Incidence and Risk Factors for Venous Thromboembolism After Spine Surgery in Korean Patients

Original Article

Incidence and Risk Factors for Venous Thromboembolism After Spine Surgery in Korean Patients Ji Hyun Park1, Kyung Eun Lee2, Yun Mi Yu3, Youngja Hwang Park1, Soo An Choi1

BACKGROUND: Data regarding the incidence of venous thromboembolism (VTE) after spine surgery are scarce. Identifying ideal candidates for pharmacologic thromboprophylaxis and balancing the risk of thromboembolic complications against the risk of permanent neurologic deficits from a spinal epidural hematoma (SEH) are difficult. Even guidelines cannot suggest the standard of thromboprophylaxis.

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OBJECTIVES: This study aimed to identify the incidence of and risk factors for VTE after spine surgery in the Korean population. In addition, the rate of pharmacoprophylaxis and the incidence of SEH after spine surgery were analyzed.

venous disease, cancer, respiratory disease, prolonged surgery hours, and increased total blood loss. Hospitalrelated risk factors were the location and hospital size. CONCLUSIONS: On the basis of the incidence of VTE and the risk factors, more active prophylaxis is suggested for patients in the Korean population who undergo spine surgery.

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METHODS: The study cohort was generated by extracting patients with disease codes of spine surgery and VTE from the Health Insurance Review & Assessment Service National Inpatient Sample in 2014. After analyzing the incidence of VTE after spine surgery, a univariate comparison was performed to examine the possible relationship between the incidence of VTE and the independent variable. Variables found to be significant were included in a multivariable analysis model for further analysis.

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RESULTS: The incidence of VTE was 2.09% among all 21,261 patients who had spine surgery, and prophylaxis was applied to 7.89% of all patients who had spine surgery. Comorbidities and surgery-related risk factors were

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Key words HIRA-NIS-2014 - Incidence - Risk factors - Spine surgery - Venous thromboembolism -

Abbreviations and Acronyms DVT: Deep vein thrombosis HIRA-NIS-2014: Health Insurance Review & Assessment Service National Inpatient Sample in 2014 KOICD-6: 6th Korean Center for Disease Classification and Information codes MSSY: Main Surgery Statistical Yearbook NHI: National Health Insurance PE: Pulmonary embolism SD: Standard deviation

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INTRODUCTION

V

enous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), is a serious complication and can lead to patient mortality. Although there is a risk of VTE after all surgery, major orthopedic surgery of the lower limbs, trauma, and spinal cord injury are associated with the highest risks for VTE.1-3 To reduce the postoperative complications associated with VTE, there has been extensive research on the benefits of thromboprophylaxis after orthopedic surgeries.4-8 International consensus statements recommend routine thromboprophylaxis in patients who are undergoing major orthopedic surgery.1,2 Pharmacoprophylaxis for VTE has not been routinely provided in Asian patients because postoperative VTE has been considered rare.9,10 However, recent studies have shown a significant incidence of VTE after major orthopedic surgeries in the Asian population.11,12 In 2012, a Korean study on the incidence of VTE during the 90-day period after hip and knee surgeries13 showed

UFH: Unfractionated heparin VTE: Venous thromboembolism From the 1College of Pharmacy, Korea University, Sejong-si, Korea; 2College of Pharmacy, Yeonje-ri, Osong-eup, Heungdeok-gu, Chungbuk National University, Cheongju-si, Republic of Korea; and 3College of Pharmacy, Yonsei University, Yeonsu-gu, Incheon, Republic of Korea To whom correspondence should be addressed: Soo An Choi, Ph.D. [E-mail: [email protected]] Ji Hyun Park and Kyung Eun Lee contributed equally to this work. Citation: World Neurosurg. (2019) 128:e289-e307. https://doi.org/10.1016/j.wneu.2019.04.140 Journal homepage: www.journals.elsevier.com/world-neurosurgery Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2019 Elsevier Inc. All rights reserved.

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that the overall incidence was 3.9% and 3.8%, respectively. Since this nationwide epidemiologic study, pharmacoprophylaxis after knee/hip replacement has been routinely offered in high-risk patient groups without contraindications. Knee and hip arthroplasty are the seventh and fifteenth most frequently performed surgeries in Korea, respectively.14 Spine surgery is the fourth most common surgery in Korea, but the annual number of these surgeries is increasing. No universal guidelines exist for thromboprophylaxis, because the incidence of and predisposition for a VTE after spine surgery have not been well documented.15-19 In addition, the occurrence of spinal epidural hematoma (SEH), which is a unique complication of spine surgery, makes postoperative management of spinal surgery more difficult.20 Pharmacoprophylaxis after spine surgery is generally not recommended because of the risk of SEH, which can cause permanent neurologic deficits.21,22 Because of the heterogeneous nature of SEH and the lack of available literature on the subject, the use of antithrombotic prophylaxis varies depending on the preferences of the spine surgeon.23,24 In addition, other epidemiologic information, such as risk factors related to VTE after spine surgery, is scarce.25-28 A study that analyzed a large Asian patient database would provide a unique contribution to the elucidation of the incidence of VTE in patients undergoing spine surgery. Therefore, the first aim of this study was to identify the incidence and risk factors of VTE in the Health Insurance Review and Assessment Service National Inpatient Sample of 2014 (HIRA-NIS-2014) data set, including the incidence of SEH and the use of prophylactic medications in patients undergoing spine surgery. The second aim was to derive the stratification of the risk into high, medium, and low categories based on the risk scales.

The analysis in this study was based on the number of pertinent cases instead of patients, because 1 patient could receive multiple spine surgeries during the study period. Spine Surgery Case Selection The Korean NHI annually publishes the Main Surgery Statistical Yearbook (MSSY), which includes a variety of current statistical information pertaining to 33 major types of surgery, to provide an important source of health data for the establishment of health and medical policies on a national scale.14 The MSSY contains surgery codes for each of 33 major types of surgery based on the Organization for Economic Co-operation and Development surgery codes as well as additional surgery codes pertaining to specific situations in Korea. Using the spine surgery codes from MSSY-2014, the case information from spine surgeries was extracted from Table 30 of the HIRA-NIS-2014. The disease codes of DVT and PE were extracted from previous nationwide epidemiologic research on VTE after knee and hip arthroplasty.32 For further code information identifying patients who underwent spine surgery, refer to Supplementary Table 1.

METHODS

VTE Case Selection VTE cases were extracted from Table 20 and Table 40, which referenced extant studies on VTE incidence and artificial knee/hip replacement surgeries in Korea (the claim codes are found in Supplementary Table 1).32 If a code of DVT or PE was detected within 90 days after spine surgery or after the discharge date, the case was considered a postoperative VTE. Cases with VTE before spine surgery or 90 days after spine surgery were excluded from the VTE group. For patients with multiple VTE events within 90 days of the surgery, only the first event was considered. Multiple VTE events during a subsequent hospitalization were also counted as 1.

National Inpatient Sample 2014 The Korean National Health Insurance (NHI) system covers approximately 98% of the total population of the Republic of Korea, and 99% of NHI claims have been electronically transferred since 2005.29 The HIRA (Seoul, South Korea) database provides scholars in medicine with stratified randomly sampled patient data. The HIRA-NIS-2014 data set represents approximately 700,000 inpatients (13%) and 400,000 outpatients (1%) who used medical services from January 1, 2014 to December 31, 2014.30 The HIRA-NIS-2014 comprises 5 tables: Table 20, Table 30, Table 40, Table 53, and the hospital information table. Table 20 contains general claim data including demographic information such as age, sex, type of insurance, and the patient’s visiting period to the clinic. In addition, it contains sample weights that are incorporated into the final analysis and represent > 97% of the underlying population. Table 30 contains specific information about the medical services provided. Table 40 contains detailed disease information and diagnostic information, such as all currently active diseases for the visit. Table 53 contains outpatient prescriptions. The hospital information table provides information on the geographic location, type of hospital, number of beds, and number of medical staff, including doctors and nurses.31 The hospital classifications are tertiary general hospital, general hospital, hospital, and clinic.30

Use of Pharmacoprophylactics In most reports and guidelines on VTE prevention, the use of VTE prophylactics is categorized as follows: mechanical and pharmacologic.33 The medications that are generally provided as pharmacoprophylactics were identified from the treatment and prevention guidelines or well-known reports on VTE.19,34,35 Table 1 lists the recommended preventive medications for VTE. The matched drug codes for each medication in Table 30 were extracted using the HIRA service medicine reference information, based on a previous national research project on VTE incidence after knee/hip arthroplasty in the Korean population.13,36 Patients who had spine surgery were considered to be on pharmacoprophylaxis during their hospitalization if they took any 1 of the following medications: aspirin, direct thrombin inhibitor, factor Xa inhibitors, low-molecular-weight heparin, unfractionated heparins (UFHs), and warfarin. Taking account of the versatile use of UFH in the inpatient setting, we detected only cases with the recommended dosing regimen for pharmacoprophylaxis. If UFH is used 0.2, 0.4, 0.6, or 0.9 (of a vial of 25,000 IU/ 5 mL) per day, it is regarded to be used for VTE prevention, because the recommended VTE prophylactic dosing is 5000 or 7500 IU 2 or 3 times a day.37-42 If UFH is used 1, 2, or 3 (25,000 IU/ vial) per day, it is also counted as VTE prevention, because the nurse could input the number of unit of bottles instead of the real

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Table 1. Pharmacoprophylaxis Medications Recommended by Major Practice Guidelines Last Updated Year

Recommendations For

American Academy of Orthopaedic Surgery

2009

Total hip/knee arthroplasty

North American Spine Society

2009

Elective spinal surgery

UFH

LMWH

Korean Society on Thrombosis and Hemostasis

2011

VTE prevention

UFH

LMWH

Korean Society for Vascular Surgery

2013

Orthopedic surgery

UFH

LMWH

American College of Chest Physicians

2016

VTE prevention

UFH

LMWH

National Institute for Health and Care Excellence

2018

Elective spinal surgery

European Society of Anaesthesiology

2018

Spinal surgery, elderly

Guidelines

Recommended Preventive Medications LMWH

Fondaparinux

Warfarin

ASA

Warfarin

ASA

Fondaparinux

Warfarin

Dabigatran

Fondaparinux

Warfarin

NOAC*

Warfarin

ASAy

NOACx

Warfarin

ASAk

LMWHz UFH

LMWH

ASA, aspirin; LMWH, low-molecular-weight heparins; NOAC, new oral anticoagulants; UFH, unfractionated heparin; VTE, venous thromboembolism. *American College of Chest Physicians commented that each of the NOACs is effective at preventing recurrent VTE without a high risk of bleeding. NOAC medications include apixaban, dabigatran, rivaroxaban, and edoxaban (edoxaban is not available in Korea). yAmerican College of Chest Physicians suggested aspirin over no aspirin to prevent recurrent VTE, in patients with an unprovoked proximal VTE who are stopping anticoagulation therapy and do not have a contraindication to aspirin. zNational Institute for Health and Care Excellence recommended to considering pharmacologic VTE prevention with LMWH for patients undergoing elective spinal surgery whose risk of VTE outweighs their risk of bleeding and demanded clinical judgment. xEuropean Society of Anaesthesiology recommended using direct oral anticoagulants in elderly patients after knee/hip replacement. kEuropean Society of Anaesthesiology recommended using aspirin for VTE prevention after orthopedic procedure.

use amount in a real situation. However, the 1000 IU/vial of UFH use was discarded, because mostly it is not used for an antithrombotic purpose. In the same way, all other dosage amounts were disregarded in this study. Detailed information on the medication codes is given in Supplementary Tables 4 and 5. Those who underwent mechanical compression were not considered because this service is not generally covered by NHI and this study aimed to analyze the use of pharmacoprophylactics after spine surgery. VTE Risk Scale This study attempted to identify risk factors and develop a VTE risk scale to describe the current prophylaxis rate in the different risk groups. This study quantified the VTE risk score for patients who had spine surgery by following the Caprini risk assessment model recommended by the 2012 CHEST guideline for VTE prevention.43 A patient earns 1 point for each positive category if they have any of the following conditions: older than 60 years, venous disease, current cancer, respiratory disease, estrogen use, current infections, diabetes, dyslipidemia medication use, Parkinson disease, presence of trauma, thyroid disease, extended surgery duration (>2 hours), and excessive blood loss (>2 L). Furthermore, the risk score was grouped into 3 categories: low (0), medium (1e2), and high risk (
3). Assessment of Postoperative SEH The incidence of postoperative SEH was assessed, although it is a rare complication after spine surgery or VTE chemoprophylaxis.22,44-46 The International Classification of Diseases, Ninth Revision diagnosis code for postoperative SEH (998.12) was adopted from the study by Awad et al.47 Furthermore, the code was converted to International Classification of Diseases, Tenth Revision48 and then to the 6th Korean Center for Disease Classification and Information

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codes (KOICD-6) on the basis of the conversion recommendations from the Centers for Disease Control and Prevention/National Center for Health Statistics and KOICD.49,50 The medical treatment codes for the removal or drainage of a hematoma in the central nervous system were simultaneously assessed to discriminate patients with SEH from patients with all other hemorrhage and hematoma. Detailed information of the SEH codes is listed in Supplementary Table 2. Data Analysis for Identifying the Incidence and Risk Factors After creating the master analytic data set, a descriptive analysis (mean, standard deviation, frequency, and percentage) was performed against the variables selected: demographic variables (age, sex, total medical payment, length of hospital stay, type of insurance, risk stratification, and type of spine surgery), currently active comorbidity variables (venous disease, cardiovascular disease, cancer, estrogen use, infections, diabetes, respiratory disease, use of dyslipidemia medications, Parkinson disease, presence of trauma, prophylaxis use, surgery hours, and amount of blood loss), and hospital-related information (location and size of the clinic). A major surgery was defined as one that had an operation time of >2 hours. The locations of the hospitals were categorized into metropolitan and rural areas. Metropolitan areas are densely populated urban areas including Seoul; however, rural areas are located outside towns and cities. Hospitals are divided into 4 categories based on the size and function: from largest to smallest, tertiary hospitals, general hospitals, small hospitals, and clinics. By applying the c2 test, this study examined the statistical difference in those selected variables between the VTE and comparison groups. For continuous variables, the t test was used to find any statistical difference between the 2 groups. On the basis of a thorough review of the extant literature on VTE risk factors and the

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descriptive analysis of this study after consideration of collinearity, a set of independent variables were selected for a logistic regression model. We selected a P value <0.2 from the univariate analysis, which was based on the epidemiologic research references.51 A P value <0.05 was considered statistically significant, and a P value between 0.05 and 0.2 was considered marginally significant. Before incorporating the selected variables to multivariate logistic analysis, we tested multicollinearity. To avoid the problem of multicollinearity between the independent variables, we dropped the variables with variance inflation factor >5.52 Sampling weight was incorporated in multivariable logistic regression to obtain better estimation. All statistical analyses were performed using STATA/ MP53 (version 14.0 for Microsoft Windows 64 [StataCorp LLC, College Station, Texas, USA]).53

RESULTS Of a total 31,964,373 inpatients, 21,261 patients who had undergone spine surgery in 2014 were selected for this study. As shown in Figure 1, the total number of DVT and PE events was 370 (1.74%) and 84 (0.4%), respectively. Among these events, 10 patients had both a DVT and PE at the same time. The overall incidence of VTE was 2.09% (n ¼ 444). Pharmacoprophylaxis was given to 1678 patients. If the multiple use of each pharmacoprophylaxis was counted, the total number of cases was 1953. A univariate analysis was performed between the VTE and non-VTE groups. Detailed descriptive analysis results are

shown in Table 2, and the results of the univariate analysis are shown in Table 3. The mean age was significantly higher in the VTE group compared with the non-VTE group (P < 0.001). There was no statistically significant difference in sex (P ¼ 0.39) between the groups. The length of hospital stay was significantly longer in the VTE group compared with the non-VTE group (P < 0.001). There was a marginal difference in insurance types between the groups (P ¼ 0.17). Among 888 patients with venous disease, 130 had VTE, and this was statistically significant (P < 0.001). Among 219 patients with cancer, 21 experienced VTE, which was statistically significant (P < 0.001). Thyroid diseases were present in 137 patients, and 5 of these patients reported VTE, which was marginally significant (P ¼ 0.12). Among 1895 patients with diabetes, 62 had VTE, which was statistically significant (P < 0.001). Among 961 patients with respiratory disease including asthma and chronic obstructive pulmonary disease, 48 patients had VTE, which was statistically significant (P < 0.001). Of 1297 patients who used dyslipidemia medication, 37 patients experienced a VTE, and this had a marginal significance (P ¼ 0.05). Among 74 patients with Parkinson disease, 4 experienced a VTE, and this had a marginal significance (P ¼ 0.05). Among 7114 patients with trauma, 197 had a VTE, which was statistically significant (P < 0.001). Among 2010 patients who had undergone major surgery (surgery duration >2 hours), 39 had VTE, which was statistically significant (P ¼ 0.03). Total blood loss during surgery was measured and ranged from 0 to 13.44 L. The mean blood loss of the VTE and non-VTE groups combined was 0.19  0.65 L, with

• Total 31,964,373 inpatient cases in 2014, regardless of disease types 31,964,373 • From 1,260,983 patients cases

21,261 cases

1447 cases

455 cases

444 cases

• Spine surgery inpatient cases were selected using spine surgery codes • From 20,354 patients

• VTE (DVT or PE) cases were selected using DVT/PE codes • Inclusion: DVT or PE occurred in patients receiving spine surgeries in 2014 • From 441 patients (a patient could receive multiple spine surgeries)

• Exclusion: DVT or PE occurred before spine surgeries, or after 91 days or more • Exclusion: 11 cases occurred multiple times in 90 days from spine surgeries

• Inclusion: DVT or PE occurred in 90 days from surgeries • DVT = 370 (1.74%) cases; PE = 84 (0.4%) cases; DVT & PE = 10 cases • From 441 patients

Figure 1. The subjective inpatient case selection from Health Insurance Review & Assessment Service National Inpatient Sample in 2014 data set. DVT, deep

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vein thrombosis; PE, pulmonary embolism; VTE, venous thromboembolism.

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Table 2. Case Demographic and Disease Characteristics Venous Thromboembolism Characteristics Age (years), mean (SD)

No Venous Thromboembolism

Deep Vein Thrombosis

Pulmonary Embolism

Total (Cases)

61.5 (15.97)

64.78 (14.04)

69.07 (13.48)

61.59 (15.94)

Sex Male Female

8900

141

36

9077

11,917

219

48

12,184

Total Medical Payment ($), mean (SD)

2569 (2234)

3539 (3399)

5816 (5033)

2598 (2289)

Length of stay (days), mean (SD)

13.55 (9.70)

16.26 (11.18)

21.12 (14.13)

13.63 (9.77)

19,389

335

73

19,797

1356

25

11

1392

72

0

0

72

Cervical

2080

19

6

2105

Lumbar

12,625

221

36

12,882

Thoracic

281

10

8

299

Not specified

5831

110

34

5975

No

20,059

244

70

20,373

Yes

758

116

14

888

No

20,619

349

74

21,042

Yes

198

11

10

219

No

20,807

370

84

21,251

Yes

10

0

0

10

No

16,635

273

40

16,948

Yes

4182

87

44

4313

No

18,984

314

68

19,366

Yes

1833

46

16

1895

No

19,904

330

66

20,300

Yes

913

30

18

961

No

19,557

339

68

19,964

Yes

1260

21

16

1297

Insurance types National Health Insurance Medical Aid Veterans Spine surgery types

Venous diseases

Cancer

Estrogen use

Infections

Diabetes

Respiratory diseases

Dyslipidemia

Parkinson disease SD, standard deviation. *There are 8 cases of concomitant deep vein thrombosis and pulmonary embolism, and these cases were reflected in the total 191 cases.

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Table 2. Continued Venous Thromboembolism Characteristics

No Venous Thromboembolism

Deep Vein Thrombosis

Pulmonary Embolism

Total (Cases)

No

20,747

358

82

21,187

Yes

70

2

2

74

No

20,685 (97.29)

357 (1.68)

82 (0.39)

21,124 (99.36)

Yes

132 (0.62)

3 (0.01)

2 (0.01)

137 (0.64)

No

13,900

215

32

14,147

Yes

6,917

145

52

7114

<1

5059

95

33

5187

1e2

13,787

232

45

14,064

2e3

1879

31

6

1916

3e4

50

1

0

51


4

42

1

0

43

Thyroid diseases, n (%)

Trauma

Surgery hours

Blood loss (L) No loss

17,748

240

50

18,038

0e1

1799

65

17

1881

1e2

905

33

9

947

2e3

189

9

2

200

>3

176

13

6

195

No

19,809

216

49

20,178

Yes

1487

159

40

1678*

1386 (6.52)

2 (0.01)

1 (0.01)

1389 (6.53)

11,546 (54.31)

162 (0.76)

10 (0.05)

11,718 (55.11)

7885 (37.09)

196 (0.92)

73 (0.34)

8154 (38.35)

Teaching hospital

3035 (14.27)

39 (0.18)

29 (0.14)

3103 (14.59)

General hospital

5153 (24.24)

71 (0.33)

39 (0.18)

5263 (24.75)

12,115 (56.98)

249 (1.17)

15 (0.07)

12,379 (58.22)

514 (2.42)

1 (0.00)

1 (0.00)

516 (2.43)

Prophylaxis use

Risk stratification, number of cases (%) Low (0) Medium (1e2) High (
3) Type of hospital, n (%)

Small hospital (hospital) Small hospital (clinic) Number of beds in hospitals (%) <200

12,173 (57.26)

240 (1.13)

17 (0.08)

12,430 (58.46)

200e500

3729 (17.54)

45 (0.21)

13 (0.06)

3787 (17.81)

>500

4915 (97.91)

75 (0.35)

54 (0.35)

5044 (23.72)

5767 (27.12)

88 (0.41)

22 (0.10)

5877 (27.64)

Location of hospitals, n (%) Metropolitan area (Seoul)

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Table 2. Continued Venous Thromboembolism Characteristics

No Venous Thromboembolism

Deep Vein Thrombosis

Pulmonary Embolism

Total (Cases)

Metropolitan area (other)

6378 (30.00)

70 (0.33)

25 (0.12)

6473 (30.45)

Rural area

8672 (40.79)

202 (0.95)

37 (0.17)

8911 (41.91)

20,817 (97.91)

370 (1.69)

84 (0.4)

21,261 (100)

Total (cases)

SD, standard deviation. *There are 8 cases of concomitant deep vein thrombosis and pulmonary embolism, and these cases were reflected in the total 191 cases.

0.55  1.20 L for the VTE group and 0.18  0.63 L for the non-VTE group. Increased blood loss in patients with VTE was statistically significant (P < 0.001). The total number of patients with VTE was 68 in teaching hospitals, 110 in general hospitals, 264 in hospitals, and 2 in clinics. The type of hospital was significant on VTE incidence (P ¼ 0.02). Other detailed information can be found in Tables 2 and 3. Multivariable logistic regression analysis was performed based on the univariate analysis results. After the consideration of multicollinearity between each variable and the statistical and clinical significance of each factor, a multivariable logistics regression model was used for the independent risk factors that included the following: sex, length of hospital stay, concurrent venous disease, cancer, infection, diabetes, respiratory disease, cardiovascular medication, dyslipidemia medication use, use of pharmacoprophylaxis, Parkinson disease, trauma, surgery duration >2 hours, spine surgery type, increased total blood loss during surgery, location of hospital, and size of hospital. The risk factors identified from the multivariable logistic regression analysis were venous disease, cancer, respiratory diseases, hospital size (small hospital), use of pharmacoprophylaxis, thoracic spine surgery type, and not specified spine surgery. Dyslipidemia medication use and metropolitan location of the hospital showed a protective effect on VTE incidence. Table 4 lists further detailed results of the multivariable logistic regression model. On the basis of the numbers of risk factors, risk stratification was performed. By applying the scale, the risks were scored from 0 to 8 for patients who had undergone spine surgery. The incidence of VTE and rate of pharmacoprophylaxis in each group were measured. Of the selected study cohort, the total number of patients who used prophylaxis was 1678 (7.89%), and 191 (0.90%) of these patients experienced a VTE. Figure 2 lists the VTE incidence in the different risk groups. The pharmacoprophylaxis pattern of use is listed in Table 5. For the low-risk group, 7 patients (0.03%) had pharmacoprophylaxis, in stark contrast to 479 patients (2.25%) and 1192 patients (5.61%) in the medium-risk and high-risk groups, respectively. For the low-risk group, none of the 7 patients who experienced VTE received prophylaxis. In the medium-risk group, VTE occurred in 62 patients who received prophylaxis, but this number increased to 129 patients who did not receive prophylaxis. For the high-risk group, the comparison was 129 patients with a VTE and prophylaxis versus 140 patients with VTE and no prophylaxis.

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To determine the pattern of use of each pharmacoprophylactic medication, aspirin, direct thrombin inhibitors, factor Xa Table 3. Univariate Analysis Result of Variables Variables

P Value

Age

0.00

Sex

0.39*

Total medical payment

0.00

Length of stay

0.00

Insurance types

0.17y

Risk stratification

0.00

Spine surgery types

0.00

Venous diseases

0.00

Cancer

0.00

Estrogen use

0.64*

Infections

0.00

Diabetes

0.00

Cardiovascular diseases

0.00

Respiratory diseases

0.00

Dyslipidemia

0.05y

Parkinson disease

0.05y

Thyroid diseases

0.12y

Trauma

0.00

Prophylaxis use

0.00

Major surgeries

0.03

Surgery hours

0.05y

Blood loss

0.00

Hospital size

0.02

Number of beds

0.04

Location of hospitals

0.00

*P value of the corresponding variable is not statistically significant. yP value of the corresponding variable is located between 0.05 and 0.20, which indicates marginal significance; P value of 0.00 is P < 0.001.

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inhibitors, low-molecular-weight heparins, UFH, and warfarin were compared. Comparison of the use rate between the different pharmacoprophylactic medications showed that UFH and the aspirin were the most frequent pharmacoprophylaxis, followed by low-molecular weight heparins, warfarin, factor Xa inhibitors, and direct thrombin inhibitors. The detailed information on prophylactic medication use is presented in Supplementary Table 3, and the medication codes in Supplementary Tables 4 and 5. DISCUSSION Related Studies This study attempted to provide rigorous research findings on DVTs and PEs for underrepresented Asian patients by using a national inpatient database. The incidence of DVT and PE was 1.74% and 0.40%, respectively, which makes the total incidence of VTE 2.09% among the 21,261 patients who had spine surgery in 2014. An increasing number of studies have recently dealt with the topic of VTE after spine surgery,15,20,21,54-61 and the reported incidence has ranged from 0.3% to 31%, varying with patient population, prophylaxis use, and surveillance method.62 Most of the extant studies concluded that DVT and PE are common after spine surgery, and the focus has shifted to whether pharmacologic prophylaxis should be administered to patients after spine surgery to prevent VTE. Takahashi et al.63 studied 1975 patients who had spine surgery in a Japanese hospital from 1990 to 2011 in an effort to determine the incidence of symptomatic and asymptomatic VTE in these patients and to evaluate therapeutic methods. The investigators divided the patients into 2 groups: the first group, which had patients from 1990 to 1996 (n ¼ 541), used no prophylaxis method, and the other group, which had patients from 2000 to 011 (n ¼ 1434), used a foot pump during and after

surgery. The former group developed symptomatic PE at a higher rate than those in the group with the foot pump (1.5% vs. 0.2%). A total of 100 patients were examined by contrastenhanced computed tomography, and asymptomatic PE and VTE were detected in 18% and 19% of the patients, respectively. The investigators emphasized the importance of mechanical prophylaxis and early ambulation after the surgery. Akeda et al.64 studied 209 Japanese patients who had spine surgery using ultrasonographic assessment of both legs after surgery. Both mechanical prophylaxis and no pharmacoprophylaxis were offered to the patients, and a VTE occurred in 11% of patients. Unlike the Japanese postsurgical setting, mechanical prophylaxis has been widely offered after surgeries in Korea as a nonreimbursement service. Fineberg et al.65 used a data set of the Nationwide Inpatient Sample from 2002 to 2009 in the United States. These investigators limited their subjects to patients who had lumbar spine surgery, and the incidence of acute DVT and PE was 2.4% and 1.0%, respectively. Andrew et al.66 reported the VTE incidence in U.S. patients who had spine surgery as 1%. In addition, the investigators pointed out that body mass index (calculated as weight in kilograms divided by the square of height in meters)
40, age
80 years, surgery time >261 minutes, and American Society of Anesthesiologists classification
3 were identified as risk factors. The VTE incidence in their study was higher than our result, but their patients were limited to those with elective lumbar spine surgery. Schulte et al.20 sought to determine the incidence of and risk factors for VTE among American patients who had spine surgery. The DVT and PE incidences in their study were 0.7% and 0.4%, respectively, and active malignancy, previous VTE, estrogen replacement therapy, discharge to a rehabilitation facility, hypertension, major depressive disorder, renal disease, congestive heart failure, and benign prostatic hyperplasia were

Table 4. Multivariable Logistic Regression Results P > jzj*

Odds Ratio (95% Confidence Interval)

Venous diseases

0.00

9.43 (7.29e12.20)

Cancer

0.00

3.99 (2.31e6.89)

Risk Factors

Respiratory diseases

0.04

1.46 (1.01e2.12)

Dyslipidemia medication use

0.01

0.54 (0.35e0.81)

Metropolitan hospitals

0.00

0.63 (0.47e0.85)

Hospital sizeesmall hospitaly

0.01

1.66 (1.21e2.28)

Prophylaxis

0.00

9.58 (7.33e12.52)

Thoracic

0.02

2.42 (1.16e5.04)

Not specified

0.00

2.08 (1.28e3.39)

Total blood loss

0.00

1.25 (1.14e1.38)

Surgery typez

*All categories had a P value <0.05; P value of 0.00 is P < 0.001. yIn the Korean health care system, hospital is classified into 4 categories, based on their function and size. From largest to smallest they are tertiary general hospital, general hospital, small hospital, and clinic. zSpine surgery type is classified as cervical, lumbar, thoracic, and not specified spine surgery.

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100%

1 2

10 73

100% 162

99%

Incidence Rate

99% 98% 98%

196

PE

1386

DVT

97%

No VTE

11546 97% 96%

7885

96% 95% Low (0)

Medium (1–2)

High(≥3)

Risk Straficaon * Risk stratification was performed based on the number of risks that each case had; if the case had no risk factor, it was categorized into low risk group. If the case had one or two risk factors, it is classified into medium risk group. High risk group comprised of the cases with 3 or more risk factors. † The number of DVT and PE cases were counted respectively. As DVT and PE can happen at the same time in one case, the simple sum of DVT and PE cases here exceed the final VTE case number of 444. Figure 2. Venous thromboembolism (VTE) incidence by the risk scales. Risk stratification was performed based on the number of risks that each case had; if the case had no risk factor, it was categorized into the low-risk group. If the case had 1 or 2 risk factors, it was classified into the medium-risk group. The high-risk

identified as risk factors, which were similar to our univariate analysis. Glotzbecker et al.62 performed a systematic review of 25 separate reports, and reported the overall VTE rate as 2.1%, which is comparable to our rate of 2.09%. The incidence of VTE for the Asian population is known to be lower than that in the Western population; thus, VTE prophylaxis has been mostly negligible in the Korean postoperative setting for the past decades.67,68 However, recent multicenter

group comprised cases with
3 risk factors. The number of deep vein thrombosis (DVT) and pulmonary embolism (PE) cases were counted. Because DVT and PE can happen at the same time in 1 patient, the simple sum of DVT and PE cases here exceeds the final VTE case number of 444.

population-based study results, as well as the studies listed earlier, have shown a similar incidence of VTE regardless of the ethnicity variable. According to the Surgical Multinational Asian Registry in Thrombosis study group, the incidence of symptomatic VTE was 0.9% (3 patients, 95% confidence interval, 0.1e3.3) between 2002 and 2004.11 The Assessment of the Incidence of Deep Vein Thrombosis in Asia study reported a 41.0% (95% confidence interval, 35.4e46.7) asymptomatic DVT incidence and a 2.5%

Table 5. Pharmacoprophylaxis Use Pattern in Each Risk Group Pharmacoprophylaxis Yes VTE No VTE No VTE No VTE Total (n ¼ 21,261) (%)y

Low Risk

Medium Risk

High Risk

Total (%)*

7 (0.50)

479 (4.09)

1192 (14.62)

1678 (7.89)

—

62 (0.53)

129 (1.58)

191 (0.90)

7 (0.50)

417 (3.56)

1062 (13.02)

1486 (6.99)

1382 (99.50)

11,239 (95.91)

6962 (85.38)

19,583 (92.11)

3 (0.22)

110 (0.94)

140 (1.72)

253 (1.19)

1379 (99.28)

11,129 (94.97)

6822 (83.66)

19,330 (90.92)

1389

11,718

8154

21,261

VTE, venous thromboembolism. Numbers without parentheses mean the number of cases. *Numbers with parentheses are the percentage of the case over the total cases in the group. yTotal, the sum of the cases from low risk to high risk; %, the case number O total cases (21,261)  100.

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incidence of clinically suspected PE in Asian patients (10 patients) after major joint arthroplasty during 2002e2003.12 Thus, the incidence of VTE in Korea after spine surgery is not negligible and requires more active prevention measures. Pharmacoprophylaxis Use The rate of pharmacoprophylaxis offered to patients after spine surgery in Korea is 7.89%. Our study could not determine the use rate of mechanical prophylaxis, because NHI does not cover this service. However, mechanical prophylaxis is being used on most postsurgical patients in Korean clinics, and the focus of our study was pharmacoprophylaxis. Despite a paucity of literature, McLynn et al.69 reported that pharmacologic prophylaxis was received by 56.3% of the patients with elective spine surgery during 2005e 2014 in the United States. In contrast, pharmacoprophylaxis offered after spine surgery in Korea is about one tenth of the Western rate. The incidence of prophylaxis in our study was 0.90% (191 patients) with a higher nonprophylaxis incidence of 1.19% (253 patients). These results indicate that more active pharmacoprophylaxis is required for the Asian population to reduce the incidence of a VTE. Although there has been no gold standard on VTE prophylactics since spine surgery was established, we gathered the common recommendations from guidelines to present the best available pharmacoprophylactics. All pharmacoprophylaxis medications were given more to the high-risk group than to the medium-risk or low-risk groups. Low-molecular-weight heparins, which were the most recommended pharmacoprophylaxis by practice guidelines, accounted for 20.02% of the total. The mean use periods of lowmolecular-weight heparins, UFH, and direct thrombin inhibitors were less than the minimum suggested use dates of at least 14e35 days.37,70-72 It clearly supports the study conclusion that pharmacoprophylaxis after spine surgery in the Korean practice setting is not only underoptimized but also inadequate. The use of aspirin or warfarin shows longer use periods, which might reflect the number of patients who had already taken those medications for purposes other than postsurgical VTE prevention. Because the nature of the data set does not provide serial information on the medication administration or past medical history, only the detection of the pattern of medication use is available. However, even considering the limits of the data set, the use of pharmacoprophylaxis falls short of expectations. Risk Factors for VTE After Spine Surgery The risk factors identified in this study, including the presence of venous disease, cancer, respiratory diseases, dyslipidemia, and total blood loss, have been well established in many studies.6,27,69,73-79 Location of a hospital in a metropolitan area showed a protective effect on the incidence of VTE in this study. Because tertiary teaching hospitals are primarily located in metropolitan areas in Korea, these hospitals tend to have clinicians with more up-to-date professional information who may practice more in these hospitals, which possibly led to a protective effect on VTE incidence. The same reasoning could explain why small hospitals were identified as risk factors for VTE. In addition, the use of dyslipidemia agents was protective and possibly the result of reduced cholesterol levels, which was a strong predisposing factor of the incidence of VTE in the previous literature.80

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The use of pharmacoprophylaxis paradoxically showed the highest odds ratio of 9.58. However, only 7.89% of the total patients in our study received pharmacoprophylaxis, and they were patients with more complicated health conditions, which are wellknown risk factors for VTE development. Therefore, the use of pharmacoprophylaxis indicates that patients have a high susceptibility to developing VTE after surgery regardless of the effectiveness of the pharmacoprophylaxis. Zacharia et al.61 also confirmed this pattern in 314 inpatients. Besides, we observed that advanced age, concurrent diabetes, cardiovascular disease, length of stay, Parkinson disease, and trauma were meaningful independent risk factors in the univariate analysis. However, their effects were diluted in the subsequent multivariable logistic analysis. Further research to determine the precise effects of these risk factors is required. The incidence of DVT and PE was significantly increased in the high-risk groups. However, even in these groups, pharmacoprophylaxis is not actively used. Although Asian populations have similar incidences of thromboembolic complications after surgery to their Western counterparts, VTE prophylaxis in Korea still follows traditional prescription patterns. Therefore, more active prophylaxis based on the risk scales should be considered to prevent VTE after spine surgery. SEH Incidence After Spine Surgery We examined the incidence of hemorrhage and hematoma disease codes and detected 723 cases. However, the corresponding KOICD-6 codes for SEH include broader complications such as other bleeding situations. Therefore, 3 medical treatment codes related to hematoma were also assessed to give a more accurate incidence. The final incidence of SEH that required medical or surgical treatment was zero in our study cohort, and this result is consistent with reports from other Korean literature.81-83 The rarity of SEH incidence might be caused by the low pharmacoprophylaxis use rate. If more active pharmacoprophylaxis is administered in the future, it is possible that the incidence of SEH will increase. Therefore. further research on the incidence of SEH in patients who have had spine surgery is needed to make more reliable decisions on the use of pharmacoprophylaxis among these patients. Limitations and Research in the Future This study has some limitations. As with any retrospective analysis, there is a potential for error as a result of selection bias. However, the HIRA-NIS data set attempted to minimize selection bias by applying stratified random sampling methods, and this has been recognized in other previous studies32,84-87 using the HIRA data set. The second limitation is that the number of prophylactics did not fully reflect mechanical methods, because most mechanical prophylaxes, such as graduated compression stockings and venous foot pumps, are not covered by the NHI (HIRA-NIS) data set. However, the focus of VTE prophylaxis in this study was pharmacologic interventions. The third limitation is that the risk factors identified were limited to the available variables of HIRA-NIS-2014, which means that other potential risk factors such as body mass index, smoking status, history of VTE, dependent functional status, or family history could not be incorporated in this analysis. Past VTE incidence is one of the most important risk factors in other postsurgical case. Also,

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asymptomatic VTE patients who use ultrasonography could not be included in this study. However, 1 year of a data set could not provide complete past information or relevant screening methods on incidence. Because of the retrospective nature of this research, the determined incidence was limited to symptomatic VTEs, and the incidence of asymptomatic VTEs was not covered.

which is SEH, we determined that the incidence of SEH was negligible. This study was the first research on the incidence of VTE after spine surgery in Korea. Given the results of this study, we recommend more active pharmacoprophylaxis after spine surgery, especially in high-risk groups. In addition, further studies could add knowledge about additional risk factors and the occurrence of SEH with the use of pharmacoprophylaxis.

CONCLUSIONS We have described the incidence of and risk factors for postoperative VTE after spine surgery in the Korean population. In addition, we suggested risk scales based on the number of risks in each case. Considering the unique complication of spine surgery,

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and spinal cord injury]. Ann Fr Anesth Reanim. 2005; 24:928-934 [in French]. 77. Platzer P, Thalhammer G, Jaindl M, et al. Thromboembolic complications after spinal surgery in trauma patients. Acta Orthop. 2006;77: 755-760. 78. Heck CA, Brown CR, Richardson WJ. Venous thromboembolism in spine surgery. J Am Acad Orthop Surg. 2008;16:656-664. 79. Lee SJ, Kim NC. Risk factors associated with venous thromboembolism in cancer patients. Asian Oncol Nurs. 2015;15:171-177. 80. Shin CM, Han K, Lee DH, et al. Association among obesity, metabolic health, and the risk for colorectal cancer in the general population in Korea Using the National Health Insurance Service-national sample cohort. Dis Colon Rectum. 2017;60:1192-1200. 81. Lee JS, Suh KT. Spontaneous lumbar spinal epidural hematoma without rist factors: a case report. J Korean Orthop Assoc. 2005;40:1013-1016.

VTE AFTER SPINE SURGERY IN KOREA

82. Chun B. Spontaneous spinal epidural hematoma associated with the ossification of ligamentum flavum of the thoracic spine. J Korean Neurosurg Soc. 1999;28:1817. 83. Lee YH, Oh SW, Kim SW, Chun YK. A case of spinal epidural hematoma due to arteriovenous malformation. Korean J Pediatr. 1996;39:436-440. 84. Cho GJ, Kim LY, Min KJ, et al. Prior cesarean section is associated with increased preeclampsia risk in a subsequent pregnancy. BMC Pregnancy Childbirth. 2015;15:24. 85. Kim SR, Lee YC, Sung MJ, Bae HW. Current epidemiological data on asthma management in South Korea from qualitative assessment of asthma management by Health Insurance Review and Assessment Service (HIRA). Tuberc Respir Dis (Seoul). 2017;80:221-225.

87. Park SC, Lee MS, Kang SG, Lee SH. Patterns of antipsychotic prescription to patients with schizophrenia in Korea: results from the health insurance review & assessment service-national patient sample. J Korean Med Sci. 2014;29:719-728. Conflict of interest statement: This study is supported by Basic Science Research Program (grant number NRF2016R1D1A1B03935819) of the National Research Foundation of Korea funded by the Korea government. Received 15 January 2019; accepted 16 April 2019 Citation: World Neurosurg. (2019) 128:e289-e307. https://doi.org/10.1016/j.wneu.2019.04.140 Journal homepage: www.journals.elsevier.com/worldneurosurgery Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2019 Elsevier Inc. All rights reserved.

86. Oh H, Boo S. Burns in South Korea: an analysis of nationwide data from the health insurance review and assessment service. Burns. 2016;42:675-681.

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Supplementary Table 1. Disease and Surgery Codes of Our Study for Case Detection Pulmonary Embolism*

Supplementary Table 1. Continued Pulmonary Embolism*

Deep Vein Thrombosis*

Spine Surgeryy

Deep Vein Thrombosis*

Spine Surgeryy

I80

N0303

N2492

I2690

I8000

N0444

N1494

I2699

I8010

N0445

I269

I802

N0446

I80209

N0447

I80219

N0451

I803

N0452

I808

N0453

I809

N0466

I82

N0467

I821

N0468

I26

I822

N0469

I82220

N0471

I82221

N0472

I823

N0473

I824

N0474

I82409

N0480

I82419

N0500

I82429

N0630

I82439

N1491

I824Y9

N1492

I82449

N1493

I824Z9

N1495

I828

N1496

I82890

N1497

I829

N1498

I8291

N1499

N2491

*Deep vein thrombosis, pulmonary embolism codes: the codes were extracted from the precedent literature on the epidemiology of venous thromboembolism in knee/hip arthroplasty of Korea, 2007e2011. ySpine surgery codes: the codes were extracted from the Main Surgery Statistical Yearbook of 2014, which was published by the Korean National Health Insurance. Main Surgery Statistical Yearbook of 2014 listed the codes in the general spine surgery section.

N2461 N2462 N2463 N2464 N2465 N2466 N2467 N2468 N2469 N2470 N2471 N2472 Continues

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Supplementary Table 2. Disease Code Conversion for Spinal Epidural Hematoma Source Awad et al.1

Classification International Classification of Diseases, Ninth Revision diagnosis code

Code conversion International Classification of Diseases, Tenth Revision diagnosis code

Code conversion

Code(s)

Meaning of Code

998.12 Hematoma complicating a procedure G97.31

Intraoperative hemorrhage and hematoma of a nervous system organ or structure complicating a nervous system procedure

G97.32

Intraoperative hemorrhage and hematoma of a nervous system organ or structure complicating other procedure

G97.51

Postprocedural hemorrhage and hematoma of a nervous system organ or structure after a nervous system procedure

G97.52

Postprocedural hemorrhage and hematoma of a nervous system organ or structure after other procedure

G97.8 6th Korean Center for Disease Classification and Information disease code

Other postsurgical disorders of nervous system

G97.9

Postprocedural disorder of nervous system, unspecified

G98

Other disorders of nervous system, not elsewhere classified

G99

Other disorder of nervous system in disease classified elsewhere

T81.7

Vascular complications after a procedure, not elsewhere classified

T81.0

Hemorrhage at any site resulting from a procedure, excluding hematoma of obstetric wound

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Supplementary Table 3. Pharmacoprophylaxis Use Pattern by Venous Thromboembolism Incidence and Risk Stratification Cases, n (%)* Medication Aspirin

No VTE

Low

Medium

High

Mean Use Period, days (Standard Deviation)

Mean Hospitalization Period, days (Standard Deviation)

81 (4.15)

0

38

43

18.41 (13.56)

19.84 (10.82)

No VTE

694 (35.54)

1

137

556

18.57 (14.95)

19.94 (11.17)

Total

775 (39.69)

1

175

599

18.56 (14.81)

19.93 (11.22)

VTE

0

0

0

0

NA

NA

No VTE

3 (0.15)

0

0

3

5.33 (2.89)

17.67 (16.17)

Total

3 (0.15)

0

0

3

5.33 (2.89)

17.67 (16.17)

VTE

18 (0.92)

0

1

17

22.33 (17.19)

36.78 (20.85)

No VTE

18 (0.92)

0

2

16

9.61 (6.23)

33.44 (10.90)

Total

36 (1.84)

0

3

33

15.97 (14.28)

35.11 (16.48)

VTE VTE

Direct thrombin inhibitorsy

Factor Xa inhibitorsz

Low-molecular-weight heparinsx

Warfarin

Unfractionated heparins

Risk Stratification (n)

VTE

121 (6.20)

0

48

73

6.17 (9.03)

17.93 (13.02)

No VTE

270 (13.82)

2

73

195

5.37 (5.29)

17.93 (13.02)

Total

391 (20.02)

2

121

268

5.62 (6.67)

21.23 (13.02)

VTE

25 (1.28)

0

3

22

22.32 (20.69)

24.52 (13.84)

No VTE

56 (2.87)

0

3

53

16.82 (16.63)

22.82 (17.36)

Total

81 (4.15)

0

6

75

18.52 (18.03)

23.35 (16.29)

VTE

38 (1.95)

0

7

31

2.63 (3.84)

25.11 (16.64)

No VTE

629 (32.21)

4

228

397

1.28 (1.43)

21.03 (12.48)

Total

667 (34.15)

4

235

428

1.36 (1.69)

21.27 (12.77)

1953

6

367

827

10.03 (11.26)

20.54 (12.32)

Total casesk

Pharmacoprophylaxis medications were suggested from the most current references and guidelines on VTE prophylaxis.2-9 VTE, venous thromboembolism; NA, not available for calculation. *% (the number of cases O total cases  100). yDirect thrombin inhibitors: dabigatran was the direct thrombin inhibitor for pharmacoprophylaxis in this study. Detailed information is in Supplementary Tables 4 and 5. zFactor Xa inhibitors: rivaroxaban and fondaparinux were the factor Xa inhibitors for pharmacoprophylaxis in this study. Detailed information is in Supplementary Tables 4 and 5. xLow-molecular-weight heparins: bemiparin, dalteparin, enoxaparin, and nadroparin were the low-molecular-weight heparins for pharmacoprophylaxis in this study. Detailed information is in Supplementary Tables 3 and 4. kTotal cases (1953) reflected use of pharmacoprophylactic medications multiple times in the study population. If the multiple use in a case counted as 1, the total case number is 1678.

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Supplementary Table 4. Anticoagulation Medication Codes of Our Study for Case Detection Factor Xa Inhibitors

Low-Molecular-Weight Heparins

Fondaparinux

450101BI

Rivaroxaban

511401AT 511402AT

Bemiparin

Dalteparin

511403AT 511404AT

461501BI

465802BI

461502BI

140201BI

Pentoxifylline

140202BI

210801AT

140203BI

210801AT

152101BI

210801BI

359601BI

152102BI

210802AT

359602BI

152103BI

210802AT

359603BI

152104BI

Mesoglycan

152105BI

430301AC

198401BI

Gabexate

Direct thrombin inhibitors Argatroban

465801BI

Nafamostat

Enoxaparin

Lepirudin

424401BI

Dabigatran

613701AC 613702AC

198402BI

164301BI

Heparin

Aspirin

198403BI

Sulfomucopolysac

168601BI

110701AT

198404BI

233001AC

168602BI

110702AT

198405BI

Sulodexide

168603BI

110703AT

198406BI

233301AC

168604BI

110704AT

447501BI

233302BI

168605BI

252900AT

447502BI

233303AC

168606BI

253000AT

447503BI

Warfarin

168607BI

111001AC

446301BI

249101AT

340600CC

111001AT

446302BI

249102AT

111002AT

446303BI

249103AT

111003AT

446304BI

249104AT

110801AT

Nadroparin

Parnaparin

Reviparin

249105AT

110802AT Anticoagulant medication codes were referenced from the preceding research on venous thromboembolism pharmacoprophylaxis comparative study after knee or hip arthroplasty.10

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Supplementary Table 5. Pharmacoprophylaxis Medication Codes Detected in Our Study Factor Xa Inhibitors

Low-Molecular-Weight Heparins

Fondaparinux

450101BI

Rivaroxaban

511401AT 511402AT

Bemiparin

465801BI

Dalteparin

140201BI

465802BI

511403AT

140202BI

Direct thrombin inhibitors Dabigatran

140203BI 613701AC

Enoxaparin

152102BI

613702AC

152103BI 152104BI

Aspirin

Warfarin

110701AT

249103AT

110702AT

249105AT

152105BI Nadroparin

198401BI 198402BI

110801AT

198403BI

111001AC Unfractionated heparin 111001AT

25,000 IU

168631BI

Aspirin, dabigatran, fondaparinux, rivaroxaban, unfractionated heparin, and low-molecular-weight heparins were selected as the pharmacoprophylaxis medications among the anticoagulant medication codes from S4, based on the major venous thromboembolism prophylaxis guidelines in Table 1. The listed pharmacoprophylaxis medication codes were detected from the 21,261 study cases.

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VTE AFTER SPINE SURGERY IN KOREA

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