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Difference in the Changings of Blood Coagulation Fibrinolysis Markers Before and After Spinal Surgery in Adolescent and Elderly Patients

Hideaki Watanabe, Hirokazu Inoue, Yasuyuki Shiraishi, Ryo Sugawara, Shinya Hayasaka, Ichiro Kikkawa, Katsushi Takeshita

Hideaki Watanabe, Ryo Sugawara, Ichiro Kikkawa, Department of Pediatric Orthopedic Surgery, Jichi Children’s Medical Center, Tochigi, Japan
Hirokazu Inoue, Yasuyuki Shiraishi, Katsushi Takeshita, Department of Orthopedic Surgery, Jichi Medical University, Tochigi, Japan
Shinya Hayasaka, Department of Health Science, Daito Bunka University, Saitama, Japan

Conflict-of-interest statement: The author(s) declare(s) that there is no conflict of interest regarding the publication of this paper.

Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http: //creativecommons.org/licenses/by-nc/4.0/

Correspondence to: Hideaki Watanabe, MD, Department of Pediatric Orthopedic Surgery, Jichi Children’s Medical Center, Tochigi, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.
Email: ujjj187kotsuko@gmail.com
Telephone: +81-285-58-7374
Fax: +81-285-44-1301

Received: February 24, 2017
Revised: March 20, 2017
Accepted: March 21 2017
Published online: April 28, 2017

ABSTRACT

AIM: The purpose of this study is to investigate the differences in changing of blood coagulation and fibrinolysis markers before and after spinal surgery in adolescent and elderly patients.

MATERIALS AND METHODS: This retrospective two-center study enrolled 56 low-risk patients between October 2012 and April 2015. 27 adolescent idiopathic scoliosis (AIS) patients (3 boys, 24 girls; mean age 15 years) underwent instrumentation for posterior fusion. 29 lumbar spinal canal stenosis (LSCS) patients (15 men, 14 women; mean age 71 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 at 1 day preoperatively and on postoperative days (PODs) 1, 3, and 7.

RESULTS: 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 continuously higher postoperative PAI-1 levels in older patients could be associated with the development and progression of symptomatic VTE.

Key words: Venous thromboembolism; Adolescent idiopathic scoliosis; D-dimer; Soluble fibrin monomer complex; Plasminogen activator inhibitor type 1

© 2017 The Author(s). Published by ACT Publishing Group Ltd. All rights reserved.

Watanabe H, Inoue H, Shiraishi Y, Sugawara R, Hayasaka S, Kikkawa I, Takeshita K. Difference in the Changings of Blood Coagulation Fibrinolysis Markers Before and After Spinal Surgery in Adolescent and Elderly Patients. International Journal of Orthopaedics 2017; 4(2): 719-723 Available from: URL: http: //www.ghrnet.org/index.php/ijo/article/view/2011

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 very few 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 of 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 differences in the changes in blood coagulation and fibrinolysis markers before and after spinal surgery in adolescent and older patients and to attempt to explore the reasons for VTE development after spinal surgery.

MATERIALS AND METHODS

The ethics review board of our university approved this 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 very few, and there is a problem with the exposure dose for young patients.

We enrolled 56 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 29 older patients (15 men, 14 women; mean age 71 years, range 52-88 years) with lumbar spinal canal stenosis (LSCS) underwent laminectomy for posterior decompression (Figure 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.

Figure 1 Flow chart 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.

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) at 1 day preoperatively and on postoperative days (PODs) 1, 3, and 7 (Figure 2). 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].

Figure 2 Flow chart of blood samples. Blood samples were obtained to measure the plasma levels of soluble fibrin monomer complex, D-dimer, and plasminogen activator inhibitor type 1 at 1 day preoperatively and on postoperative days 1, 3, and 7.

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 preoperatively were compared with those on 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 was compared with an unpaired t-test. And volume of intraoperative hemorrhage, and operation time were compared with Mann-Whitney test. The level of statistical significance was set at p < 0.05 for all tests.

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 PODs 1 (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 3). 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 4).

Figure 3 Changes in soluble fibrin monomer complex (SFMC), D-dimer, and plasminogen activator inhibitor type 1 (PAI-1) levels before and after surgery in the AIS group. Open circles: outliers. *External value. pre, preoperatively. **P < 0.05, versus the preoperative level according to the Wilcoxon signed rank test with correction by Bonferroni’s inequality.

Figure 4 Changes in SFMC, D-dimer, and PAI-1 levels before and after surgery in the LSCS group. Open circles,outliers. *External value. pre, preoperatively. **P < 0.05, versus the preoperative level according to the Wilcoxon signed rank test with correction by Bonferroni’s inequality.

Changes in blood coagulation and fibrinolysis markers after LSCS surgery

The SFMC level was significantly higher on POD 1 (median 3.7 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 3.6 μg/mL, p = 0.01), 3 (median 1.9 μg/mL, p = 0.01), and 7 (median 5.0 μg/mL, p = 0.01) than preoperatively (median 0.6 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 4).

There were significant differences between the two groups with regard to age, sex, volume of intraoperative hemorrhage, and operation time (Table 1).

Table 1 Patient Demographics.
  AISLSCSP
Mean age (range) 15 yr (11-19) 71 yr (52-88)0.01*
Sex (Male:Female)3:2415:140.01**
Mean intraoperative hemorrhage (range) 653 ml (0-1285) 147 ml (20-460)0.01***
Mean operation time (range) 430 min (238-799) 99 min (37-203)0.01***
Operation area (range)11 vertebral bodies (5-14)3 vertebral bodies (2-5)0.01***
AIS, Adolescent idiopathic scoliosis; LSCS, Lumbar spinal canal stenosis; *Unpaired t-test; **Fisher's exact test, ***Mann-Whitney U-test

DISCUSSION

In daily clinical practice, orthopedic surgeons are aware that the incidence of VTE after orthopedic surgery in young patients is very few 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 POD 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. Hamidi et al.[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. A few studies have compared these markers in patients with and without VTE only after spinal surgery. Based on these two data from the patients without VTE of Hamidi and Yoshioka, we speculated that SFMC levels on POD 1 and D-dimer levels on PODs 1, 3, and 7 would be elevated before and after spinal surgery without VTE, 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 1 and 3 represent responses without VTE, those means 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 7 in patients with VTE following total hip arthroplasty. Watanabe et al.[15] reported that the PAI-1 level 90 s 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 very few in this age group[4,5]. The other limitations are that the same spinal surgery in adolescent and old patients was not undergone and the sample size was relatively small.

CONCLUSIONS

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 continuously higher level of postoperative PAI-1 in older patients could be associated with the development and progression of symptomatic VTE.

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Peer reviewer: Thomas Pagonis

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