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Interaction of admission platelet count with current medications and the risk for chronic subdural recurrence

Shawn R. Eagle, Aditya M. Mittal, Ryan T. Kellogg, Jan Vargas, Enyinna Nwachuku, Hansen Deng, Thomas J. Buell, David O. Okonkwo, and Matthew Pease

OBJECTIVE

Chronic subdural hematoma (cSDH) has a reported 10%–24% rate of recurrence after surgery, and prognostic models for recurrence have produced equivocal results. The objective of this study was to leverage a data mining algorithm, chi-square automatic interaction detection (CHAID), which can incorporate continuous, nominal, and binary data into a decision tree, to identify the most robust predictors of repeat surgery for cSDH patients.

METHODS

This was a retrospective cohort study of all patients with SDH from two level 1 trauma centers at a single institution. All patients underwent cSDH evacuation performed by 15 neurosurgeons between 2011 and 2020. The primary outcome was the rate of repeat surgery for recurrent cSDH following the initial evacuation. The authors used CHAID to identify relevant predictors of repeat surgery, including age, sex, comorbidities, postsurgical complications, platelet count prior to the first procedure, midline shift prior to the first procedure, hematoma volume, and preoperative use of anticoagulants, antiplatelets, or statins.

RESULTS

Sixty (13.8%) of 435 study-eligible patients (average age 74.0 years) had a cSDH recurrence. These patients had 2.0 times greater odds of having used anticoagulants. The final CHAID model had an overall accuracy of 87.4% and an area under the curve of 0.76. According to the model, the predictor with the strongest association with cSDH recurrence was admission platelet count. Approximately 26% of patients (n = 23/87) with an admission platelet count < 157 × 109/L had a cSDH recurrence, whereas none of the 44 patients with admission platelets > 313 × 109/L had a recurrence. Approximately 17% of patients in the 157–313 × 109/L platelet group who had used preoperative statins required a second procedure, which was associated with a 2.3 times increased risk for repeat surgery compared to those who had not used statins preoperatively. Among those who had not used preoperative statins, a platelet count ≤ 179 × 109/L on admission for the first procedure was the strongest differentiator for a second surgery (n = 5/22 [23%]), which increased the risk of recurrence by 4.5 times. Among the patients using preoperative statins, the use of anticoagulants was the strongest differentiator for requiring repeat surgery (n = 11/33 [33%]).

CONCLUSIONS

The described model identified platelet count on admission as the most important predictor of repeat cSDH surgery, followed by preoperative statin use and anticoagulant use. Critical cutoffs for platelet count were identified, which future studies should evaluate to determine if they are modifiable or reflective of underlying disease states.

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Introduction. Antithrombotic medication in neurosurgery: management and controversies of a growing clinical dilemma

Jehuda Soleman, R. Loch Macdonald, David Seiffge, and Ladina Greuter

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Perioperative continuation or ultra-early resumption of antithrombotics in elective neurosurgical cranial procedures

Jonathan Rychen, Valentin F. Weiger, Florian S. Halbeisen, Florian Ebel, Muriel Ullmann, Luigi Mariani, Raphael Guzman, and Jehuda Soleman

OBJECTIVE

Discontinuation of antithrombotics (AT) prior to elective cranial procedures is common practice, despite the higher risk of thromboembolic complications in these patients. The aim of this study was to investigate the risks and benefits of a new perioperative management protocol of continuation or ultra-early AT resumption in elective cranial procedures.

METHODS

This study was an analysis of a prospectively collected cohort of patients undergoing elective cranial surgery with (AT group) and without (control group) AT. For extraaxial or shunt surgeries, acetylsalicylic acid (ASA) was continued perioperatively. For intraaxial pathologies, ASA was discontinued 2 days before surgery and resumed on postoperative day 3. All other AT were discontinued according to their pharmacokinetics, and resumed on postoperative day 3 after unremarkable postoperative imaging. Additionally, the authors performed a retrospective analysis of patients with AT who underwent surgery before implementation of this new AT management protocol (historical AT group). Primary and secondary outcomes were the incidence of hemorrhagic and thromboembolic complications within 3 months after surgery.

RESULTS

Outcomes of 312 patients were analyzed (83 [27%] in the AT group, 106 [34%] in the control group, and 123 [39%] in the historical AT group). For all 3 patient groups, the most common type of surgery was craniotomy for intraaxial tumors (14 [17%] in the AT group, 28 [26%] in the control group, and 60 [49%] in the historical AT group). The most commonly used AT were ASA (38 [46%] in the AT group and 78 [63%] in the historical AT group), followed by non–vitamin K oral anticoagulants (32 [39%] in the AT group and 18 [15%] in the historical AT group). The total perioperative discontinuation time in the AT group was significantly shorter than in the historical AT group (median of 4 vs 16 days; p < 0.001). The rate of hemorrhagic complications was 4% (95% CI 1–10) (n = 3/83) in the AT group, 6% (95% CI 2–12) (n = 6/106) in the control group, and 7% (95% CI 3–13) (n = 9/123) in the historical AT group (p = 0.5). The rate of thromboembolic complications was 5% (95% CI 1–12) (n = 4/82) in the AT group, 8% (95% CI 3–15) (n = 8/104) in the control group, and 7% (95% CI 3–13) (n = 8/120) in the historical AT group (p = 0.7).

CONCLUSIONS

The presented perioperative management protocol of continuation or ultra-early resumption of AT in elective cranial procedures does not seem to increase the hemorrhagic risk. Moreover, it appears to potentially protect patients from thromboembolic complications.

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Safety and comparative efficacy of initiating low-molecular-weight heparin within 24 hours of injury or surgery for venous thromboembolism prophylaxis in patients with spinal cord injury: a prospective TRACK-SCI registry study

Austin Lui, Christine Park, Timothy Chryssikos, Hannah Radabaugh, Arati Patel, Alexander A. Aabedi, Adam R. Ferguson, Abel Torres Espin, Praveen V. Mummaneni, Sanjay S. Dhall, Xuan Duong-Fernandez, Rajiv Saigal, Austin Chou, Jonathan Pan, Vineeta Singh, Debra D. Hemmerle, Nikos Kyritsis, Jason F. Talbott, Lisa U. Pascual, J. Russell Huie, William D. Whetstone, Jacqueline C. Bresnahan, Michael S. Beattie, Philip R. Weinstein, Geoffrey T. Manley, and Anthony M. DiGiorgio

OBJECTIVE

Venous thromboembolism (VTE) following traumatic spinal cord injury (SCI) is a significant clinical concern. This study sought to determine the incidence of VTE and hemorrhagic complications among patients with SCI who received low-molecular-weight heparin (LMWH) within 24 hours of injury or surgery and identify variables that predict VTE using the prospective Transforming Research and Clinical Knowledge in SCI (TRACK-SCI) database.

METHODS

The TRACK-SCI database was queried for individuals with traumatic SCI from 2015 to 2022. Primary outcomes of interest included rates of VTE (including deep vein thrombosis [DVT] and pulmonary embolism [PE]) and in-hospital hemorrhagic complications that occurred after LWMH administration. Secondary outcomes included intensive care unit and hospital length of stay, discharge location type, and in-hospital mortality.

RESULTS

The study cohort consisted of 162 patients with SCI. Fifteen of the 162 patients withdrew from the study, leading to loss of data for certain variables for these patients. One hundred thirty patients (87.8%) underwent decompression and/or fusion surgery for SCI. DVT occurred in 11 (7.4%) of 148 patients, PE in 9 (6.1%) of 148, and any VTE in 18 (12.2%) of 148 patients. The analysis showed that admission lower-extremity motor score (p = 0.0408), injury at the thoracic level (p = 0.0086), admission American Spinal Injury Association grade (p = 0.0070), and younger age (p = 0.0372) were significantly associated with VTE. There were 3 instances of postoperative spine surgery–related bleeding (2.4%) in the 127 patients who had spine surgery with bleeding complication data available, with one requiring return to surgery (0.8%). Thirteen (8.8%) of 147 patients had a bleeding complication not related to spine surgery. There were 2 gastrointestinal bleeds associated with nasogastric tube placement, 3 cases of postoperative non–spine-related surgery bleeding, and 8 cases of other bleeding complications (5.4%) not related to any surgery.

CONCLUSIONS

Initiation of LMWH within 24 hours was associated with a low rate of spine surgery–related bleeding. Bleeding complications unrelated to SCI surgery still occur with LMWH administration. Because neurosurgical intervention is typically the limiting factor in initializing chemical DVT prophylaxis, many of these bleeding complications would have likely occurred regardless of the protocol.

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Safety and functional outcomes of early antiplatelet therapy within 24 hours following mechanical thrombectomy for secondary prevention in emergent large-vessel occlusion strokes: a registry study

Hepzibha Alexander, Chad F. Claus, Doris Tong, Robert McCabe, Lucas Garmo, Joseph Gabrail, Prashant Kelkar, Julius Griauzde, Teck M. Soo, and Boyd Richards

OBJECTIVE

The aim of this study was to demonstrate the safety and functional outcomes of antiplatelet use within 24 hours following mechanical thrombectomy (MT).

METHODS

A retrospective review of prospectively collected data for consecutive patients who underwent MT for acute ischemic stroke (AIS) between 2016 and 2020 was performed. Patient demographics, comorbidities, Alberta Stroke Program Early CT Score (ASPECTS), antiplatelet use, neurological status, and tissue plasminogen activator use were collected. Patients were stratified into two groups, early (< 24 hours) or late (> 24 hours), based on when antiplatelet therapy was initiated post-MT. The primary outcome was safety, determined based on the rate of symptomatic intracranial hemorrhage (sICH) and inpatient mortality. The secondary outcome was functional independence (defined as modified Rankin Scale [mRS] score ≤ 2) at discharge and 30 days and 90 days postoperatively. The two cohorts were compared using univariate analysis. Multiple imputations were used to create complete data sets for missing data. Multivariable analysis was used to identify predictors for sICH and functional outcomes.

RESULTS

A total of 190 patients met inclusion criteria (95 per group). Significant differences between the early and late groups included sex, preoperative intravenous thrombolysis, angioplasty, stent placement, and thrombectomy site. ICH (symptomatic and asymptomatic) and inpatient mortality were not significantly different between the groups. The mRS score was significantly lower at discharge (p < 0.001), 30 days (p = 0.011), and 90 days (p = 0.024) following MT in the early group. Functional independence was significantly higher in the early antiplatelet group at discharge (p = 0.015) and at 30 days (p = 0.006). Early antiplatelet use was independently associated with significantly increased odds of achieving functional independence at discharge (OR 3.07, p = 0.007) and 30 days (OR 5.78, p = 0.004). Early antiplatelet therapy was not independently associated with increased odds of sICH.

CONCLUSIONS

Early antiplatelet initiation after MT in patients with AIS was independently associated with significantly increased odds of improved postoperative functional outcomes without increased odds of developing sICH.

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Safety of dual antiplatelet therapy in the acute phase of aneurysmal subarachnoid hemorrhage: a propensity score–matched study

Farid Qoorchi Moheb Seraj, Mohammad Hossein Mirbolouk, Marjan Vaezi, Feizollah Ebrahimnia, Reza Gorji, Sajjad Najafi, Hashem Pahlavan Shamsi, Ali Sadeghian Shahi, Payam Sasannejad, Samira Zabihyan, Ashkan Mowla, Daniel Kheradmand, and Humain Baharvahdat

OBJECTIVE

With the evolution of neuroendovascular treatments, there is a great trend to treat acutely ruptured wide-necked aneurysms with stent-assisted coiling (SAC) and flow diverters (FDs), which inevitably requires dual antiplatelet therapy (DAPT). This therapy can increase the rate of hemorrhagic complications following other neurosurgical maneuvers, such as external ventricular drain (EVD) placement or removal. In this study, the authors aimed to evaluate the safety of DAPT in patients with aneurysmal subarachnoid hemorrhage (SAH) treated with SAC or FDs and the therapy’s potential benefit in reducing cerebral ischemia and cerebral vasospasm.

METHODS

In this retrospective study, the authors reviewed the records of patients who had been admitted to their hospital with acute aneurysmal SAH and treated with SAC, FDs, and/or coiling between 2012 and 2022. Patients were classified into two groups: a DAPT group, including patients who had received DAPT for SAC or FDs, and a non-DAPT group, including patients who had not received any antiplatelet regimen and had been treated with coiling. Perioperative hemorrhagic and ischemic complications and clinical outcomes were compared between the two groups.

RESULTS

From among 938 cases of acute ruptured aneurysms treated during 10 years of study, 192 patients were included in this analysis, with 96 patients in each treatment group, after propensity score matching. All basic clinical and imaging characteristics were equivalent between the two groups except for the neck size of aneurysms (p < 0.001). EVD-related hemorrhage was significantly higher in the DAPT group than in the non-DAPT group (p = 0.035). In most patients, however, the EVD-related hemorrhage was insignificant. Parent artery or stent-induced thrombosis was higher in the DAPT group than in the non-DAPT group (p = 0.003). The rate of cerebral ischemia was slightly lower in the DAPT group than in the non-DAPT group (11.5% vs 15.6%, p = 0.399). In the multivariate analysis, cerebral ischemia, rebleeding before securing the aneurysm, extracranial hemorrhage, and cerebral vasospasm were the predictive factors of a poor clinical outcome (p < 0.001, p < 0.001, p = 0.038, and p = 0.038, respectively).

CONCLUSIONS

The DAPT regimen may be safe in the setting of acute aneurysmal SAH. Although EVD-related hemorrhage is more common in the DAPT group than the non-DAPT group, it is usually insignificant without any neurological deficit.

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Stroke risk related to intentional discontinuation of antithrombotic therapy for invasive procedures

Nobuyuki Mitsui, Manabu Kinoshita, Jun Sawada, Mikihiro Fujiya, and Hiroyuki Furukawa

OBJECTIVE

Antithrombotic medications pose a challenge for conducting surgical or invasive procedures, because their discontinuation is required to avoid postprocedural hemorrhagic complications but potentially increases the ischemic risk for the patient. This study aimed to estimate the increased risk of developing cerebral ischemic events during hospitalization requiring discontinuation of antithrombotic therapy.

METHODS

This investigation was a single-center retrospective observational study. Clinical data in patients scheduled for admission between January 1, 2021, and December 31, 2022, were collected. Patients requiring discontinuation of antithrombotic therapy were identified by referring to the admission database. Patients who developed cerebral ischemia were identified by referring to the institution’s stroke center database.

RESULTS

Seven hundred ninety-six patients scheduled for nonneurosurgical procedures and 39 scheduled for neurosurgical procedures underwent discontinuation of antithrombotic therapy. Anticoagulation therapy was prescribed in 40.0%, and antiplatelet therapy was prescribed in 69.1% of the patients. A total of 9.2% of the entire cohort of patients were receiving both anticoagulation and antiplatelet therapy. Bridging therapy was administered in 20.9% of nonneurosurgical patients. No ischemic event was observed in the patients undergoing neurosurgical procedures. Among the entire cohort, 3 patients encountered some kind of thrombotic event—2 of which were cerebral ischemia—accounting for an incidence of 0.24%, which was significantly higher than incidental in-hospital stroke unrelated to discontinuation of antithrombotic therapy (p = 0.04). Patients undergoing both anticoagulation and antiplatelet therapy harbored a significantly higher risk for cerebral ischemia related to discontinuation of antithrombotic therapy (p < 0.0001).

CONCLUSIONS

Discontinuing antithrombotic therapy during hospitalization for elective invasive procedures—including neurosurgical procedures—entailed a relatively small risk of developing cerebral ischemic events, but the risk was significantly higher compared to hospitalized patients without discontinuation of antithrombotic therapy.

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Systematic review and meta-analysis of topical tranexamic acid in spine surgery

Chiemela Izima, Shailen G. Sampath, Anthony J. Tang, Vardhaan S. Ambati, Dean Chou, and Andrew K. Chan

OBJECTIVE

Tranexamic acid (TXA) is an antifibrinolytic drug associated with reduced blood loss in a range of surgical specialties, including neurosurgery, orthopedic surgery, and cardiac surgery. Concerns about venous thromboembolism and seizures from intravenous (IV) TXA have led to increased use of topical TXA. Given the relative scarcity of the literature on topical TXA compared with that on IV TXA within neurosurgery, the authors aimed to conduct a systematic review and meta-analysis on the safety, efficacy, and optimal administration of topical TXA in a wide range of spinal procedures and pathologies.

METHODS

The PRISMA guidelines, Cochrane risk of bias tool, and Newcastle-Ottawa Scale were used to extract randomized controlled trials and high-quality case-control and cross-sectional/cohort studies (adult studies only) from PubMed, Web of Science, Cochrane Library, and Embase published between 2016 and 2023. Studies were analyzed by two independent reviewers for variables including dosage, TXA administration route, type of spine procedure, blood loss, adverse events including thromboembolism and infection, postoperative hemoglobin level, and hospitalization length. Pooled analysis comparing intraoperative and postoperative blood loss, postoperative hemoglobin levels, and hospitalization length of stay on the basis of route of TXA administration was conducted.

RESULTS

Four cohort studies, 1 cross-sectional study, 1 case-control study, and 12 randomized controlled trials, together involving 2045 patients, were included. The most common route of topical TXA administration was via TXA in saline solution. Other routes of topical TXA included retrograde injection and TXA-soaked Gelfoam. In pooled analysis, topical TXA significantly reduced visible blood loss (standardized mean difference [SMD] −0.22, 95% CI −0.45 to −0.00001), postoperative blood loss (SMD −1.63, 95% CI −2.03 to −1.22), and length of hospital stay (SMD −1.02, 95% CI −1.42 to −0.61), as well as higher postoperative hemoglobin (SMD 0.59, 95% CI 0.34–0.83), compared with non-TXA controls. No significant differences in outcomes were found between topical and IV TXA or between combined (topical and IV) and IV TXA. Thromboembolism and infection rates did not significantly differ between any TXA administration group and non-TXA controls.

CONCLUSIONS

In pooled analyses, topical TXA was associated with decreased perioperative blood loss in a wide range of scenarios, including cervical spine surgery and thoracolumbar trauma, as well as in patients with a thromboembolic history.

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Thrombocyte transfusion and rebleeding rate in patients using antiplatelet agents before aneurysmal subarachnoid hemorrhage

Martina Sebök, Natalie Zaugg, Emanuela Keller, Jan Willms, Luca Regli, and Menno Germans

OBJECTIVE

The reason for a rebleed after an initial hemorrhage in patients with aneurysmal subarachnoid hemorrhage (aSAH) is considered multifactorial. Antiplatelet use is one of the factors that has been related to early rebleed and worse outcome after aSAH. Thrombocyte transfusion overcomes the inhibitory effects of antiplatelet agents by increasing the number of functional thrombocytes, but its impact on the rebleed rate and clinical outcome remains unknown. The aim of this study was to assess the effect of thrombocyte transfusion on rebleeding and clinical outcome in patients with aSAH and prehemorrhage antiplatelet use, considering confounding factors.

METHODS

Data were prospectively collected at a single tertiary reference center for aSAH in Zurich, Switzerland. Patients with aSAH and prehemorrhage antiplatelet use were divided into "thrombocyte transfusion" and "nontransfusion" groups based on whether they did or did not receive any thrombocyte transfusion in the acute stage of aSAH after hospital admission and before the exclusion of the bleeding source. Using multivariate logistic regression analysis, the impact of thrombocyte transfusion on the rebleed rate and on clinical outcome (defined as Glasgow Outcome Scale score 1–3) was calculated.

RESULTS

One hundred fifty-seven patients were included, 87 (55.4%) of whom received thrombocyte transfusion. Eighteen (11.5%) of 157 patients had a rebleed during the hospital stay. The rebleed risk was 6.9% in the thrombocyte transfusion group and 17.1% in the nontransfusion group. After adjusting for confounders, thrombocyte transfusion showed evidence for a reduction in the rebleed rate (adjusted OR [aOR] 0.29, 95% CI 0.10–0.87). Fifty-seven patients (36.3%) achieved a poor outcome at 6 months’ follow-up. Among those 57 patients, 31 (54.4%) underwent at least one thrombocyte transfusion. Thrombocyte transfusion was not associated with poor clinical outcome at 6 months’ follow-up (aOR 0.91, 95% CI 0.39–2.15).

CONCLUSIONS

Thrombocyte transfusion in patients with aSAH and prehemorrhage antiplatelet use is independently associated with a reduction in rebleeds but shows no impact on clinical outcome at 6 months’ follow-up. Larger and randomized studies are needed to investigate the impact of thrombocyte transfusion on rebleed and outcome.

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To use or not to use antithrombotics in unruptured cerebrovascular malformations? A systematic review focusing on this clinical and surgical dilemma

Andrea Bianconi, Marco Ceraudo, Elsa Nico, Massimiliano Minardi, Mario Allevi, Alessandro Prior, Diego Garbossa, Gianluigi Zona, and Pietro Fiaschi

OBJECTIVE

Antithrombotic medications (ATMs), including antiplatelet therapy (APT) and oral anticoagulants (OACs), are widely used in current clinical practice for the prevention and treatment of a variety of cardiovascular diseases, deep vein thrombosis, and pulmonary thromboembolisms. The long-term usage of these drugs, associated with an inherent risk of bleeding, raises concerns for unruptured cerebrovascular malformations (UCVMs), such as arteriovenous malformations (AVMs), cerebral cavernous malformations (CCMs), and intracranial aneurysms (IAs), in which the bleeding risk also poses a major threat. The aim of this study was to assess the safety and risk-benefit ratio of ATMs in these various neurosurgical diseases and to give neurosurgeons a safe and reasonable choice regarding whether to administer ATMs to these patients during the course of the disease.

METHODS

The authors conducted a systematic review of the literature (PubMed/MEDLINE and Embase) according to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines, which yielded 4 papers about CCMs, 2 about AVMs, and 9 about IAs. The risk of bias was assessed using the Cochrane Collaboration’s tool.

RESULTS

For AVMs, only 2 studies with a total of only 14 patients were included. Data on AVMs and ATMs are limited and weak, relying on small case series. Nevertheless, there is no evidence for either an increased risk of intracranial hemorrhage in patients with AVMs who are receiving ATMS or the need to interrupt ATMs in those patients who have been diagnosed with sporadic, unruptured brain AVMs. With respect to CCMs, the literature search resulted in 4 cohort studies and 1 meta-analysis. These studies affirmed the absence of a correlation between ATMs and an increased risk of CCM bleeding while simultaneously suggesting a protective role of ATMs against bleeding. Concerning IAs, the topic is more complex and debated, despite larger case series on IAs than on AVMs or CCMs. The benefits of ATMs for IAs may vary according to the type of intervention and specific drug administered. Evidence supports the continuation of long-term APT for all patients newly diagnosed with an IA, whereas starting APT in patients with incidentally discovered IA as a means of prophylaxis against rupture is unclear.

CONCLUSIONS

The findings of this review should be taken as a wide overview of UCVM and ATM. Future research should consider the relationship of AVM, CCM, and IA with APT and OAC independently.