Dose Of Enoxaparin Research Articles

Bivalirudin vs. Enoxaparin in Intubated COVID-19 Patients: A Pilot Multicenter Randomized Controlled Trial.

(1) Background: In COVID-19 patients, the occurrence of thromboembolic complications contributes to disease progression and mortality. In patients at increased risk for thrombotic complications, therapeutic enoxaparin should be considered. However, critically ill COVID-19 patients could develop resistance to enoxaparin. Bivalirudin, a thrombin inhibitor, may be an alternative. This pilot multicenter randomized controlled trial aims to ascertain if bivalirudin may reduce the time spent under invasive mechanical ventilation, as compared to enoxaparin. (2) Methods: Intubated COVID-19 patients at risk for thrombo-embolic complications were randomized to receive therapeutic doses of enoxaparin or bivalirudin. We ascertained the time spent under invasive mechanical ventilation during the first 28 days from Intensive Care Unit (ICU) admission. A standardized weaning protocol was implemented in all centers. In addition, we assessed the occurrence of thromboembolic complications, the number of patients requiring percutaneous tracheostomy, the gas exchange, the reintubation rate, the ICU length of stay, the ICU and 28-days mortalities. (3) Results: We enrolled 58 consecutive patients. Bivalirudin did not reduce the time spent under invasive mechanical ventilation as compared to enoxaparin (12 [8; 13] vs. 13 [10; 15] days, respectively; p = 0.078). Thrombotic (p = 0.056) and embolic (p = 0.423) complications, need for tracheostomy (p = 0.423) or reintubation (p = 0.999), the ICU length of stay (p = 0.076) and mortality (p = 0.777) were also similar between treatments. Patients randomized to bivalirudin showed a higher oxygenation at day 7 and 15 after randomization, when compared to enoxaparin group. (4) Conclusions: In intubated COVID-19 patients at increased risk for thromboembolic complications, bivalirudin did not reduce the time spent under invasive mechanical ventilation, nor improved any other clinical outcomes.

S2992 Extensive Portomesenteric Venous Thrombosis Due to JAK2 V617F Mutation as an Indication for Multivisceral Transplantation

Introduction: Cavernous transformation of the portal vein (CTPV) involving periportal or intrahepatic venous collateral network is a sequelae of chronic portal vein thrombosis (PVT). This adaptation increases the risk of complications and poor outcomes from revascularization procedures. In cases with diffuse portomesenteric venous thrombosis, multivisceral transplantation (MT) may be indicated. Case Description/Methods: An otherwise healthy female was diagnosed with Janus kinase 2 V617F (JAK2) mutation at age 43 during work up for PVT of unknown etiology. Her disease progressed with bleeding esophageal varices, portal hypertensive gastropathy, and splenomegaly. Liver biopsy was negative for cirrhosis. Bone marrow biopsy was negative for leukemia or fibrosis. She developed mesenteric vein thrombosis (MVT) at age 45 and was started on rivaroxaban, but then transitioned to high dose enoxaparin due to worsening thrombus progression. At age 47 she underwent thrombolysis for new MVT. Four months later, on current presentation, she endorsed worsening abdominal pain. Physical exam demonstrated ascites and pitting lower extremity edema. Abdominal ultrasound with venous duplex demonstrated absent flow in the portal vein. Computed tomography angiography (CTA) revealed progressive portal, superior mesenteric, and splenic vein thromboses despite anticoagulation (AC) compliance. Transjugular intrahepatic portosystemic shunt (TIPS) procedure was unsuccessful. Post-procedure CTA demonstrated an enlarging hepatic hematoma treated by embolization (figure 1). AC was discontinued resulting in worsening clot burden and hepatic ischemia. Given the extent of clot burden, the patient was transferred to another facility for a MT. Discussion: Presented is a rare case of chronic PVT in a patient with JAK2 mutation leading to CTPV refractory to anticoagulation or endovascular intervention, eventually requiring MT. Though JAK2 is associated with myeloproliferative disorders, it is an independent risk factor for the development of PVT. With worsening thrombus chronicity and burden, cavernous transformation may occur which decreases the chance of successful TIPS. When organ ischemia develops due to extensive portomesenteric venous thrombosis, orthotopic liver transplantation is no longer an option. Multivisceral transplantation replaces the liver, small bowel, and other abdominal organs. Replacement of the thrombosed portomesenteric system may be the only recourse to reverse portal hypertension and address the primary disease.Figure 1.: Computed tomography angiography of hematoma in liver segments VII and VIII, demarcated by green lines. A complication from attempted portal vein access.

Low-Molecular-Weight Heparin Resistance and Its Viscoelastic Assessment in Critically Ill COVID-19 Patients.

Critically ill COVID-19 patients present an inflammatory and procoagulant status with a high rate of relevant macro- and microvascular thrombosis. Furthermore, high rates of heparin resistance have been described; yet, individualized anticoagulation by drug monitoring has not been sufficiently researched. We analyzed data from critically ill COVID-19 patients treated at Innsbruck Medical University Hospital with routinely adapted low-molecular-weight heparin (LMWH) doses according to anti-Xa peak levels, and regularly performed ClotPro analyses (a viscoelastic hemostatic whole blood test). A total of 509 anti-Xa peak measurements in 91 patients were categorized as below (<0.008 IU/mL/mg), within (0.008-0-012 IU/mL/mg) or above (> 0.012 IU/mL/mg) expected ranges with respect to the administered LMWH doses. Besides intergroup comparisons, correlations between anti-Xa levels and ClotPro clotting times (CTs) were performed (226 time points in 84 patients). Anti-Xa peak levels remained below the expected range in the majority of performed measurements (63.7%). Corresponding patients presented with higher C-reactive protein and D-dimer but lower antithrombin levels when compared with patients achieving or exceeding the expected range. Consequently, higher enoxaparin doses were applied in the sub-expected anti-Xa range group. Importantly, 47 (51.6%) patients switched between groups during their intensive care unit (ICU) stay. Anti-Xa levels correlated weakly with IN test CT and moderately with Russell's viper venom (RVV) test CT. Critically ill COVID-19 patients present with a high rate of LMWH resistance but with a variable LMWH response during their ICU stay. Therefore, LMWH-anti-Xa monitoring seems inevitable to achieve adequate target ranges. Furthermore, we propose the use of ClotPro's RVV test to assess the coagulation status during LMWH administration, as it correlates well with anti-Xa levels but more holistically reflects the coagulation cascade than anti-Xa activity alone.

Science, Medicine, and the Anesthesiologist

Science, Medicine, and the Anesthesiologist

Safety and Effectiveness of Reduced Dose Versus Standard Dose Enoxaparin Venous Thromboembolism Prophylaxis in Underweight Medically Ill Patients.

Background: Enoxaparin is commonly used for venous thromboembolism (VTE) prophylaxis in hospitalized patients. Published literature exists for dose adjustment in higher body weights and renal dysfunction, but sparse literature on optimal dosing of prophylactic enoxaparin in underweight patients exists. Objective: To determine if there is a difference in adverse outcomes or effectiveness if enoxaparin VTE prophylaxis dosing is reduced to 30 mg subcutaneously once daily from standard dosing in underweight medically ill patients. Methods: This study was a retrospective chart review of a total of 171 patients, with 190 individual courses of enoxaparin included. Patients were ≥18 years of age, weighed ≤50 kg, and were given at least 2 days of consecutive therapy. Patients were excluded if they were taking anticoagulation upon admission, had a creatinine clearance <30 mL/min, were admitted to the ICU or a trauma or surgical service, or presented with bleeding or thrombosis. The Padua score and a modified score from the IMPROVE trial were used to evaluate baseline thrombotic risk and bleeding risk, respectively. Bleeding events were classified using the Bleeding Academic Research Consortium criteria. Results: No difference was seen in baseline risk of bleeding or thrombosis when comparing the reduced and standard dosing groups. No differences were observed with rates of bleeding, thrombotic events, mortality, or 30-day readmission. Conclusion: Both reduced and standard dosing strategies appeared effective for VTE prophylaxis, but neither showed superiority in reducing bleeding events. Additional larger studies are needed to evaluate safety and effectiveness of reduced dose of enoxaparin in this patient population.

958 Enoxaparin Venous Thromboembolism Prophylaxis in Bariatric Surgery: A Best Evidence Topic Update

Abstract Aim To examine the literature and identify the best dosing regimen of enoxaparin for perioperative venous thromboembolism (VTE) prophylaxis in patients undergoing bariatric surgery. This presentation reviewed publications from 2015 to 2021 to determine whether previous recommendations based on a similar examination of evidence conducted in 2015 needed to be updated, considering new evidence. Method A literature search was conducted in accordance with a structured format. One hundred and one papers were identified using a standardised literature search from 2015 to 2021 on Medline and EMBASE using the same search terms “bariatric surgery” AND “venous thromboembolism” AND “enoxaparin”. The author, date and country of publication, patient groups and VTE prophylaxis strategy, level of evidence, outcomes, key results, and study weaknesses were tabulated. Results Three studies were selected as the best available evidence to answer the question. All three articles were non-randomised cohort studies analysing VTE and major bleeding rates following different bariatric thromboprophylaxis regimens. There was still no level 1 evidence available to answer this question. Conclusion Enoxaparin 40mg/day starting 12 hours after the operation, continuing for at least one-week post-discharge may be the best enoxaparin dosing regimen for VTE prophylaxis in bariatric surgery patients based on the best evidence available to 2021. New evidence suggests that the previously recommended 40mg enoxaparin twice daily for in-hospital patients may increase major bleeding risk. A Randomised Controlled Trial would probably require 3500 patients in each arm to identify the best enoxaparin dosing regimen.

Anti-factor X activity levels with continuous intravenous infusion and subcutaneous administration of enoxaparin after coronary artery bypass grafting: A randomized clinical trial.

Low-molecular-weight heparin enoxaparin is widely used in pharmacological thromboprophylaxis after coronary artery bypass grafting (CABG). The aim of this study was to compare anti-factor X activity (anti-Xa) levels when the thromboprophylactic dose of enoxaparin was provided after CABG, with two different administration routes: continuous intravenous infusion (CIV) and subcutaneous bolus (SCB) injection. We hypothesized that the current standard method of SCB administration might lead to lower anti-Xa levels than recommended in other patient groups, due to reduced bioavailability. In this prospective, randomized, controlled clinical trial, 40 patients scheduled for elective CABG were randomized to receive 40 mg of enoxaparin per day either as CIV or SCB for 72 h. Enoxaparin was initiated 6-10h after CABG. Anti-Xa levels were measured 12-14 times during the study period. The primary outcome, that is, the maximum anti-Xa concentration over 0-24 h (Cmax0-24h ), was calculated from these measured values. Secondary outcomes were Cmax25-72h and the trough concentration of anti-Xa after 72 h of enoxaparin initiation (C72h ). Twenty patients were randomized to the CIV-group and 19 to the SCB-group. The median anti-Xa Cmax0-24h was significantly lower in the CIV-group than in the SCB-group: 0.15 [interquartile range (IQR) 0.13-0.19] IU/ml versus 0.25 (IQR 0.18-0.32) IU/ml, p < .005. The median anti-Xa Cmax25-72h was 0.12 (IQR, 0.1-0.17) IU/ml versus 0.23 (IQR 0.19-0.31) IU/ml, respectively, p < .005. At 72 h, there was no difference between the groups in their anti-Xa levels. In this low-risk CABG patient population, SCB administration of a thromboprophylactic dose of enoxaparin provided anti-Xa levels that are considered sufficient for thromboprophylaxis in other patient groups. CIV administration resulted in lower anti-Xa levels compared to the SCB route.

WE6.9 Enoxaparin venous thromboembolism prophylaxis in bariatric surgery: A best evidence topic update

Abstract Aim To examine the literature and identify the best dosing regimen of enoxaparin for perioperative venous thromboembolism (VTE) prophylaxis in patients undergoing bariatric surgery. This presentation reviewed publications from 2015 to 2021 to determine whether previous recommendations based on a similar examination of evidence conducted in 2015 needed to be updated, considering new evidence. Method A literature search was conducted in accordance with a structured format. One hundred and one papers were identified using a standardised literature search from 2015 to 2021 on Medline and EMBASE using the same search terms “bariatric surgery” AND “venous thromboembolism” AND “enoxaparin”. The author, date and country of publication, patient groups and VTE prophylaxis strategy, level of evidence, outcomes, key results and study weaknesses were tabulated. Results Three studies were selected as the best available evidence to answer the question. All three articles were non-randomised cohort studies analysing VTE and major bleeding rates following different bariatric thromboprophylaxis regimens. There was still no level 1 evidence available to answer this question. Conclusion Enoxaparin 40mg/day starting 12 hours after the operation, continuing for at least one week post-discharge may be the best enoxaparin dosing regimen for VTE prophylaxis in bariatric surgery patients based on the best evidence available to 2021. New evidence suggests that the previously recommended 40mg enoxaparin twice daily for in-hospital patients may increase major bleeding risk. A Randomised Controlled Trial would probably require 3500 patients in each arm to identify the best enoxaparin dosing regimen.

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.

The use of enoxaparin as venous thromboembolism prophylaxis in bariatric surgery: A retrospective cohort study

IntroductionVenous thromboembolism (VTE) is one of the major causes of morbidity and mortality in bariatric patients. The use of low-molecular-weight heparin (LMWH), as enoxaparin, is considered one of the mainstays thromboprophylaxis regimens in postoperative bariatric patients. Despite the universal agreement on the importance of thromboprophylaxis in these patients, there are inadequate strong recommendations for its dosing and duration. The aim of our study is to explore the current practice on using enoxaparin in bariatric patients, as well as to assess both the efficacy and safety of varying dosing regimens. Material and methodsThis is a retrospective cohort study of morbidly obese patients who underwent bariatric procedure at a tertiary care hospital between 2016 and 2019. All adult patients who met the eligibility criteria for bariatric surgery and received enoxaparin with a minimum follow-up period of one month were included in our study. Participants with a history of coagulopathy, renal or hepatic insufficiency were excluded from the study. Data collected include patient demographics, VTE risk factors, and co-morbidities. The outcome of treatment failure was defined as the composite of either VTE or major bleeding. ResultsA total of 1,169 patients who underwent bariatric surgery were included in the study. The mean age was 35.54 years, with mean body mass index (BMI) of 45.78 kg/m2. The mean duration of enoxaparin use was 9 days, and the majority of patients (78%) received a prophylaxis dose of 40 mg subcutaneously (SC) once daily. The overall rate of VTE at 90 days was 1.4% while only 0.1% of patients developed major bleeding. There was no statistically significant difference in patients’ age, gender, BMI, or various enoxaparin dosing regimens between patients who developed VTE or bleeding versus patients who did not develop. Patient’s weight was the only statistically significant risk factor that directly correlated to higher risk of complications (P = 0.006). In the multivariable logistic regression model, higher BMI was significantly associated with treatment failure, either VTE or major bleeding [OR 1.05 (95% CI 1.0–1.09); P = 0.038]. ConclusionsThe rate of VTE or major bleeding did not differ in patients who received various enoxaparin regimens. Patients undergoing bariatric surgery may benefit from enoxaparin thromboprophylaxis dose of 40 mg SC daily for a total duration of 14 days, with higher doses may be needed for extremely obese patients. We recommend standardizing the current practice of VTE prophylaxis post bariatric surgery and unifying the optimal dose and duration.

Impact of Increased Enoxaparin Dosing on Anti-Xa Levels for Venous Thromboembolism Prophylaxis in Trauma Patients.

Venous thromboembolism (VTE) contributes to significant morbidity in trauma patients while increasing hospital costs and length of stay. Standard trauma prophylaxis dosing with enoxaparin 30mg twice daily may be inadequate to prevent VTEs. The objective of this study was to compare standard dosing of enoxaparin to an increased dose of enoxaparin 40mg twice daily for trauma patients. We hypothesized that increasing thromboprophylaxis dosing leads to an increase in therapeutic anti-Xa levels and reduced VTE rates. A retrospective study was performed from January 2020 to June 2021 at a Level I trauma center, following implementation of an increased enoxaparin dosing strategy. Patients with increased enoxaparin dosing were compared with those who received standard dosing. The primary outcome evaluated was the incidence of subtherapeutic anti-Xa levels. Secondary outcomes evaluated VTE rates and clinically significant bleed. A total of 204 trauma patients were identified. Ninety-one patients received an increased enoxaparin dose compared to 113 who received standard dosing. The baseline demographics of both groups were similar (P > .05). Subtherapeutic levels were higher with standard dosing compared to the increased dose (50 vs 22%, P = .003). Higher VTE rates were observed with standard dosing compared to higher dosing (6.2 vs 3.3%) but with a lower incidence of major bleed (1.8 vs 4.4%). Overall annual VTE rates decreased from 1.6 to 1.3% after implementation of the increased dosing regimen. This study demonstrated that an increased dosing strategy decreased rates of subtherapeutic anti-Xa levels and trended toward lower overall VTE rates in trauma.

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

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

A073 Analyzing the adequacy of BMI-tiered enoxaparin dosing for venous thromboembolism prophylaxis in the bariatric surgery population based on anti-factor Xa assay data

A073 Analyzing the adequacy of BMI-tiered enoxaparin dosing for venous thromboembolism prophylaxis in the bariatric surgery population based on anti-factor Xa assay data

Association of Changes in Antithrombin Activity Over Time With Responsiveness to Enoxaparin Prophylaxis and Risk of Trauma-Related Venous Thromboembolism

Venous thromboembolism (VTE) affects 2% to 20% of recovering trauma patients, despite aggressive prophylaxis with enoxaparin. Antithrombin is a primary circulating anticoagulant and crucial component of enoxaparin thromboprophylaxis. Approximately 20% of trauma patients present with antithrombin deficiency (antithrombin activity <80%). To examine time-dependent changes in antithrombin activity, responsiveness to enoxaparin, as measured by anti-factor Xa (anti-FXa) levels, and incidence of VTE after severe trauma and to assess the association of ex vivo antithrombin supplementation with patients' sensitivity to enoxaparin prophylaxis. This single-center, prospective cohort study was performed at a level 1 trauma center between January 7, 2019, and February 28, 2020. Adult trauma patients admitted to the trauma service at high risk for VTE, based on injury pattern and severity, were screened and enrolled. Patients who were older than 70 years, were pregnant, had a known immunologic or coagulation disorder, or were receiving prehospital anticoagulants were excluded. Blood samples were collected on emergency department arrival and daily for the first 8 days of hospitalization. Patients' antithrombin activity and anti-FXa levels were measured by a coagulation analyzer, and thrombin generation was measured by calibrated automated thrombography. Responsiveness to enoxaparin was assessed by measuring anti-FXa levels 4 to 6 hours after the first daily enoxaparin dose and compared between patients who developed VTE and who did not. In addition, the associations of ex vivo supplementation of antithrombin with plasma anti-FXa levels were assessed. Among 150 patients enrolled (median [IQR] age, 35 [27-53] years; 37 [24.7%] female and 113 [75.3%] male; 5 [3.3%] Asian, 32 [21.3%] Black, and 113 [75.3%] White; and 51 [34.0%] of Hispanic ethnicity), 28 (18.7%) developed VTE. Patients with VTE had significantly lower antithrombin activity on admission compared with patients without VTE (median [IQR], 91% [79%-104%] vs 100% [88%-112%]; P = .04), as well as lower antithrombin activity on hospital days 5 (median (IQR), 90% [83%-99%] vs 114% [99%-130%]; P = .011), 6 (median [IQR], 97% [81%-109%] vs 123% [104%-134%]; P = .003), 7 (median [IQR], 82% [74%-89%] vs 123% [110%-140%]; P < .001), and 8 (median [IQR], 99% [85%-100%] vs 123% [109%-146%]; P = .011). Anti-FXa levels were significantly lower in patients with VTE vs those without VTE at hospital day 4 (median [IQR], 0.10 [0.05-0.14] IU/mL vs 0.18 [0.13-0.23] IU/mL; P = .006), day 6 (median [IQR], 0.12 [0.08-0.14] IU/mL vs 0.22 [0.13-0.28] IU/mL; P = .02), and day 7 (median [IQR], 0.11 [0.08-0.12] IU/mL vs 0.21 [0.13, 0.28] IU/mL; P = .002). Multivariable analyses found that for every 10% decrease in antithrombin activity during the first 3 days, the risk of VTE increased 1.5-fold. The results of this cohort study suggest that after severe trauma, antithrombin deficiency is common and contributes to enoxaparin resistance and VTE. Interventional studies are necessary to determine the efficacy of antithrombin supplementation in the reduction of VTE incidence.

Standard Fixed Enoxaparin Dosing for Venous Thromboembolism Prophylaxis Leads to Low Peak Anti-Factor Xa Levels in Both Head and Neck and Breast Free Flap Patients.

Venous thromboembolism (VTE) is a serious complication, particularly in cancer patients undergoing free flap reconstruction. Subcutaneous enoxaparin is the conventional prophylaxis for VTE prevention, and serum anti-factor Xa (afXa) levels are being increasingly used to monitor enoxaparin activity. In this study, free flap patients receiving standard enoxaparin prophylaxis were prospectively followed to investigate postoperative afXa levels and 90-day VTE and bleeding-related complications. Patients undergoing free tissue transfer during an 8-month period were identified and prospectively followed. Patients received standard fixed enoxaparin dosing at 30 mg twice daily in head and neck (H&N) and 40 mg daily in breast reconstructions. Target peak prophylactic afXa range was 0.2 to 0.5 IU/mL. The primary outcome was the occurrence of 90-day postoperative VTE- and bleeding-related events. Independent predictors of afXa level and VTE incidence were analyzed for patients that met the inclusion criteria. Seventy-eight patients were prospectively followed. Four (5.1%) were diagnosed with VTE, and six (7.7%) experienced bleeding-related complications. The mean afXa levels in both VTE patients and bleeding patients were subprophylactic (0.13 ± 0.09 and 0.11 ± 0.07 IU/mL, respectively). Forty-six patients (21 breast, 25 H&N) had valid postoperative peak steady-state afXa levels. Among these, 15 (33%) patients achieved the target prophylactic range: 5 (33%) H&N and 10 (67%) breast patients. The mean afXa level for H&N patients was significantly lower than for breast patients (p = 0.0021). Patient total body weight was the sole negative predictor of afXa level (R 2 = 0.47, p < 0.0001). Standard fixed enoxaparin dosing for postoperative VTE prophylaxis does not achieve target afXa levels for the majority of our free flap patients. H&N patients appear to be a particularly high-risk group that may require a more personalized and aggressive approach. Total body weight is the sole negative predictor of afXa level, supporting a role for weight-based enoxaparin dosing.

P400 CLINICAL IMPACT OF PROPHYLACTIC ANTICOAGULANT TREATMENT WITH ENOXAPARIN IN CORONAVIRUS DISEASE 2019 (COVID–19)ELDERLY PATIENTS

IntroductionCOVID–19 patients are at increased risk of venous thromboembolism. The WHO/ISSrecommends daily prophylactic anticoagulation therapy with low–molecular weight heparins in COVID–19 patients. Our study evaluated the efficacy of a prophylactic therapy with enoxaparin on clinical outcomes in COVID–19 patients.MethodsThis is a retrospective analysis of 125 SARS–CoV–2 patients hospitalized from 16 MARCH 2020 to MAY 7th, 2021. In this phase of COVID–19 pandemic, man and woman in–patients and out–patients received enoxaparin either at prophilattics or therapeutic dosage. Based on these criteria, we examined 85 patients who received PROPHILATTICenoxaparin (group E, Enoxaparin) and 40 subjects undergone THERAPEUTIC Enoxaparin (group T, Therapeutic). Of them, 95 patients were hospitalized after Sars–Cov2 positive swab and 30 received prophilatic dosage at home.ResultsAfter applying a propensity score matching for age and gender, considering hospitalized patients, there were no significant differences between the two groups (E, T). During hospitalization, a significantly higher percentage of patients of E group developed ARDS (37 vs 13, p = 0.0001) and needed for non–invasive ventilation No significative difference between the two groups was found about incidence of intubation (20 in E vs. 19 in T group; p = 0.4) and pulmonary embolism (17 vs 5, p = 0.4). In–hospital death occurred in 17 E group patients and in 10 T group patients (p = 0.251). No difference on 30–days mortality was found between two groups (p = 0.287). N. 15 patients of T group experienced emorragic events and interrupted enoxaparin therapy. N. 17 of them experienced adverse events (mailny thrombocitopenia).ConclusionsAmong patients with SARS–CoV–2 infection, a therapeutic dose of enoxaparin is not associated with prognostic benefit and did not affect in–hospital and 30–days mortality. A risk–adapted approach to reduce the dose of anticoagulation agent should be considered in selected COVID–19 patients with evidence of coagulopathy. In summary, current data suggest the use of therapeutic–dose LMWH to reduce VTE, it, may increase bleeding, and should be avoided in hospitalized patients with severe COVID–19 in critical care settings.. Lastly, randomized trials in this patient population are still ongoing and novel antithrombotic strategies in critically ill COVID–19 patients are needed.

The efficacy of weight-based enoxaparin dosing for venous thromboembolism prophylaxis in trauma patients: A systematic review and meta-analysis.

Trauma patients are at high risk of developing venous thromboembolism (VTE), and standard dosing enoxaparin regimens may be inadequate for prophylaxis. This meta-analysis was performed to clarify the efficacy of alternative dosing regimens for VTE prophylaxis in this high-risk group. The objective of this systematic review was to review the evidence regarding weight-based dosing of enoxaparin for VTE prophylaxis in trauma patients. A systematic database search was undertaken for studies comparing standard versus weight-based dosing of enoxaparin for VTE prophylaxis in adult trauma patients, 18 years or older. The primary outcome was the achievement of anti-factor Xa (AFXa) levels within the prophylactic range. Secondary outcomes included subprophylactic AFXa levels, supraprophylactic AFXa levels, VTE incidence, and bleeding events. Meta-analysis was conducted using both fixed- and random-effects models, and presented as odds ratios, risk ratios (RRs), and risk differences (RDs) with 95% confidence intervals (CIs). Four cohort studies were eligible for inclusion. Compared with standard dosing, weight-based enoxaparin prophylaxis dosing was associated with increased odds of prophylactic AFXa levels (odds ratio, 5.85; 95% CI, 3.02-11.30; p < 0.00001) and reduced risk of subprophylactic AFXa levels (RR, 3.97; 95% CI, 3.02-5.22; p < 0.00001). Standard dosing was associated with a reduced risk of supratherapeutic AFXa levels (RR, 0.23; 95% CI, 0.11-0.50; p = 0.0002), but this was not associated with a difference in risk of bleeding events (RD, -0.00; 95% CI, -0.02 to 0.01; p = 0.55). There was no statistical difference in incidence VTE between the two groups (RD, 0.01; 95% CI, -0.02 to 0.03; p = 0.64). Compared with standard dosing, weight-based enoxaparin dosing regimens are associated with increased odds of prophylactic range AFXa levels. Further investigation is required to determine if this translates into improved VTE prophylaxis and reduced VTE incidence. Systematic Review and Meta-Analysis; Level III.

Idiopathic combined retinal vessels occlusion in a pregnant woman: a case report

BackgroundOcular vascular occlusion is an extremely rare event, especially in the young population. This diagnosis is always associated with active systemic diseases in young adults and needs thrombophilia workup. Nevertheless, we present the case of a pregnant woman suffering from idiopathic combined central retinal vein and cilioretinal artery occlusion.Case presentationA 36-year-old pregnant Iranian woman at the 36th week of her second pregnancy complained of subacute unilateral painless decreased vision of her left eye. She had experienced a transient vision loss that lasted several minutes, but attacks gradually became more frequent and finally persistent over a several-day period. Finally combined central retinal vein and cilioretinal artery occlusion was established. Her visual acuity improved to 4/10 in a month without any ocular intervention except for a short duration of prophylactic dose enoxaparin, and the acuity reached 8/10 without any complications in the third month follow-up visit. At 1 year follow-up, the visual acuity had not changed and no macular edema was seen.ConclusionsOcular vascular occlusion is extremely rare among young adults, and even rarer among pregnant women. According to this, any suspected retinal vascular event in this population should raise suspicion for underlying diseases such as hypertension, diabetes, autoimmune diseases, migraine, preeclampsia syndrome, and thrombophilia. However, as seen in this presented case, idiopathic ocular vascular occlusion events can occur also.

Outcomes of Prophylactic Enoxaparin Against Venous Thromboembolism in Hospitalized Children

To assess the biochemical and clinical outcomes of hospitalized children who received prophylactic enoxaparin. We conducted a retrospective observational study of hospitalized children aged <18 years who received prophylactic enoxaparin against hospital-acquired venous thromboembolism (HA-VTE). Weight-based enoxaparin dosing was administered using a pharmacy-driven protocol, which later included a low molecular weight, anti-Xa level directed-dose adjustment strategy. Primary biochemical and clinical outcomes were achievement of goal anti-Xa range of 0.2 to 0.5 IU/mL and development of HA-VTE, respectively. Secondary clinical outcome was development of clinically relevant bleed. We analyzed 194 children with 13 (6.7%) infants aged <1 year and 181 (93.3%) older children aged ≥1 year. After the initial dose, only 1 (11.1%) infant, but 62 (57.9%) older children, achieved goal. Median number of anti-Xa levels until goal was 2 (interquartile range: 2-3) in infants and 1 (interquartile range: 1-2) in older children (P = .01). HA-VTE developed in 2 (15.4%) infants and 9 (5.0%) older children. Among children with anti-Xa level, HA-VTE developed less frequently in children who achieved (2.1%) than in those who did not achieve (13.6%) goal (P = .046). A total of 4 (2.1%) older children and no infants developed clinically relevant bleed. Among children with anti-Xa level, frequency of bleeding was comparable between children who did (3.2%) and did not achieve (0%) goal (P >.99). Our findings suggest the effectiveness and safety of an anti-Xa level directed strategy of prophylactic enoxaparin. However, this strategy should be investigated in prospective controlled studies.

WEIGHT-BASED DOSING OF ENOXAPARIN AND ANTIFACTOR XA LEVELS FOR VENOUS THROMBOEMBOLISM PROPHYLAXIS IN MEDICALLY-ILL PATIENTS

Objective: The objective of the study was to evaluate peak antifactor Xa (aFXa) levels in low-weight patients receiving enoxaparin for VTE prophylaxis. Methods: Retrospective cohort of adult patients weighing &lt;55 kg who was hospitalized at tertiary care Center between January 2019 through February 2020. All patients received enoxaparin for VTE prophylaxis with a peak aFXa level drawn. The primary end point was the proportion of patients achieving peak aFXa levels within the goal range of 0.2–0.5 units/ml. Results: Of 65 patients receiving enoxaparin for VTE prophylaxis with an appropriately timed peak aFXa level, 74% achieved goal peak aFXa levels and the median daily dose of enoxaparin was 30 mg. The mean weight was about 44 kg. No significant correlations between aFXa level and body mass index or body weight were found. Conclusion: A lower dose of enoxaparin may be reasonable in low-weight patients for VTE prophylaxis. There appears to be no safety concerns with reduced enoxaparin dosing in low-weight patients. More robust data are needed to confirm these findings.