Enoxaparin titrated by anti-Xa levels reduces venous thromboembolism in trauma patients

Gates, Rebecca; Lollar, Daniel I; Collier, Bryan R.; Smith, Jacob; Faulks, Emily R.; Gillen, Jacob R.

doi:10.1097/ta.0000000000003418

Cited by 19 publications

(39 citation statements)

References 24 publications

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“…At the other end of the spectrum, patients in our study with subprophylactic anti-Xa levels were more likely to develop PE ( p < 0.001). This echoes prior literature, where active adjustment of anticoagulation to achieve and sustain target prophylactic anti-Xa levels has been demonstrated to significantly reduce VTE incidence, 31 whereas remaining at subprophylactic anti-Xa levels confers significantly elevated risk of VTE and subsequent morbidity and mortality 30 . It should be noted that, of the 12 patients in our study classified as having pulmonary emboli, only 3 were also diagnosed with DVT.…”

Section: Discussionsupporting

confidence: 82%

One size does not fit all: Sex bias in pharmacologic venous thromboembolism prophylaxis

Modi

Borst

Kirchberg

et al. 2022

J Trauma Acute Care Surg

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BACKGROUND:The optimal enoxaparin dosing strategy to achieve venous thromboembolism (VTE) prophylaxis in trauma patients remains unclear.Current dosing guidelines often include weight, age, and renal function but still fail to achieve appropriate prophylactic anti-Xa levels in many patients. We hypothesized that additional patient factors influence anti-Xa response to enoxaparin in trauma patients. METHODS:This is a retrospective review of patients admitted to a Level 1 trauma center for ≥4 days from July 2015 to September 2020, who received enoxaparin VTE prophylaxis per protocol (50-59 kg, 30 mg/dose; 60-99 kg, 40 mg/dose; ≥100 kg, 50 mg/dose; all doses every 12 hours) and had an appropriately timed peak anti-Xa level. Multivariate regression was performed to identify independent predictors of prophylactic anti-Xa levels (0.2-0.4 IU/mL) upon first measurement. RESULTS:The cohort (N = 1,435) was 76.4% male, with a mean ± SD age of 49.9 ± 20.0 years and a mean ± SD weight of 82.5 ± 20.2 kg (males, 85.2 kg; females, 73.7 kg; p <0.001). Overall, 68.6% of patients (n = 984) had a prophylactic anti-Xa level on first assessment (69.6% of males, 65.1% of females). Males were more likely to have a subprophylactic level than females (22.1% vs. 8.0%, p <0.001), whereas females were more likely to have supraprophylactic levels than males (26.9% vs. 8.3%, p < 0.001). When controlling for creatinine clearance, anti-Xa level was independently associated with dose-to-weight ratio (odds ratio, 0.191 for 0.5 mg/kg; p < 0.001; confidence interval, 0.151-0.230) and female sex (odds ratio, 0.060; p < 0.001; confidence interval, 0.047-0.072). Weight and age were not significant when controlling for the other factors. CONCLUSION:Male patients have a decreased anti-Xa response to enoxaparin when compared with female patients, leading to a greater incidence of subprophylactic anti-Xa levels in male patients at all dose-to-weight ratios. To improve the accuracy of VTE chemoprophylaxis, sex should be considered as a variable in enoxaparin dosing models.

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Section: Discussionsupporting

confidence: 82%

One size does not fit all: Sex bias in pharmacologic venous thromboembolism prophylaxis

Modi

Borst

Kirchberg

et al. 2022

J Trauma Acute Care Surg

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“…Additionally, we identified four observational studies ( n = 5180), that examined the use of intermediate–high enoxaparin dose (40 mg every 12 h) versus conventional dose (30 mg every 12 h) [ 68 – 71 ]. The pooled estimates showed that intermediate–high enoxaparin dose was associated with reduced VTE (RR 0.64, 95% CI 0.42–0.97; very low quality) and PE (RR 0.32, 95% CI 0.14–0.76; very low quality).…”

Section: Resultsmentioning

confidence: 99%

“…However, the reduction in DVT risk was statistically nonsignificant (RR 0.65, 95% CI 0.37–1.14; very low quality). Three observational studies ( n = 5111) reported on mortality outcome with unclear benefit (RR 1.14, 95% CI 0.93–1.40; very low quality) [ 68 , 69 , 71 ].…”

Section: Resultsmentioning

confidence: 99%

Saudi Critical Care Society clinical practice guidelines on the prevention of venous thromboembolism in adults with trauma: reviewed for evidence-based integrity and endorsed by the Scandinavian Society of Anaesthesiology and Intensive Care Medicine

Amer,

Alshahrani,

Arabi

et al. 2023

Ann. Intensive Care

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Background To develop evidence-based clinical practice guidelines on venous thromboembolism (VTE) prevention in adults with trauma in inpatient settings. Methods The 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). Results The 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. Conclusion The 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.

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“…The most common fixed dose comparison was enoxaparin 30 mg SC BID. 13,20,22,30,31,33,[35][36][37]40 The median (Q1-Q3) in-hospital VTE incidence was 4.9% (3.3%-9.2%). There were 6 studies reporting use of screening ultrasound for detection of DVT, 19,22,30,34,38,41 for which the median (Q1-Q3) VTE incidence was 9.1% (4.9%-10.2%).…”

Section: Resultsmentioning

confidence: 99%

Efficacy and Safety of Anti-Xa-Guided Versus Fixed Dosing of Low Molecular Weight Heparin for Prevention of Venous Thromboembolism in Trauma Patients

et al. 2022

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Purpose: Trauma patients are at high risk of venous thromboembolism (VTE). We summarize the comparative efficacy and safety of anti-Xa-guided versus fixed dosing for low molecular weight heparin (LMWH) for the prevention of VTE in adult trauma patients. Methods: We searched Medline and Embase from inception through June 1, 2022. We included randomized controlled trials or observational studies comparing anti-Xa-guided versus fixed dosing of LMWH for thromboprophylaxis in adult trauma patients. We incorporated primary data from 2 large observational cohorts. We pooled effect estimates using a random-effects model. We assessed risk of bias using the ROBINS-I tool for observational studies and assessed certainty of findings using GRADE methodology. Results: We included 15 observational studies involving 10,348 patients. No randomized controlled trials were identified. determined that, compared to fixed LMWH dosing, anti-Xa-guided dosing may reduce deep vein thrombosis [adjusted odds ratio (aOR); 0.52, 95% CI: 0.40–0.69], pulmonary embolism (aOR: 0.48, 95% CI: 0.30–0.78) or any VTE (aOR: 0.54, 95% CI: 0.42–0.69), though all estimates are based on low certainty evidence. There was an uncertain effect on mortality (aOR: 1.06, 95% CI: 0.85–1.32) and bleeding events (aOR: 0.84, 95% CI: 0.50–1.39), limited by serious imprecision. We used several sensitivity and subgroup analyses to confirm the validity of our assumptions. Conclusion: Anti-Xa-guided dosing may be more effective than fixed dosing for prevention of deep vein thrombosis, pulmonary embolism, and VTE for adult trauma patients. These promising findings justify the need for a high-quality randomized study with the potential to deliver practice changing results.

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Enoxaparin titrated by anti-Xa levels reduces venous thromboembolism in trauma patients

Cited by 19 publications

References 24 publications

One size does not fit all: Sex bias in pharmacologic venous thromboembolism prophylaxis

One size does not fit all: Sex bias in pharmacologic venous thromboembolism prophylaxis

Saudi Critical Care Society clinical practice guidelines on the prevention of venous thromboembolism in adults with trauma: reviewed for evidence-based integrity and endorsed by the Scandinavian Society of Anaesthesiology and Intensive Care Medicine

Efficacy and Safety of Anti-Xa-Guided Versus Fixed Dosing of Low Molecular Weight Heparin for Prevention of Venous Thromboembolism in Trauma Patients

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