The influence of perioperative enoxaparin on bleeding after TORS oropharyngectomy.

Perioperative enoxaparin is often avoided in patients undergoing transoral robotic (TORS) oropharyngectomy. Our goal was to quantify the risk of postoperative hemorrhage (POH) in patients receiving enoxaparin after TORS oropharyngectomy. This was a retrospective database cohort study set up in 89 separate healthcare organizations. The TriNetX electronic database was queried for patients with OPSCC who underwent TORS oropharyngectomy. Propensity-score matching was used to create two cohorts, one receiving and one not receiving perioperative enoxaparin. Outcome measures were the POH rate within 1 day of surgery ("primary") and POH rate within 2-30 days of surgery ("secondary"). 1109 patients undergoing TORS for OPSCC were identified, 400 of which received perioperative enoxaparin. One-to-one propensity score matching resulted in 310 patients per cohort. After matching, the primary POH rates between patients receiving and not receiving enoxaparin were 3.23% for both cohorts (OR 1.000, 95% CI 0.410 to 2.438). The secondary POH rates between those receiving and not receiving enoxaparin were 5.47% vs. 3.54% (OR 1.577, 95% CI 0.726 to 3.424). The number needed to harm (NNH) with perioperative enoxaparin use for secondary POH after TORS was 53; no difference was found in primary POH rates. While not statistically significant, the use of perioperative enoxaparin after TORS is associated with increased odds of secondary POH with a NNH of 53; no difference was found in rates of primary POH. For patients undergoing TORS, enoxaparin use requires careful weighing of the risks and benefits.

Cost-effectiveness of enoxaparin versus aspirin in the prevention of venous thromboembolism after total hip or knee arthroplasty: an analysis from the CRISTAL cluster-randomized trial.

Aims: The aim of this study was to evaluate the healthcare costs and benefits of enoxaparin compared to aspirin in the prevention of symptomatic venous thromboembolism (VTE) after total hip arthroplasty (THA) or total knee arthroplasty (TKA) using data from the CRISTAL trial. Methods: This trial-based economic analysis reports value for money as incremental cost per quality-adjusted life-year (QALY) gained in 2022 Australian dollars, compared to a single threshold value of AUD$70,000 per QALY. Event costs were estimated based on occurrence of VTEs and bleeds, and on published guidelines for treatment. Unit costs were taken from Australian sources. QALYs were estimated using CRISTAL six-month follow-up data. Sensitivity analyses are presented that vary the cost of VTE treatment, and extend the analyses to two years. Results: The CRISTAL trial found that enoxaparin was more effective than aspirin in preventing symptomatic VTE within 90 days of THA or TKA (risk difference 1.97% (95% confidence interval (CI) 0.54% to 3.41%; p = 0.007)). The additional cost after a THA or TKA was AUD$83 (95% CI 68 to 97) for enoxaparin, and enoxaparin resulted in an additional 0.002 QALYs (95% CI -0.002 to 0.005). Incremental cost per QALY gained was AUD$50,567 (95% CI 15,513, dominated) for enoxaparin. We can be 60% confident that the incremental cost per QALY does not exceed the willingness-to-pay threshold of AUD$70,000. Increasing the cost of VTE treatment and extension of costs and consequences to two years suggested greater confidence that enoxaparin is good value for money (70% and 63% confidence, respectively). Conclusion: This analysis provides strong evidence that enoxaparin thromboprophylaxis following THA or TKA reduced VTEs, but weak evidence of net economic benefits over aspirin. If the value of avoiding VTEs is high, and there is a strong likelihood of VTE-related health impairments, we can be more confident that enoxaparin is cost-effective compared to aspirin.

In situ ascending aortic thrombus in a patient with metastatic lung adenocarcinoma and no aortic atherosclerosis or cisplatin exposure: a case report.

BACKGROUND: An ascending aortic thrombus is exceedingly rare. Two instances have been reported in the setting of lung cancer, but only after cisplatin use, which is associated with hypercoagulability. We present the first case of a patient with lung cancer who developed an ascending aortic thrombus without structural risk factors or chemotherapy use. CASE: A 60-year-old white female with significant smoking history presented with several weeks of malaise. A chest computed tomography scan revealed a 2.2-cm right upper lobe mass. As an outpatient, right hilar lymph node immunohistochemistry (IHC) samples via endobronchial ultrasound confirmed thyroid transcription factor-1 adenocarcinoma. After the procedure, the patient endorsed dyspnea and was advised to go to the emergency department. A chest computed tomography angiography identified a new 2.4 × 1.1 × 1.1 cm thrombus within the proximal aortic arch. No pulmonary emboli or intrapulmonary shunts were identified. A hypercoagulable workup was negative. Transthoracic echocardiogram was without left ventricular thrombus, akinesis or hypokinesis, left atrial dilation, or intracardiac shunts. A lower extremity ultrasound was negative for deep vein thrombosis. Given the procedural risk, thrombectomy was deferred. The patient was transitioned to enoxaparin, and a repeat computed tomography for resolution is in process. CONCLUSION: To our knowledge, this is the only case detailing an in situ ascending aortic thrombus in the setting of lung cancer, without structural risk factors, chemotherapy use, or other hypercoagulable comorbidities. Optimal management for an aortic thrombus and malignant disease is less clear. Clinicians should be vigilant for unusual arterial thromboses in patients with high metastatic burden.

Effect of Enoxaparin and Daikenchuto Coadministration on Hepatic Disorder Markers in Gynecological Cancer Patients after Abdominal Surgery.

Enoxaparin and daikenchuto are commonly administered to prevent venous thromboembolism and intestinal obstruction after gynecological malignancy surgery. However, the effects of their combined use on hepatic function are not well studied. This study aimed to clarify the effects of the coadministration of enoxaparin and daikenchuto on hepatic function. First, Japanese Adverse Drug Event Report (JADER) data were analyzed to identify signals of hepatic disorders. Second, a retrospective observational study of patients who underwent surgery for gynecological malignancies was conducted. This study defined hepatic disorders as an increase in aspartate aminotransferase (AST) or alanine aminotransaminase (ALT) levels above the reference values, using 1-h postoperative values as the baseline. The analysis of JADER data revealed an increased risk for hepatic disorders with the coadministration of enoxaparin and daikenchuto. An observational study also showed higher odds ratios (95% confidence intervals) for the occurrence of hepatic disorders in the coadministration group (4.27; 2.11-8.64) and enoxaparin alone group (2.48; 1.31-4.69) than in the daikenchuto alone group. The median increase in the ALT level was also higher in the coadministration group (34; 15-59) than in the enoxaparin alone (19; 6-38) and daikenchuto alone groups (8; 3-33). In conclusion, our study suggests that compared with the use of enoxaparin or daikenchuto alone, enoxaparin and daikenchuto coadministration increases the risk of hepatic disorders, with more significant increases in AST and ALT levels. Healthcare workers need to be aware of these potential side effects when combining these drugs after surgery for gynecological malignancies.

Intra-abdominal hematomas and identifiable risk factors in patients receiving subcutaneous enoxaparin.

BACKGROUND: Low molecular weight heparin has proven to be safe and effective but is not without potential risks such as spontaneous bleeding in the abdominal cavity. There is limited evidence evaluating the true incidence of this potential risk and the available literature is primarily via case reports. CASE SUMMARY: The purpose of this study was to identify the incidence and risk factors associated with enoxaparin use (prophylaxis or treatment) abdominal hematomas in a 350-bed community hospital during an 8-month time period. A total of 44 patients were identified as clinically significant bleeds receiving enoxaparin treatment or prophylactic therapy. Ultimately, 25 patients were excluded from the analysis due to an external cause of the abdominal hematoma or a temporal mismatch in enoxaparin administration and hematoma formation. After exclusion, there were a total of 19 patients that were assessed for the risk factors such as age, gender, renal function, and weight. After evaluation of risks, over half of the patients developing a clinically significant bleed were considered elderly (>65 years of age) and impaired renal function with a creatinine clearance of 60ml/min or less. CONCLUSION: Patients at risk for an enoxaparin associated hematoma include female patients with a CrCl <60ml/min and/or BMI >30 kg/m2 receiving enoxaparin treatment dosing.

Aspirin or enoxaparin for VTE prophylaxis after primary partial, total or revision hip or knee arthroplasty: A secondary analysis from the CRISTAL cluster randomized trial.

BACKGROUND: This study compares aspirin to enoxaparin for symptomatic VTE prophylaxis within 90 days of any type of hip or knee arthroplasty performed for any diagnosis, in patients enrolled in the CRISTAL trial. MATERIALS AND METHODS: CRISTAL was a cluster-randomised crossover, registry-nested non-inferiority trial across 31 hospitals in Australia. The primary publication was restricted to patients undergoing primary total hip or knee arthroplasty for a diagnosis of osteoarthritis. This report includes all enrolled patients undergoing hip or knee arthroplasty procedures (partial or total, primary or revision) performed for any indication. Hospitals were randomized to administer patients aspirin (100mg daily) or enoxaparin (40mg daily), for 35 days after hip arthroplasty and 14 days after knee arthroplasty. Crossover occurred after the patient enrolment target had been met for the first group. The primary outcome was symptomatic VTE within 90 days. Analyses were performed by randomization group. RESULTS: Between April 20, 2019 and December 18, 2020, 12384 patients were enrolled (7238 aspirin group and 5146 enoxaparin). Of these, 6901 (95.3%) given aspirin and 4827 (93.8%) given enoxaparin (total 11728, 94.7%) were included in the final analyses. Within 90 days, symptomatic VTE occurred in 226 (3.27%) aspirin patients and 85 (1.76%) enoxaparin patients, significant for the superiority of enoxaparin (estimated treatment difference 1.85%, 95% CI 0.59% to 3.10%, p = 0.004). Joint-related reoperation within 90 days was lower in the enoxaparin group (109/4827 (2.26%) vs 171/6896 (2.47%) with aspirin, estimated difference 0.77%; 95% CI 0.06% to 1.47%, p = 0.03). There were no significant differences in the other secondary outcomes. CONCLUSION: In patients undergoing hip or knee arthroplasty (of any type, performed for any indication) enrolled in the CRISTAL trial, aspirin compared to enoxaparin resulted in a significantly higher rate of symptomatic VTE and joint-related reoperation within 90 days. These findings extend the applicability of the CRISTAL trial results. TRIAL REGISTRATION: Anzctr.org.au, identifier: ACTRN12618001879257.

Structured benefit-risk assessment for enoxaparin, in the context of its label extension, for the extended treatment of deep vein thrombosis and pulmonary embolism, and prevention of its recurrence in patients with active cancer.

PURPOSE: Guidelines recommend low-molecular-weight heparins (LMWHs) for patients with cancer-associated thrombosis. However, until recently, only dalteparin and tinzaparin were approved in the European Economic Area (EEA) for these patients. This study compares the benefit-risk profile of enoxaparin with dalteparin and tinzaparin for the extended treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrence in adult patients with active cancer. METHODS: A semi-quantitative structured benefit-risk assessment was conducted for the label-extension application of enoxaparin based on the benefit-risk action team descriptive framework: define decision context; determine key benefit and risk outcomes; identify data sources; extract data; interpret results. RESULTS: The key benefits were defined as reduced all-cause mortality and venous thromboembolism (VTE) recurrence (including symptomatic DVT, fatal PE or non-fatal PE); the key risks were major and non-major bleeding of clinical significance, and heparin-induced thrombocytopenia (HIT). Enoxaparin demonstrated comparable effects for the reduction of VTE recurrence and all-cause mortality versus other EEA-approved LMWHs (dalteparin, tinzaparin). There was no evidence of a significant difference between enoxaparin and the comparator groups with regard to incidence of major and non-major bleeding. The data on HIT were too limited to assess the difference between the two groups. CONCLUSIONS: The assessment demonstrated a favourable benefit-risk profile for enoxaparin similar to that of other EEA-approved LMWHs for the treatment of DVT and PE and the prevention of recurrence in patients with active cancer and thus supported the label-extension approval.

Prophylaxis of microvascular thrombosis using direct oral anticoagulants (DOAC) in microvascular free tissue transplantation - a pilot study.

INTRODUCTION: We conducted this pilot study to assess direct oral anticoagulants (DOACs) in the prevention of microvascular thrombosis. MATERIALS AND METHODS: Five patients undergoing microvascular free tissue transplantation received rivaroxaban or apixaban (depending on their home medication). We compared this group to 19 patients who received enoxaparin subcutaneously. We evaluated the rate of graft loss due to microvascular thrombosis and the number of transfusions administered intra- and postoperatively. RESULTS: There was no graft loss due to microvascular thrombosis in either of the groups. There was no significant difference in the number of intraoperative (study group mean 1.00 (SE 0.32) vs. control group mean 1.11 (SE 0.59); p = 0.876) and postoperative (study group mean 1.2 (SE 0.37) vs. control group mean 1.74 (SE 0.34); p = 0.310) red blood cell transfusions. CONCLUSION: Based on our results in this pilot study, DOACs can be used with microvascular flaps. Further studies with larger sample sizes should be performed to find an optimal medication regimen both for patients already taking DOACs and perhaps even for those not taking DOACs.

Warfarin dosage in a postpartum woman while breastfeeding: A case report.

Warfarin is the only oral anticoagulant recommended in women who are breastfeeding. Although warfarin is a compatible and recommended agent in the postpartum period and during lactation, little is known regarding changes to warfarin dose requirements in this patient population. Here, we report the case of a 40-year-old woman who transitioned from enoxaparin monotherapy back to warfarin at 2 months postpartum, while she was breastfeeding. Despite resuming warfarin at her previously therapeutic dose, her international normalized ratio (INR) remained subtherapeutic and required multiple dose increases. She ultimately required a 100% increase in her warfarin dose postpartum, compared to pre-pregnancy, to achieve a therapeutic INR. This case suggests patients may require higher warfarin doses postpartum, compared to pre-pregnancy, especially if breastfeeding. Clinicians should closely monitor these patients and adjust warfarin doses as necessary.

Safety and Efficacy of Enoxaparin During Low-Risk Elective Percutaneous Coronary Intervention.

Intravenous unfractionated heparin (UFH) is the most frequently used anticoagulant for percutaneous coronary intervention (PCI). Intravenous enoxaparin, a low-molecular-weight heparin, has superior pharmacokinetic and pharmacodynamic properties compared with UFH. Multiple trials have shown enoxaparin to be safe and effective in PCI. However, there has not been a contemporary study evaluating its safety and efficacy. To assess its efficacy and safety, intravenous enoxaparin during PCI through radial artery access was evaluated in PCI patients from January 2015 to December 2019. Outcomes included procedural success, all-cause mortality, ischemic complications, and bleeding complications from the time of the procedure until hospital discharge. A total of 1019 consecutive eligible patients were identified. Median age was 63 years, and 70% were men. The indication for PCI was stable and unstable angina in two-thirds of cases (77%). Few patients had myocardial infarction (MI) (2.2%) as the indication for intervention. The procedure was successful in 98.2% of cases. There were no deaths. Procedural MI occurred in 0.3% of patients. Acute stent thrombosis occurred in 0.4%. Urgent revascularization and stroke occurred in 0.1% each. Small wrist hematomas occurred in 0.3% and all were managed conservatively. There was one radial artery pseudoaneurysm. There were no cases of major bleeding. In conclusion, this single-center study showed that intravenous enoxaparin is a reasonable alternative anticoagulant for use in low-risk and elective non-MI PCI through radial artery access.

Implementation of the Caprini risk assessment model (RAM) in surgical patients to decrease postsurgical venous thromboembolism and enoxaparin prescription at hospital discharge.

Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), has been an increasingly common post-surgical complication for surgical patients. In the United States, VTE has become a leading cause of preventable hospital death with more than half occurring after discharge and are directly linked to a recent (within 30 days) hospitalization or surgery [1]. In large, hospital-associated/acquired VTE (HA-VTE) are preventable through measures such as the use of risk stratification tools and chemoprophylaxis. The project institution, a community, academic, medical center, for multiple years has consistently remained a high outlier for postoperative VTE. Also, the choice of VTE chemoprophylaxis in surgical patients at the time of discharge depended on, and varied between, the individual prescribing physician. The goal was to implement and determine the efficacy of a standardized intervention tool, the Caprini risk assessment model (RAM), for reducing postoperative VTE complications and its influence on the physician's prescription of enoxaparin at discharge. Results: Risk assessment scoring pre-operatively increased from 0% baseline to 26.3% at Plan-Do-Study-Act (PDSA) cycle 1 and demonstrated a statistically significant change (p-value = 0.006). Risk assessment scoring pre-operatively was 42.9% by PDSA cycle 2 but was not statistically significantly different from PDSA cycle 1. Risk assessment scoring post-operatively (for eligible patients) remained the same throughout all three cycles at 0%. Appropriate prescription of anticoagulation declined from baseline (12.5%) to PDSA cycle 1 (0%), and improved at PDSA cycle 2 (33.3%), however no differences were significant (p-value 0.302). The National Surgical Quality Improvement Project (NSQIP) database showed a decline in VTE occurrences at the projects institution from baseline (1.02%, 6 occurrences, 2021) to PDSA cycle 2 (0.92%, 4 occurrences, 2022) when compared to the national benchmark (1.0%) for the first time since 2018. Given the significant national problem HA-VTE pose to the public, and the rise in occurrences, this quality improvement (QI) project is clinically relevant.

Prophylactic Enoxaparin Dosing Using Anti-Factor Xa Levels in Hepatic Surgery Patients: A Pilot Study.

This study examines the safety and efficacy of using peak anti-Xa levels to achieve prophylactic enoxaparin (Lovenox, Sanofi-Aventis) levels in patients who underwent hepatic surgery. Prospectively enrolled patients undergoing major and minor hepatic procedures received postoperative enoxaparin dosing. The enoxaparin dose was adjusted to attain a peak anti-Xa level ≥ 0.20 U/ml. This group was compared to a historical cohort of patients who underwent similar procedures and received standard postoperative VTE chemoprophylaxis dosing. Inpatient postoperative VTE rates were higher in the control group when compared to the experimental group (0 patients [0.00%] vs 4 patients [8.16%]; P = .035). There was no statistically significant difference in number of postoperative blood transfusions, discharge hemoglobin, or in-hospital bleeding events. Adjusting enoxaparin dosing to achieve prophylactic peak anti-Xa levels of ≥0.20 IU/ml was associated with a reduced incidence of symptomatic inpatient postoperative VTE in patients who underwent hepatic surgery without increasing postoperative bleeding events.

Safety and efficacy of apixaban vs. enoxaparin in thromboprophylaxis after spinal stenosis and degenerative spine surgery.

INTRODUCTION: Degenerative spine surgeries often require postoperative immobilization or reduced mobility, predisposing patients to the formation of thrombosis and higher risk of thromboembolic complications. Despite the significance of this issue, there remains a lack of consensus on the optimal anticoagulant agent for postoperative thromboprophylaxis in spinal stenosis and degenerative spine surgeries. Low molecular weight heparins and direct Xa inhibitors represent two anticoagulant groups with high chemoprophylactic potential. METHODS: This study included a prospective cohort of patients undergoing posterior decompressive surgery with or without instrumentation for degenerative spine disease and/or spinal stenosis. Patients receiving postoperative prophylactic Enoxaparin and Apixaban were selected to evaluate the rate of complications, as assessed by Clavien-Dindo classification, thromboembolic events, and 30-day mortality, readmission, and reoperation rate between the two anticoagulants. RESULTS: 130 patients were included in the analysis. 65 patients received Apixaban and Enoxaparin in each group. Mean age of the participants was 57.6±11.0. 83.1% underwent laminectomy and posterior spinal fusion, while 22 patients underwent decompressive surgery only. The incidence of venous thromboembolism (P-value=0.403), deep vein thrombosis (p-value=0.999), hematoma formation (p-value=0.403), surgical site infection (p-value=0.901), readmission (p-value=0.545), reoperation (p=0.510), mortality (p=0.648), and complications rate (p-value=0.232) were not statistically different between Enoxaparin and Apixaban. DISCUSSION: Both Apixaban and Enoxaparin may be viable options for postoperative thromboprophylaxis in spine surgeries with comparable efficacy and safety profile. Future research endeavors should investigate the efficacy of these agents in comparison to placebo in a randomized setting.

Neonatal arterial thrombosis: an arcane COVID sequelae.

We describe a case of a term neonate with a swollen right arm and weakened pulses, diagnosed with arterial thromboembolism in the right axillary and brachial arteries. Treatment involved heparin, followed by enoxaparin, resulting in significant improvement. Maternal SARS-CoV-2 infection during pregnancy was considered as a potential factor, supported by the newborn's reactive COVID antibodies. The authors hypothesise a potential correlation between neonatal thrombosis and maternal SARS-CoV-2 infection during pregnancy. It is important to note that this association remains speculative and warrants further investigation for validation. The case underscores the importance of recognising and managing neonatal arterial thrombosis, especially in the context of maternal illness. We discuss the case in detail and review current knowledge on this condition.

Weight-Based Dosing for Low-Molecular-Weight Heparin (Enoxaparin) Administration to Achieve Optimal VTE Prophylaxis in Trauma Patients.

INTRODUCTION: Patients admitted after traumatic injuries are at high risk for developing venous thromboembolism (VTE). Low-molecular-weight heparin (LMWH) is commonly used to prevent VTE in this patient population; however, the optimal dosing strategy has yet to be determined. To address this question, a fixed-dosing strategy of LMWH was compared to a weight-based dosing strategy of LMWH for VTE prophylaxis. METHODS: A retrospective, pre-post implementation cohort study compared a fixed vs a weight-based dosing strategy of LMWH for VTE prophylaxis. Patients admitted to our level 1 trauma center were included if they had an estimated glomerular filtration rate >30 mL/min/1.73 m2, received at least 3 doses of LMWH, and had an appropriately drawn anti-Xa level on their initial dosing regimen. Patients in the pre-cohort received 30 mg LMWH subcutaneously twice daily as the initial dosing regimen. Patients in the post-cohort received .5 mg/kg (max 60 mg) LMWH subcutaneously every 12 h as the initial dosing regimen. A goal anti-Xa of .2-.4 IU/mL was targeted for prophylaxis. RESULTS: There were 817 patients in the fixed-dosing group (FDG) and 874 patients in the weight-based dosing group (WBDG). In the FDG, 42.8% of the patients achieved the goal initial anti-Xa level, with 54.1% and 3.1% reaching sub- and supratherapeutic doses, respectively. In the WBDG, 66.5% of patients reached goal initial anti-Xa levels, with 23.5% and 10.1% at sub- and supratherapeutic levels. The distribution of dose ranges was significantly different between the dosing strategies (P-value <.001). There was no difference in the number of patients who received blood products (39.1% vs 41.7%. P-value = .299). CONCLUSIONS: In our study, weight-based dosing of LMWH yielded a significantly higher proportion of patients who achieved goal prophylactic anti-Xa levels than fixed-dosing of LMWH. Larger-scale studies are needed to assess the risk of VTE events and bleeding with these dosing strategies.

A ten-year comparison of treatment and outcomes of cancer-associated thrombosis to non-cancer venous thromboembolism: from traditional anticoagulants to direct oral anticoagulants.

DOACs have emerged as first-line treatment in most cancer-associated thrombosis (CAT), representing a paradigm shift in its management. However, CAT management remains challenging and requires careful risk-benefit considerations. A retrospective analysis of CAT presentations to a tertiary referral centre from January 2011 to December 2020. Outcomes in CAT patients were compared to VTE patients without malignancy. Subgroup analysis was also conducted for CAT according to anticoagulation type. 514 CAT cases from 491 patients were identified from 3230 total VTE cases. CAT patients had higher rates of major VTE (PE and/or proximal DVT) compared to patients without malignancy (78.4% vs. 66.8%, p < 0.001). CAT patients also had higher rates of VTE recurrence (HR 1.66, 95%CI 1.23-2.26), major bleeding (HR 3.41, 95%CI 2.36-4.93), VTE-related mortality (HR 2.59, 95%CI 1.46-4.62) and bleeding-related mortality (HR 2.66, 95%CI 1.05-6.73). There were no significant differences in rates of VTE recurrence, major bleeding, VTE-related mortality or fatal bleeding between CAT patients treated with DOACs, enoxaparin or warfarin. In the subgroup of CAT treated with DOACs, there was no significant difference in rates of GI bleeding compared to the enoxaparin subgroup (HR 0.17, 95%CI 0.02-1.26). CAT was associated with a larger clot burden and higher rates of VTE recurrence, major bleeding and mortality compared to VTE patients without malignancy in this large real-world study. This study demonstrated no significant differences in complication rates for CAT patients treated with DOACs over enoxaparin, suggesting that DOACs can be safely used in most cases of CAT.