Timing of Prophylactic AC
There were 36/65 patients (56%) who received prophylactic AC in addition to mechanical prophylaxis. Thirty-one patients received subcutaneous heparin, three patients received dalteparin, and two patients received enoxaparin as first agent. The mean day to start was postoperative day 3. There were 22 patients who received prophylactic AC from days 1 to 3 (61.1%; early group) and 14 who received in from day 4 onward (38.9%; delayed group).
General and operative demographics between the early and delayed groups are compared in Table 3. Average age (P = 0.202), sex (P = 0.171), and BMI (P = 0.568) were not found to be significantly different between groups. In terms of comorbidities, no significant differences were found between groups at a threshold P level of 0.05; however, 50% of patients in the delayed group were found to be smokers compared with 22.7% in the early group (P = 0.091) and this parameter was included in the multivariate model. Similarly, the modified Bauer score (P = 0.081) and use of laminectomy (P = 0.049) were also included in the regression model.
Incidence of Venous Thromboembolism
The overall incidence of VTE was 11/65 (16.9%). All of them developed DVTs, with two patients subsequently developing nonfatal PE (3.1%). The rate of VTE was 9.1% in the early group (days 1–3) and 35.7% in the delayed group (26.6% absolute risk reduction; P = 0.049) (Figure 1). There was one case of epidural hematoma requiring surgical decompression (1.5% from the overall cohort; 2.8% for patients who received prophylactic AC vs. 0.0% for patients who did not, P = 0.366). This was a 60-year-old man with prostate cancer and history of aspirin use (stopped 1 wk before surgery) who underwent a T4-6 laminectomy, T5 transpedicular corpectomy, and T1-T8 transpedicular fixation. On postoperative day number two he developed weakness in both legs and CT of the thoracic spine showed focal compression at T4/5 from an epidural collection, for which patient underwent emergent evacuation of an epidural hematoma. This patient had received prophylactic AC on day two. Fortunately, he returned to his neurological baseline without further deficits.
A multivariate analysis controlling for patient age, sex, presence of MESCC, ambulatory status, smoking history, modified Bauer score, and use of laminectomy was performed to assess the independent effect of timing of prophylactic AC on development of VTE. This analysis showed that the delayed group did have a significantly higher risk of VTE compared with the early group (OR 6.43; 95% CI, 1.01–41.2; P = 0.049).
VTE is a known complication in cancer patients and spine surgery patients. Patients with metastatic tumors to the spine who undergo surgery are at an increased risk of VTE compared with other pathologies such as spondylosis or deformity,8 owing to both the cancer itself and also to known associated conditions such as nonambulatory status, poor preoperative functional status, and surgical intervention. Although other surgical subspecialties have clear guidelines on the use of prophylactic AC postsurgically,12 no definitive guidelines exist for spine surgery patients, with further limited data on patients with spinal tumors.
In this study, we examined the incidence of VTE for patients who received early versus delayed prophylactic AC, finding a significantly lower incidence of VTE for patients who received anticoagulation within the first 3 postoperative days. There was an overall DVT/PE incidence of 16.9%, in addition to a 1.5% incidence of epidural hematoma. More importantly, the risk of VTE was 9.1% for patients receiving prophylactic AC within the first 3 days compared with 35.7% in patients receiving it after day 3, consistent with a 26.6% absolute risk reduction.
Commensurate with our findings, Yoshioka et al8 reported a 22% incidence of VTE in patients undergoing surgery for spinal tumors. In their study, the authors prospectively followed 340 patients who underwent spinal surgery and screened for DVT/PE during postoperative days 7 to 10. They found a 22% risk of VTE in patients undergoing surgery for tumors, compared with 15.2% for patients with spinal stenosis, 13.3% for thoracolumbar spondylosis, and 4.5% for patients with cervical spondylosis.8 Although our rate was similar to Yoshioka et al's (16.9% vs. 22%), other studies have found lower rates for patients with metastatic spine disease.13 While the exact reason for this finding is unclear, differences in rates may occur due to variability in screening protocols, detection methods, as well as studied populations. In our case, for example, our population has a much higher smoking prevalence than the national one (47.7% vs. 15%), which could also account for differences in VTE rates.14
Use and timing of prophylactic AC after spinal surgery is variable. Although VTE is a recognized perioperative complication, there are lack of guidelines and established protocols for patients who undergo surgery for metastatic spine disease. Furthermore, there exists concern for the development of epidural bleeding and further/new spinal cord compression and deficits. Kim et al15 performed a retrospective analysis at a level 1 trauma center and examined 206 patients who underwent surgery for spine fractures. They found that among patients receiving “early” prophylactic AC (within 48 hours) the rate of VTE was lower compared with patients who received it in a delayed fashion (though it did not reach statistical significance, probably due to the limitation in the power of the analysis). In addition, there was no increased risk of bleeding or neurological complications in their study.15 In a more recent investigation of 6869 patients using a single-center administrative database, the authors found that administration of prophylactic AC within the first 3 postoperative days did not increase the risk of epidural hematoma.16
However, none of the two previous studies addressed anticoagulation in patients with metastatic disease and it is thus difficult to generalize the results. Our findings suggest that patients who receive “early” prophylactic AC may in fact benefit from a reduced risk of VTE without a significant increase in the incidence of epidural hematoma. Although milder forms of epidural bleeding may have occurred, only one of our patients deteriorated neurologically to the point of necessitating emergency imaging and evacuation of an epidural hematoma. In their study of 6869 patients, Dhillon et al16 found a rate of epidural hematoma of 0.2%, with an average onset of 10.8 days—furthermore, only 25% of patients experienced neurological deficits. These findings suggest that this complication is indeed very rare and will only result in a clinically significant deficit in a subset of patients. Reported risk factors include high alcohol consumption, multilevel procedures, history of previous spinal surgery, history of coagulopathy or anticoagulant use, highly vascular lesions, and others.17–19
Although the most feared complication of DVT development is progression to PE, only two cases of PE were found in the present study (3.1%) and both cases were nonfatal. Overall, the findings of this study support the administration of early prophylactic AC in addition to mechanical prophylaxis as a potential method to decrease the risk of VTE after surgery for metastatic tumors of the spine, with a small and nonstatistically significant risk of epidural bleeding requiring surgical intervention.
These findings, however, should be corroborated by further investigations and ideally in a prospective and randomized trial. Although most patients who received prophylactic AC did so in the first 3 postoperative days (61.1%), the decision to start and when to start prophylactic AC was mostly surgeon-dependent and did not follow a specific protocol. Thus, this imposes an opportunity for further research and validation of the potential benefits of early administration of pharmacologic agents for VTE prevention.
While there was a significant difference in VTE rates based on timing of anticoagulation, other comparisons may not have been statistically significant given the sample size from a single institution compared with much higher numbers from national databases or multicenter studies. For example, there was a higher rate of patients with previous history of VTE and home anticoagulation in the early group, which may have led to a higher perceived risk of recurrent DVT/PE and thus an earlier initiation of prophylactic AC. Despite these limitations, the relative safety and potential benefit of early prophylactic AC in spine surgery has also been shown in previous studies,15,16 further supporting the findings presented herein.
VTE is a known complication in patients undergoing surgery for metastatic tumors of the spine. In this study, administration of prophylactic AC in addition to mechanical prophylaxis between days 1 and 3 after surgical intervention significantly reduced the risk of DVT and PE occurring within 30 days, with a 26.6% absolute risk reduction. There was one case of epidural hematoma (1.5%). Although further research is needed ideally in a prospective randomized trial, these findings suggest that early prophylactic AC is a relatively safe practice and can potentially decrease the risk of thromboembolic events.
1. Caine GJ, Stonelake PS, Lip GY, et al. The hypercoagulable state of malignancy: pathogenesis and current debate. Neoplasia
2. Klimo P Jr, Schmidt MH. Surgical management of spinal metastases. Oncologist
3. Pascal-Moussellard H, Broc G, Pointillart V, et al. Complications of vertebral metastasis surgery. Eur Spine J
4. Lau D, Leach MR, Than KD, et al. Independent predictors of complication following surgery for spinal metastasis. Eur Spine J
5. Patil CG, Lad SP, Santarelli J, et al. National inpatient complications and outcomes after surgery for spinal metastasis from 1993-2002. Cancer
6. Jansson KA, Bauer HC. Survival, complications and outcome in 282 patients operated for neurological deficit due to thoracic or lumbar spinal metastases. Eur Spine J
7. Dea N, Versteeg A, Fisher C, et al. Adverse events in emergency oncological spine surgery: a prospective analysis. J Neurosurg Spine
8. Yoshioka K, Murakami H, Demura S, et al. Comparative study of the prevalence of venous thromboembolism after elective spinal surgery. Orthopedics
9. De la Garza Ramos R, Goodwin CR, Jain A, et al. Development of a Metastatic Spinal Tumor
Frailty Index (MSTFI) using a nationwide database and its association with inpatient morbidity, mortality, and length of stay after spine surgery. World Neurosurg
10. Hill J, Treasure T, Guideline Development G. Reducing the risk of venous thromboembolism (deep vein thrombosis
and pulmonary embolism
) in patients admitted to hospital: summary of the NICE guideline. Heart
11. Glotzbecker MP, Bono CM, Wood KB, et al. Thromboembolic disease in spinal surgery: a systematic review. Spine (Phila Pa 1976)
12. Falck-Ytter Y, Francis CW, Johanson NA, et al. Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest
13. Luksanapruksa P, Buchowski JM, Zebala LP, et al. Perioperative complications of spinal metastases surgery. Clin Spine Surg
14. Jamal A, Phillips E, Gentzke AS, et al. Current cigarette smoking among adults—United States, 2016. MMWR Morb Mortal Wkly Rep
15. Kim DY, Kobayashi L, Chang D, et al. Early pharmacological venous thromboembolism prophylaxis is safe after operative fixation of traumatic spine fractures. Spine (Phila Pa 1976)
16. Dhillon ES, Khanna R, Cloney M, et al. Timing and risks of chemoprophylaxis after spinal surgery: a single-center experience with 6869 consecutive patients. J Neurosurg Spine
17. Amiri AR, Fouyas IP, Cro S, et al. Postoperative spinal epidural hematoma (SEH): incidence, risk factors, onset, and management. Spine J
18. Glotzbecker MP, Bono CM, Wood KB, et al. Postoperative spinal epidural hematoma: a systematic review. Spine (Phila Pa 1976)
19. Ahn DK, Shin WS, Kim GW, et al. Postoperative spinal epidural hematoma: the danger caused by the misuse of thrombin-containing local hemostatics. Asian Spine J
Keywords:Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
deep vein thrombosis; metastatic tumor; prophylactic anticoagulation; pulmonary embolism; spinal tumor