Enoxaparin Treatment Research Articles

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 10mM glutamate, a group treated with enoxaparin at concentrations ranging from 25 to 200µM, and a group receiving both 10mM glutamate and enoxaparin at concentrations ranging from 25 to 200µM. 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 200µM 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.

Assessment of enoxaparin‐related knowledge, administration technique, and self‐reported adherence among women after caesarean section delivery

AbstractBackgroundVenous thromboembolism is among the main causes of maternal morbidity and mortality, with caesarean section (CS) delivery carrying greater risk. Outpatient thromboprophylaxis, such as enoxaparin, is administered subcutaneously and prescribed as an outpatient; raising the issue of medication adherence.AimThis study aimed to evaluate women's adherence to enoxaparin administration after CS delivery, explore the reasons for non‐adherence, and assess the factors associated with patients' adherence to enoxaparin.MethodWomen after CS delivery, who had been given enoxaparin at discharge were included in the study. Eligible patients were contacted via telephone at the middle and the end of the enoxaparin treatment. Syringe count determined the main outcome of adherence during direct telephone interviews with the patient. Optimal adherence was defined as all the doses of enoxaparin being administered and suboptimal adherence was at least one dose not administered. Ethical approval was granted by the Malaysian Registry Ethics Committee belonging to National Medical Research Registry (Reference no: NMRR ID‐22‐02859‐P41) and the study conforms with the Declaration of Helsinki. Informed consent was obtained from all participants through completion of written consent forms, after an explanation of the study was provided by investigators.ResultsOut of 201 women included, the majority (91.5%) were fully adherent to enoxaparin, while 8.5% missed at least one dose. Most patients administering at home missed the dose due to reporting they were unwell (n = 6), busy (n = 4), or forgot to administer (n = 2). Among missed doses in patients administered in a healthcare setting, all participants (n = 5) forgot to bring their medication to the appointment. Only medication knowledge had a significant association with adherence to enoxaparin administration (p = 0.008).ConclusionThe study raised concern about the substantial percentage of patients missing at least one dose of enoxaparin, particularly among patients injecting at home. Initiatives should focus on customised enoxaparin administration counselling and providing educational materials.

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

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. To perform TSP and assess postoperative complications and iASD closure over a minimum of 4 weeks. Eleven healthy adult horses. 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. 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. 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.

The effects of enoxaparin treatment in a xenograft mouse model of oral squamous cell carcinoma: A pilot study.

Recent studies suggest that enoxaparin may have therapeutic effects on oral squamous cell carcinoma. We aimed to assess this effect utilizing xenograft mouse model through evaluations of proliferation and angiogenesis markers at the RNA and protein levels. Mice were divided into enoxaparin treatment (n = 4), positive control (n = 4) and negative control (n = 3) groups. Immunohistochemical analyses were performed utilizing Bcl-2, Bax and Ki-67 antibodies. Expression levels of proliferation and apoptosis related genes were calculated utilizing qRT-PCR. Time-dependent proliferation assays were performed in OSC-19 and HEK293 cell-lines. Bax antibody showed positive staining in the cytoplasm and nuclei of tumor cells, while Bcl-2 antibody displayed staining only in the cytoplasm. A proliferation index of 15%-20% was found in all groups with the Ki-67 marker indicating no metastasis. Enoxaparin treatment caused decrease in BCL2, BAX and CCNB1 genes' expressions. Compared to HEK293, proliferation assays demonstrated higher division rates in OSC-19 with a significant decrease in viability after 96 h. Reduced BCL-2 expression indicates a regression of tumor growth, but reduced BAX expression is not correlated with increased apoptosis. Despite the aggressive nature of OSC-19, our results showed a low cell viability with a high division rate when compared with the control HEK293. This paralleled our in vivo findings that showed absence of lymph node metastasis across all mice groups. This discrepancy with the literature suggests that further investigations of the underlying mechanisms and protein-level analyses are needed to draw definitive conclusions about the effect of enoxaparin on OSC-19 behavior.

Enoxaparin treatment dosing for venous thromboembolism in pediatric patients with obesity.

The optimal enoxaparin dosing for treatment of venous thromboembolism (VTE) in pediatric patients with obesity remains uncertain. We described the mean enoxaparin dose required to attain anti-factor Xa (anti-Xa) levels of 0.5-1unit/mL in pediatric patients with obesity. Pediatric patients with obesity (body mass index [BMI]≥95th percentile) who received treatment dose of enoxaparin from 2013 to 2022 and had at least one appropriately timed anti-Xa level were retrospectively evaluated. Daily enoxaparin dose required to achieve an anti-Xa level of 0.5-1unit/mL was reviewed and compared by the severity of obesity. The correlation coefficients between enoxaparin dose requirement and BMI, BMI percentile, and weight were measured by Spearman's rank correlation coefficient. Pediatric patients with obesity (n=89) required a mean enoxaparin dose of 0.8±0.18mg/kg twice daily to attain a therapeutic anti-Xa level. Children with BMI 95th-99th percentile and weight ≤100kg achieved the target level on a significantly higher weight-based enoxaparin dose compared to BMI greater than 99th percentile (0.95±0.15 vs. 0.75±0.15mg/kg twice daily; p<.001) and weight greater than 100kg (0.95±0.14 vs. 0.7±0.12mg/kg twice daily; p<.001). BMI, BMI percentile, and weight showed a moderate to strong negative correlation with enoxaparin dose requirement. Pediatric patients with obesity required a lower weight-based dose of enoxaparin to achieve a therapeutic anti-Xa than the recommended starting dose of 1mg/kg twice daily for treatment of VTE. Among obesity indices, weight showed the strongest negative correlation with total daily enoxaparin requirement.

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

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. 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. 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.

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

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. 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. 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). 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.

Enoxaparin for VTE thromboprophylaxis during inpatient rehabilitation care: assessment of the standard fixed dosing regimen

BackgroundWe aimed to examine the efficiency of fixed daily dose enoxaparin (40 mg) thromboprophylaxis strategy for patients undergoing inpatient rehabilitation.MethodsThis was an observational, prospective, cohort study that included 63 hospitalized patients undergoing rehabilitative treatment following sub-acute ischemic stroke (SAIS) or spinal cord injury (SCI), with an indication for thromboprophylaxis. Anti-Xa level measured three hours post-drug administration (following three consecutive days of enoxaparin treatment or more) was utilised to assess in vivo enoxaparin activity. An anti-Xa level between 0.2-0.5 U/ml was considered evidence of effective antithrombotic activity.ResultsWe found sub-prophylactic levels of anti-Xa (<0.2 U/ml) in 19% (12/63). Results were within the recommended prophylactic range (0.2-0.5 U/ml) in 73% (46/63) and were supra-prophylactic (>0.5 U/ml) in 7.9% (5/63) of patients. Anti-Xa levels were found to inversely correlate with patients’ weight and renal function as defined by creatinine clearance (CrCl) (p<0.05).ConclusionsOur study confirmed that a one-size-fits-all approach for venous thromboembolism (VTE) prophylaxis may be inadequate for rehabilitation patient populations. The efficacy of fixed-dose enoxaparin prophylaxis is limited and may be influenced by renal function and weight. This study suggests that anti-Xa studies and prophylactic enoxaparin dose adjustments should be considered in certain patients, such as those who are underweight, overweight and or have suboptimal renal function.Trial registrationNo. NCT103593291, registered August 2018.

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.

PO40 Hyperfiltration Syndrome as a Cause of Low Anti-Xa Activity Levels during Enoxaparin Treatment in a Critically Ill Patient

PO40 Hyperfiltration Syndrome as a Cause of Low Anti-Xa Activity Levels during Enoxaparin Treatment in a Critically Ill Patient

Comparison of postpartum anti-Xa levels following enoxaparin administration to prevent venous thromboembolism using 2 weight-based protocols: a randomized controlled trial

During the postpartum period, enoxaparin is given to high-risk women to prevent venous thromboembolism, a leading cause of maternal mortality. Enoxaparin activity is measured by peak plasma anti-Xa levels. The prophylactic range of anti-Xa is 0.2 to 0.6 IU/mL. Values above and below this range represent subprophylactic and supraprophylactic levels, respectively. Weight-based enoxaparin administration was superior to fixed-dose enoxaparin administration in achieving an anti-Xa prophylactic range. However, it is unknown which weight-based enoxaparin administration is superior (once daily weight categories vs 1 mg/kg body weight). This study aimed to compare the efficacy in reaching prophylactic anti-Xa levels and adverse effects profile of the 2 weight-based enoxaparin dosing protocols. A randomized open-label controlled trial was conducted. Women after delivery, who were intended to receive enoxaparin, were randomized to receive either enoxaparin treatment according to 1 mg/kg (up to 100 mg) or weight categories (≤90 kg, 40 mg; 91-130 kg, 60 mg; 131-170 kg, 80 mg; >170 kg, 100 mg). Plasma anti-Xa levels were obtained 4 hours after the second enoxaparin administration (day 2 of enoxaparin treatment). If the woman was still hospitalized, anti-Xa levels were also obtained on day 4. The primary endpoint was the proportion of women with anti-Xa levels within the prophylactic range at day 2. In addition, data regarding anti-Xa levels in different weight groups and rates of venous thromboembolism and adverse effects were evaluated. Of note, 60 and 64 women received enoxaparin according to 1 mg/kg and weight categories, respectively; moreover, 55 (92%) and 27 (42%) women reached the prophylactic range of anti-Xa at day 2, respectively (P<.0001). The mean anti-Xa levels on day 2 were 0.34±0.09 and 0.19±0.06 IU/mL, respectively (P<.0001). The anti-Xa levels were higher in the 1 mg/kg group than in the weight categories group in the subanalysis of different weight categories (51-70, 71-90, and 91-130 kg). There was no difference in anti-Xa levels on day 4 compared with day 2 in both cohorts (n=25). There was no case of supraprophylactic anti-Xa levels, venous thromboembolism events, or serious hemorrhage. Postpartum enoxaparin administration at 1 mg/kg was superior to weight categories in reaching anti-Xa prophylactic levels without leading to serious adverse effects. Given the high efficacy and safety profile, enoxaparin at 1 mg/kg once daily should be considered the preferred protocol for postpartum venous thromboembolism prophylaxis.

Anti-Factor Xa Level Monitoring for Enoxaparin Prophylaxis and Treatment in High-Risk Patient Groups.

Description Monitoring anti-factor Xa levels is a controversial topic in the inpatient setting due to resource utilization and unclear conditional guideline recommendations regarding this practice. Enoxaparin dosing in certain high-risk patient populations such as those with low body weight, obesity, renal insufficiency, and pregnancy has not been determined. The objective of this review was to assess the safety and efficacy of enoxaparin monitoring via anti-factor Xa levels in high-risk patient populations. The PubMed database was searched for articles related to low-molecular-weight heparin monitoring. Randomized controlled trials and meta-analyses that evaluated the safety and efficacy of enoxaparin prophylaxis and treatment in patients with extremes of weight, renal insufficiency, and pregnancy were selected. Fourteen studies representing four high-risk population patient groups were included. Patients with extremes of weight or who were pregnant were found to have subtherapeutic anti-factor Xa levels due to the weight-based dosing of enoxaparin. Those with renal insufficiency were found to be accumulating enoxaparin, indicating the need for a lower dose. Studies have shown that monitoring may be required in specific high-risk patient groups. Dose adjustments based on anti-factor Xa levels can prevent adverse events associated with enoxaparin. Further research involving larger patient populations would be necessary to determine the clinical efficacy of enoxaparin monitoring with anti-factor Xa levels.

LPS-Induced Coagulation and Neuronal Damage in a Mice Model Is Attenuated by Enoxaparin.

Background. Due to the interactions between neuroinflammation and coagulation, the neural effects of lipopolysaccharide (LPS)-induced inflammation (1 mg/kg, intraperitoneal (IP), n = 20) and treatment with the anti-thrombotic enoxaparin (1 mg/kg, IP, 15 min, and 12 h following LPS, n = 20) were studied in C57BL/6J mice. Methods. One week after LPS injection, sensory, motor, and cognitive functions were assessed by a hot plate, rotarod, open field test (OFT), and Y-maze. Thrombin activity was measured with a fluorometric assay; hippocampal mRNA expression of coagulation and inflammation factors were measured by real-time-PCR; and serum neurofilament-light-chain (NfL), and tumor necrosis factor-α (TNF-α) were measured by a single-molecule array (Simoa) assay. Results. Reduced crossing center frequency was observed in both LPS groups in the OFT (p = 0.02), along with a minor motor deficit between controls and LPS indicated by the rotarod (p = 0.057). Increased hippocampal thrombin activity (p = 0.038) and protease-activated receptor 1 (PAR1) mRNA (p = 0.01) were measured in LPS compared to controls, but not in enoxaparin LPS-treated mice (p = 0.4, p = 0.9, respectively). Serum NfL and TNF-α levels were elevated in LPS mice (p < 0.05) and normalized by enoxaparin treatment. Conclusions. These results indicate that inflammation, coagulation, neuronal damage, and behavior are linked and may regulate each other, suggesting another pharmacological mechanism for intervention in neuroinflammation.

Optimal dosing of enoxaparin in overweight and obese children.

Current enoxaparin dosing guidelines in children are based on total body weight. This is potentially inappropriate in obese children as it may overestimate the drug clearance. Current evidence suggests that obese children may require lower initial doses of enoxaparin, therefore the aim of this work was to characterise the pharmacokinetics of enoxaparin in obese children and to propose a more appropriate dosing regimen. Data from 196 unique encounters of 160 children who received enoxaparin treatment doses were analysed. Enoxaparin concentration was quantified using the chromogenic anti factor Xa (anti-Xa) assay. Patients provided a total of 552 anti-Xa samples. Existing published pharmacokinetic (PK) models were fitted and evaluated against our dataset using prediction-corrected visual predictive check plots (pcVPCs). A PK model was fitted using a nonlinear mixed-effects modelling approach. The fitted model was used to evaluate the current standard dosing and identify an optimal dosing regimen for obese children. Published models of enoxaparin pharmacokinetics in children did not capture the pharmacokinetics of enoxaparin in obese children as shown by pcVPCs. A one-compartment model with linear elimination best described the pharmacokinetics of enoxaparin. Allometrically scaled fat-free mass with an estimated exponent of 0.712 (CI 0.66-0.76) was the most influential covariate on clearance while linear fat-free mass was selected as the covariate on volume. Simulations from the model showed that fat-free mass-based dosing could achieve the target anti-Xa activity at steady state in 77.5% and 78.2% of obese and normal-weight children, respectively, compared to 65.2% and 75.5% for standard total body weight-based dosing. A population PK model that describes the time course of anti-Xa activity of enoxaparin was developed in a paediatric population. Based on this model, a unified dosing regimen was proposed that will potentially improve the success rate of target attainment in overweight/obese patients without the need for patient body size categorisation. Therefore, prospective validation of the proposed approach is warranted.

Concomitant acute lower extremity arterial and deep vein thrombosis developing in a patient under anticoagulant therapy after COVID 19 infection.

The hypercoagulable state continues after the Coronavirus 2019 (Covid 19) infection and prophylactic anticoagulants are recommended in this period. However, arterial and venous thromboembolic events can be observed during the convalescence period after the Covid 19. Here, we present the case of acute lower extremity arterial and venous thromboembolism developed in the post-Covid 19 period in a 77-years-old patient, under therapeutic doses of anticoagulant therapy (enoxparin 1mg/kg of weight every 12 hours). The patient, who had no previous history of arterial or venous thrombosis, was taken to emergency surgery with the diagnosis of ALI (acute limb ischemia) due to acute arterial thrombosis. An arterial thrombectomy was performed with the help of a 4F Fogarty catheter inserted from the left femoral artery under local anesthesia. All distal pulses of the patient were palpable in the postoperative period. After the platelet count became &gt;100,000 mm3, 100 mg of acetylsalicylic acid daily was added to the therapeutic dose of enoxaparin sodium treatment. The patient was discharged, uneventfully, except for a minimal diameter increase secondary to deep venous thrombosis (DVT) on the fifth postoperative day, with a combination of enoxaparin and acetylsalicylic acid treatment. Endothelial injury, chronic immuno-thrombogenicity, and increased platelet aggregation in the post-Covid 19 recovery period can cause major thrombotic events, even weeks after the recovery. Anticoagulant therapy is recommended for thromboprophylaxis when the following statuses exist: ≥65 years, critical illness, cancer, prior VTE, thrombophilia, severe immobility, and elevated Ddimer. Combination treatment with long-term antiaggregant therapy may be prudent in thromboembolic events developed under anticoagulant therapy.

Pulmonary Embolism Developing Despite the Use of Anticoagulants in Covid-19 Pneumonia: A case report

COVID-19 pneumonia is one of the diseases that can cause hypercoagulability. It is not uncommon to encounter arterial or venous thromboembolic events during COVID-19 infection. In this case, we wanted to discuss a case of a pulmonary embolism due to COVID-19 infection, which developed despite the usage of therapeutic dosage of anticoagulants. A 41-year-old male patient with a known diabetes mellitus was admitted to our clinic with complaints of cough and headache. The patient was found to be COVID-19 positive. Along with steroid treatment, 2x6,000 IU enoxaparin treatment was initiated for the patient. He developed sudden respiratory distress and showed an increase in oxygen demand. D-dimer value increased abruptly to 35.2 mg/L. Pulmonary CT angiography showed multiple bilateral subsegmental pulmonary embolisms. Since COVID-19 infection can cause arterial and venous thromboembolic events in patients following up with COVID-19 pneumonia, prophylactic anticoagulation should be initiated in hospitalized patients. Attention should be paid to signs of bleeding, and dose adjustment should be made by monitoring coagulation parameters.

Antithrombin III Supplementation in a Premature Infant: Is There a Target Antithrombin Level?

The optimal antithrombin (AT) activity for low-molecular-weight heparin efficacy and the benefits of antithrombin III (ATIII) supplementation in premature infants diagnosed with venous thromboembolism are unknown. Currently, there are no neonatal-specific guidelines directing the appropriate target AT activity during supplementation. This case report describes a critically ill premature infant with a progressive, occlusive inferior vena cava thrombus who received supplemental ATIII during enoxaparin treatment. The patient did not achieve therapeutic anti-Xa levels despite increasing enoxaparin dosing to 3 mg/kg every 12 hours. ATIII supplementation sufficient to attain an AT activity of >40%, in combination with an enoxaparin dosing of >2 mg/kg every 12 hours, was needed to achieve therapeutic anti-Xa levels. Future large studies are needed to determine if there is an optimal target AT activity for critically ill premature infants.

Outcomes of Catheter-Related Arterial and Venous Thrombosis After Enoxaparin Therapy in Neonates and Infants With Congenital Heart Disease.

Outcomes of catheter-related arterial and venous thrombosis after enoxaparin therapy in neonates and infants with congenital heart disease. A single-center retrospective cohort study. Cardiac ICU. Patients under 1 year old cared for in the cardiac ICU at Nicklaus Children's Hospital from January 2015 to January 2019 and treated with enoxaparin for central vascular catheter-related arterial and venous thrombosis. None. One-hundred fifty-six events of central catheter-related arterial and venous thrombosis were included in the study. Arterial thrombi accounted for 109 (69.9%) and venous thrombi for 47 (30.1%) of the events. Femoral vessels were the most commonly affected site (88.5%). Therapeutic outcomes were analyzed in 106 events, excluding those without follow-up imaging. The analysis was stratified by age into neonates and infants and catheter types into arterial and venous catheter groups. Therapeutic dose of enoxaparin was higher in neonates (median 1.8 mg/kg/dose) compared with infants (1.6 mg/kg/dose; p = 0.001). Complete resolution was seen in 68%, partial resolution in 19%, nonresolution in 13% of the events. The complete resolution was higher for arterial than venous (85% vs 65.6%; p = 0.032) thrombi with a shorter duration of enoxaparin treatment (23 vs 43 d; p = 0.014). Complete resolution was lowest in neonates with venous thrombosis (42.9%). The median time to complete resolution by Kaplan-Meier analysis was 24.9 days in the overall cohort, 34.3 days in neonates, 24.9 days in infants, 20 days in arterial, and 44.9 days in venous catheter group. A high proportion of vascular catheter-related thrombi identified in infants with congenital heart disease resolve with enoxaparin treatment. In all patients with thrombosis, arterial versus venous thrombosis is associated with greater odds of resolution.

Evaluation of a Treatment-Dose Enoxaparin Protocol for Patients With Obesity

Background: Treatment-dose enoxaparin is not well studied in obese patients. Guidelines suggest that obese patients receiving enoxaparin therapy for acute venous thromboembolism (VTE) should receive a standard initial dose, 1 mg/kg, based on actual body weight. It is possible that this dosing strategy in obese patients may be overestimated, leading to a higher bleeding risk compared to non-obese patients. Objective: To gather data regarding enoxaparin treatment dosing and anti-Xa level monitoring in patients who are obese to guide dose adjustments. Methods: A single-center, retrospective chart review that included patients who were ordered treatment-dose enoxaparin and had a BMI ≥ 40 kg/m2, which resulted in an automatic pharmacy consult.The primary endpoint of this study was incidence of bleeding. Results: The analysis included 102 patients. Most patients (92.1%) had a BMI of ≥ 40-60 kg/m2 while 7.8% of patients had a BMI of > 60 kg/m2. The average initial and final doses were 1.0 ± 0.1 mg/kg and 0.9 ± 0.2 mg/kg, respectively. The incidence of bleeding was 4.9%. The average dose for those that bled was 0.7 ± 0.1 mg/kg. On average, patients who bled had higher BMIs than patients who did not bleed (51.6 kg/m2 vs. 48.0 kg/m2). Of the 71 patients with an initial anti-Xa level, 42 of the levels were considered supratherapeutic (59.2%). Conclusion: A 1 mg/kg starting dose of enoxaparin may be too high for patients who are obese as many patients required an adjustment to their dose after initial anti-Xa levels.

Enoxaparin Reduces Catheter-associated Venous Thrombosis After Infant Cardiac Surgery

BackgroundCentral venous catheter (CVC) related venous thrombosis (VT) after pediatric cardiac surgery increases morbidity and mortality. Although VT prevention using low-dose anticoagulation therapy has proven ineffective, anticoagulation therapy using high-dose enoxaparin to achieve a therapeutic anti-Xa level has not been studied. We hypothesized that high-dose enoxaparin would reduce VT after pediatric cardiac surgery. MethodsEnoxaparin was administered to infants aged less than 150 days when postoperative CVC duration was anticipated to extend beyond 5 days. The primary outcome was the rate of VT, reexploration for bleeding, and postoperative red blood cell transfusions per 1000 CVC days. ResultsFrom 2012 to 2019, 157 infants were treated with enoxaparin. Infants were divided into two groups: (1) subtherapeutic (n = 51), in which therapeutic anti-Xa level (0.5 to 1.0 IU/mL) was not achieved; and (2) therapeutic (n = 106), in which therapeutic anti-Xa level was achieved. Baseline demographics demonstrated a lower age at operation in the therapeutic group. The subtherapeutic group had a higher VT rate per 1000 CVC days (8.2) compared with the therapeutic group (2.6; P = .005). Reexploration for bleeding was similar between groups. The number of postoperative red blood cell transfusions per 1000 CVC days was significantly greater in the subtherapeutic group (109.4 vs 81.6; P = .008). Multivariate analysis demonstrated that higher median anti-Xa levels reduced the risk of VT (odds ratio 0.02; 95% confidence interval, 0.001 to 0.63; P = .02). ConclusionsThese data suggest that enoxaparin treatment resulting in a therapeutic anti-Xa level reduces postoperative CVC-associated VT without increasing bleeding complications.