- Department of Neurosurgery, University of Arizona, Tucson, United States.
- Department of Neurosurgery, University of Arizona College of Medicine, Phoenix, Arizona, United States.
Mauricio J. Avila, Department of Neurosurgery, University of Arizona, Tucson, Arizona, United States.
DOI:10.25259/SNI_837_2022Copyright: © 2022 Surgical Neurology International This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
How to cite this article: Mauricio J. Avila1, José Manuel Orenday-Barraza2, María José Cavagnaro1, Isabel M. Strouse2, Dara S. Farhadi2, Naushaba Khan2, Amna Hussein2, Ali A. Baaj2. Antifibrinolytics use during surgery for oncological spine diseases: A systematic review. 02-Dec-2022;13:567
How to cite this URL: Mauricio J. Avila1, José Manuel Orenday-Barraza2, María José Cavagnaro1, Isabel M. Strouse2, Dara S. Farhadi2, Naushaba Khan2, Amna Hussein2, Ali A. Baaj2. Antifibrinolytics use during surgery for oncological spine diseases: A systematic review. 02-Dec-2022;13:567. Available from: https://surgicalneurologyint.com/surgicalint-articles/12034/
Background: Data exist of the benefits of antifibrinolytics such as tranexamic acid (TXA) in general spine surgery. However, there are limited data of its use in oncological spine patients.
Methods: A systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Cochrane, OVID, and Embase databases were searched. Search terms: “tranexamic acid”, “aprotinin,” “aminocaproic acid,” “spine surgery,” “spine tumors,” and “spine oncology.” Included studies were full text publications written in English with patients treated with either agent or who had surgery for oncological spine disease (OSD).
Results: Seven hundred results were reviewed form the different databases, seven were selected. A total of 408 patients underwent spine surgery for OSD and received antifibrinolytics. There was a male predominance (55.2%) and mean age ranged from 43 to 62 years. The most common tumor operated was metastatic renal cancer, followed by breast and lung. Most studies administered TXA as a bolus followed by an infusion during surgery. Median blood loss was of 667 mL (253.3–1480 mL). Patients with TXA required 1–2 units less of transfusion and had 56–63 mL less of postoperative drainage versus no TXA. The median incidence of deep venous thrombosis (DVT) was 2.95% (0–7.9%) and for pulmonary embolism (PE) was 4.25% (0–14.3%). The use of TXA reduced intraoperative blood loss, transfusions and reduced postoperative surgical drainage output compared to no TXA use in patients with OSD.
Conclusion: In this review, we found that TXA may diminish intraoperative blood loss, the need for transfusion and postoperative drainage from surgical drains when used in OSD without major increase in rates of DVT or PE.
Keywords: Antifibrinolytics, Metastatic spine disease, Spine oncology, Spine surgery, Tranexamic acid
Metastases are indeed the most common type of tumor in the spine.[
Patients with cancer present commonly with nutritional deficiencies and sarcopenia compared to those with spine deformity or degenerative disorders that need spine surgery.[
Given the exponential growth of spine surgery, in particular larger surgeries, recent studies have shown the benefits of using antifibrinolytic therapy in spine surgery to limit blood loss. A recent meta-analysis by Li et al.[
In this study, we aim to investigate the use of antifibrinolytic therapy in patients undergoing spine surgery for tumors (metastatic or primary) of the spine with particular interest of blood loss parameters and complications.
A systematic review of the literature was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines[
Search strategy and screening
Databases were used included: PubMed, PubMed Central, Cochrane Library, Clinicaltrials.gov, and Embase. The search was catered to gather English language articles published from any beginning date to September 2021. The following antifibrinolytics agents were included: tranexamic acid (TXA), Aminocaproic Acid and Aprotinin. Combinations and variations of key phrases including: “tranexamic acid,” “aprotinin,” “aminocaproic acid,” “Spine tumors,” “spine oncology,” “spine metastasis,” “spine surgery,” “spine fusion,” “Spine fixation,” “spine decompression,” “spinal surgery” with the use of Boolean AND and OR in multiple configurations.
Inclusion and exclusion criteria
Eligible studies used antifibrinolytics during their spinal surgery for spine oncological diseases (metastatic or primary). The inclusion criteria for the reviewed articles included case reports, case series, retrospective, and prospective studies as well. Studies were limited to those written in the English language. Screened studies such as abstracts, posters, indexes, commentaries, author notes, and literature reviews were excluded from the study.
All data were taken directly from tables, figures, and texts of included articles. The relevant data was extracted and placed into a custom table which included article’s first author and year published, study type, number of patients included, type of antifibrinolytics agent, age and sex details, oncological diagnosis, treatment approach, outcome, and venous thromboembolism events. When data were unclear or unspecified, it was noted in the table as “-”.
Characteristics and quality of included studies
To assess the risk of bias of randomized controlled trials, the Jadad Scale[
Although initially planned, a meta-analysis was not performed given the heterogeneity of data including multiple study design, poor quality of reports, missing data, different antifibrinolytics administration protocols, and lack of control group in most studies as well as the inconsistency in reporting clinical outcomes. Therefore, only descriptive statistics were performed. Data were presented as mean and standard deviation or median and interquartile range, if appropriate. For categorical variables, absolute values and percentages were used.
A total of 700 articles were found in the different databases. After selection by title and abstract, 43 articles were downloaded for full text review. Of these, 36 articles were removed given lack of data for spine oncology patients and seven articles[
All studies used TXA as the antifibrinolytic of choice.
The studies reported that the use of TXA was done due to the high risk of intraoperative bleeding in these patients. All the studies reported that their patients’ cohort who received TXA did not have coagulopathy before surgery measured by preoperatively blood coagulation analysis. Moreover, four studies[
TXA dosing and timing
Six out of the seven studies reported the dosage used. The TXA dose range was from 1 mg/kg to up to 20 mg/kg with 10 mg/kg being the most common. There were two methods for the timing of TXA administration within the different studies: (a) one dose bolus at the beginning and (b) bolus plus a maintenance infusion during surgery. Five out of the six studies that reported the dose performed a maintenance infusion of TXA throughout the surgery. One study[
Intraoperative blood loss
All studies reported intraoperative blood loss [
Five studies reported the need and amount of blood transfusion [
Postoperative blood loss
For this section, we compiled studies that reported postoperative blood loss in surgical drains. Three studies reporting the use of postoperative drains. The study by Zhang et al.[
Deep venous thrombosis (DVT)
Six out of the seven studies reported the incidence of DVT. Median combined DVT for the studies was 2.95%. In individual studies, fours studies reported 0 DVT events and the highest reported was by Pennington et al.[
Pulmonary embolism (PE)
Six out of the seven studies reported the incidence of PE. Four studies reported an incidence of 0% while using TXA. The higher incidence of PE was reported by Pennington et al.[
Given the baseline frailty of cancer patients, adjuvants for intraoperative hemorrhage control while undergoing spine surgery are needed to avoid massive blood loss that may complicate their postoperative course. In addition, cancer patients tend to be anemic at baseline before surgery[
In this study, we found that patients who received TXA undergoing treatment for tumors in the spine (metastatic and primary) had diminished blood loss, diminished postoperative blood loss (from surgical drains), and less need for transfusions without major increase in venous thromboembolism events. Nonetheless, some individual studies showed no statistically significant difference in blood loss between TXA and non-TXA groups.
Antifibrinolytics agents have shown good results in spine deformity surgery, but they are less studied in spine oncology. Tsantes et al.[
On a broader perspective, the pooled median EBL for the included studies with TXA was 667 mL (range 252–1480 mL) when compared to surgeries such as minimally invasive tumor resection,[
Although only seven studies were selected these included an overall sample of 408 patients, this is quite comparable with a meta-analysis by Li et al.[
Interestingly, our results showed a wide variety of spinal oncological diseases. Metastatic cancer was the most common diagnosis with renal carcinoma as the number one followed by breast cancer. Additional tumors included sarcomas, thyroid metastases, lung metastases, nerve sheath tumors, myeloma, and meningiomas which show the benefit of TXA in a variety of oncological spine disease treated surgically making our study quite unique in terms of the diversity of diagnosis. To the best of our knowledge, this is the first study to incorporate different oncological diagnosis and the use of TXA during spine surgery.
Only two studies reported preoperative embolization; Yonezawa et al. who presented the largest series of renal carcinoma metastasis performed embolization in all their patients[
There was variety in the dosing and method of administering TXA in the different studies; the majority of the studies performed an initial bolus of TXA and continued an infusion throughout the surgery. As with the published literature for spine deformity, there is no clear agreement on the optimal dosing. A recent review and meta-analysis favored a lower dose of TXA (200–500 mg) compared to higher dose (1–3 g).[
Our results showed that despite the administration of TXA, spine tumor patients do not appear to be at an unusual increased risk of venous thromboembolism events, one of the major concerns of using these hemostatic agents. Several of the included studies reported 0% incidence of DVT/PE.[
There is a lack of randomized trials in spine oncology and use of antifibrinolytics agents. Despite our extensive database search only one RCT was found, and this study included a mix of degenerative and oncological patients, the rest of the studies were retrospective case series from individual hospitals. Ideally, a multi-center prospective randomized trial may help validate our findings. In particular, if there are any differences in terms of the spinal oncological diagnosis and the effectiveness of the antifibrinolytics agent. Our results suggest that there is probably no difference.
With the advancement of separation surgery[
The study has several limitations. The majority of included studies are retrospective case series which renders our results of a low evidence given the available studies. The highest level of evidence in this series is a Level I for Elwaitidy et al.[
The use of antifibrinolytics agents in surgery for spine tumors is not well studied. In this systematic review, we found that the use of TXA during surgery for spine tumors may diminish intraoperative blood loss, the need for transfusion and postoperative drainage from surgical drains without major increase in rates of DVT or PE. Additional randomized controlled multi-center studies are needed to further support these findings.
Portions of this work were presented as an Oral presentation at the 2022 AANS/CNS Spine summit in Las Vegas, NV.
Patients’ consent not required as patients’ identities were not disclosed or compromised.
There are no conflicts of interest.
The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Journal or its management. The information contained in this article should not be considered to be medical advice; patients should consult their own physicians for advice as to their specific medical needs.
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