Acta Med. Okayama, 2015
Vol. 69, No. 4, pp. 205ﾝ212
CopyrightⒸ 2015 by Okayama University Medical School.

http://escholarship.lib.okayama-u.ac.jp/amo/

Venous Thromboembolism after Total Hip Arthroplasty
Diagnosed by Enhanced Computed Tomography: Comparisonof Selective Thromboprophylaxis and No Thromboprophylaxis
Yoshiki Okadaa, Hirosuke Endob＊, Shigeru Mitanic, Kazuo Fujiwarad, Tomonori Tetsunagae,
Yohei Kagawae, Yosuke Fujiie, Toshiyuki Kunisadae, and Toshifumi Ozakie
a
b

d

‑

e
c

‑

‑

Total hip arthroplasty (THA) is the most eﬀective treatment for advanced or end-stage hip osteoarthritis. However, venous thromboembolism (VTE) remains one of its unresolved complications. We
reviewed the records of 322 patients undergoing primary THA and investigated the eﬃcacy of anticoagulant prophylaxis for VTE. Our study cohort consisted of 60 patients who received no anticoagulants, 100 patients who received a factor Xa inhibitor (fondaparinux), 100 patients who received low
molecular weight heparin (enoxaparin), and 62 patients who selectively received no anticoagulant
prophylaxis due to perioperative bleeding, weight, and/or hemoglobin concentration. Enhanced
64-slice multidetector row computed tomography was performed postoperatively for 7 days in allcases. The incidence of VTE in the four groups was 15ｵ, 9.0ｵ, 6.0ｵ, and 6.4ｵ, respectively. The
incidence of VTE was signiﬁcantly lower in the groups receiving anticoagulant prophylaxis and thegroup selectively receiving no anticoagulant prophylaxis than in the group receiving no anticoagulants.
Complications of fondaparinux therapy included hepatic dysfunction in 4 cases (4.0ｵ), minor bleedingin 2 cases (2.0ｵ), persistent wound drainage in 3 cases (3.0ｵ), and eruption in 1 case (1.0ｵ). The
complications of enoxaparin therapy were persistent wound drainage in 1 case (1.0ｵ) and progressionof anemia in 1 case (1.0ｵ). The incidence of VTE was low in patients who selectively received no
anticoagulant prophylaxis, so we conclude that anticoagulant prophylaxis should be used selectively in
THA cases.
Key words: total hip arthroplasty, venous thromboembolism, anticoagulant prophylaxis, complications

V

enous thromboembolism (VTE) is a perioperative complication of total hip arthroplasty(THA). According to the Japanese guideline for theprevention of venous thromboembolism [1], patients
Received December 1, 2014 ; acceptecl March 2, 2015.
Corresponding author. Phone :＋81ﾝ86ﾝ235ﾝ7273; Fax :＋81ﾝ86ﾝ223ﾝ9727
E-mail : hirosukeendol@yahoo.co.jp (H. Endo)＊undergoing THA are at high risk for developing VTE
and are recommended to receive preventive therapy.
The recommended methods of preventing VTE are theuse of compression stockings, intermittent pneumatic
compression (IPC), anticoagulants, and other theraConﬂict of Interest Disclosures: No potential conﬂict of interest relevantto this article was reported.

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Acta Med. Okayama Vol. 69, No. 4

pies. The usefulness of anticoagulants for the prevention of VTE has been described by the American
Academy of Orthopedic Surgeons (AAOS) and theAmerican College of Chest Physicians (ACCP) [2],as well as in recent studies [3‑5]. However, complications such as bleeding can be serious [6]. In Japan,
secondary osteoarthritis of the hip is the leading reason
for THA [7]. The operation for secondary osteoarthritis is more complicated than that for primaryosteoarthritis of the hip, so the operative time andlevels of perioperative bleeding are diﬀerent in eachcase.
Duplex ultrasonography (US) is commonly used for
VTE screening [8], but it cannot detect pulmonary
thromboembolism (PE). In our institute, enhanced
computed tomography (e-CT) was performed one week
after surgery to screen for deep vein thromboembolism (DVT) and PE simultaneously. We hypothesizedthat anticoagulant prophylaxis should be used selectively in THA cases, and that enhanced CT would bea useful screening method for asymptomatic VTE.

Materials and Methods
Patients undergoing primary THA between May
2006 and December 2010 were divided into 4 groups
after written informed consent was obtained. Based on
the method of VTE prophylaxis, group A (n ＝ 60)
received no anticoagulant prophylaxis between May
2006 and July 2007, group B (n ＝ 100) received afactor Xa inhibitor (fondaparinux; FPX) between July
Table 1

2007 and December 2008, group C (n ＝ 100) received
low molecular weight heparin (enoxaparin; LMWH)
between January 2009 and December 2010, and group
D (n ＝ 62) patients selectively received no anticoagulant prophylaxis― , neither LMWH nor FPX―
between July 2007 and December 2010 (Table 1).
The dose of FPX was 2.5mg in patients with a creatinine clearance of ＞ 30 ml/min, and 1.5mg in patientswith a creatinine clearance of 20‑30ml/min. The
dose of LMWH was 4,000IU/day in patients with acreatinine clearance of ＞ 50ml/min, and 2,000IU/dayin patients with a creatinine clearance of 30‑50ml/
min. Patients who could not receive anticoagulants
due to a volume of postoperative blood loss of ＞ 600ml
on postoperative days 0 to 2, weight ＜ 50kg, and/ora hemoglobin level of ＜ 9g/dl the day after surgery
belonged to group D. We used a navigation system toposition the acetabular cup prosthesis in all cases of
cemented THA (n ＝ 73) and cementless THA (n ＝ 249).
The transtrochanteric, anterolateral, or posterior
approach was used with the patient placed in the supine
or lateral decubitus position. All patients received
1,500ml of Ringerʼs solution or hydroxyethyl starchdaily for 3 days postoperatively. IPC was applied for
2 days postoperatively, with the application limited tonighttime hours for 1 week postoperatively, after
ambulation was permitted. In groups B and C, prophylaxis began on postoperative day 2 and was continued for 10 days. Those receiving anticoagulants suchas warfarin and heparin preoperatively, those not able
to undergo examination for VTE by e-CT because ofPatient demographics, body mass index, and operative time for each group

Group

A
No
anticoagulants

B

C

Fondaparinux

LMWH

D
No anticoagulants
selectively

Hips

60

100

100

62

Disease(OA, RA, ION)

53 : 4 : 3

83 : 8 : 9

88 : 3 : 9

41 : 12 : 9

Gender (F/M)

53 : 478 : 22

91 : 959 : 3Age

66 (41～84)

58 (35～82)

61 (40～86)

62 (25～80)

BMI

24 (14～34)

23 (16～40)

24 (17～45)

22 (14～30)

Operative time (min)115 (60～220)

103 (59～185)

101 (60～180)

113 (60～180)

LMWH, low molecular weight heparin; OA, osteoarthritis; RA, rheumatoid arthritis; ION, idiopathic osteonecrosis; F/M, female/male;
BMI, body mass index. The number of hips and gender distribution are diﬀerent in group A, because group A included 3 bilateral cases.

August 2015

VTE Incidence after THA

allergy and renal dysfunction, and those not able toreceive anticoagulants due to renal dysfunction were
excluded from this study.
Enhanced 64-slice multidetector row computed
tomography (MDCT) was performed in all 322 cases
at 7 days postoperatively, and VTE was diagnosed by
our in-hospital radiologists. Complications of anticoagulant prophylaxis including hepatic dysfunction,
bleeding, persistent wound drainage, eruptions, andprogression of anemia were assessed. Hepatic dysfunction was deﬁned as an increase in aspartate aminotransferase (AST) or alanine aminotransferase (ALT)levels by two or more times the upper limit of normal(AST 70IU/l, ALT 84IU/l). Bleeding was deﬁned as
marked swelling and internal hemorrhaging at thewound site. Persistent wound drainage was deﬁned aswound drainage that continued more than 2 weeks
postoperatively. Eruptions that developed afteradministration of anticoagulants were diagnosed bydermatologists. Progression of anemia was deﬁned asa decrease in the hemoglobin level of ＞ 2g/dl at 3 days
postoperatively; treatment with anticoagulant prophylaxis was stopped when this diagnosis was made.
Plasma D-dimer levels were also assessed with arandom access, high-volume coagulation analyzer(CS-5100; Sysmex Corporation, Kobe, Japan). The
normal range was lower than 0.9 g/ml. We also
compared the hemoglobin values and D-dimer levels ineach group on postoperative days 1, 3, 5, and 7.
Statistical analyses were carried out using SPSS
version 19.0 (IBM, New York, NY, USA). The chisquared test was used to compare the incidence of
VTE, and the unpaired Studentʼs -test was employed
to compare diﬀerences in hemoglobin and D-dimer
levels between groups. A -value of ＜ 0.05 was considered statistically signiﬁcant.
This study was conducted in accordance with theHelsinki Declaration. Ethical approval was obtained
from the institutional review board of Okayama
University (approval number: 982).

Results
A total of 9 cases of venous thromboembolism(VTE; 15ｵ), including 4 cases of deep vein thromboembolism (DVT; 6.7ｵ), 3 cases of pulmonary
embolism (PE; 5.0ｵ), and 2 cases of both DVT andPE (3.0ｵ), were detected in group A. Nine cases of207

VTE (9.0ｵ), including 6 cases of DVT (6.0ｵ), 1 caseof PE (1.0ｵ), and 2 cases (2.0ｵ) of both DVT andPE, were detected in group B. Six cases of VTE(6.0ｵ), including 4 cases (4.0ｵ) of DVT and 2 cases(2.0ｵ) of PE, were detected in group C. Four cases(6.4ｵ) of VTE, including 3 cases (4.8ｵ) of DVT and1 case (1.6ｵ) of both DVT and PE, were detected ingroup D (Fig. 1). Statistically signiﬁcant diﬀerenceswere not found between groups. There were no casesof symptomatic VTE. After thrombolytic therapy, thethrombi disappeared or became smaller on e-CT reexamination.
Complications in group B (10 cases, 10.0ｵ) included
hepatic dysfunction in 4 cases (4.0ｵ), minor bleedingin 2 cases (2.0ｵ), persistent wound drainage in 3 cases(3.0ｵ), and eruption in 1 case (1.0ｵ). Complications
in group C (2 cases, 2ｵ) included persistent wounddrainage in 1 case (1.0ｵ) and progression of anemia in
1 case (1.0ｵ). The prevalence of hepatic dysfunction
in group B was signiﬁcantly higher than that in group
C. There were no cases of severe bleeding requiring
blood transfusion.
Postoperative hemoglobin and D-dimer levels werecompared. The mean hemoglobin level was signiﬁcantly
lower in group D compared with the other groups on
postoperative day 1 (Fig. 2). The mean D-dimer level
reached its nadir on postoperative day 3 in each group,
then increased gradually, and was signiﬁcantly lower

20

(%)

DVT

PE

PE+DVT

15
10
5
0
group

15%

9%

6%

6.4%

Ａ

Ｂ

Ｃ

D

Fig. 1The bar graph shows the VTE incidence in group A(receiving no anticoagulants), group B (receiving FDX), group C(receiving enoxaparin), and group D (selectively receiving no anticoagulants). The incidences of DVT, PE, and both PE and DVT
are indicated by the white bar, striped bar, and dotted bar, respectively.

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Acta Med. Okayama Vol. 69, No. 4

in groups B and C than in groups A and D on postoperative day 7 (Fig. 3). In patients with VTE on postoperative day 7, the mean D-dimer level was ＞ 10 g/ml
in groups A and D and ＜ 10 g/ml in groups B and C(Fig. 4). If we set the cutoﬀ value for the D-dimer levelas 10 g/ml, the sensitivity in groups A, B, C, andD was 0.778, 0.556, 0.500, and 0.750, respectively.
The speciﬁcity in groups A, B, C, and D was 0.412,
0.637, 0.628, and 0.414, respectively (Table 2).
This patient was a 58-year-old Japanese
woman who underwent a closed reduction for developmental dislocation of the hip. Her height, weight, andbody mass index (BMI) were 155cm, 55kg, and 23,

11(g/dl)

18
16

※

14
12

※

10

8
6
4

Ａ

2
0

day 1

day 3

Ｃ

B

(60)

(100)

(100)

day 5
Post-op

25
※

D

(62)

day 7
※ P <0.05(μg/ml)

20
15

8

Ａ

B

(60)
7

(μg/ml)Fig. 3
The average D-dimer level in each group. Values areshown for postoperative days 1, 3, 5 and 7. Values under the groupare the cases in each group.

10

9

20

day 1

day 3

(100)
day 5

Post-op

Ｃ

(100)

D

(62)

day 7
※ P <0.05

Fig. 2
The average hemoglobin level in each group. Values areshown for postoperative days 1, 3, 5 and 7, plotted for group A(receiving no anticoagulants), group B (receiving FDX), group C(receiving enoxaparin), and group D (selectively receiving no anticoagulants), and indicated by rhombuses, squares, triangles, and Xs,
respectively. Values under the group are the cases in each group.

(A)

Fig. 5

10

5
0

Ａ
(9)

day 1

day 3

day 5

B

(9)

Ｃ
(6)

Ｄ
(4)

day 7

Post-op
Fig. 4
The average D-dimer level in VTE patients of each group.
D-dimer levels are shown on postoperative days 1, 3, 5 and 7.
Values under the group are the cases in each group.

(B)

The anteroposterior (AP) view of the hip joints in case 1. (A) Preoperative and (B) postoperative radiographs.

August 2015
Table 2VTE Incidence after THA

209

Diagnosis of VTE using a D-dimer level cutoﬀ of 10 µg/ml on postoperative day 7 in each group
A

B

C

No anticoagulants

Fondaparinux

LMWH

D
No anticoagulants
selectively

10≧

7

5

3

3

10＜

2

4

3

1

sensitivity

0.778

0.556

0.500

0.750

spesiﬁcity

0.412

0.637

0.628

0.414

Group

VTE(+)(A)(B)

Fig. 6
Enhanced CT scan of the lung and the lower leg in case 1. (A) PE was not detected in the entire lung. (B) DVT was notdetected in the lower legs, neither.

(A)

Fig. 7(B)

Anteroposterior (AP) view of the hip joints in case 2. (A) Preoperative and (B) postoperative radiographs.

respectively. Cemented THA was performed. The
operative time, intraoperative blood loss (Fig. 5A, B),
and perioperative blood loss were 175min, 500ml,
and ＞ 600ml, respectively, so she did not require
anticoagulant prophylaxis and could ambulate 2 days
postoperatively. One week after surgery, her
D-dimer level was 22.3 g/ml, but no VTE wasdetectable on e-CT (Fig. 6).
This patient was a 59-year-old American
woman who lived in Japan. She had systemic lupus

erythematosus and osteonecrosis of the right femoral
head. Her height, weight, and BMI were 168cm,
88kg, and 31, respectively. Ten years after the onsetof right coxalgia, cementless THA was performed(Fig. 7A, B). The operative time and intraoperative
blood loss were 90min and 100ml, and no bloodtransfusion, including auto-blood transfusion, wasperformed. She could ambulate with a walker 2 days
after surgery, after which prophylactic LMWH wasstarted. Seven days postoperatively, she had a hemo-

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Acta Med. Okayama Vol. 69, No. 4

(A)

(B)

Fig. 8Enhanced CT scan of the lung and the lower leg in case 2. (A) The axial image showed thrombus (arrow) in the A10
artery of the right lung. (B) The axial image revealed no DVT in the lower legs.

globin level of 6g/dl and did not complain of any
symptoms. On e-CT, a PE alone was detected (Fig.
8). Thrombolytic treatment with heparin was started.
Reevaluation by e-CT after treatment found no
thrombi and no VTE recurrence.

Discussion
In the United States and Europe, VTE has beenrecognized as a serious complication of orthopedic
surgery since the 1960s. Screening for VTE and VTE
prevention have been previously discussed [9]. Hume. [10] evaluated the incidence of lower leg DVT
in 140 THA cases by impedance phlethysmographyand 125I-ﬁbrinogen leg scanning; they found that onequarter (35 patients) had VTE and mentioned thenecessity of monitoring and routine prophylaxis.
Harris. [11] screened for VTE by cuﬀ-impedance phlebography and 125I-ﬁbrinogen scanning. They
found that the accuracy of DVT detection was 80ｵ by
cuﬀ-impedance phlebography and 78ｵ by 125I ﬁbrinogen scanning; the eﬀectiveness of cuﬀ-impedance
phlebography for detecting proximal thrombi wasnoted. Moskovitz. [12] administered low dose
heparin for prevention of VTE in 67 patients undergoing THA. In their randomized double-blinded study,
they used 125I-ﬁbrinogen and venography to ﬁnd VTE
and radionuclide lung scanning to detect the onset of
PE. VTE incidence was signiﬁcantly lower in theprophylactic heparin group (23ｵ) than in the placebogroup (59ｵ). However, the prophylactic heparingroup required a signiﬁcantly larger volume of transfused blood than the placebo group.

Two decades after these reports, VTE began to berecognized as a major complication of hip and knee
arthroplasty in Japan. Using venograms to screen for
VTE in 164 THA cases, Fujita. [13] found
DVT in 22.6ｵ and proximal DVT in 9.8ｵ. At our
institute, Shiota. [14] used bilateral venography
to screen 54 patients with THA and found DVT in 22of these cases (40.1ｵ). As a result of their report,
the use of IPC and early ambulation are now recommended in Japan. Recently, anticoagulant prophylaxis
was also initiated for cases of TKA, THA, and hip
fracture in Japan.
In a double-blinded, randomized study of the eﬃcacy
of fondaparinux (FDX; placebo, 0.75, 1.5, 2.5, and3.0mg) in 74, 62, 65, 68, and 70 patients, respectively, Fuji
. [15] reported that the incidence ofVTE (detected by ascending venography 11‑17 days
postoperatively) was 33.8ｵ, 24.2ｵ, 4.6ｵ, 7.4ｵ,
and 9.5ｵ, respectively. Although there was a doseresponse eﬀect, there were no statistically signiﬁcantinter-group diﬀerences in major events; it was concluded that FDX has a favorable beneﬁt-to-risk proﬁlein patients with VTE. Yamaguchi. [3] administered 2.5mg of FDX for 2 postoperative weeks to 71
patients undergoing THA and screened for VTE byultrasonography on postoperative days 1, 4, and 14.
DVT was detected in 27ｵ of patients on postoperative day 4, but in only 11.9ｵ of patients on postoperative day 14. Yukizawa. [16] investigated 170
THA cases, including 67 cases treated with IPC only
and 103 cases treated with IPC and FDX. The incidence of VTE detected by MDCT and duplex ultrasonography was 25ｵ in patients treated with IPC

August 2015

only and 8ｵ in patients treated with IPC and FDX.
These recent reports indicate that anticoagulant prophylaxis is eﬀective for the prevention of VTE in THA
cases.
In our study, VTE was detected by 64-slice MDCT
7 days postoperatively, and the VTE incidence was
15ｵ in group A (no anticoagulants), 9ｵ in group B(FDX), and 6ｵ in group C (LMWH). The diﬀerence
between groups was not statistically signiﬁcant.
However, previous reports indicated a decrease in
VTE incidence as a result of prophylaxis [3, 15,17]. VTE incidence was lower in our report than in
Shiotaʼs report [14]; prophylaxis for VTE consistedof only IPC without anticoagulants and patients ambulated 1 week postoperatively. For this reason, we
consider that anticoagulant prophylaxis and an early
ambulation protocol will decrease VTE incidence.
Duplex ultrasonography is a common VTE screening method because of its low cost and convenience.
On the other hand, e-CT has some disadvantages suchas exposure to radiation, allergy to iodinated contrast
media, and high cost. However, the e-CT scan covers
the entire body and can detect sites of PE and DVT
simultaneously. In the current study, 1.9ｵ, 5.3ｵ,
1.6ｵ, and 8.7ｵ of all 322 patients had PE, DVT,
PE ＋ DVT, and VTE 1 week postoperatively,
respectively; PE completely resolved on reexamination. Thus, we consider that the PEs detected bye-CT were not fat emboli, so e-CT is needed forscreening of asymptomatic VTE.
When using the D-dimer level as a screening test
for VTE 1 week postoperatively, Shiota. [14]
set the cutoﬀ value at 10 g/ml. In our current study,
the D-dimer level at 1 week postoperatively was signiﬁcantly higher in groups A and D ( ＞ 10 g/ml) thanin groups B and C, so we set the cutoﬀ value at
10 g/ml to screen for VTE at 1 week postoperatively.
Yukizawa. [16] deﬁned the cutoﬀ value as theincrease in plasma soluble ﬁbrin and plasminogenactivator inhibitor-1 levels from the preoperative to
1-day postoperative period, and found that the sensitivity and speciﬁcity were 100ｵ and 67ｵ, respectively, in the IPC group and 88ｵ and 97ｵ, respectively, in the FDX group. They also mentioned that
it was ineﬃcient to investigate the D-dimer level as amarker for VTE 1 week postoperatively, because theplasma D-dimer level increases following thrombus
cleavage and activated plasmin is already formed. In

VTE Incidence after THA

211

the current study, the average plasma D-dimer levelin the groups with anticoagulant prophylaxis was lower
than that in those receiving no anticoagulant prophylaxis (Fig. 3 and 4). It is useful to set a D-dimer cutoﬀ
value of 10 g/ml in the cases receiving no anticoagulant prophylaxis, but this does not apply in the anticoagulant prophylaxis cases (Table 2). Shimoyama.
[17] reported that a preoperative D-dimer level of
0.85 g/ml is a useful screening tool for VTE.
Although they concluded that the evaluation of VTE
risk before surgery is useful, their study included afairly small number of cases. In the current study, thepreoperative D-dimer level was not determined for allcases, and thus further prospective research is needed.
Bleeding is an inevitable complication of anticoagulant prophylaxis, as previously reported [6, 12].
Although the ACCP recommends the use of enoxaparin sodium for VTE prophylaxis, Burnett.
[6] reported that major complications such as bleeding
occurred 3 times more often in patients receiving
enoxaparin sodium prophylaxis than in those treatedwith prophylactic warfarin. In this study, the incidence of VTE was low in both the FDX and LMWH
groups, but without a signiﬁcant diﬀerence between
the 2 groups. The complication rate was higher in the
FDX group. VTE incidence was as low in the group
selectively receiving no anticoagulant prophylaxis, asin the groups receiving anticoagulant prophylaxis.
VTE was not symptomatic in this series, so we consider that it is suﬃcient to use anticoagulants selectively for VTE prophylaxis. Sugano. [18]
reviewed 3016 patients undergoing elective hip surgery. Patients received intraoperative IPC, early
ambulation, postoperative compression stockings, andprophylactic IPC. Although one patient with PE(0.003ｵ) and 4 patients with DVT (0.013ｵ) were
symptomatic, no case of PE was fatal. In our study,
all cases of VTE were detected by e-CT. In Suganoʼsstudy, no deaths had occurred within 6 months oftreatment, even in symptomatic cases. They concluded
that mechanical thromboprophylaxis without anticoagulant prophylaxis was eﬀective enough. Although we
agree with their opinion, not all their patients werescreened. We consider that the incidence of asymptomatic VTE in THA cases is higher than previously
reported and the risk of death in patients with asymptomatic PE remains high.
Our study was limited in that it had a retrospec-

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Okada et al.

Acta Med. Okayama Vol. 69, No. 4tive design and was not a randomized controlled trial.
In addition, there was a signiﬁcant bias in gender andthe cause of THA between the 4 groups. Finally, we
did not continue to screen for VTE after discharge.
In the future, a randomized controlled trial with alarge number of patients, as well as more detailed
pre- and postoperative assessments, will be needed.
In conclusion, we investigated the postoperative
VTE incidence in THA cases for which anticoagulant
prophylaxis was applied selectively based on e-CT.
The results indicated that THA cases with perioperative blood loss ＞ 600ml and a hemoglobin level ＜ 9.0g/
dl may not need anticoagulant prophylaxis to avoid thecomplication of bleeding.
Acknowledgments. The authors thank the following for theircontributions: Dr. Hiroshi Minagawa, Dr. Yoshiaki Miyake, and all theorthopedic surgeons at Okayama University (Hospital) who participated inthis study.

7.

8.

9.
10.

11.

12.

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