Research Article
Changes in Blood Coagulation and Fibrinolysis Markers Before and After Spinal Surgery in Adolescent and Older Patients
Hideaki Watanabe1*, Hirokazu Inoue2, Akira Murayama2, Shinya Hayasaka3, Ichiro Kikkawa1 and Katsushi Takeshita2
1Department of Pediatric Orthopedic Surgery, Jichi Children’s Medical Center, Japan
2Department of Orthopedic Surgery, Jichi Medical University, Japan
3Department of Human Life Sciences, Tokyo City University, Japan
*Corresponding author: Hideaki Watanabe, Department of Pediatric Orthopedic Surgery, Jichi Children’s Medical Center, 3311-1 Yakushiji, Shimotsuke, Tochigi 329- 0498, Japan
Published: 22 Dec 2016
Cite this article as: Watanabe H, Inoue H, Murayama A,
Hayasaka S, Kikkawa I, Takeshita K.
Changes in Blood Coagulation and
Fibrinolysis Markers Before and After
Spinal Surgery in Adolescent and Older
Patients. Clin Surg. 2016; 1: 1255.
Abstract
Aim: To investigate changes in blood coagulation and fibrinolysis markers before and after spinal surgery in adolescent and older patients and to explore possible reasons for the development of
postoperative venous thromboembolism (VTE).
Methods: This retrospective two-center study enrolled 57 low-risk patients who underwent spinal
surgery at either our children’s institution or our public hospital between October 2012 and April
2015. Altogether, 27 adolescent idiopathic scoliosis (AIS) patients (3 boys, 24 girls; mean age
15 years, range 11–19 years) underwent instrumentation for posterior fusion. Also, 30 lumbar
spinal canal stenosis (LSCS) patients (16 men, 15 women; mean age 71 years, range 52–88 years)
underwent laminectomy for posterior decompression. Plasma levels of soluble fibrin monomer
complex (SFMC), D-dimer, and plasminogen activator inhibitor type 1 (PAI-1) were measured 1
day preoperatively and on postoperative days (PODs) 1, 3, and 7.
Results: No patients in this study developed symptomatic or asymptomatic VTE postoperatively.
The SFMC level showed significant increases on PODs 1 and 3 in the AIS patients and on POD 1
in the LSCS patients. The D-dimer level showed significant increases on PODs 1, 3, and 7 in both
groups. The PAI-1 levels showed significant increases on POD 7 in the AIS patients and on PODs 1,
3, and 7 in the LSCS patients.
Conclusion: The significantly higher postoperative PAI-1 levels in older patients could be associated
with the development and progression of symptomatic VTE.
Keywords: Venous thromboembolism; Adolescent idiopathic scoliosis; Spinal surgery; Blood coagulation-fibrinolysis marker; D-dimer; Soluble fibrin monomer complex; Plasminogen activator inhibitor type 1
Introduction
Venous thromboembolism (VTE) is a common complication after spinal surgery in adults.
It is important to identify postoperative VTE, particularly fatal pulmonary embolism (PE) and
symptomatic PE, which can be life threatening. Antithrombotic drugs are administered to reduce
the postoperative risk of VTE, but these medications cannot be administered during or after spinal
surgery because of the risk of postoperative paralysis resulting from hematoma. The overall reported
incidence of symptomatic deep vein thrombosis (DVT) associated with spinal surgery ranges from
0.3% to 31.0% [1], and that of symptomatic VTE associated with spinal fusion surgery is 0.4% [2]. In
Japan, the reported incidence of symptomatic PE is 0.6% [3] and that of asymptomatic VTE is 19%
(DVT 5%, PE 18%) [3].
The incidence of VTE after spinal surgery in adolescent patients [4,5], as in younger children
[6,7], is rare compared with the incidence among older patients. It is not known how blood
coagulation and fibrinolysis, which are related to VTE, change after spinal surgery in adolescent
patients, whereas a few studies have investigated those changes in older patients. It is possible that
VTE could be prevented if differences in the changes in blood coagulation and fibrinolysis markers
after spinal surgery in adolescent and older patients without VTE could be clarified. The purpose
of this study was to investigate the changes in blood coagulation and
fibrinolysis markers before and after spinal surgery in adolescent
and older patients and to attempt to determine the reasons for VTE
development after spinal surgery.
Figure 1
Figure 1
Flowchart of the 36 patients before surgery in the LSCS group. DVT: Deep Vein Thrombosis; LSCS: Lumbar Spinal Canal Stenosis; n: Number of Patients; PE: Pulmonary Embolism; VTE: Venous Thromboembolism
Figure 2
Materials and Methods
The ethics review board of our university approved the study
protocol. This retrospective two-center study enrolled patients who
underwent spinal surgery at our children’s institution or public
hospital between October 2012 and April 2015. Patients with a
past history of symptomatic VTE, cerebral hemorrhage, cerebral
infarction, cardiac infarction, or allergy to contrast medium were
excluded from the study. Patients with liver disease, renal disease,
or congenital clotting factor deficiencies and those undergoing
antithrombotic therapy or hemodialysis were also excluded, as were
older patients with asymptomatic VTE diagnosed with preoperative
and postoperative contrast-enhanced 16-row multidetector row
computed tomography (MDCT) (Figure 1). Older patients with
hypertension, diabetes mellitus, or rheumatoid arthritis were included
in this study. We did not investigate preoperative and postoperative
VTE with MDCT in adolescent patients because the incidence of VTE
before and after spinal surgery in this age group is rare, and there is a
problem with the exposure dose for young patients.
We enrolled 57 consecutive low-risk patients who underwent
spinal surgery. A total of 27 patients (3 boys, 24 girls; mean age 15
years, range 11–19 years) with adolescent idiopathic scoliosis (AIS)
underwent instrumentation for posterior fusion. A group of 30 older
patients (15 men, 15 women; mean age 71 years, range 52–88 years)
with lumbar spinal canal stenosis (LSCS) underwent laminectomy
for posterior decompression (Figure 1). There were significant
differences between the two groups with regard to age, sex, volume of
intraoperative hemorrhage, and operation time (Table 1).
Instrumentation for posterior fusion and laminectomy for
posterior decompression were performed under general anesthesia,
with all patients in a prone position. During and after surgery, both
groups of patients wore elastic stockings and used an intermittent
pneumatic compression device until the initiation of walking
training, in accordance with the Japanese Guideline for Prevention
of Venous Thromboembolism [8]. No postoperative prophylactic
antithrombotic therapy was administered in either group. If a patient
developed symptomatic VTE, the study was discontinued and
aggressive antithrombotic therapy initiated.
Blood coagulation and fibrinolysis markers
Blood samples were obtained to measure the plasma levels of
soluble fibrin monomer complex (SFMC), D-dimer, and plasminogen
activator inhibitor type 1 (PAI-1) 1 day preoperatively and on
postoperative days (PODs) 1, 3, and 7. Citrated plasma samples were
stored at –80°C until analysis. Plasma SFMC and D-dimer levels
were measured with latex immunoagglutination assays (Mitsubishi
Chemical Medience Corporation, Tokyo, Japan) using the
monoclonal antibodies IF-43 and JIF-23, respectively [9,10]. Plasma
PAI-1 levels were measured with a latex photometric immunoassay
(Mitsubishi Chemical Medience Corporation) using the polyclonal
antibody F(ab′) fragment [11].
Statistical analysis
Statistical analyses were performed with IBM SPSS for Windows,
version 20.0 (SPSS, Chicago, IL, USA). If the SFMC, D-dimer, and
PAI-1 levels did not fit a normal distribution, they were analyzed
using the Shapiro–Wilk test. The SFMC, D-dimer, and PAI-1 levels
1 day preoperativelywere compared with thoseon PODs 1, 3, and 7
using the Friedman test. If a significant difference was noted, the data
were compared using the Wilcoxon signed rank test and corrected
with Bonferroni’s inequality. Patients’ sex in the AIS and LSCS groups
was compared with Fisher’s exact test. Age, volume of intraoperative
hemorrhage, and operation time were compared with an unpaired
t-test. The level of statistical significance was set at P< 0.05 for all tests.
Table 1
Results
No patients in either the AIS or LSCS group developed
symptomatic VTE after spinal surgery. Also, MDCT showed that
none of the patients in the LSCS group developed asymptomatic VTE
after spinal surgery.
Changes in blood coagulation and fibrinolysis markers after AIS surgery
The SFMC level was significantly higher on PODs1 (median
10.0 μg/ml, P = 0.01) and 3 (median 10.0 μg/ml, P= 0.01) than
preoperatively (median 3.0 μg/ml) (Figure 2). The D-dimer level
was significantly higher on PODs 1 (median 1.8 μg/ml, P =0.01), 3
(median 2.8 μg/ml, P=0.01), and 7 (median 5.5 μg/ml, P=0.01) than
preoperatively (median 0.3 ng/ml) (Figure 2). The PAI-1 level was
significantly higher on POD 7 (median 16.0 ng/ml, P=0.01) than
preoperatively (median 14.0 ng/ml) (Figure 2).
Changes in blood coagulation and fibrinolysis markersafter LSCS surgery
The SFMC level was significantly higher on POD 1 (median 3.6
μg/ml, P=0.01) than preoperatively (median 2.9 μg/ml) (Figure 3).
The D-dimer level was significantly higher on PODs 1 (median 3.5
μg/ml, P=0.01), 3 (median 1.9 μg/ml, P=0.01), and 7 (median 4.8 μg/
ml, P=0.01) than preoperatively (median 0.5 μg/ml) (Figure 3). The
PAI-1 level was significantly higher on PODs 1 (median 25.0 ng/ml,
P=0.01), 3 (median 25.0 ng/ml, P=0.01), and 7 (median 30.0 ng/ml,
P=0.01) than preoperatively (median 17.0 ng/ml) (Figure 3).
Discussion
In daily clinical practice, orthopedic surgeons are aware that the
incidence of VTE after orthopedic surgery in young patients is rare
compared with the incidence in older patients. There are few articles
to prove this difference, however, because young and older patients
do not undergo the same surgery. For this reason, we selected the
most popular spinal surgery performed in these two groups- although
there was the difference in the severity of the surgery between the
groups- and compared three markers in each before and after surgery.
The significant elevations in SFMC and D-dimer levels beginning
on POD 1 indicated that changes in coagulation and fibrinolysis
developed at an early stage after spinal surgery in patients treated
for AIS and for LSCS. After this initial increase, coagulation was
inhibited and fibrinolysis remained activated. After that, fibrinolysis
was inhibited on PODs 3−7, as indicated by the significantly elevated
PAI-1 levels on those days in both the AIS and LSCS groups.
Few studies have investigated changes in blood coagulation and
fibrinolysis markers before and after spinal surgery, although a few
have compared these markers in patients with and without VTEbut
only after spinal surgery. Hamidi and Riazi [12] reported that
D-dimer levels were significantly elevated on PODs 1,3, and 10 in
spinal surgery patients with VTE compared with those without VTE.
Yoshioka et al. [13] reported that SFMC levels were significantly
elevated on POD 1 and that D-dimer levels were significantly elevated
on POD 7 in spinal surgery patients with VTE compared with those
without VTE. Based on these data from the patients without VTE,
we speculated that SFMC levels on POD 1 and D-dimer levels on
PODs 1,3, and 7 would be elevated, although the elevation was not
statistically significant. And based on our results and those from past
articles, we think it is possible that the elevation in the D-dimer levels
on PODs 1,3, and 7 and the elevated SFMC on PODs 1and 3 represent
normal coagulation−fibrinolysis responses after spinal surgery. Also,
based on the data from the past articles, changes in the D-dimer and
SFMC levels after spinal surgery might be greater in patients with
VTE than in those without VTE.
The PAI-1 level on PODs 1−3 was significantly higher in our
patients treated for LSCS than in those treated for AIS. These findings
indicate that older patients had more coagulative changes inhibiting
fibrinolysis than did the adolescent patients because it is more difficult
for older patients to form a thrombus. The significantly higher level
of postoperative PAI-1 in older patients could be associated with
the development and progression of symptomatic VTE. Few studies
have investigated PAI-1 levels in patients undergoing spinal surgery.
Yukizawa et al. [14] reported that PAI-1 levels were significantly
elevated on PODs 1 and 7in patients with VTE following total hip
arthroplasty. Watanabe et al. [15] reported that the PAI-1 level 90s
after release of a pneumatic tourniquet during total knee arthroplasty
was significantly elevated in patients with VTE. PAI-1 inhibits
plasminogen activator and leads to production of fibrin or thrombus
[16]. We believe that continuously inactivated fibrinolysis due to
PAI-1 may lead to VTE in older patients after spinal surgery.
A limitation of this study is that we did not investigate postoperative
VTE using modalities such as MDCT or ultrasonography in the
adolescent patients because the incidence of VTE after spinal surgery
is rare in this age group [4,5]. Another limitation is that the sample
size was relatively small.
Conclusion
We investigated changes in blood coagulation and fibrinolysis markers before and after spinal surgery in adolescent and older patients. The PAI-1 level was significantly elevated on PODs 1−3 after spinal surgery in patients treated for LSCS compared with that of patients treated for AIS. The significantly higher level of postoperative PAI-1 in older patients could be associated with the development and progression of symptomatic VTE.
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