Timing of Initiation of Pharmacologic Venous Thromboembolism Prophylaxis in Patients With Intracerebral Hemorrhage.

When Is It Safe to Start Pharmacologic Venous Thromboembolism Prophylaxis After Pelvic Fractures? A Prospective Study From a Level I Trauma Center

To examine the efficacy and safety of the initiation of pharmacologic venous thromboembolism (VTE) prophylaxis within 24 hours of admission for major trauma patients at risk for VTE. Pharmacologic VTE prophylaxis following major trauma is essential, but there is a fear of bleeding complications. The safety of initiating treatment within 24 hours of admission has not been established. We examined the efficacy and safety of early initiation of pharmacologic VTE prophylaxis. Patients were stratified by time to initiation [≤24h (EARLY) or >24h (LATE)] and compared. VTE, VTE prophylaxis agents, and bleeding complications secondary to VTE prophylaxis were analyzed. A generalized linear mixed model (GLMM) was performed to identify predictors of VTE. There were 3369 EARLY group patients and 3200 LATE group patients. More patients in the LATE group developed VTE (7.8% vs. 2.8%; P <0.001). Among 345 patients with VTE, deep venous thrombosis (DVT) alone [181 (72%) vs. 61 (65%)], pulmonary embolism (PE) alone [46 (18%) vs. 22 (23%)] and both DVT and PE [24 (10%) vs. 11 (12%)] were present in the LATE compared with the EARLY group. The LATE group had a higher incidence of increased or new intracranial hemorrhage following prophylaxis initiation (0.5% vs. 0.2%; P =0.009) and higher mortality (1.8% vs. 0.6%; P <0.001). GLMM demonstrated that EARLY VTE prophylaxis was associated with a lower risk of VTE [odds ratio (OR): 0.58; 95% CI: 0.44-0.78; P <0.001], after controlling for covariates. Initiating VTE prophylaxis within the first 24 hours after admission resulted in a 42% reduction of the risk of VTE without increased risk of bleeding and should be regarded as the standard of care, even in traumatic brain injury patients.

There is a lack of evidence regarding the effectiveness and safety of pharmacologic venous thromboembolism (VTE) prophylaxis among patients who undergo neurosurgical interventions for traumatic brain injury (TBI). To measure the association between timing of VTE prophylaxis after urgent neurosurgical intervention for TBI and thromboembolic and intracranial complications. This retrospective cohort study included adult patients (aged ≥16 years) who underwent urgent neurosurgical interventions (craniotomy/craniectomy or intracranial monitor/drain insertion within 24 hours after admission) for TBI at level 1 and 2 trauma centers participating in the American College of Surgeons Trauma Quality Improvement Program between January 1, 2012, and December 31, 2016. Data were analyzed from January to August 2020. Timing of pharmacologic VTE prophylaxis initiation after urgent neurosurgical intervention (prophylaxis delay) measured in days (24-hour periods). The primary outcome was VTE (deep vein thrombosis or pulmonary embolism). Secondary outcomes were repeated neurosurgery (neurosurgical reintervention after initiation of VTE prophylaxis) and mortality. Hierarchical logistic regression models were used to evaluate the association between prophylaxis delay and each outcome at the patient level and were adjusted for patient baseline and injury characteristics. The study included 4951 patients (3676 [74%] male; median age, 50 years [IQR, 31-64 years]) who underwent urgent neurosurgical intervention for TBI at 304 trauma centers. The median prophylaxis delay was 3 days (IQR, 1-5 days). After adjustment for patient baseline and injury characteristics, prophylaxis delay was associated with increased odds of VTE (adjusted odds ratio [aOR], 1.08 per day; 95% CI, 1.04-1.12). Earlier initiation of prophylaxis was associated with increased risk of repeated neurosurgery. During the first 3 days, each additional day of prophylaxis delay was associated with a 28% decrease in odds of repeated neurosurgery (aOR, 0.72 per day; 95% CI, 0.59-0.88). After 3 days, each additional day of prophylaxis delay was associated with an additional 15% decrease in odds of repeated neurosurgery (aOR, 0.85 per day; 95% CI, 0.80-0.90). Earlier prophylaxis was associated with greater mortality among patients who initially underwent intracranial monitor/drain procedures, such that each additional day of prophylaxis delay was associated with decreased odds of death (aOR, 0.94 per day; 95% CI, 0.89-0.99). In this cohort study of patients who underwent urgent neurosurgical interventions for TBI, early pharmacologic VTE prophylaxis was associated with reduced risk of thromboembolism. However, earlier initiation of prophylaxis was associated with increased risk of repeated neurosurgery. These findings suggest that although timely initiation of prophylaxis should be prioritized, caution should be used particularly during the first 3 days after the index procedure, when this risk appears to be highest.

Retrospective cohort study. To examine the impact of early (<48 hr) versus late (≥48 hr) initiation of pharmacological venous thromboembolism (VTE) prophylaxis on outcomes and complications among trauma patients undergoing operative fixation of spine fractures. VTE complications are associated with poor outcomes after trauma. Although pharmacological prophylaxis decreases the risk of VTE after trauma, concerns regarding bleeding-related complications among certain patient subgroups persist. At present, there are limited data regarding the safety of early VTE prophylaxis in trauma patients undergoing operative fixation of spine fractures. We performed a 5-year retrospective analysis of our level 1 trauma center registry to identify consecutive patients undergoing operative fixation of spine fractures. Demographics, injury patterns and severity, details of operative procedures, timing of administration of VTE prophylaxis, and outcomes were analyzed. Patients receiving early VTE prophylaxis were compared with patients receiving late VTE prophylaxis. Multivariate analysis was performed to identify independent predictors of VTE. Of 1432 patients with spine fractures, 206 patients (14.4%) underwent operative fixation. Forty-eight (23.3%) received early VTE prophylaxis and 158 (76.7%) received late VTE prophylaxis. No patient developed an epidural hematoma or postoperative bleeding necessitating intervention in either group. Thirteen patients (6.2%) developed VTE, of which 12 occurred in the late VTE prophylaxis group. Age 45 years or more (odds ratio = 5.12, 95% confidence interval = 1.01-25.94, P = 0.048) and traumatic brain injury (odds ratio = 6.94, 95% confidence interval = 1.19-40.35, P = 0.031) were independently associated with an increased risk for VTE. Pharmacological VTE prophylaxis initiated within 48 hours of operative fixation of traumatic spine fractures seems to be safe and is not associated with an increased risk of bleeding or neurological complications. Large, multicenter prospective studies are required to further define the efficacy and safety of an early pharmacological VTE prophylaxis strategy in this at-risk patient population. 3.

The aims of this study were to evaluate the timing and trend of venous thromboembolism (VTE) prophylaxis initiation following surgical intervention, and the impact of VTE prophylaxis timing on the occurrence of VTE complications, across North American trauma centers in patients with complete traumatic cervical spinal cord injury (SCI). This retrospective, observational cohort study utilized data from the American College of Surgeons (ACS) Trauma Quality Improvement Program (TQIP) from 2013 to 2020. We identified surgically treated patients with complete traumatic cervical SCI. Patient variables included age, sex, race, insurance coverage, and comorbidity status. Outcomes of interest included time to VTE prophylaxis following surgery and the occurrence of VTE complications. Mixed-effect regression models were constructed to evaluate the adjusted estimate for each outcome accounting for patient-, injury-, and hospital-level covariates. The study included 5,325 patients treated across 463 trauma centers. The mean age in the cohort was 46.7 ± 18.9 years, with male predominance (81.1%). Race was predominantly White (62.3%) and Black (23.0%). The mean time to VTE prophylaxis initiation was 90 ± 112 hours, and the median time was 65 hours (interquartile range, 39 to 105 hours). The annual trend of VTE prophylaxis initiation after surgery was a decrease by 5.2 hours per year over the 8-year study interval. This was associated with an annual reduction of 6.2% in the odds of VTE complication occurrence. Multivariable mixed-effect regression models demonstrated a significant reduction in time to VTE prophylaxis (mean difference, -3.7 hours per year [95% confidence interval [CI], -5.3 to -2.1 hours per year]; p < 0.001) and VTE complications (odds ratio, 0.93 per year [95% CI, 0.88 to 0.98 per year]; p = 0.01) over the study period, after adjustment. This analysis provides insight into VTE prophylaxis practice patterns following surgery for complete cervical SCI across North American trauma centers from 2013 to 2020. The timing of VTE prophylaxis initiation consistently decreased, which appeared to be associated with a significant reduction found in VTE complications. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Body Mass Index and Pharmacologic Venous Thromboembolism Prophylaxis in Traumatic Brain Injury

Early Venous Thromboembolism Prophylaxis for Isolated High-Grade Blunt Splenic Injury

BackgroundTimely initiation of venous thromboembolism prophylaxis (VTEp) has been known to decrease venous thromboembolism (VTE after trauma; however, early VTEp in patients undergoing neurosurgical interventions (NSIs) is controversial with conflicting reports in the literature from retrospective studies. We aimed to evaluate the safety and outcomes of early VTEp in this high-risk cohort.MethodsThe study was a secondary analysis from the prospective multicenter Consortium of Leaders in the Study of Traumatic Thromboembolism database. Traumatic brain injury (TBI) patients receiving NSI were included. Patients were divided into early (≤72 hours) and late (>72 hours) VTEp groups. Mortality, VTE, deep vein thrombosis (DVT), pulmonary embolism, and bleeding adverse events including progression of intracranial hemorrhage (pICH) were compared.ResultsAmong the total 238 patients, 233 (97.9%) underwent craniotomy or craniectomy, and 140 (58.8%) received early VTEp. Patients with a head Abbreviated Injury Scale score of 5 and craniectomy were more likely to delay VTEp (>72 hours) (all p<0.05). Compared with late VTEp, early VTEp exhibited lower rates of VTE (10.7% vs 16.3%, p=0.28) and DVT (8.6% vs 15.3%, p=0.16), though without achieving statistical significance. Through generalized estimating equation and competing risk analysis, early VTEp did not demonstrate a significant decrease of VTE risk (OR) 0.74, 95% CI 0.33 to 1.67; HR 0.90, 95% CI 0.45 to 1.84), whereas the risk of adverse bleeding events (OR 0.79, 95% CI 0.24 to 2.57) or pICH (OR 1.10, 95% CI 0.30 to 4.03) did not increase with early VTEp either.ConclusionEarly VTEp is not significantly associated with reduced rates of VTE or DVT in patients with severe TBI requiring emergent NSI, but it also does not increase the risk of adverse bleeding event or pICH.Level of evidenceLevel IV; therapeutic/care management.

Patients are at a high risk for developing venous thromboembolism (VTE) following traumatic injury. We examined the relationship between timing of initiation of pharmacologic prophylaxis with VTE complications. Trauma quality collaborative data from 34 American College of Surgeons Committee on Trauma-verified levels I and II trauma centers were analyzed. Patients were excluded if they were on anticoagulant therapy at the time of injury, had hospitalization <48 hours, or received no or nonstandard pharmacologic VTE prophylaxis (heparin drip). Patient comparison groups were based on timing of initiation of VTE prophylaxis relative to hospital presentation (0 to <24 hours, 24 to <48 hours, ≥48 hours). Risk-adjusted rates of VTE events were calculated accounting for patient factors including type of pharmacologic agent in addition to standard trauma patient confounders. A sensitivity analysis was performed excluding patients who received blood in the first 4 hours and/or patients with a significant traumatic brain injury. Within the 79,386 patients analyzed, there were 1,495 (1.9%) who experienced a VTE complication and 1,437 (1.8%) who died. After adjusting for type of prophylaxis and patient factors, the risk of a VTE event was significantly increased in the 24- to <48-hour (odds ratio, 1.26; 95% confidence interval, 1.09-1.47; p = 0.002) and ≥48-hour (odds ratio, 2.35; 95% confidence interval, 2.04-2.70; p < 0.001) cohorts relative to patients initiated at 0 to <24 hours. These VTE event findings remained significant after exclusion of perceived higher-risk patients in a sensitivity analysis. Early initiation of pharmacologic VTE prophylaxis in stable trauma patients is associated with lower rates of VTE. Diagnostic, level III.

Efficacité et sécurité des anticoagulants oraux directs (DOA) versus la thromboprophylaxie conventionnelle dans les fractures de l’extrémité supérieure du fémur: revue systématique et méta-analyse des essais randomisés

The effectiveness and safety of direct oral anticoagulants compared to conventional pharmacologic thromboprophylaxis in hip fracture patients: A systematic review and meta-analysis of randomized controlled trials

There are no consensus guidelines demonstrating that early venous thromboembolism prophylaxis (VTEP) is safe in patients with traumatic brain injury (TBI) who undergo neurosurgical interventions. We hypothesized that early initiation of VTEP in patients with TBI would decrease the incidence of venous thromboembolism (VTE) and intracranial hemorrhage expansion (ICHE). This was a retrospective single-center study of adult patients with TBI who underwent neurosurgical intervention from 2012 to 2023 at a level 1 trauma center. Early (72 hours or less) and late (more than 72 hours) VTEP initiation after neurosurgery were compared. Outcomes were VTE, ICHE, and mortality. A Cox proportional hazard regression was completed comparing late and early and VTEP vs No VTEP groups. Of 845 patients, 618 received VTEP, 180 received VTEP within 72 hours and 438 received VTEP more than 72 hours after neurosurgical intervention. There were no differences in age, race, sex, Abbreviated Injury Scale head score, or comorbidities. There was no difference in VTE (hazard ratio [HR] 1.38, 95% CI 0.39 to 4.84, p = 0.62). The Late cohort had lower odds of ICHE (HR 0.53, 95% CI 0.28 to 0.99, p = 0.05) and mortality (HR 0.04, 95% CI 0.24 to 0.80, p = 0.007). Increased risk of VTE of 50% with each missed dose was seen up to 3 missed doses (odds ratio 1.52, 95% CI 0.64 to 3.40, p = 0.31). Although VTE rates were similar between early and late chemoprophylaxis initiation in patients with TBI who underwent neurosurgical intervention, the late cohort had lower mortality and risk of ICHE. Missed doses had an increased risk of VTE.

BackgroundTo develop evidence-based clinical practice guidelines on venous thromboembolism (VTE) prevention in adults with trauma in inpatient settings.MethodsThe Saudi Critical Care Society (SCCS) sponsored guidelines development and included 22 multidisciplinary panel members who completed conflict-of-interest forms. The panel developed and answered structured guidelines questions. For each question, the literature was searched for relevant studies. To summarize treatment effects, meta-analyses were conducted or updated. Quality of evidence was assessed using the Grading Recommendations, Assessment, Development, and Evaluation (GRADE) approach, then the evidence-to-decision (EtD) framework was used to generate recommendations. Recommendations covered the following prioritized domains: timing of pharmacologic VTE prophylaxis initiation in non-operative blunt solid organ injuries; isolated blunt traumatic brain injury (TBI); isolated blunt spine trauma or fracture and/or spinal cord injury (SCI); type and dose of pharmacologic VTE prophylaxis; mechanical VTE prophylaxis; routine duplex ultrasonography (US) surveillance; and inferior vena cava filters (IVCFs).ResultsThe panel issued 12 clinical practice recommendations—one, a strong recommendation, 10 weak, and one with no recommendation due to insufficient evidence. The panel suggests starting early pharmacologic VTE prophylaxis for non-operative blunt solid organ injuries, isolated blunt TBIs, and SCIs. The panel suggests using low molecular weight heparin (LMWH) over unfractionated heparin (UFH) and suggests either intermediate–high dose LMWH or conventional dosing LMWH. For adults with trauma who are not pharmacologic candidates, the panel strongly recommends using mechanical VTE prophylaxis with intermittent pneumatic compression (IPC). The panel suggests using either combined VTE prophylaxis with mechanical and pharmacologic methods or pharmacologic VTE prophylaxis alone. Additionally, the panel suggests routine bilateral lower extremity US in adults with trauma with elevated risk of VTE who are ineligible for pharmacologic VTE prophylaxis and suggests against the routine placement of prophylactic IVCFs. Because of insufficient evidence, the panel did not issue any recommendation on the use of early pharmacologic VTE prophylaxis in adults with isolated blunt TBI requiring neurosurgical intervention.ConclusionThe SCCS guidelines for VTE prevention in adults with trauma were based on the best available evidence and identified areas for further research. The framework may facilitate adaptation of recommendations by national/international guideline policymakers.

Introduction: The use of pharmacologic venous thromboembolism (VTE) prophylaxis in patients with acute intracranial hemorrhage has been controversial due to concerns of hemorrhage expansion. We hypothesize that pharmacologic VTE prophylaxis is associated with better functional outcomes, without excess bleeding risk, compared to mechanical prophylaxis alone. METHODS: In a prospective study of intracranial hemorrhage patients (SAH N=116; intracerebral hemorrhage N=125 and subdural hemorrhage N=130) conducted between 7/2008-11/2011, we compared bleeding complications, VTE rates and 3-month functional outcomes between patients who received pharmacologic VTE prophylaxis (either heparin or enoxaparin) plus compression boots versus mechanical prophylaxis (compression boots) alone. RESULTS: Of 371 patients, 265 (70%) received pharmacologic prophylaxis in addition to compression boots, while 106 (29%) received compression boots alone. The median time to initiation of pharmacological prophylaxis was 4 days post hemorrhage onset and 2 days from surgical intervention, while mechanical prophylaxis was started at hospital admission. Compared to mechanical prophylaxis alone, those who received pharmacologic prophylaxis were younger (median age 60 versus 69, P=0.002), more likely to have a SAH (41% versus 8%, P&lt;0.0001), less likely to have SDH (25% versus 60%, P&lt;0.0001) and less likely to be DNR/comfort care (14% versus 27%, P&lt;0.0001). Admission GCS and APACHE 2 scores did not vary between groups. ICH expansion was less common in those receiving pharmacologic prophylaxis (7% versus 2%; P=0.030) and there were no differences in other bleeding events (EVD associated hemorrhage, new ICH, new SDH, SDH reaccumulation, bleeding at the craniotomy site, GI bleeding or anemia requiring transfusion) or thombotic events (DVT or PE). Pharmacologic prophylaxis was significantly protective against death at 3 months after adjusting for age, admission GCS, bleed type, and DNR/comfort care status (aOR 0.2, 95% CI 0.1-0.5, P&lt;0.0001). CONCLUSIONS: In intracranial hemorrhage patients, pharmacological VTE prophylaxis is not associated with higher bleeding risks and predicts improved 3-month mortality rates compared to mechanical VTE prophylaxis alone.

Introduction: Despite high rates of venous thromboembolism (VTE) among critically ill patients with intracranial hemorrhage, there is a reluctance to use pharmacologic VTE prophylaxis in patients with external ventricular drains (EVD) due to concerns of procedure site hemorrhage. METHODS: In a prospective study of intracranial hemorrhage patients with an EVD (subarachnoid hemorrhage N=64; intracerebral hemorrhage N=41 and subdural hemorrhage N=5) conducted between 7/2008-11/2011, we compared bleeding complications, VTE rates and 3-month functional outcomes between patients who received pharmacologic VTE prophylaxis (either heparin or enoxaparin) plus compression boots versus mechanical prophylaxis (compression boots) alone. RESULTS: Of 110 patients with an EVD, 98 (89%) received pharmacologic prophylaxis (heparin BID N=3 [3%]; heparin TID N= 34 [31%]; enoxaparin N=61 [56%]) in addition to compression boots, while 11 (11%) received compression boots alone. The median time to initiation of pharmacological prophylaxis was 4 days post hemorrhage. Compared to mechanical prophylaxis alone, pharmacologic prophylaxis patients were more likely to have SAH (60% versus 22%, P=0.028), less likely to have SDH (2% versus 33%, P&lt;0.0001) and less likely to be DNR/comfort care (19% versus 44%, P=0.035). Admission GCS and APACHE 2 scores did not differ between groups. There were no significant differences in bleeding events (EVD associated hemorrhage, ICH expansion, new ICH, new SDH, SDH reaccumulation, bleeding at the craniotomy site, GI bleeding or anemia requiring transfusion) or thombotic events (DVT or PE) between groups. At 3-months, fewer patients receiving pharmacologic prophylaxis were dead (25% versus 67%, P=0.012) or severely disabled (51% versus 89%, P=0.049). After adjusting for admission GCS, age, DNR status, and bleed type this trend for reduced 3-month mortality remained (adjust OR 0.1, 95%CI 0.004-1.2,P=0.065). CONCLUSIONS: In intracranial hemorrhage patients with EVDs, pharmacological VTE prophylaxis is not associated with higher bleeding risks and is associated with improved 3-month mortality rates compared to mechanical VTE prophylaxis alone.