Evidence-Based Clinical Guidelines

Multidisciplinary Spine Care Antithrombotic Therapies for Adults Undergoing Spine Surgery

Second Edition

Recommendations:

Effectiveness of Prophylactic Measures

Question 13. Do prophylactic antithrombotic measures, including compression stockings, mechanical sequential compression devices and chemoprophylaxis medications, decrease the rate of clinically symptomatic DVT and/or PE (including fatal PE) following elective spinal surgery not performed for tumor or trauma (cervical, thoracic or lumbar)?
Question 14. Do prophylactic antithrombotic measures, including compression stockings, mechanical sequential compression devices and chemoprophylaxis medications, decrease the rate of clinically symptomatic DVT and/or PE (including fatal PE) following spinal surgery (cervical, thoracic or lumbar) for spine trauma (with spinal cord injury and without spinal cord injury)?
Question 15. Do prophylactic antithrombotic measures, including compression stockings, mechanical sequential compression devices and chemoprophylaxis medications, decrease the rate of clinically symptomatic DVT and/or PE (including fatal PE) following spinal surgery (cervical, thoracic or lumbar) for malignancy (with spinal cord injury and without spinal cord injury)?

Question 13: Do prophylactic antithrombotic measures, including compression stockings, mechanical sequential compression devices and chemoprophylaxis medications, decrease the rate of clinically symptomatic DVT and/or PE (including fatal PE) following elective spinal surgery not performed for tumor or trauma (cervical, thoracic or lumbar)?

There is fair evidence to suggest that the addition of chemoprophylaxis to mechanical prophylaxis does not appear to provide additional benefit in the prevention of thromboembolic events in the majority of patients undergoing routine elective spine surgery. Grade of Recommendation: B

In a prospective randomized control trial study, Hamidi et al1 aimed to assess the incidence of VTE following an elective instrumental spine surgery, for those receiving preoperative chemoprophylaxis in relation to patients who did not receive it. The authors concluded that “The difference in the incidence of thromboembolic complications between the two groups was not significant. Moreover, we found that preoperative prophylactic LMWH injection has no major bleeding complications altering postoperative course; still, the issue concerning the initiation time of chemoprophylaxis in spine surgery remains unclear.” The work group downgraded this potential Level I study due to small sample size. This paper provides Level II evidence that chemoprophylaxis before elective spine surgery does not necessarily reduce risk of DVT/PE.

In a retrospective comparative study, Cunningham et al2 aimed to correspond the incidence of preoperative DVT prophylaxis administration and the rate of postoperative DVT, PE, and SEH following elective spine surgery. The authors concluded that “Preoperative DVT prophylaxis does not influence the rate of postoperative DVT or PE among elective spinal patients. It probably does not influence EH rate, and it is noted that spinal epidural hematoma (SHE) may present quite late, in contrast to currently accepted time courses.” This paper provides Level IV evidence that chemoprophylaxis does not influence the rate of postoperative DVT and PE. Dhillon et al3 conducted a single-center, retrospective comparative study of patients who received chemoprophylaxis (1 day before and up to 3 days after surgery) compared to those who did not. The average time to institution of chemoprophylaxis was 1.5 days after surgery. This paper provides Level III evidence that the presence of an epidural hematoma is similar with and without chemoprophylaxis. Risks of spinal epidural hematoma in patients receiving VTE prophylaxis are low. Treatment from 1-3 days after surgery is safe. In a retrospective comparative study, Fang et al4 aimed to evaluate the outcomes and use of venous thromboembolism prophylaxis following spine surgery. The authors concluded that “Substantial variation exists in the use of thromboembolism prophylaxis after spinal fusion surgery in the USA. Nevertheless, overall rates of diagnosed thromboembolism after spinal fusion appear to be low.” This study provides Level IV evidence that despite adjusting for the propensity to receive VTE prophylaxis, we continued to observe in multivariable models a higher risk of postoperative VTE among patients who received prophylaxis. In a retrospective observational study, McLynn et al5 aimed to distinguish the incidence and risk factors for VTE and the relation of pharmacologic prophylaxis with VTE and bleeding complications following elective spine surgery. The authors concluded “Pharmacologic prophylaxis, primarily with unfractionated heparin, after elective spine surgery was not associated with a significant reduction in VTE. However, there was a significant increase in postoperative hematoma requiring reoperation among patients undergoing prophylaxis.” This study provides Level III evidence that VTE is a well-recognized and potentially dangerous complication of elective spine surgery, creating a need for safe and effective prophylactic measures. This study determined that pharmacologic prophylaxis predominantly with unfractionated heparin did not notably reduce the likelihood of VTE but markedly increased the risk of bleeding occurrences thereby necessitating reoperation. At this time, guidelines lack strong evidence for the standard use of chemoprophylaxis in patients with a low risk, and the findings of this study bolster the importance of further risk-benefit considerations. In a retrospective observational study, Zeng et al6 assessed the efficacy and safety of the use of low-molecular-weight heparin (LMWH) for the prevention of thromboembolic complications following spine surgery. The authors concluded that “The use of LMWH significantly decreases the incidence of thrombosis and thromboembolic complications after spine surgery, but increase the incision bleeding, leading to an elevated risk of symptomatic spinal epidural hematoma.” This paper provides Level IV evidence that LMWH reduces thromboembolic complications after spine surgery not performed for tumor or trauma.

References

  1. Hamidi S, Riazi M. Incidence of venous thromboembolic complications in instrumental spinal surgeries with preoperative chemoprophylaxis. J Korean Neurosurg Soc. 2015;57(2):114-118. doi:10.3340/jkns.2015.57.2.114
  2. Cunningham JE, Swamy G, Thomas KC. Does preoperative DVT chemoprophylaxis in spinal surgery affect the incidence of thromboembolic complications and spinal epidural hematomas? J Spinal Disord Tech. 2011;24(4):E31-E34. doi:10.1097/BSD.0b013e3181f605ea
  3. 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. 2017;27(6):681-693. doi:10.3171/2017.3.SPINE161076
  4. Fang MC, Maselli J, Lurie JD, Lindenauer PK, Pekow PS, Auerbach AD. Use and outcomes of venous thromboembolism prophylaxis after spinal fusion surgery. J Thromb Haemost. 2011;9(7):1318-1325. doi:10.1111/j.1538-7836.2011.04326.x
  5. McLynn RP, Diaz-Collado PJ, Ottesen TD, et al. Risk factors and pharmacologic prophylaxis for venous thromboembolism in elective spine surgery. Spine J. 2018;18(6):970-978. doi:10.1016/j.spinee.2017.10.013
  6. Zeng XJ, Peng H. Prevention of Thromboembolic Complications After Spine Surgery by the Use of Low-Molecular-Weight Heparin. World Neurosurg. 2017;104:856-862. doi:10.1016/j.wneu.2017.05.050

The addition of chemoprophylaxis to mechanical prophylaxis may be considered to reduce the risk of VTE in high risk patients and those undergoing anterior approaches for elective spine surgery. Grade of Recommendation: C

Fawi et al1 published a retrospective comparative study of 2,181 patients undergoing elective thoracolumbar surgery and compared the use of anti-embolic stockings only versus subcutaneous enoxaparin given 6 hours postoperatively, using the rate of VTE, mortality, SSI, and epidural hematoma. Only symptomatic patients had either duplex ultrasound of the extremities or CT angiogram/VQ scan. In the 689 patients that received enoxaparin, there were no VTE recorded. Seven patients had a negative doppler ultrasound and 10 had a negative CT angiogram. In the 1677 patients with anti-embolic stockings only, 25 required CT angiogram, with 9 (0.5%) positives for PE, and 10 required doppler ultrasound, of which 1 was positive for DVT (0.06%). There was not an epidural hematoma identified in either group. This study provides Level III evidence that anti-embolism stockings and LMWH reduce the rate of postoperative VTEs. Fourman et al2 conducted a retrospective comparative study assessing the use of chemoprophylaxis starting on POD2 following elective thoracolumbar surgery, in patients deemed to be high risk for VTE. All patients received pneumatic compression devices (PCD) and either aspirin (ASA) for 30 days or fondaparinux during hospitalization and then ASA for a total of 30 days. During the study period, there were 377 identified as high risk-102 had ASA+PCD and 275 had fondaparinux+ASA+PCD. In the control group, there were 3(2.9%) DVT and 2 (2%) PE. In the fondaparinux group, there were no DVT and 1(0.4%) PE. There were no epidural hematoma in either group. This study provides Level III evidence that fondaparinux in patients undergoing elective lumbar spine surgery reduces DVT and PE rates. Pateder et al3 retrospectively reviewed 407 patients undergoing surgery for adult deformity over 8 years ending in 2000. The authors only looked for PE and found 10 patients. All patients had compression stockings and SCDs pre- and postoperatively, and Coumadin for the first 7 years of the study and LMWH for the last year. They noted that these measures may have reduced PE in ventral surgeries by 50% compared to historical controls. The work group downgraded this potential Level III study due to no control group, retrospective nature, differing protocol, and no assessment of DVT. This study provides Level IV evidence that anticoagulation prevents PE in patients undergoing surgery for adult deformity.

  1. Fawi HMT, Saba K, Cunningham A, et al. Venous thromboembolism in adult elective spinal surgery: a tertiary centre review of 2181 patients. Bone Joint J. 2017;99-B(9):1204-1209. doi:10.1302/0301-620X.99B9.BJJ-2016-1193.R2
  2. Fourman MS, Shaw JD, Nwasike CO, et al. Use of Fondaparinux Following Elective Lumbar Spine Surgery Is Associated With a Reduction in Symptomatic Venous Thromboembolism. Global Spine J. 2020;10(7):844-850. doi:10.1177/2192568219878418
  3. Pateder DB, Gonzales RA, Kebaish KM, et al. Pulmonary embolism after adult spinal deformity surgery. Spine (Phila Pa 1976). 2008;33(3):301-305. doi:10.1097/BRS.0b013e31816245e1

Early postoperative rehabilitation may be considered as a route to reduce VTE risk in patients undergoing elective spine surgery. Grade of Recommendation: C

In a retrospective comparative study, Liu et al1 aimed to evaluate the effect of systematic lower-limb rehabilitation training in elderly patients who had undergone lumbar fusion surgery due to degenerative intervertebral disc diseases. The authors concluded “In early postoperative stage, systematic lower-limb rehabilitation training can effectively speed up the recovery, beneficial to reducing lower-limb DVT and increasing patient satisfaction rate.” This study provides Level IV evidence that lower limb rehabilitation can effectively reduce lower-limb DVT. In a retrospective comparative study, Wang et al2 assessed the clinical rehabilitation effect of lower-limb training on patients who had undergone oblique lumbar interbody fusion (OLIF) procedures. The authors concluded that “Postoperative lower-extremity rehabilitation exercise can effectively accelerate patients’ health recovery from OLIF surgery and increase their satisfaction.” This study provides Level IV evidence that DVT incidence with postoperative rehabilitation training is significantly lower than the control group at final follow-up.

References

  1. Liu SK, Song YL, Ding WY, Yang DL, Ma L, Yang SD. The effect of systematic lower-limb rehabilitation training in elderly patients undergoing lumbar fusion surgery: a retrospective study. Oncotarget. 2017;8(68):112720-112726. Published 2017 Nov 28. doi:10.18632/oncotarget.22746
  2. Wang H, Huo Y, Zhao Y, et al. Clinical Rehabilitation Effect of Postoperative Lower-Limb Training on the Patients Undergoing OLIF Surgery: A Retrospective Study. Pain Res Manag. 2020;2020:1065202. Published 2020 Jan 16. doi:10.1155/2020/1065202

Future Directions for Research

The work group does not have any recommendations for future research on this topic.

Question 14: Do prophylactic antithrombotic measures, including compression stockings, mechanical sequential compression devices and chemoprophylaxis medications, decrease the rate of clinically symptomatic DVT and/or PE (including fatal PE) following spinal surgery (cervical, thoracic or lumbar) for spine trauma (with spinal cord injury and without spinal cord injury)?

Administration of chemoprophylaxis may be considered in trauma patients requiring spine surgery, after ensuring there are no active contraindications/coagulopathy. While the evidence is low-level, it is all consistent. If chemoprophylaxis is to be used, it may be initiated within 24-48 hours of injury or surgery.

Grade of Recommendation: C

In a retrospective observational study, Ahlquist et al1 assessed the effectiveness and safety of chemoprophylaxis within 72 hours of a spinal cord injury. The authors concluded that “Early VTE chemoprophylaxis is effective with lower VTE rates when initiated within 24 hours of surgery for SCI and is safe with no observed postoperative bleeding complications.” This study provides Level III evidence that early VTE chemoprophylaxis is effective with lower VTE rates when initiated within 24 hours of surgery for SCI and is safe with no observed postoperative bleeding complications.

In a retrospective observational study, Chang et al2 aimed to assess whether chemoprophylaxis used to prevent VTE can lead to an increased risk of intraspinal hematoma (ISH). The authors concluded that “Early heparinoid therapy was associated with decreased VTE and PE risk in SCI patients without concomitant increase in ISH expansion.” This study provides Level IV evidence that early administration of heparin decreased VTE and PE risk without increasing ISH risk.

In a retrospective comparative study, Sharpe et al3 evaluated the effect of preoperative anticoagulation on VTE and bleeding complications in patients with blunt spine fractures that required operative stabilization. The authors concluded that “Preoperative anticoagulation in patients with operative spine fractures reduced the risk of pulmonary embolism without increasing bleeding complications. Preoperative anticoagulation is both safe and beneficial in patients with operative spine fractures.” This study provides Level IV evidence that preoperative anticoagulation in patients with operative spine fractures reduced the risk of PE without increased morbidity from bleeding.

In a prospective randomized study, Shiqing et al4 evaluated the effectiveness of low molecular weight heparin (LMWH) therapy in patients with spinal trauma after having undergone part concentrated screw (PCS) pedicle screw spine surgery (PSS), while also assessing its influence on blood parameters and the incidence of deep venous thrombosis. The authors concluded that “LMWH effectively alleviates the hypercoagulability and hyperviscosity of blood and accelerates blood flow in patients with spinal trauma after undergoing PCS PSS. It also lowered the expression levels of inflammatory factors, which is beneficial in reducing the incidence of deep venous thrombosis in lower extremities in patients with spinal injuries.” This study provides Level II evidence that LMWH decreases the risk of DVT in this population.

In a retrospective study, Zeeshan5 assessed the impact of early versus late initiation of venous thromboprophylaxis in patients with spine trauma who had undergone operative intervention. The authors concluded that “Early VTE prophylaxis is associated with decreased rates of DVT in patients with operative spinal trauma without increasing the risk of bleeding and mortality. The VTE prophylaxis should be initiated within 48 hours of surgery to reduce the risk of DVT in this high-risk patient population.” This study provides Level IV evidence that chemoprophylaxis should be used within 48 hours

In a retrospective observational study, Zeng et al6 aimed to assess the efficacy and safety of the use of low-molecular-weight heparin (LMWH) for the prevention of thromboembolic complications following spine surgery. The authors concluded that “The use of LMWH significantly decreases the incidence of thrombosis and thromboembolic complications after spine surgery, but increase the incision bleeding, leading to an elevated risk of symptomatic spinal epidural hematoma.” This paper provides Level IV evidence that LMWH reduces thromboembolic complications after spine surgery not performed for tumor or trauma.

References

  1. Ahlquist S, Park HY, Kelley B, Holly L, Shamie AN, Park DY. Venous Thromboembolism Chemoprophylaxis Within 24 Hours of Surgery for Spinal Cord Injury: Is It Safe and Effective? Neurospine. 2020;17(2):407-416. doi:10.14245/ns.1938420.210
  2. Chang R, Scerbo MH, Schmitt KM, et al. Early chemoprophylaxis is associated with decreased venous thromboembolism risk without concomitant increase in intraspinal hematoma expansion after traumatic spinal cord injury. J Trauma Acute Care Surg. 2017;83(6):1088-1094. doi:10.1097/TA.0000000000001675
  3. Sharpe JP, Gobbell WC, Carter AM, et al. Impact of venous thromboembolism chemoprophylaxis on postoperative hemorrhage following operative stabilization of spine fractures. J Trauma Acute Care Surg. 2017;83(6):1108-1113. doi:10.1097/TA.0000000000001640
  4. Shiqing W, Shengzhong M, Cheng Z, Guangqing C, Chunzheng G. Efficacy of low molecular weight heparin in spinal trauma patients after part concentrated screw surgery and its influence on blood parameters and the incidence of deep venous thrombosis. Med Hypotheses. 2019;132:109330. doi:10.1016/j.mehy.2019.109330
  5. Zeeshan M, Khan M, O'Keeffe T, et al. Optimal timing of initiation of thromboprophylaxis in spine trauma managed operatively: A nationwide propensity-matched analysis of trauma quality improvement program. J Trauma Acute Care Surg. 2018;85(2):387-392. doi:10.1097/TA.0000000000001916
  6. Zeng XJ, Peng H. Prevention of Thromboembolic Complications After Spine Surgery by the Use of Low-Molecular-Weight Heparin. World Neurosurg. 2017;104:856-862. doi:10.1016/j.wneu.2017.05.050

Future Directions for Research

The work group would appreciate the presence of higher-level studies comparing different prophylactic modalities in this patient population.

Question 15: Do prophylactic antithrombotic measures, including compression stockings, mechanical sequential compression devices and chemoprophylaxis medications, decrease the rate of clinically symptomatic DVT and/or PE (including fatal PE) following spinal surgery (cervical, thoracic or lumbar) for malignancy (with spinal cord injury and without spinal cord injury)?

There is insufficient evidence to make a recommendation for or against early vs. delayed use of chemoprophylaxis for decreasing the rate of VTE in patients operated upon for malignant disease of the spine. Grade of Recommendation: I

In a retrospective case series, De la Garza et al1 aimed to evaluate the impact of timing of initiation of prophylactic anticoagulation (AC) on the incidence of venous thromboembolism (VTE) following surgery for metastatic tumors of the spine. The authors concluded that “Administration of prophylactic AC between days 1 and 3 after surgery for metastatic tumors of the spine may significantly reduce the risk of postoperative thromboembolic events.” This study provides Level IV evidence that the addition of early chemoprophylaxis to mechanical prophylaxis in this population may reduce the risk of VTE.

References

  1. De la Garza Ramos R, Longo M, Gelfand Y, Echt M, Kinon MD, Yassari R. Timing of Prophylactic Anticoagulation and Its Effect on Thromboembolic Events After Surgery for Metastatic Tumors of the Spine. Spine (Phila Pa 1976). 2019;44(11):E650-E655. doi:10.1097/BRS.0000000000002944

There is insufficient evidence to make a recommendation for or against the use of chemo prophylaxis for decreasing the rate of VTE in patients operated upon for malignant disease of the spine. Grade of Recommendation: I

In a retrospective observational study, Groot et al1 sought to determine the percentage of patients and the associated factors for those individuals who developed symptomatic VTE within 90-days of surgical intervention for spine metastases. This study also evaluated the relationship between the development of postoperative symptomatic VTE and 1-year survival among patients who had surgery for spine metastases as well as evaluate if chemoprophylaxis increases the risk of wound complications among patients who had surgery for spine metastases. The authors concluded that “The risk of both symptomatic PE and fatal PE is high in this patient population, and those with symptomatic VTE were less likely to survive 1-year than those who did not, though this may reflect over all infirmity as much as anything else, because many of these patients did not die from VTE related complications.” This study provides Level III evidence that there is no significant association between patients’ chemoprophylaxis and symptomatic VTE.

References

  1. Groot OQ, Ogink PT, Paulino Pereira NR, et al. High Risk of Symptomatic Venous Thromboembolism After Surgery for Spine Metastatic Bone Lesions: A Retrospective Study. Clin Orthop Relat Res. 2019;477(7):1674-1686. doi:10.1097/CORR.0000000000000733

Future Directions for Research

The work group recommends prospective comparatives studies looking at the utility of different chemoprophylaxis regimens in preventing VTE in patients operated upon for malignant disease of the spine.