Intravenous enoxaparin guided by anti-Xa in venovenous extracorporeal membrane oxygenation: A retrospective, single-center study.

BACKGROUND: Unfractionated heparin is used as the most common anticoagulation for venovenous extracorporeal membrane oxygenation (VV ECMO) patients. However, it is accompanied by frequent bleeding and thrombotic complications. The aim of the study was to demonstrate the feasibility of Enoxaparin anticoagulation for VV ECMO patients. METHODS: This study is a retrospective analysis of VV ECMO patients on continuous intravenous Enoxaparin anticoagulation. The primary outcome was the incidence of bleeding, thrombotic, and neurological complications during ECMO support. The secondary outcome was an analysis of secondary and primary hemostasis profiles. RESULTS: Data from 38 patients were analyzed in this study. The incidence of bleeding complications was 5.3%, for thrombotic complications it was 2.6% and for neurological (bleeding/ischemic events) complications it was 10.5%. The targeted anti-Xa activity of 0.4-0.6 IU/mL was achieved and maintained during whole ECMO period in 28 patients (73.8%), not affecting the hemocoagulation profile represented by APTT-r 1.15 ± 0.2, TT 18.67 ± 3.35 s, PT/INR 1.21 ± 0.19, fibrinogen 5.39 ± 1.49 g/L, antithrombin, and platelet count. Primary hemostasis pathology was diagnosed in all patients by PFA 200 tests Col/EPI 279 ± 38 s and Col/ADP 249 ± 66 s. The running time of ECMO was 7.8 ± 3.4 days. CONCLUSIONS: Enoxaparin anticoagulation appears to be feasible for VV ECMO patients without an increase in adverse events. Further larger-sampled and comparative studies are needed in the future to support our findings.

Comprehensive chromatographic profiling and structural analysis of key anticoagulant components in enoxaparin.

Heparin is the most widely used anticoagulant in clinical practice, with enoxaparin being one of the most important low molecular weight heparins (LMWHs). In this study, an antithrombin III (ATIII) affinity column was used. Enoxaparin and its oligosaccharides of varying sizes, prepared using preparative size exclusion chromatography (SEC), were fractionated through the ATIII affinity column. The different affinity fractions from each oligosaccharide size were profiled using strong anion exchange (SAX) chromatography. Each peak was automatically transferred to an SEC column for desalting prior to mass spectrometry (MS) analysis, which enabled structural identification using a multiple heart-cut (MHC) 2D LC-MS system (SAX-SEC-MS). The high-affinity fraction from enoxaparin was further analyzed using the MHC 2D LC system (SEC-SAX). SAX profiles of the high-affinity oligosaccharides, prepared by both size and affinity fractionation, were consistent with those obtained by direct SEC-SAX analysis. The possible sequences of several high-affinity hexasaccharides and the domain compositions of high-affinity octa- and decasaccharides in enoxaparin were further elucidated by disaccharide analysis after manual collection of the oligosaccharides. This work advances the understanding of enoxaparin's structural features and offers a potential approach to improve the quality of enoxaparin, as well as to identify key structural motifs in heparin/LMWHs that contribute to protein binding.

Enoxaparin Protects C6 Glioma Cells from Glutamate-Induced Cytotoxicity by Reducing Oxidative Stress and Apoptosis.

Recent studies suggest enoxaparin may protect the central nervous system (CNS) from damage. However, its specific effects on glial cells and the underlying mechanisms involving cell death and oxidative stress require further investigation. Therefore, this research investigated enoxaparin's potential to safeguard C6 glioma cells against glutamate-induced cytotoxicity, specifically focusing on its influence on oxidative stress and apoptotic mechanisms. To investigate the neuroprotective effects of enoxaparin against glutamate-induced cytotoxicity in C6 cells, four groups were established: a control group, a group exposed to 10 mM glutamate, a group treated with enoxaparin at concentrations ranging from 25 to 200 µM, and a group receiving both 10 mM glutamate and enoxaparin at concentrations ranging from 25 to 200 µM. Cell viability was measured using an XTT assay. To evaluate the effects of enoxaparin on oxidative stress, superoxide dismutase (SOD) and malondialdehyde (MDA) levels were measured using ELISA, along with total antioxidant status (TAS) and total oxidant status (TOS). Apoptosis was evaluated using flow cytometry, and caspase-3 activity, a key marker of apoptosis, was assessed using caspase-3 immunofluorescence staining. Enoxaparin at 50, 100, and 200 µM markedly increased cell viability in the enoxaparin + glutamate group. Enoxaparin treatment in the enoxaparin + glutamate group also significantly elevated levels of SOD and TAS, while concurrently decreasing MDA and TOS levels. These changes indicate a reduction in oxidative stress. Enoxaparin treatment further resulted in a significant decline in cleaved caspase-3 levels, a marker of apoptosis. Enoxaparin pre-treatment reduced cell death according to flow cytometry analysis. This study suggests enoxaparin's potential to shield C6 glioma cells from glutamate-induced cell death by mitigating both oxidative stress and apoptotic pathways. More research is needed to confirm this effect.

Randomized, controlled, multi-center phase II study of postoperative enoxaparin treatment for venous thromboembolism prophylaxis in patients undergoing surgery for hepatobiliary-pancreatic malignancies.

Purpose: Postoperative venous thromboembolism (VTE) risk is pronounced after abdominal cancer surgery. Enoxaparin shows promise in preventing VTE in gastrointestinal, gynecological, and urological cancers, but its application after surgery for hepatobiliary-pancreatic malignancy has been under-evaluated due to bleeding concerns. We confirmed the safety of enoxaparin administration in patients undergoing curative hepatobiliary-pancreatic surgery for malignancies in a prospective, multi-center, phase I study. Methods: The study was conducted from April 2015 to May 2021 across eight specialized centers. Patients (n = 262) were randomized to enoxaparin prophylaxis given postoperatively for 8 days (n = 131) or control (n = 131). The primary endpoint was the efficacy in reducing VTE. Secondary endpoints examined safety. Results: The full analysis set included 259 patients (131 control, 129 enoxaparin). The per-protocol population included 233 patients (117 control, 116 enoxaparin). Most cases were hepatic malignancies (111 control, 111 enoxaparin). The median administration duration of enoxaparin was 7 days, with 92% receiving 4000 units/day. Despite a reduction in the relative risk (RR) of VTE due to postoperative enoxaparin administration, the results were not significant (control: four cases, 3.4% vs. treatment: two cases, 1.7%; RR 0.50, 95% CI 0.09-2.70; p = 0.6834). No significant difference was found in the incidence of bleeding events (control: five cases, 4.3% vs. treatment: five cases, 4.3%, RR 1.00, 95% CI 0.53-1.89; p = 1.0000). Conclusions: The perioperative administration of enoxaparin in hepatobiliary-pancreatic malignancies is feasible and safe. However, further case accumulation and investigation are necessary to assess its potential in reducing the occurrence of VTE.

Impact of an updated venous thromboembolism prophylaxis guideline in critically ill trauma patients on rates of venous thromboembolisms.

INTRODUCTION: The objective of this analysis was to evaluate differences in incidence of venous thromboembolisms (VTE) in critically ill trauma patients between pre- and post-implementation of updated VTE prophylaxis guidelines. METHODS: This was a pre-post analysis of critically ill trauma patients receiving pharmacologic VTE prophylaxis. Trauma patients were included if they had an intensive care unit admission during their hospitalization. The primary outcome was incidence of detected VTE and was analyzed using a Chi-Squared test. A multivariate analysis assessed the effects of guideline implementation on VTE development when controlling for confounders. RESULTS: There were 220 patients included. There was a significant increase in low molecular weight heparin use in initial (p â€‹= â€‹0.003) and final (p â€‹= â€‹0.004) prophylactic regimens between groups. There was no significant difference in VTE incidence between the pre and post groups (6.3% vs 1.9%, p â€‹= â€‹0.10). The multivariate analysis showed guideline implementation was independently associated with an 88% reduced odds of VTE (p â€‹= â€‹0.04). CONCLUSION: This analysis suggests the updated VTE prophylaxis guideline implementation was associated with a trend toward reduced VTE development among critically ill trauma patients.

Postpartum thromboprophylaxis with enoxaparin: a prospective cohort study on patients' adherence, injection experience, and information retention after counselling by pharmacists.

OBJECTIVES: This research aimed to determine postpartum females' self-reported adherence to and experience with short-term thromboprophylaxis using enoxaparin injection, after counselling by pharmacists. It also sought to assess their knowledge of thromboprophylaxis, injection techniques, and confidence in self-injecting. METHODS: This prospective cohort study was conducted at a public tertiary hospital in Malaysia from March to June 2023. Self-injection-naïve postpartum females who were initiated on thromboprophylaxis and counselled by a pharmacist were conveniently sampled. Knowledge regarding thromboprophylaxis, injection readiness, and technique were assessed one day after the counselling session. A telephonic interview was conducted at the end of the 10-day therapy to determine adherence and adverse effects experienced. KEY FINDINGS: A total of 259 subjects were successfully followed up, with 87.6% (n = 227) adherent to the therapy. Nonadherence was predominantly due to forgetfulness; four had their treatment withheld due to bleeding. One-third of subjects experienced localised pain and bruising. Subjects answered a median of 5/7 knowledge questions and recalled a median of 8/10 injection steps correctly, with those who read the information leaflet provided after counselling scoring significantly higher (P = .02). The majority declared moderate confidence in their ability to self-inject. Subjects who intended to self-inject (P < .01) and were more confident (P = .02) demonstrated better injection technique. CONCLUSIONS: Postpartum females counselled by pharmacists largely adhered to short-term enoxaparin for thromboprophylaxis. The impact of the counselling session may be enhanced by addressing their psychological readiness to self-inject, awareness of adverse effects identification, mitigation, and management, as well as setting reminders to prevent forgetfulness to inject.

Evaluation of Anti-Xa Target Attainment with Prophylactic Enoxaparin Dosing Regimens for Venous Thromboembolism Prophylaxis in Morbidly Obese Patients.

Subcutaneous enoxaparin has been shown to reduce the risk of venous thromboembolism (VTE) among hospitalized patients. However, alternative enoxaparin dosing strategies may be necessary in morbid obesity. The objective of this study was to assess the rate of target anti-Xa attainment with three enoxaparin dosing regimens for venous thromboembolism (VTE) prophylaxis in morbidly obese patients. In this retrospective study, anti-Xa target attainment was assessed among adult patients with a body mass index (BMI) ≥ 40 kg/m2 receiving enoxaparin 40 mg twice daily (BID), 60 mg BID, or 0.5 mg/kg BID. Univariate and multivariate analyses were conducted. Target anti-Xa levels were defined as a steady-state, peak level of 0.2-0.5 IU/mL. This study included 120 patients with 55 patients receiving 40 mg BID, 44 patients receiving 60 mg BID, and 21 patients receiving 0.5 mg/kg BID. Target anti-Xa levels were achieved in 29.1% of patients in the 40 mg BID arm, 54.5% in the 60 mg BID arm, and 90.5% in the 0.5 mg/kg BID arm. Anti-Xa target attainment was significantly increased in both the 60 mg BID arm (p = 0.01) and the 0.5 mg/kg arm (p < 0.0001), compared to the 40 mg BID arm. In morbidly obese patients, weight-based dosing was associated with a greater attainment of target anti-Xa levels. Further studies are needed to determine the impact of these dosing regimens on clinical outcomes.

Evaluating the Effectiveness of Enoxaparin in Treating Pediatric Arterial Thrombosis in Saudi Arabia.

BACKGROUND: Thrombosis is the abnormal formation of blood clots within blood vessels; it results from an imbalance between fibrinolytic, pro-coagulant, and anticoagulant systems. Pediatric arterial thrombosis, especially related to catheter usage, is an emerging issue with limited evidence. This study evaluates the efficacy of enoxaparin in treating arterial thrombosis in pediatric patients at a single center. METHODS: A retrospective single-center study included children under 14 years old diagnosed with catheter-related arterial thrombosis (CAT) and treated with low-molecular-weight heparin (LMWH) at King Abdulaziz Medical City between 2016 and 2021. Patients without follow-up at our institution or those using other anticoagulants were excluded. Data collected included age, sex, weight, catheter type, location and degree of thrombosis, ultrasonographic results, treatment duration, hemoglobin and platelet levels, and missed refills. Radiologic confirmation of CAT was required for inclusion. RESULTS: This study included 111 children treated with enoxaparin for non-cerebral arterial thrombosis. The median age at diagnosis was 3 months, with 58% being male patients. Most cases (87%) involved cardiac catheterization, and all were confirmed using ultrasonography. Complete thrombus resolution was achieved in 90% of patients, partial resolution in 8.1%, and 1.8% had no resolution. The median duration of enoxaparin therapy was 20 days. Multivariate analysis indicated that higher age and lower body weight were associated with a higher risk of non-resolution. Indwelling catheters also posed a greater risk of non-resolution compared to cardiac catheters. CONCLUSIONS: Enoxaparin proved effective in treating catheter-related arterial thrombosis in children, with high resolution rates and few side effects. This study helps inform treatment strategies in pediatric thrombosis management and highlights the need for further research to refine treatment durations and address patient risk factors.

Fondaparinux versus Enoxaparina no Tratamento de Pacientes Obesos com Síndrome Coronariana Aguda / Fondaparinux versus Enoxaparin in the Treatment of Obese Patients with Acute Coronary Syndrome

Resumo Fundamento: O fondaparinux é um anticoagulante eficaz e seguro usado no tratamento de síndromes coronarianas agudas (SCAs). No entanto, devido à baixa representatividade de indivíduos obesos em ensaios clínicos, os efeitos de se aplicar os resultados desse medicamento nesta população continuam incertos. Objetivos: Comparar o fondaparinux à enoxaparina no tratamento de obesos com SCA. Métodos: Este é um estudo do tipo coorte retrospectivo, incluindo indivíduos obesos (IMC ≥ 30 Kg/m2) internados com Infarto do Miocárdio sem Elevação do Segmento ST (IAMSSST) ou Angina Instável (AI) e tratados com fondaparinux ou enoxaparina entre 2010 e 2020. Os grupos que receberam fondaparinux e enoxaparina foram comparados quanto suas características clínicas e laboratoriais usando o teste do qui-quadrado e o teste de Mann-Whitney, conforme apropriado. A incidência dos desfechos primários (morte, reinfarto, acidente vascular cerebral, sangramento maior) foi comparada entre os grupos. Um p<0,05 foi considerado estatisticamente significativo em todas as análises. Resultados: Um total de 367 pacientes obesos com IAMSSST ou AI foi incluído, dos quais 258 usaram fondaparinux e 109 usaram enoxaparina. A idade média foi 64 ± 12 anos, 52,9% eram do sexo masculino. A prevalência e diabetes, hipertensão, dislipidemia, doença arterial coronariana prévia, acidente vascular cerebral prévio, e implementação de estratégia invasiva foi similar entre os grupos. A incidência do desfecho primário foi 4,7% no grupo fondaparinux e 5,5% no grupo enoxaparina (p = 0,729). Não houve diferença entre os grupos quando os componentes do desfecho primário foram analisados separadamente. Conclusão: Em uma amostra de pacientes obesos com IAMSSST ou AI, não houve diferença na ocorrência do desfecho composto (morte, acidente vascular cerebral, reinfarto, sangramento maior) entre os pacientes que utilizaram fondaparinux ou enoxaparina.

Abstract Background: Fondaparinux is an effective and safe anticoagulant in the treatment of acute coronary syndromes (ACS). However, due to the low representation of obese individuals in clinical trials, the effects of applying the results of this drug to this population remain uncertain. Objectives: To compare Fondaparinux to Enoxaparin in the treatment of obese patients with ACS. Methods: This is a retrospective cohort study, including obese individuals (BMI ≥ 30 Kg/m2) admitted with non-ST-segment elevation myocardial infarction (NSTEMI) or unstable angina (UA) and treated with Fondaparinux or Enoxaparin between 2010 and 2020. The Fondaparinux and Enoxaparin groups were compared for their clinical and laboratory characteristics using chi-square and Mann-Whitney tests, as appropriate. The incidence of primary outcomes (death, reinfarction, stroke, major bleeding) was compared between groups. P-value < 0.05 was considered significant for all analyses. Results: A total of 367 obese patients with NSTEMI or UA were included, of whom 258 used Fondaparinux and 109 used Enoxaparin. Mean age was 64 ± 12 years, and 52.9% were male. The prevalence of diabetes, hypertension, dyslipidemia, prior coronary artery disease, prior stroke, and implementation of invasive strategy was similar between groups. The incidence of the primary outcome was 4.7% in the Fondaparinux group and 5.5% in the Enoxaparin group (p = 0.729). There was no difference between groups when analyzing the components of the primary outcome separately. Conclusion: In a sample of obese patients with NSTEMI or UA, there was no difference in the occurrence of the composite outcome (death, stroke, reinfarction, major bleeding) between patients who used Fondaparinux or Enoxaparin.

Development of mucoadhesive 3D-printed Carbopol/Eudragit/SNAC tablets for the oral delivery of enoxaparin: In vitro and ex vivo evaluation.

3D-printed dosage forms comprised of Carbopol and Eudragit were fabricated through semi-solid extrusion, combining Enoxaparin (Enox) and the permeation enhancer SNAC in a single-step process without subsequent post-processing. Inks were characterized using rheology and Fourier-transform infrared (FTIR) spectroscopy. The stability of Enox in the fabricated dosage forms was assessed by means of Nuclear Magnetic Resonance (NMR) and Circular Dichroism (CD) analysis. In vitro release studies revealed the release of Enox in a sustained manner, whereas ex vivo experiments demonstrated the mucoadhesive properties of the 3D-printed dosage forms and their ability to enhance Enox permeability across intestinal mucosa. Cellular assays (CCK-8 assay) revealed a dose- and time-dependent response following incubation with the 3D-printed dosage forms. The encapsulation of SNAC in the 3D-printed dosage forms demonstrated their capacity to increase the transcellularly transport of macromolecule across Caco-2 monolayer in a reversible manner, as confirmed by Transepithelial Resistance (TEER) measurements.

Therapeutic Enoxaparin Dosing in Obesity.

OBJECTIVE: This review aims to systematically summarize the available data on efficacy and safety of therapeutic enoxaparin in obese patients and to identify gaps to guide future research. DATA SOURCES: Medline and Embase were systematically searched for eligible studies (last searched December 20, 2023). Studies were included if they reported on therapeutic dosing regimens, adverse bleeding, thrombotic outcomes, or antifactor Xa (AFXa) monitoring in obese adult patients. STUDY SELECTION AND DATA EXTRACTION: The systematic review management tool Covidence was used to manage the study selection and data extraction process. The reference list from eligible studies was screened to determine any additional eligible studies. DATA SYNTHESIS: Sixteen studies were included in the analysis. Studies used a variety of doses, indications, and study designs making comparison difficult. Twelve studies reported the incidence of thrombotic events (median = 1.3% [interquartile range [IQR] = 0.3%-2.3%]) and all studies reported the incidence of bleeding events (median = 5.7% [IQR = 2.4%-14.5%]). Two of the 8 studies analyzing the influence of weight/body mass index (BMI) or dose per kg on AFXa levels reported statistically significant results. One study concluded that BMI did not affect achievement of target AFXa levels. However, the second study found that dosing using actual body weight was an independent predictor of supratherapeutic AFXa levels in the obese population. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This is the first comprehensive review with a focus on therapeutic dosing of enoxaparin in obesity and has been conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement. Seven of the included studies were published since 2018 indicating that new evidence on this topic is emerging. CONCLUSION: There was inadequate evidence to support an optimal dosing strategy in obese patients due to the heterogeneity of the studies. The AFXa monitoring may be appropriate to guide dosing in this population. Further research is required to determine a suitable dosing regimen.

Finding individualised treatment in obese needing enoxaparin (FIT ONE): a multicentre study of therapeutic enoxaparin and the role of anti-factor Xa monitoring.

Enoxaparin is dosed according to actual body weight in treatment of arterial and venous thrombosis. Due to its hydrophilic nature, it distributes according to lean body mass which may be problematic when dosing obese patients as this may increase the risk of bleeding events in this population. The aim was to evaluate current therapeutic enoxaparin dosing strategies, including Antifactor Xa (AFXa) level monitoring, in obese patients and to identify factors that contribute to treatment failure and excess anticoagulation. A retrospective cohort study was conducted reviewing patients administered therapeutic enoxaparin between May 2020 and April 2021. Data were collected on patient characteristics, enoxaparin therapy, AFXa monitoring, and outcomes. Regression models were constructed to assess variables of interest to estimate any association with AFXa levels. In total 762 patients were included in the analysis. The mean initial weight-based dose was 0.95 mg/kg twice daily (SD: ± 0.12, IQR 0.92-1.01) and 1.04 mg/kg once daily (SD: ± 0.26, IQR 0.93-1.12) and 14.4% of patients had AFXa monitoring. Treatment failure was experienced by 2.2%, 5% experienced bleeding. There was no association between the mean actual milligram per kilogram weight-based twice daily doses and subtherapeutic, therapeutic and supratherapeutic AFXa levels (P = 0.135). Obesity was not included in the final regression models due to lack of significance. At a mean therapeutic enoxaparin dose of 0.95 mg/kg twice daily and 1.04 mg/kg once daily no excess in treatment failure or bleeding events were observed in obese patients compared to the product information. Obesity was not an independent variable that affected the achievement of target AFXa levels.

Venous Thromboembolism Rates in Trauma Patients Significantly Increase With Missed Prophylactic Enoxaparin Doses.

Background: Current literature demonstrates prophylactic enoxaparin to be efficacious in reducing venous thromboembolism (VTE) rates without significantly increasing risk for bleeding complications. Despite this evidence, prophylactic enoxaparin doses are frequently withheld for surgery or procedures. This exploratory study aims to quantify the risk of a VTE event in trauma patients associated with missed doses of prophylactic enoxaparin. Methods: This retrospective cohort study evaluated trauma patients admitted to our Level 1 trauma center from January 1, 2012 to January 31, 2021. A 1:1 propensity match with ten variables was performed to compare patients receiving prophylactic enoxaparin that had a VTE and those that did not. The primary outcome was a VTE event. Results: 493 patients met inclusion criteria; 1:1 propensity score matching was performed resulting in a cohort of 184 patients. The percentage of patients that missed a prophylactic enoxaparin dose in the VTE group was higher than the no VTE group (34.8% vs 21.7%, P = 0.049). This is consistent when examining total missed doses (P = 0.038) and consecutively missed doses (P = 0.035). The odds of having a VTE for patients that missed at least one dose or more of enoxaparin are nearly two times greater (OR 1.92, 95% CI 0.997, 3.7). Conclusion: Missing enoxaparin doses significantly increases the risk of VTE in matched populations. Most prophylactic enoxaparin doses were held for procedures, and not for bleeding events. Trauma teams should carefully weigh the risk of bleeding complications associated with continuing enoxaparin prophylaxis against the significant thromboembolic risk of withholding it.

Intracardiac ultrasound-guided transseptal puncture in horses: Outcome, follow-up, and perioperative anticoagulant treatment.

BACKGROUND: Cardiac catheterizations in horses are mainly performed in the right heart, as access to the left heart traditionally requires an arterial approach. Transseptal puncture (TSP) has been adapted for horses but data on follow-up and closure of the iatrogenic atrial septal defect (iASD) are lacking. HYPOTHESIS/OBJECTIVES: To perform TSP and assess postoperative complications and iASD closure over a minimum of 4 weeks. ANIMALS: Eleven healthy adult horses. METHODS: Transseptal puncture was performed under general anesthesia. Serum cardiac troponin I concentrations were measured before and after puncture. Weekly, iASD closure was monitored using transthoracic and intracardiac echocardiography. Relationship between activated clotting time and anti-factor Xa activity during postoperative enoxaparin treatment was assessed in vitro and in vivo. RESULTS: Transseptal puncture was successfully achieved in all horses within a median duration of 22 (range, 10-104) minutes. Balloon dilatation of the puncture site for sheath advancement was needed in 4 horses. Atrial arrhythmias occurred in 9/11 horses, including atrial premature depolarizations (N = 1), atrial tachycardia (N = 5), and fibrillation (N = 3). Serum cardiac troponin I concentrations increased after TSP, but remained under the reference value in 10/11 horses. Median time to iASD closure was 14 (1-35) days. Activated clotting time correlated with anti-factor Xa activity in vitro but not in vivo. CONCLUSIONS AND CLINICAL IMPORTANCE: Transseptal puncture was successfully performed in all horses. The technique was safe and spontaneous iASD closure occurred in all horses. Clinical application of TSP will allow characterization and treatment of left-sided arrhythmias in horses.

Investigation of the effects of treatment with enoxaparin sodium and hyperbaric oxygen therapy on the recovery of rats with achilles tendon rupture.

PURPOSE: In this study, we aimed to investigate the effects of hyperbaric oxygen therapy and enoxaparin sodium, which are known to accelerate bone tissue healing as well as tendon and soft tissue healing, on the healing of Achilles tendon rupture. METHODS: Thirty-six rats were used in the present study. All rats were divided into groups of nine. The groups were the enoxaparin sodium group, enoxaparin sodium and hyperbaric oxygen group, hyperbaric oxygen group and control group. After 21 days, the process was completed, and the rats were sacrificed. Achilles tendon samples were evaluated histopathologically. RESULTS: The groups were compared according to the results of statistical analysis based on the histopathological data. There was no significant difference between the groups in terms of acute inflammation (p = 0.785) or chronic inflammation (p = 0.827) scores, but there were significant differences in neovascularization (p = 0.009), proliferation (p < 0.001) and fibrosis (p = 0.006) scores. CONCLUSION: Our study showed that the use of enoxaparin sodium and hyperbaric oxygen had a positive effect on the healing of the Achilles tendon. Based on these results, we believe that the use of enoxaparin sodium and hyperbaric oxygen therapy after Achilles tendon rupture will be beneficial for healing and preventing complications.

Anti-Xa activity below range is related to thrombosis in patients with severe COVID-19.

OBJECTIVE: We aimed to anlayse the relationship between anti-Xa activity below range and thomboembolic events. DESIGN: Single center prospective observational longitudinal cohort study (February-November 2021). SETTING: Patients admitted to the ICU of a University Hospital. PARTICIPANTS: Patients with severe COVID-19 pneumoniae. INTERVENTIONS: Enoxaparin was used for prophylactic and therapeutic anticoagulation. Enoxaparin dosing and dose adjustment were based on anti-Xa activity according to the hospital protocol. MAIN VARIABLES OF INTEREST: Target: thomboembolic events. PREDICTORS: demographics, pharmacotherapy, anti-Xa measurements, clinical data, and laboratory results. Logistic regression was used to identify independent risk factors for thomboembolic events. RESULTS: Data were available for 896 serum anti-Xa measurements from 228 subjects. Overall, 71.9% were male, with a median age of 62. Most patients needed invasive mechanical ventilation (87.7%) and mortality was 24.1%. A total of 28.9% new thomboembolic events were diagnosed. There were 27.1% anti-Xa measesurements below range. When multivariable logistic regression analysis was performed anti-Xa activity below range (RR, 4.2; p = 0.000), C-reactive protein (25 mg/L increase) (RR, 1.14; p = 0.005) and D-dimer (1000 ng/L increase) (RR, 1.06; p = 0.002) were the independent factors related to new thomboembolic events in patients with severe COVID-19. CONCLUSIONS: Anti-Xa activity below range, C-reactive protein and D-dimer were the independent factors related to thomboembolic events in patients with severe COVID-19. Purposely designed clinical trials should be carried out to confirm the benefit of an anti-Xa monitoring.

Anti factor Xa monitoring for venous thromboprophylaxis in severely burn-injured patients: A systematic review.

INTRODUCTION: Patients with severe burn injuries are at risk of venous thromboembolism (VTE) and associated sequelae. Burn-injured patients may require larger doses of VTE prophylaxis so underdosing may occur with standard regimens. Monitoring anti-factor Xa (AFXa) levels may allow tailoring of dosage but is currently uncommon. The purpose of this systematic review was to methodically review the available literature with respect to AFXa in severe burn-injured patients, and thereby assess its efficacy. METHODS: Using PRISMA guidelines, "Xa" and "burns" were used to systematically review MEDLINE (1946 - present) and EMBASE (1974 - present) databases for publications regarding the monitoring of AFXa levels for thromboprophylaxis in burn-injured patients. RESULTS: Eight studies (432 patients) met inclusion. Peak AFXa level at initial measurement was reported in all studies and was within the range for prophylaxis in 184 of 432 cases (42.6%), below range in 246 of 432 cases (56.9%) and above range for 2/432 (0.5%). Complications were reported in 7 studies (412 patients), with a total of 30 (7.3%) complications, comprising of 16 (53.3%) VTE events and 14 (46.7%) mortalities. Three studies comprising 270 patients compared complications between patients who were within the reference range with patients who were below the range. There were 164 patients from the 'within the reference range' groups that had a total of 6 (3.7%) complications, comprised of 4 (66.7%) VTE events and 2 (33.3%) mortalities. There were 106 patients from the 'below reference range group' that had a total of 11 (10.4%) complications, comprised of 9 (81.8%) VTE events and 2 (18.2%) mortalities. CONCLUSION: Our findings suggest standard prophylactic anticoagulation dosing risks underdosing and therefore, an increased risk in the development of VTE. AFXa monitoring allows individually tailored dose adjustment to reach therapeutic levels, which may be efficacious in reducing VTE events and is therefore recommended where possible.

How enoxaparin underdosing and sex contribute to achieving therapeutic anti-Xa levels.

Introduction: Anti-Xa serves as a clinical surrogate for assessing the efficacy and bleeding risk in patients treated with enoxaparin for thromboembolic events. Evidence from the literature and empirical observations suggest that patients are underdosed in clinical practice to avoid bleeding complications. This study aimed to investigate such underdosing of enoxaparin and its potential impact on achieving therapeutic anti-Xa levels. Methods: This multicentric, retrospective, observational study included patients with acute ischemic stroke due to atrial fibrillation. All patients received enoxaparin in the therapeutic setting with subsequent anti-Xa measurements. The one-sample, one-tailed Wilcoxon signed-rank test was used to identify a significant difference between the doses administered and the recommended daily dose. Logistic regression model analysis was performed to identify additional predictors affecting achievement of the therapeutic anti-Xa target range. Stepwise forward-backward selection with Akaike's information criterion as metric was applied to refine the logistic regression model. Results: A total of 145 patients from the university hospitals of St. Pölten and Tulln in Lower Austria were included. The median daily enoxaparin dose administered was 1.23 mg/kg, resulting in an overall target range achievement rate of 66%. As compared to recommended therapeutic doses, significant underdosing of enoxaparin was evident in both participating centers (p < 0.001). The calculated threshold dose to achieve the therapeutic target range with a 90% probability was 1.5 mg/kg enoxaparin daily. Female sex was found to be a strong independent predictor of achieving a therapeutic target range (OR 9.44; 95% CI 3.40-30.05, p < 0.001). Conclusion: Despite the underdosing observed in both centers, therapeutic anti-Xa levels were achieved with lower than recommended doses of enoxaparin, and women required even lower doses than men. These findings warrant further confirmation by prospective studies.

A child with sickle cell disease admitted with coronavirus disease 2019 pneumonia and acute chest syndrome in pediatric intensive care unit: A case report.

Management of sickle cell disease complications in the setting of the coronavirus disease 2019 (COVID-19) pandemic is complicated with little published pediatric data. We report the first documented case of a 9-year-old boy with sickle cell disease, presenting with fever, cough, and shortness of breath, diagnosed to have acute chest syndrome and coronavirus disease 2019 (COVID-19) pneumonia with inflammatory storm requiring ventilation, exchange blood transfusion, immunomodulatory agents, and prophylactic anticoagulation. The patient responded satisfactorily to the management of the acute illness and was found to be well at the next visit to the pediatric hematology outpatient department following hospital discharge.