0.6 0.8 1.0
bleeding groups.
1 - Specificity
To investigate the clinical usefulness of the TEG
parameters, their negative and positive predictive FIGURE 3. ROC curve for ␣ angle used to predict bleeding.
Sensitivity is plotted against 1 – specificity, corresponding to the
values were analyzed. From this analysis, it was true-positive rate against the false-positive rate. The ␣ angle is used
shown that the ␣ angle (upon extrinsic activation) to predict bleeding of 400 mL or less.
showed a particularly strong negative predictive Madsen et al. Blood Loss During Orthognathic Surgery. J Oral
value and that an ␣ angle (upon extrinsic activa- Maxillofac Surg 2012.
e552
TEG analysis contributes with a more precise classifi-
cation of these patients into low and high postoper-
ative bleeding risk compared with standard coagula-
tion tests.17 Other studies have shown a correlation
between TEG values obtained postoperatively from
heart surgery patients and postoperative bleeding ten-
dencies.18,19 Yet another study investigated the cor-
relation between preoperative TEG data and intraop-
erative bleeding in a patient group undergoing
coronary artery bypass surgery, but no correlation
was observed.6 Surgical procedures in the heart in-
volve controlled cauterization of relatively large but
few vessels, in contrast to orthognathic surgery,
which involves lesions of many small vessels. These
surgical differences may explain the lacking consis-
tency between our results and the results obtained
from patients subjected to open heart surgery.
The procedure used for quantification of intraoper-
ative blood loss in our study facilitates accurate deter-
mination of the blood volume lost during the surgical
procedure. The study population is rather small, but
the study was undoubtedly able to show a predictive
power of TEG with respect to bleeding. To consoli-
date the correlations observed during this preliminary
study, further studies on larger patient populations
are needed.
When implementing a new analysis in the clinical
setting, it is important to compare the cost of the new
analysis with conventional methods. TEG is used in-
tensively in heart and liver surgery, and cost analyses
have shown that the economic burden of TEG com-
pared with standard coagulation tests is considerably
smaller.20 In our setting, the manual workload of TEG
and routine analysis is comparable, whereas the re-
agent costs for the TEG method are less than one-fifth
of the reagent costs of the routine analysis.
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