Question 2. What Is the Defined Risk of Anticoagulation After Spine Surgery by Type of Anticoagulation?
We identified 7 comparative studies that evaluated adverse events in 2 categories of anticoagulation: anticoagulants, which include fractionated and unfractionated heparin and Warfarin, or antiplatelet agents, which include aspirin, nonsteroidal anti-inflammatory agents, and Plavix.
The risk of bleeding from anticoagulant agents in spinal surgery in 5 prospective and 1 retrospective cohort study was small; risk of major bleeding ranged from 0.0% to 4.3% across several types of anticoagulants. Hematoma was reported in only 10 cases in 2507 patients (Table 2).
In a prospective study, Rokito et al26 assessed complications associated with anticoagulation methods in 110 patients who underwent major spine surgery. Patients were randomized to receive bilateral thigh-high thrombosis embolic deterrent (TED) compression stockings placed before surgery and worn until discharge (n = 42), TED stockings and thigh-length cuffs that provided sequential pneumatic compression to the calf and thigh (n = 33), or TED stockings and 10 mg Coumadin administered on the evening before surgery followed by daily Coumadin until duplex Doppler studies were obtained (fifth to seventh postoperative day) to maintain the prothrombin time level at 1.3 to 1.5 times control (n = 35). No bleeding complications were reported in the TED or TED and thigh-length cuff groups. In the Coumadin group, 1 patient experienced an excessive amount of drainage on postoperative day 1 (minor bleeding complication, 2.9%), and another experienced excessive intraoperative blood loss (major bleeding complication, 2.9%). Both of these patients required blood transfusions. No other adverse events were reported.
Another prospective study included 179 patients scheduled for surgical procedures because of a prolapsed lumbar-intervertebral disc.27 Individuals were randomized to receive either 32 mg low-molecular-weight heparin (LMWH) and 0.5 mg dihydroergotamine (DHE) once a day plus 1 placebo injection per day (LMWH/DHE; n = 87) or 5000 U unfractionated heparin plus 0.5 mg DHE (HDHE) twice a day (n = 92). The medication was administered 2 hours before the surgical procedure and every 12 hours for at least 7 days. Excessive intraoperative blood loss, determined via subject assessment of the surgeon, was observed in 0 (0.0%) patients receiving HDHE, and 4 (4.3%) in the LMWH/DHE group. Excessive postoperative loss of blood in drains (minor bleeding complication) was found in 8 (9.2%) treated with LMWH/DHE and 3 (3.3%) in the HDHE group. Five (5.7%) patients in the LMWH/DHE group required blood transfusions, whereas 4 (4.3%) who received HDHE required transfusions. No hematomas, deaths, or other adverse events were reported.
Gruber et al16 reported the results of a prospective study of 50 patients undergoing lumbar disc surgery. Patients were randomized to receive either 2500 IU HDHE twice daily (n = 25) or placebo (n = 25) beginning 2 hours before surgery and every 12 hours afterward for at least 7 days (if determined to be clinically necessary) or until discharge from the hospital. Intraoperative increased bleeding was determined via surgeon assessment. Six (24%) patients in the HDHE group and 7 (28%) in the placebo group experienced minor intraoperative increased bleeding. No major bleeding complications were reported in either group. One (4.0%) hematoma, which resolved spontaneously, was reported in the placebo group. No other adverse events were reported.
The use of the LMWH, Bemiparin, was studied in a prospective, multicenter cohort study by Otero-Fernandez et al.28 The authors enrolled 231 spine surgery patients into the study, who were planned to receive extended prophylaxes after their hospital stay. Patients received once-daily, subcutaneous administration of Bemiparin 3500 IU/day (high risk) or 2500 IU/day (moderate risk) for a median of 21 days. Major bleeding was defined as any bleeding in critical organs, fatal bleeding, bleeding requiring reoperation to control bleed, or any bleeding requiring treatment cessation. Minor bleeding was bleeding that did not meet criteria for major bleeding. In the 225 patients who completed the study, 0.89% (2 of 225) had a major bleeding episode and 3.56% (8 of 225) experienced a minor bleeding episode. No other adverse events were reported.
Schizas et al29 prospectively followed a consecutive cohort of 270 patients who underwent spinal surgery. Compressive stockings were used on all patients on admission. Enoxoparin was administered once daily starting during the eighth postoperative hour (20 mg for the first 3 postoperative days and 40 mg thereafter) and discontinued on discharge. Postoperative hematomas requiring surgical evacuation were recorded. Two (0.7%) patients developed postoperative hematomas requiring emergency evacuation. Neither patient developed neurologic signs or symptoms.
In 1 retrospective cohort study, Gerlach et al31 analyzed the rate of postoperative hemorrhage associated with early (<24 hours after surgery) postoperative daily administration of 0.3 mL of nadroparin calcium (Fraxiparin, 2850 IU anti-Xa) plus intra- and postoperative compression stockings until discharge in a cohort of 1954 consecutive patients who underwent spine surgery. Major postoperative hemorrhage was defined as a hemorrhage associated with a mass effect on postoperative spinal magnetic resonance imaging or neurologic deterioration, as well as a large-wound hematoma with intractable pain. Major postoperative hemorrhage occurred in 0.7% (13 of 1954) of spinal procedures, and 0.4% (8 of 1954) of major postoperative epidural hematomas developed after administration of nadroparin. Hematomas were surgically evacuated immediately after diagnosis. Six of the patients with postoperative hematomas developed a progressive neurologic deficit, which resulted in a hemorrhage-related residual neurologic impairment in 0.2% (3 of 1954) patients.
The risk of adverse bleeding events from antiplatelet agents was evaluated in 1 prospective cohort study that examined bleeding risks associated with Ketorolac.30 Forty-four consecutive patients undergoing lumbar microdiscectomy were given a single 30-mg intravenous dose of Ketorolac immediately before wound closure and were prospectively observed until discharge, whereas 45 patients who did not receive Ketorolac during lumbar microdiscectomy were evaluated retrospectively. There were no incidences of postoperative incisional bleeding complications or bleeding from the wound site. Platelet counts remained normal after surgery, and no abnormal laboratory values were noted.
Question 3. Is There a Safe Perioperative Window of Nonanticoagulation for These High-Risk Patients?
We found no studies that attempted to define a safe perioperative window of nonanticoagulation in spine surgery patients, nor did we identify any study that assessed this safe perioperative window in general surgery.
The overall strength of evidence with respect to incidence of thromboembolic events after spine surgery is “very low” to “low,” that is, any estimate of the effect reported for the various spine conditions is uncertain and further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. The overall strength of evidence for the incidence of significant hemorrhage secondary to anticoagulation use is also “very low,” that is, any estimate of effect is very uncertain. Finally, we found no evidence to support any preventive measures with respect to a safe perioperative window of nonanticoagulation for high-risk spinal surgery patients (Table 3).
This systematic review demonstrated that the risk of DVT in elective spine surgery without chemical prophylaxis was 1% to 2% and up to 18% in the trauma population. The risk of fatal PE in elective surgery is extremely low (no case identified) except in the trauma patients. We could not identify significant risk factors for thromboembolic diseases except for trauma in spine surgery patients.
Postoperative bleeding with possibility of epidural hematoma and neurologic complications occur in 1% to 3.5% of cases of patients receiving heparin but did not occur in single studies of patients receiving aspirin, Ketorolac or Warfarin. If heparin is to be used, careful monitoring of the wound and neurologic examination should be performed. Postoperative hemorrhage from wounds also occurred in 1% to 3% of cases treated with chemical prophylaxis, but the significance seemed minor. The data reviewed did not provide adequate information of the timing of administration of chemical prophylaxis and its effect on patient safety; therefore, we could not identify any evidence regarding the safe timing of chemical anticoagulation.
We stratified risk of bleeding complications in patients receiving anticoagulation therapy by the agent administered. However, the small number of studies available limits the conclusions with respect to which agents provide the least risk. Additional studies added to those collected here will provide a more robust estimate in determining whether one agent is safer than another.
This systematic review will likely under represent the true incidence of VTE because the sensitivity of diagnostic tests are <100%, and episodes of VTE may occur after such testing has been performed. Further, the many confounding variables present in these patients may obscure important factors associated with VTE risk and the evaluation of the safety of prophylaxis.
Previous Clinical Guidelines
The American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition) provides recommendations for prevention of VTE in elective spinal surgery.1 For patients with no additional risk factors, the recommendations are against the routine use of any thromboprophylaxis modality beyond early and persistent mobilization. For patients with additional risk factors such as advanced age, malignancy, presence of neurologic deficit, previous thromboembolism, or an anterior surgical approach, any of the following prophylaxis options are recommended: (1) postoperative low-dose unfractionated heparin (LDUH) alone, (2) postoperative LMWH alone, or (3) perioperative intermittent pneumatic compression (IPC) alone. Other considerations include perioperative graduated compression stockings (GCS) alone or perioperative IPC combined with GCS. In patients with multiple risk factors for VTE, it is recommended to combine LDUH or LMWH with GCS or IPC.
Similarly, the North American Spine Society Evidence-Based Clinical Guideline on Antithrombotic Therapies in Spine Surgery has provided evidence-based recommendations regarding antithrombotic therapies in spine surgery.32 Mechanical compression devices in the lower extremities are suggested to be initiated in elective spinal surgery just before surgery, and continuing until the patient is fully ambulatory. Chemoprophylaxis may not be warranted in most common elective spine surgeries performed through a posterior approach. LMWH or LDUH may be used after surgery after elective combined anterior-posterior spine surgery or in patients identified as having a high risk for VTE, such as multiple trauma, malignancy, or hypercoagulable state.
Based on the low risks of fatal PE in elective surgery, it was the opinion of experts that chemical prophylaxis to prevent thromboembolic disease is not routinely indicated. The use of thromboembolic stockings and mechanical compression devices is recommended on a case-by-case basis. Chemical prophylaxis should be considered in patients with significant neurologic dysfunction or who require prolonged bed rest, although this scenario was not evaluated in this study. If heparin is used, then careful observation of the wound and neurologic functions should be performed (Figure 3). Chemical prophylaxis should be considered in spinal trauma patients and those with spinal cord injuries.
- In elective spine surgery, the incidence of DVT and nonfatal pulmonary embolism without chemical prophylaxis is 1% to 2%. Fatal pulmonary embolism is extremely rare.
- Trauma patients are at increased risk, and chemical prophylaxis should be considered.
- The safe timing of the administration of anticoagulation agents is unknown.
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.spinejournal.com).
The authors thank Ms. Nancy Holmes, RN, for her administrative assistance and Ms. Erika Ecker, BS, for her assistance in searching the literature, abstracting data, and proofing.
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venous thromboembolism; deep venous thrombosis; pulmonary embolism; chemical prophylaxis; spine surgery
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