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.

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.

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.

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.

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.

Postprocedural Anticoagulation After Primary Percutaneous Coronary Intervention for ST-Segment-Elevation Myocardial Infarction: A Multicenter, Randomized, Double-Blind Trial.

BACKGROUND: Postprocedural anticoagulation (PPA) is frequently administered after primary percutaneous coronary intervention in ST-segment-elevation myocardial infarction, although no conclusive data support this practice. METHODS: The RIGHT trial (Comparison of Anticoagulation Prolongation vs no Anticoagulation in STEMI Patients After Primary PCI) was an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled, superiority trial conducted at 53 centers in China. Patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention were randomly assigned by center to receive low-dose PPA or matching placebo for at least 48 hours. Before trial initiation, each center selected 1 of 3 PPA regimens (40 mg of enoxaparin once daily subcutaneously; 10 U·kg·h of unfractionated heparin intravenously, adjusted to maintain activated clotting time between 150 and 220 seconds; or 0.2 mg·kg·h of bivalirudin intravenously). The primary efficacy objective was to demonstrate superiority of PPA to reduce the primary efficacy end point of all-cause death, nonfatal myocardial infarction, nonfatal stroke, stent thrombosis (definite), or urgent revascularization (any vessel) within 30 days. The key secondary objective was to evaluate the effect of each specific anticoagulation regimen (enoxaparin, unfractionated heparin, or bivalirudin) on the primary efficacy end point. The primary safety end point was Bleeding Academic Research Consortium 3 to 5 bleeding at 30 days. RESULTS: Between January 10, 2019, and September 18, 2021, a total of 2989 patients were randomized. The primary efficacy end point occurred in 37 patients (2.5%) in both the PPA and placebo groups (hazard ratio, 1.00 [95% CI, 0.63 to 1.57]). The incidence of Bleeding Academic Research Consortium 3 to 5 bleeding did not differ between the PPA and placebo groups (8 [0.5%] vs 11 [0.7%] patients; hazard ratio, 0.74 [95% CI, 0.30 to 1.83]). CONCLUSIONS: Routine PPA after primary percutaneous coronary intervention was safe but did not reduce 30-day ischemic events. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03664180.

Clinical and molecular determinants of bleeding-related adverse outcomes in high-grade glioma.

PURPOSE: Cancer is an independent risk factor for the development of venous thromboembolism (VTE). However, patients with high-grade glioma (HGG) including glioblastoma (GBM) are at a particularly high risk of VTE with an incidence up to 20-30% per year. Patients are often placed on anticoagulation if they are found to have VTE. However, patients with primary brain tumors such as HGG are at increased risk for intracerebral hemorrhage (ICH) even without the administration of anticoagulation. The combination of risk factors for ICH with anticoagulation and HGG complicates decision-making. Currently it is not known which of the direct oral anticoagulants (DOACs) are safest for patients with HGG in terms of adverse bleeding-related outcomes such as ICH. Furthermore, a deeper understanding of the clinical and molecular determinants of bleeding-related adverse outcomes in HGG is not fully characterized. METHODS: In this retrospective study, we identified and gathered data on 75 consecutive patients with pathology-confirmed HGG with hospital encounters at two academic medical center hospitals in Austin between July 1, 2017 and June 30, 2022. We compared clinical and treatment-related factors among cohorts who had received various forms of anticoagulation or no anticoagulation. RESULTS: Patients who were on rivaroxaban (3/7 (43%)) had a statistically significant association with more bleeding-related adverse events compared to those on apixaban (0/12 (0%)) or enoxaparin (0/5 (0%), p = 0.022) even though the groups were similar in characteristics including total time on the respective anticoagulation. Patients on anticoagulation vs those never on anticoagulation did not differ in terms of their studied demographic and clinical characteristics. Intriguingly, logistic regression analysis revealed that patients Astrocytoma, isocitrate dehydrogenase (IDH) mutant, grade 4 had a significant association with more adverse bleeding-related events even when controlling for other relevant factors (Odds Ratio compared to reference GBM: 49.4, 95% CI: 2.8, 2084.7; p = 0.013). CONCLUSION: In this study we found that the use of rivaroxaban was associated with more bleeding-related events compared to apixaban and enoxaparin in patients with high-grade glioma. In this study we also found that the diagnosis of astrocytoma, IDH mutant, grade 4 was associated with more bleeding events. However, this is based on a small study and there is a need for larger studies to further evaluate these results.

Evaluation of enoxaparin for bridging of warfarin in outpatients with left ventricular assist devices (LVADs).

BACKGROUND: Patients with left ventricular assist devices (LVADs) require systemic anticoagulation. The use of enoxaparin for bridging to warfarin remains understudied in this population. METHODS: This single-center retrospective study was performed to characterize enoxaparin use and associated thrombotic and bleeding outcomes in adult outpatients with LVADs from January 2018 to July 2021. RESULTS: Fifty-four enoxaparin bridging events were evaluated in 49 patients. Most patients with HeartMate II (HM2) and HeartWare (HVAD) devices received enoxaparin dosed 1 mg/kg every 12 h. In patients with HeartMate 3 (HM3) devices, an equal number of patients received 0.5 mg/kg every 12 h and 1 mg/kg every 12 h, with a smaller subset receiving intermediate doses. The median duration of bridging was 6 days (4-8 [IQR]). One major bleeding event required discontinuation of enoxaparin and hospitalization in a patient with an HM3 device. Thrombotic events occurred in four patients with two incidents of pump thrombosis requiring pump exchange and two ischemic strokes. All thrombotic events occurred in patients with HVAD or HM2 devices. CONCLUSION: These results suggest that enoxaparin bridging in LVAD patients was well-tolerated with low bleeding and thrombotic rates, particularly with the HM3 device.

Evaluating residual anti-Xa levels following discontinuation of treatment-dose enoxaparin in patients presenting for elective surgery: a prospective observational trial.

INTRODUCTION: Prior studies have demonstrated that patients presenting for elective surgery may have higher-than-expected residual anti-Xa level activity at or beyond 24 hours following their last treatment dose of enoxaparin. Given that 24 hours of abstinence is currently recommended by both European and American societies before the performance of neuraxial or deep anesthetic/analgesic procedures, determining the actual timeframe at which residual anti-Xa level activity reliably falls below 0.2 IU/mL, the lower limit of the target range for thromboprophylaxis, is critical. METHODS: This was a prospective observational trial. Consenting patients on treatment-dose enoxaparin were randomized to either a 24-hour group (last dose at 07:00 the day prior to surgery) or a 36-hour group (last dose at 19:00 2 days prior to surgery). On arrival for surgery, blood samples were obtained to assess residual anti-Xa level activity and renal function. The primary outcome was residual anti-Xa level activity following the last treatment dose of enoxaparin. Incorporating all patients, linear regression modeling was performed to predict the timepoint at which the level of anti-Xa activity reliably fell below 0.2 IU/mL. RESULTS: 103 patients were analyzed. Time from the last dose at which residual anti-Xa activity fell below 0.2 IU/mL, based on the upper bound of the 95% CI, was 31.5 hours. No correlation overall between age, renal function, or sex was found. CONCLUSION: Residual levels of anti-Xa activity do not reliably fall below 0.2 IU/mL 24 hours following discontinuation of treatment-dose enoxaparin. Therefore, current time-based guidelines are not conservative enough. Routine anti-Xa testing should be strongly considered, or current time-based guidelines should be reassessed. TRIAL REGISTRATION NUMBER: NCT03296033.

Risk Stratification for Supratherapeutic Peak Anti-Xa Levels in Adult Patients on Therapeutic Enoxaparin.

BACKGROUND: The American Society of Hematology Guidelines for the management of venous thromboembolism recommend against the use of anti-Xa monitoring for assessing enoxaparin dosing based on a low level of evidence associating supratherapeutic levels with an increased risk of bleeding. However, institutions still utilize anti-Xa levels in select patient populations with altered volume of distribution and/or excretion to monitor and adjust therapy. OBJECTIVE: The primary objective of this study was to identify risk factors associated with supratherapeutic peak anti-Xa levels (≥1.10 IU/mL) for patients receiving therapeutic enoxaparin. METHODS: This was a retrospective single-center study performed at an academic tertiary care hospital. Patients who received enoxaparin at 1 mg/kg twice daily and peak anti-Xa monitoring were separated into supratherapeutic and therapeutic/subtherapeutic cohorts. RESULTS: A total of 436 patients were screened, and 215 were included, with a mean age of 62 years. There were 108 in the therapeutic/subtherapeutic cohort and 107 in the supratherapeutic cohort. Acute kidney injury (AKI), body mass index (BMI), weight, female sex, intensive care unit (ICU) service, Sequential Organ Failure Assessment (SOFA) score ≥4, and creatinine clearance at the time of peak anti-Xa level collection were associated with supratherapeutic anti-Xa levels in univariate models. Adjusted logistic regression models were created and identified BMI in the 30 to 34.9 kg/m2 (odds ratio [OR] 4.35; 95% confidence interval [CI] 1.70-11.13, P < 0.005) and ≥35 kg/m2 (OR 6.75; 95% CI 3.05-14.94, P < 0.005) and AKI (OR 2.62; 95% CI 1.04-6.62, P = 0.042) as significant risk factors for supratherapeutic anti-Xa levels. CONCLUSION AND RELEVANCE: Our study identified BMI ≥ 30 kg/m2, AKI, female sex, ICU service, SOFA score ≥4, and creatinine clearance as risk factors for supratherapeutic anti-Xa levels in patients receiving 1 mg/kg twice daily dosing of enoxaparin. Further research should be done to provide evidence for the association between anti-Xa levels and bleeding risk.

Event rates and risk factors for venous thromboembolism and major bleeding in a population of hospitalized adult patients with acute medical illness receiving enoxaparin thromboprophylaxis.

BACKGROUND: We aimed to describe the event rates and risk-factors for symptomatic venous thromboembolism (VTE) and major bleeding in a population of hospitalized acutely ill medical patients. METHODS: Patients ≥40 years old and hospitalized for acute medical illness who initiated enoxaparin prophylaxis were selected from the US Optum research database. Rates of symptomatic VTE and major bleeding at 90-days were estimated via the Kaplan-Meier (KM) method. Risk factors were identified via the Cox proportional hazards model. RESULTS: A total of 123,022 patients met the selection criteria. The KM rates of VTE and major bleeding at 90-days were 3.5 % and 2.2 %, respectively. Among subgroups, the risk of VTE varied from 3.0 % in patients with ischemic stroke to 6.9 % in patients with a cancer-related hospitalization, and the risk of major bleeding varied from 1.9 % in patients with inflammatory conditions to 3.6 % in patients with ischemic stroke. Key risk factors for VTE were prior VTE (HR=4.15, 95 % confidence interval [CI] 3.80-4.53), cancer-related hospitalization (HR=2.35, 95 % CI 2.10-2.64), and thrombophilia (HR=1.64, 95 % CI 1.29-2.08). Key risk factors for major bleeding were history of major bleeding (HR=2.17, 95 % CI 1.72-2.74), history of non-major bleeding (HR=2.46, 95 % CI 2.24-2.70), and hospitalization for ischemic stroke (2.42, 95 % CI 2.11-2.78). CONCLUSION: There is substantial heterogeneity in the event rates for VTE and major bleeding in acute medically ill patients. History of VTE and cancer related hospitalization represent profiles with a high risk of VTE, where continued VTE prophylaxis may be warranted.

Low-molecular-weight heparin for the prevention of clinical worsening in severe non-critically ill COVID-19 patients: a joint analysis of two randomized controlled trials.

Coronavirus disease 2019 (COVID-19) carries a high risk of vascular thrombosis. However, whether a specific anticoagulation intensity strategy may prevent clinical worsening in severe COVID-19 patients is still debated. We conducted a joint analysis of two randomized controlled trials, COVID-19 HD (NCT044082359) and EMOS-COVID (NCT04646655), to assess the efficacy and safety of two anticoagulant regimens in hospitalized severe COVID-19 patients. Subjects with COVID-19-associated respiratory compromise and/or coagulopathy were randomly assigned to low (4000 IU qd) or high (70 IU Kg-1 every 12 h) enoxaparin dose. The primary efficacy endpoint was clinical worsening within 30 days, defined as the occurrence of at least one of the following events, whichever came first: in-hospital death, evidence of arterial or venous thromboembolism, acute myocardial infarction, need for either continuous positive airway pressure (CPAP) or non-invasive ventilation (NIV) in patients receiving standard oxygen therapy or none at randomization, and need for mechanical ventilation in any patient. The safety endpoint was major bleeding. We estimated the relative risk (RR) and its 95% confidence interval (CI) for the outcomes. Among 283 patients included in the study (144 in the low-dose and 139 in the high-dose group), 118 (41.7%) were on NIV or CPAP at randomization. 23/139 (16.5%) patients in the high-dose group reached the primary endpoint compared to 33/144 (22.9%) in the low-dose group (RR 0.72, 95% CI 0.45-1.17). No major bleeding was observed. No significant differences were found in the clinical worsening of hospitalized COVID-19 patients treated with high versus low doses of enoxaparin.

Venous Thromboembolism Prophylaxis in Low Body Weight Critically Ill Patients.

OBJECTIVE: To compare bleeding and thromboembolic events in low body weight patients receiving reduced-dose venous thromboembolism (VTE) prophylaxis versus standard-dose VTE prophylaxis. DESIGN: Multicenter, retrospective, cohort study. SETTING: Five Ascension Health Hospitals. PATIENTS: Adult, critically ill, low body weight (≤50 kg) patients who received either reduced-dose VTE prophylaxis (n = 140) or standard-dose VTE prophylaxis (n = 279) for at least 48 h. INTERVENTION: Reduced-dose prophylaxis (enoxaparin 30 mg daily or heparin 5000 units every 12 h subcutaneously) or standard-dose prophylaxis (enoxaparin 40 mg daily, enoxaparin 30 mg every 12 h, or heparin 5000 units every 8 h subcutaneously). MEASUREMENTS AND MAIN RESULTS: A total of 419 patients were included with a mean weight of 45.1 ± 4.2 kg in the standard-dose group and 44.0 ± 5.1 kg in the reduced-dose prophylaxis group (P = .02). The primary endpoint, composite bleeding, was significantly lower in patients receiving reduced-dose prophylaxis (5% vs 12.5%, P = .02). After adjusting for confounding factors, results remained consistent demonstrating reduced composite bleeding with reduced-dose prophylaxis (odds ratio: 0.36, 95% confidence interval: 0.14-0.96). Major bleeding events occurred in 3.6% of reduced-dose patients compared with 8.6% in standard-dose patients (P = .056). Clinically relevant nonmajor bleeding (5.4% vs 2.9%, P = .24) and VTE (2.2% vs 0%, P = .08) events were similar between groups. CONCLUSIONS: A reduced-dose VTE prophylaxis strategy in low body weight, critically ill patients was associated with a lower risk of composite bleeding and similar rate of thromboembolism.

Biosimilar versus branded enoxaparin to prevent postoperative venous thromboembolism after surgery for digestive tract cancer: Randomized trial.

Cancer and/or major surgery are two factors that predispose to post-operative thrombosis. The annual incidence of venous thromboembolic disease (VTED) in cancer patients was estimated at 0.5%-20%. Surgery increases the risk of VTED by 29% in the absence of thromboprophylaxis. Enoxaparin is a low molecular weight heparin that is safe and effective. Branded Enoxaparin and biosimilar Enoxaparin are two enoxaparin treatments. This study aimed to compare Branded Enoxaparin with biosimilar Enoxaparin in patients operated on for digestive cancer regarding the prevention of postoperative thrombosis event, to compare the tolerance of the two treatments and to identify independent predictive factors of thromboembolic incident. A randomized controlled trial conducted in a single-centre, surgical department B of Charles Nicolle Hospital, over a 5-year period from October 12th, 2015, to July 08th, 2020. We included all patients over 18 who had cancer of the digestive tract newly diagnosed, operable and whatever its nature, site, or stage, operated on in emergency or elective surgery. The primary endpoint was any asymptomatic thromboembolic event, demonstrated by systematic US Doppler of the lower limbs on postoperative day 7 to day 10. The sonographer was unaware of the prescribed treatment (Branded Enoxaparin [BE] or biosimilar Enoxaparin [BSE]). Of one hundred sixty-eight enrolled patients, six patients (4.1%) had subclinical venous thrombosis. Among those who had subclinical thrombosis, four patients (5.6%) were in the Branded Enoxaparin group and two patients (2.7%) in the Biosimilar Enoxaparin group without statistically significant difference (p = 0.435). Analysis of the difference in means using Student's t test demonstrated the equivalence of the two treatments. Our study allowed us to conclude that there was no statistically significant difference between Branded Enoxaparin and Biosimilar Enoxaparin regarding the occurrence of thromboembolic accidents postoperatively. BE and BSE are equivalent. Trial registration. Trial registration: The trial was registered on CLINICALTRIALS.GOV under the number NCT02444572.

The Treatment of Venous Thromboembolism in the Emergency Department in the DOACs Era.

BACKGROUND: Low-risk venous thromboembolism (VTE) patients are advised to be discharged from the emergency department (ED) on direct oral anticoagulants (DOACs) treatment. There is no data on whether this recommendation is followed in Israel. OBJECTIVES: To characterize newly diagnosed VTE patients who were discharged from the ED, their anticoagulation treatment at the ED, the recommended discharge protocol, and patient adherence. METHODS: We conducted a retrospective cohort study, which included all newly diagnosed VTE patients who were discharged from the ED. Collected data included demographic and clinical background; anticoagulation treatment at the ED, recommended discharge protocol and its subsequent adherence, patient subsequent, recommended hematological evaluation, and adverse events. RESULTS: The study group included 443 patients, 89% with deep vein thrombosis (DVT). Approximately three-quarters were treated with anticoagulants in the ED, 98% with enoxaparin. At discharge, anticoagulants were recommended for all; 49% continued enoxaparin, 47% DOACs, and 4% warfarin. After 4 weeks, 67% were treated with DOACs, 22% with enoxaparin, 5% with warfarin. Approximately 6% discontinued all treatment. After 12 weeks, 90% of the patients who were taking DOACs adhered to the protocol, whereas only 70% and 50% among the enoxaparin and warfarin users, respectively, did. Only 56% were referred for hematological evaluation. The 12-week rate of adverse reactions was approximately 2%. The use of DOACs and the recommendation for further hematological evaluation increased over time. CONCLUSIONS: Clinician training regarding discharge of VTE patients from the ED should continue.

Intermediate dose enoxaparin in hospitalized patients with moderate-severe COVID-19: a pilot phase II single-arm study, INHIXACOVID19.

BACKGROUND: Randomized clinical trials in non-critically ill COVID-19 patients showed that therapeutic-dose heparin increased survival with reduced organ support as compared with usual-care thromboprophylaxis, albeit with increased bleeding risk. The purpose of the study is to assess the safety of intermediate dose enoxaparin in hospitalized patients with moderate to severe COVID-19. METHODS: A phase II single-arm interventional prospective study including patients receiving intermediate dose enoxaparin once daily according to body weight: 60 mg for 45-60 kg, 80 mg for 61-100 kg or 100 mg for > 100 kg for 14 days, with dose adjustment according to anti-factor Xa activity (target range: 0.4-0.6 UI/ml); an observational cohort (OC) included patients receiving enoxaparin 40 mg day for comparison. Follow-up was 90 days. Primary outcome was major bleeding within 30 and 90 days after treatment onset. Secondary outcome was the composite of all-cause 30 and 90-day mortality rates, disease severity at the end of treatment, intensive care unit (ICU) admission and length of ICU stay, length of hospitalization. All outcomes were adjudicated by an independent committee and analyzed before and after propensity score matching (PSm). RESULTS: Major bleeding was similar in IC (1/98 1.02%) and in the OC (none), with only one event observed in a patient receiving concomitantly anti-platelet therapy. The composite outcome was observed in 53/98 patients (54%) in the IC and 132/203 (65%) patients in the OC (p = 0.07) before PSm, while it was observed in 50/90 patients (55.6%) in the IC and in 56/90 patients (62.2%) in the OC after PSm (p = 0.45). Length of hospitalization was lower in the IC than in OC [median 13 (IQR 8-16) vs 14 (11-21) days, p = 0.001], however it lost statistical significance after PSm (p = 0.08). At 30 days, two patients had venous thrombosis and two pulmonary embolism in the OC. Time to first negative RT-PCR were similar in the two groups. CONCLUSIONS: Weight adjusted intermediate dose heparin with anti-FXa monitoring is safe with potential positive impact on clinical course in COVID-19 non-critically ill patients. TRIAL REGISTRATION: The study INHIXACOVID19 was registred on ClinicalTrials.gov with the trial registration number (TRN) NCT04427098 on 11/06/2020.