anti-Xa Levels Research Articles

Effectiveness of Body Mass Index–Based Prophylactic Enoxaparin Dosing in Bariatric Surgery Patients

IntroductionEnoxaparin is administered for venous thromboembolic (VTE) prophylaxis in bariatric surgery patients. There is concern whether body mass index (BMI)-based enoxaparin dosing consistently achieves prophylactic targets in patients with severe obesity. MethodsThis retrospective study included patients who underwent bariatric surgery at an academic medical center from Jan 2015-May 2021 and had an anti-Xa level drawn 2.5-6 h after ≥3 doses of BMI-based prophylactic enoxaparin. The primary outcome was the percentage of patients who achieved a target anti-Xa level. Secondary outcomes were prevalence of venous thromboembolic and bleeding events within 30 d post-operatively. ResultsOverall, 137 patients were included. Mean BMI was 59.1 ± 10.4 kg/m2, mean age was 43.9 ± 13.3 y and 110 patients (80.3%) were female. Target anti-Xa levels were achieved in 116 patients (84.7%); 14 (10.2%) were above target and 7 (5.1%) were below target. Patients with above target anti-Xa levels were significantly shorter in height than those within target range (167.1 versus 159.8 cm, P = 0.003). Five patients (3.6%) had a bleeding event; no thromboembolisms occurred. Anti-Xa levels correlated more strongly with enoxaparin dose per unit estimated blood volume (EBV) than dose per unit BMI (Rho = 0.54 versus Rho = 0.33). ConclusionsTarget range anti-Xa levels were achieved in 85% of patients using BMI-based enoxaparin dosing. Patients with above target anti-Xa levels were significantly shorter by nearly 3 inches, suggesting an increased risk of overdosing enoxaparin in shorter, obese patients. An EBV-based dosing regimen may better account for patient height and is supported by a greater correlation with anti-Xa levels with dosing based on EBV than BMI.

Single-Bolus Tinzaparin Anticoagulation in Extended Hemodialysis Session: A Feasibility Study.

Few studies have assessed the use of low-molecular weight heparins for anticoagulation during extended hemodialysis sessions. This study aimed to evaluate the efficacy of a single-bolus of tinzaparin for anticoagulation of the extracorporeal circuit and dialyzer in 8-hour hemodialysis sessions. This single-center study included all patients who underwent a single 8-hour simulation session as part of their nocturnal home hemodialysis training between 2009 and 2020. Tinzaparin was delivered as a single bolus injection at time 0 with dosing based on doubling of standard 4-hour session dose. Tinzaparin efficacy was examined via visual observations (score 1-4) of the dialyzer and venous bubble trap at the end of dialysis, and using anti-Xa measured at 15-, 30-minute and 1-, 2-, 4-, 6-, 8-hour after hemodialysis start. Forty-seven patients were included. Mean tinzaparin dose was 107 ± 20 IU/Kg. Anti-Xa levels peaked at 15-minutes with 1.3 ± 0.4 IU/mL and progressively declined reaching 0.9 ± 0.3 IU/mL at 1-hour, 0.4 ± 0.21 IU/mL at 4-hour, and 0.15 ± 0.15 IU/mL at 8-hour. After the 8-hour session, none of the patients had severe clotting of their dialyzer or venous chamber. Moderate blood clotting was observed in the dialyzer of 6 (20%) patients and in the venous chamber of 22 (61%) patients. Based on the simulation results, tinzaparin dose was increased in 27 (58%) patients with a mean home-discharge dose of 123 ± 28 IU/Kg. This study shows that anti-Xa levels stabilized rapidly after administration on tinzaparin for 8-hour hemodialysis. Administration of a single bolus tinzaparin at the start of an 8-hour dialysis session appeared effective, although dose adjustment may be required.

Low Early Antifactor Xa Target Achievement Rate of Low-Molecular-Weight Heparin for Treating Venous Thromboembolism in Patients in Intensive Care.

This study aimed to evaluate whether early antifactor Xa (anti-Xa) achieved the target range when venous thromboembolism (VTE) was treated with low-molecular-weight heparin (LMWH), based on body weight and renal function in patients treated in intensive care units (ICUs). Anti-Xa levels in patients treated with LMWH for VTE in ICU and medical wards between January 1,2021, and June 30,2022, were retrospectively assessed. The demographics, laboratory parameters, and early anti-Xa peak levels of patients were collected. All patients were followed up for 3months to collect VTE recurrence/bleeding events. Univariate and multivariate linear regression analyses were used to identify the factors affecting anti-Xa levels. A total of 108 patients were enrolled in this study, including 70 patients in ICU and 38 patients on medical wards. The early anti-Xa level (0.36 vs 0.61IU/mL, P<.001) and target achievement rate (21.4% vs 39.5%, P=.015) of patients in ICU were lower than those in medical wards. Multivariate linear regression showed that only antithrombin (AT) significantly affected anti-Xa levels in patients in ICU (β=0.008, 95%CI 0.005 to 0.011, P<.001). There was no significant difference in VTE recurrence events (11.8% vs 7.5%, P=.628) and bleeding events (29.4% vs 17.0%, P=.304) between the early anti-Xa within-target group and the early anti-Xa below-target group. Low anti-Xa peak levels are common in patients in ICU. AT activity should be monitored when using LMWH in critically ill patients.

Residual anti-Xa activity in plasma of patients presenting for electively planned neuraxial regional anesthesia

ObjectiveTo determine the incidence of increased anti-Xa activity within plasma levels 24 hours after administration of therapeutic dose low-molecular-weight heparin in patients presenting for elective neuraxial anesthesia.BackgroundGuidelines for neuroaxial regional...

Cerebral venous thrombosis and B12 deficiency

Infants with prematurity and necrotizing enterocolitis (NEC) are at increased risk for short bowel syndrome and subsequent nutritional deficiencies. In particular, ileal resection is associated with vitamin B12 malabsorption, which interferes with normal myelination and homocysteine metabolism.1, 2 Vitamin B12 deficiency is associated with neurodevelopmental delay as well as hyperhomocysteinemia, which increases the risk for venous thrombosis.2, 3 This eight-year-old boy presented with severe headache, dehydration, and lethargy. He developed acute onset severe frontal headache followed by decreased oral intake, decreased urine output, and recurrent vomiting. The headache was dull and radiating to the back of his head. At the same time, he appeared to be sleepy and less active. These symptoms lasted for two to three days before he was brought to the primary doctor's office and then referred to the emergency department. On assessment, he was tired-looking and exhibited mild microcephaly, but his neurological examination was normal, as was an examination by an ophthalmologist. He experienced mild global developmental delay. He was born at 25 weeks gestational age and had a prolonged stay in the neonatal intensive care unit, complicated by NEC and a hemicolectomy with ileostomy and removal of ileocecal valve. He had low normal levels of B12 for several years prior to presentation and was not treated (151 pg/ml after surgery [normal 160-950]). Brain magnetic resonance imaging and magnetic resonance venography (MRV) showed filling defects in the inferior sagittal, straight, torcula, and proximal transverse sinuses consistent with cerebral venous sinus thrombosis (CVST) with no evidence of acute infarction (Figure 1). Dehydration was initially considered to be the cause. Enoxaparin sodium was started at 1 mg/kg every 12 h with the goal of anti-Xa level between 0.5 and 1.0 U/ml. The hypercoagulation evaluation was normal. The B12 level was 86 pg/ml. His hematocrit was 33.3, and his mean corpuscular volume (MCV) was 87.4. He was not treated at that time. He was discharged within a week after the repeat imaging remained stable with the goal to continue enoxaparin sodium for three months. After three months, he again developed headache and lethargy, and MRV showed a new thrombus. Enoxaparin was switched to warfarin. After a year of warfarin, the clot resolved but he still had headaches. Two B12 levels were obtained, both below 200. His anemia worsened (hematocrit 24.7) and his MCV increased to 96.9. The homocysteine level was 184 μmol/L (normal <11.4). At this point, he began B12 injections (1000 mcg daily for one week followed by monthly and then quarterly injections thereafter). His B12 levels normalized and remained normal throughout his course. The warfarin was discontinued and thrombus has not recurred. Our patient had a difficult-to-treat CVST secondary to a condition predisposing to nutritional deficiency. His chronic B12 deficiency was overlooked by his treating physicians until he presented with a profound deficiency with megaloblastic anemia. The association between B12 deficiency and CVST has been described in children with nutritional deficiency and megaloblastic anemia.4 Previous authors suggested that testing for hyperhomocysteinemia and with B12 supplementation should be considered in pediatric patients with CVST.5 The diagnosis becomes even more crucial in patients with conditions known that promote nutritional deficiencies, such as a history of NEC and ileal surgery. In such children, early recognition of vitamin B12 deficiency and timely vitamin supplementation may prevent the occurrence of CVST as well as other manifestations of B12 deficiency, such as developmental delay.6, 7 In this patient, the B12 deficiency was chronic. While it is difficult to prove that the deficiency caused the CVST, it likley played a substantial role. Hyperhomocysteinemia can damage the vascular endothelium, predisposing to thrombus formation.8, 9 Consequently, vitamin B12 deficiency is a potential risk factor in children with CVST. Fatemeh Mohammadpour Touserkani: Conceptualization; supervision; writing – original draft; writing – review and editing. Theodora Andriotis: Conceptualization; investigation; writing – original draft; writing – review and editing. Yaoping Zhang: Conceptualization; supervision; writing – original draft; writing – review and editing. Steven Pavlakis: Conceptualization; supervision; writing – original draft; writing – review and editing. We would like to thank the patient's parents for their consent for this publication. The authors declare no conflict of interest.

Monitoring anti-Xa Levels to Optimize Low-Molecular-Weight-Heparin Thromboprophylaxis in High-Risk Hospitalized Patients: A Stratified Meta-Analysis.

It is uncertain whether monitoring or targeting anti-Xa levels is necessary when using low-molecular-weight-heparin (LMWH) to prevent venous thromboembolism (VTE). This stratified meta-analysis assessed whether monitoring trough or peak anti-Xa levels with LMWH dosing would reduce risk of VTE. Twelve non-randomized studies involving 3604 hospitalized patients met the inclusion criteria and were subject to meta-analysis. Eight studies assessed the association between VTE and peak anti-Xa levels (between .2 and .5 IU/ml) and four studies assessed the benefits of targeting the trough anti-Xa levels (>.1 IU/ml). Achieving an adequate peak or trough anti-Xa level was associated with a reduced risk of VTE (random-effects model odds ratio [OR] .52, 95% confidence interval [CI] .34-.77; P = .001, I2 = 30% and P-value for heterogeneity = .171) compared with using a fixed standard dose of LMWH. Targeting the trough level (OR .40, 95%CI 0.22-.75, P = .004) appeared to be more effective than targeting the peak level (OR .62, 95%CI 0.37-1.03, P = .066), although a formal interaction analysis did not confirm they were statistically different (ratio of ORs = 1.52, 95%CI 0.68-3.40; z score = 1.03, P = .306). Targeting a higher anti-Xa level did not appear to increase the risk of bleeding or transfusion (OR 1.20, 95%CI 0.46-3.17, P = .707).

Evaluation of anti-Xa levels in patients with venous thromboembolism within the first 48 h of anticoagulation with unfractionated heparin.

Background: A 2019 study by Prucnal and colleagues found that the majority of patients treated with unfractionated heparin for pulmonary embolism did not maintain therapeutic activated partial thromboplastin time levels during the first 48 h of therapy. Objective: The purpose of this study was to evaluate the ability of an institution's unfractionated heparin dosing protocol to achieve and maintain therapeutic anti-Xa levels within the first 48 h of therapy in patients with venous thromboembolism. Methods: This retrospective study included 205 patients from May 2016 through September 2020. Patients were divided into two cohorts: bolus plus infusion (N = 89) and infusion only (N = 116). The primary objective was to determine the number of patients who achieved at least one therapeutic level. Results: Overall, 200 patients (97.6%) had at least one therapeutic level with no statistically significant difference between cohorts (p = 0.65). No more than 60% of patients achieved a therapeutic level at any of the 6-h intervals throughout the timeframe. The median time to the first therapeutic level in the overall group was 12.8 h with no statistically significant difference between the bolus plus infusion and infusion-only cohorts (13.3 h versus 12.7 h, respectively, p = 0.48). Conclusions: Most patients were able to achieve at least one therapeutic level within the first 48 h, but fewer were able to maintain therapeutic levels. Further studies are warranted to determine whether alternative dosing strategies would yield consistent achievement of therapeutic levels and affect patient-oriented outcomes.

Dose adjusted prophylactic lovenox dosing in hepatic surgery

Background: Recommended prophylactic doses of enoxaparin are often associated with sub-prophylactic anti-Factor Xa (anti-Xa) levels. This study examines the safety and efficacy of using anti-Xa levels to achieve prophylactic enoxaparin levels in patients who underwent major hepatic surgery.

Comparison of postpartum anti-xa levels following enoxaparin administration to prevent venous thromboembolism using two protocols

Comparison of postpartum anti-xa levels following enoxaparin administration to prevent venous thromboembolism using two protocols

Venous thromboembolism in burn patients – low incidence or underdiagnosis?

Venous thromboembolism (VTE), essentially deep venous thrombosis and pulmonary embolism, urinary tract infection, and renal failure are the main unplanned hospital events with negative long-term impact on burn patients’ rehabilitation. Due to the hypercoagulable state induced by severe critical burns, either in the acute or recovery phase and the intimal vascular damage, the risk of VTE is increased, with an incidence varying from 0.4% to almost 60%. Other risk factors for VTE in burn patients are prolonged immobilization, long and multiple surgical interventions, central venous catheterization, wound infection and sepsis, extensive burns, and red blood cell transfusion. To avoid underdiagnosing VTE, in face of increased incidence of asymptomatic venous thromboembolism, high risk-patients should be routinely screened using Doppler ultrasound. Patients’ weight and burn size, as well as the high incidence of heparin resistance in the first weeks after injury, should be considered when establishing the optimal dose for venous thromboembolism prophylaxis, targeting an anti-Xa level of 0.2-0.5 IU/mL.

Anticoagulation for mechanical heart valves during pregnancy: A case report and a literature review

Most previous treatment guidelines for pregnant women with mechanical heart valves recommend that low molecular weight heparin (LMWH) should be applied once every 12 hours and only as required to reach peak anti-Xa levels of approximately 1.0 to 1.2 IU/mL, but it is commonly associated with subtherapeutic trough levels, consequently with an inadequate level of anticoagulation. Our case report here together with a literature review suggests that dose-adjusted (Target trough anti-Xa levels of 0.6 to 0.7 IU/mL and with peak anti-Xa levels of around 1.0 to 1.2 IU/mL or < 1.5 IU/mL) LMWH should be given thrice daily throughout pregnancy. In addition, the findings of this rare case indicate that a combination of LMWH and warfarin is effective in the treatment of small thromboses in pregnancy. In the 1st trimester of pregnancy, a 28-year old pregnant female with a mechanical valve had a significant increase in the aortic valve flow rate and suspected mechanical valve thrombosis. The peak velocity of the pregnant female aortic mechanical valve increased, and mechanical valve thrombosis was suspected. We adjusted the enoxaparin sodium dose every 12 hours to 1 injection every 8 hours, with a total daily dose of 160 mL. Based on the original application of LMWH, warfarin (3 mg/day) was recommended. The pregnant woman delivered a live baby by cesarean section, and the peak flow velocity of the mechanical valve in the aortic position was reduced to nearly equivalent to the patient's pre-pregnancy status. The mother and the baby were in good health at the time of discharge. LMWH is administered twice daily, and anti-Xa trough levels are mostly in a subtherapeutic state, which may lead to insufficient anticoagulation and thrombosis. Dose-adjusted LMWH thrice daily throughout pregnancy is the recommended treatment for pregnant women with mechanical heart valves. The combination of LMWH and warfarin exhibited good efficacy for the treatment of small thromboses.

Low and Highly Variable Exposure to Prophylactic LMWH Nadroparin in Critically Ill Patients: Back to the Drawing Board for Prophylactic Dosing?

Low-molecular-weight heparins are routinely administered to patients in the intensive care unit to prevent venous thromboembolisms. There is considerable evidence that low-molecular-weight heparin doses should be personalised based on anti-Xa levels, but pharmacokinetic data in intensive care unit patients are lacking. This study aimed to characterise the pharmacokinetics and associated variability of the low-molecular-weight heparin nadroparin in critically ill patients. Critically ill adult patients who were admitted to the intensive care unit and received nadroparin for prophylaxis of venous thromboembolism were included in a study. Population pharmacokinetic analysis was performed by means of parametric non-linear mixed-effects modelling (NONMEM). A total of 30 patients were enrolled with 12 patients undergoing continuous veno-venous hemodialysis and 18 patients not undergoing continuous veno-venous hemodialysis. Very high variability in pharmacokinetics was observed with an inter-individual variability in the volume of distribution of 63.7% (95% confidence interval 46.5-90.6), clearance of 166% (95% confidence interval 84.7-280) and relative bioavailability of 40.2% (95% confidence interval 29.5-52.6). We found that standard doses of 2850 IE and 5700 IE of nadroparin resulted in sub-prophylactic exposure in critically ill patients. Low exposure and highly variable pharmacokinetics of nadroparin were observed in intensive care unit patients treated with a prophylactic dose. It can be debated whether nadroparin is currently dosed optimally in intensive care unit patients and our findings encourage the investigation of higher and tailored dosing of nadroparin in the critically ill.

Single-Center Experience Using the Cardiohelp System for Neonatal and Pediatric Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) systems have continued to evolve and improve with the development of smaller and portable systems. The Cardiohelp (Maquet Getinge Cardiopulmonary AG, Rastatt, Germany) portable life support device is a compact ECMO system used widely in adults and for ECMO transport. Reports of its use in neonatal and pediatric centers remain limited. In this single-center retrospective review, we describe our institutional experience with the Cardiohelp. Single-center retrospective review. Neonatal ICUs and PICUs in a tertiary-care children's hospital. Seventeen pediatric patients on ECMO. None. Median (interquartile range, IQR) of patient age was 0.5 years (0-7 yr). Eleven of 17 patients were on veno-arterial ECMO, five on veno-venous ECMO, and one on veno-venoarterial ECMO. All veno-venous and veno-venoarterial runs ( n = 6) were accomplished with bicaval, dual-lumen cannulae. Median duration on Cardiohelp was 113 hours (IQR 50-140 hr). Median anti-Xa level for patients was 0.43 IU/mL (IQR 0.35-0.47 IU/mL), with median heparin dose of 23.6 U/kg/hr (IQR 17.6-28.1 U/kg/hr). Median plasma-free hemoglobin was 41.4 mg/dL (IQR 30-60 mg/dL). Circuit change was required in three cases. Fourteen patients survived ECMO, with 13 patients surviving to discharge. We have used the Cardiohelp system to support 17 neonatal and pediatric ECMO patients, without complications. Further studies are warranted to compare complications, outcomes, and overall cost with other institutions and other existing ECMO systems.

Population pharmacokinetics of nadroparin for thromboprophylaxis in COVID-19 intensive care unit patients.

Nadroparin is administered to COVID-19 intensive care unit (ICU) patients as thromboprophylaxis. Despite existing population pharmacokinetic (PK) models for nadroparin in literature, the population PK of nadroparin in COVID-19 ICU patients is unknown. Moreover, optimal dosing regimens achieving anti-Xa target levels (0.3-0.7IU/mL) are unknown. Therefore, a population PK analysis was conducted to investigate different dosing regimens of nadroparin in COVID-19 ICU patients. Anti-Xa levels (n= 280) from COVID-19 ICU patients (n= 65) receiving twice daily (BID) 5700 IU of subcutaneous nadroparin were collected to perform a population PK analysis with NONMEM v7.4.1. Using Monte Carlo simulations (n= 1000), predefined dosing regimens were evaluated. A 1-compartment model with an absorption compartment adequately described the measured anti-Xa levels with interindividual variability estimated for clearance (CL). Inflammation parameters C-reactive protein, D-dimer and estimated glomerular filtration rate based on the Chronic Kidney Disease Epidemiology Collaboration equation allowed to explain the interindividual variability of CL. Moreover, CL was decreased in patients receiving corticosteroids (22.5%) and vasopressors (25.1%). Monte Carlo simulations demonstrated that 5700 IU BID was the most optimal dosing regimen of the simulated regimens for achieving prespecified steady-state t= 4h anti-Xa levels with 56.7% on target (0.3-0.7IU/mL). In our study, clearance of nadroparin is associated with an increase in inflammation parameters, use of corticosteroids, vasopression and renal clearance in critically ill patients. Furthermore, of the simulated regimens, targeted anti-Xa levels were most adequately achieved with a dosing regimen of 5700 IU BID. Future studies are needed to elucidate the underlying mechanisms of found covariate relationships.

748: EVALUATION OF ANTI-XA TARGET ATTAINMENT WITH PROPHYLACTIC ENOXAPARIN DOSING REGIMENS IN OBESITY

Introduction: Venous thromboembolism (VTE) is a common complication among hospitalized patients, especially among the critically ill. Obesity doubles the risk of a patient experiencing a VTE event during their hospitalization. To combat this increased risk pharmacologic prophylaxis with enoxaparin is commonly utilized. The optimal dosing strategy for enoxaparin in morbidly obese patients is currently unknown. Previous studies have demonstrated a negative correlation between body weight and anti-Xa activity and enoxaparin 40 mg daily resulted in subtherapeutic anti-Xa levels in 82% of patients. The objective of this study was to assess anti-Xa target attainment in patients receiving enoxaparin at a dose of 40 mg twice daily, 60 mg twice daily, or 0.5 mg/kg twice daily. Methods: This study was a single-center retrospective cohort study of critically ill patients with a BMI ≥ 40 kg/m2 receiving prophylactic enoxaparin at a dose of 40 mg twice daily, 60 mg twice daily, or 0.5 mg/kg twice daily. The primary outcome was attainment of a target anti-Xa level (0.2-0.5 IU/mL). Secondary outcomes included the incidence of VTE, major bleeding, subtherapeutic anti-Xa, and supratherapeutic anti-Xa. Results: Sixty-five patients were evaluated, and four patients were excluded. Twenty-eight patients received 40 mg twice daily, twenty-two patients received 60 mg twice daily, and eleven patients received 0.5 mg/kg twice daily. Target anti-Xa levels were achieved more often among patients receiving 0.5 mg/kg twice daily compared to both 60 mg twice daily and 40 mg twice daily (100% versus 59.1% versus 21.4%, p < 0.001). VTE was rare occurring in one patient receiving 60 mg twice daily. Major bleeding occurred in three patients, two were receiving 60 mg twice daily and one was receiving 40 mg twice daily. Conclusions: Among morbidly obese ICU patients, enoxaparin 0.5 mg/kg twice daily was associated with a significantly greater rate of anti-Xa target attainment. This indicates that an aggressive, weight-based dosing method may be optimal among morbidly obese critical care patients. Future studies are necessary to determine the impact of this dosing regimen on clinically relevant outcomes.

Evaluation of Anti-Factor Xa Level Usage for Low Molecular Weight Heparin in a Healthcare System

Background: Low-molecular-weight heparin (LMWH) is a commonly used anticoagulant for treatment of venous thromboembolism (VTE). Routine monitoring of therapeutic effects through anti-Xa levels is not recommended but may be beneficial in patients with altered pharmacokinetics.1,2 Inappropriate monitoring leads to excessive testing and premature dose adjustments, compromising safety and efficacy. The purpose of this project was to assess appropriateness of monitoring LMWH anti-Xa levels and identify opportunities to optimize utilization within a community health system.

Anti-factor Xa vs aPTT for heparin monitoring in extracorporeal membrane oxygenation.

The goal of this study was to evaluate the correlation of anti-factor Xa (anti-Xa) and activated partial thromboplastin time (aPTT) measures with heparin dosing in adult patients on extracorporeal membrane oxygenation (ECMO) support. This was a retrospective cohort study evaluating adult patients managed on ECMO for at least 24 hours who received unfractionated heparin for systemic anticoagulation and were monitored per protocol using anti-Xa and/or aPTT coagulation assays. The primary outcome was the correlation between aPTT and anti-Xa measures. The secondary outcomes included, but were not limited to, the number of hemorrhagic and thrombotic events. Twenty-seven patients were included in this study. In the 227 events where both laboratory values were collected, a weak correlation was found between anti-Xa and aPTT (Spearman's correlation coefficient = 0.4, P = 0). In the 12 hemorrhagic events that occurred, aPTT was collected for only 10 events. Fifty percent of those events were associated with supratherapeutic aPTT, while none of the hemorrhagic events were associated with a supratherapeutic anti-Xa level. Two thrombotic events occurred, one of which had subtherapeutic anti-Xa and aPTT and the other of which had neither an anti-Xa nor aPTT measure on the day the event occurred. In a population of patients on ECMO, many of whom had coronavirus disease 2019 (COVID-19), there was a weak association between aPTT and anti-Xa measures. Hemorrhagic evens were more common than thrombotic events; however, a relationship between these events and aPTT or anti-Xa levels was not determined. The applicability of these findings to an ECMO population without COVID-19 is unknown and will require further study.

Rate of prophylactic anti-Xa achievement and impact on venous thromboembolism following oncologic hepato-pancreatico-biliary surgery: A prospective cohort study

BackgroundHepato-pancreatico-biliary (HPB) patients experience competing risk of venous thromboembolism (VTE) and bleeding. We sought to evaluate the effect of anti-Xa levels on VTE and bleeding, and to characterize factors associated with subprophylaxis. MethodsThis prospective cohort study evaluated adult HPB surgical patients; cohorts were described by anti-Xa levels as subprophylactic (<0.2 IU/mL), prophylactic (0.2–0.5 IU/mL), and supraprophylactic (>0.5 IU/mL). Primary outcome evaluated bleeding and VTE complications. Secondary outcomes evaluated factors associated with subprophylaxis. ResultsWe included 157 patients: 68 (43.6%) attained prophylactic anti-Xa and 89 (56.7%) were subprophylactic. Subprophylactic patients experienced more VTE compared to prophylactic patients (6.9% vs 0%; p = 0.028) without differences in bleeding complications (14.6% vs 5.9%; p = 0.081). Factors associated with subprophylactic anti-Xa included female sex (OR 2.90, p = 0.008), and Caprini score (OR 1.30, p = 0.035). Enoxaparin was protective against subprophylaxis compared to tinzaparin (OR 0.43, p = 0.029). ConclusionsMany HPB patients have subprophylactic anti-Xa levels, placing them at risk of VTE. Enoxaparin may be preferential, however, studies evaluating optimized prophylaxis are needed.

Tinzaparin for venous thromboembolism in patients with renal impairment: a single-centre, prospective pilot study.

Low molecular weight heparins (LMWH) are used extensively for prophylaxis and treatment of venous thromboembolism (VTE), bridging therapy for warfarin and standard of care in cancer-associated VTE (CA-VTE). Tinzaparin has the highest molecular weight of all LMWH and relies least on renal clearance to Cockcroft-Gault creatinine clearance (CrCl) of 20 mL/min. Previous pharmacological studies have demonstrated safety and effectiveness in elderly patients. Prospective clinical trials have confirmed these findings to CrCl 20 mL/min and in CA-VTE. We describe the pilot program developed at Concord Repatriation General Hospital for tinzaparin. We aim to confirm the deliverability of tinzaparin in patients with renal insufficiency. Twenty patients were established on tinzaparin as therapeutic anticoagulation with CrCl or CKD-EPI estimated glomerular filtration rate (eGFR) 20-50 mL/min with an indication for anticoagulation. Tinzaparin was given as a subcutaneous injection at 175 units/kg as a single daily dose, rounded to the nearest vial size. Tinzaparin anti-Xa levels were tested at Days 2, 7 and 14 (±1 day) and transition to oral anticoagulants were allowed at clinician discretion. No accumulation of tinzaparin was seen into Day 14. Two patients required dose-adjustment, five patients had bleeding complications (two major, three minor) and four patients died during follow-up, all attributable to patients' comorbidities. CrCl and body surface area-standardised CrCl were significantly correlated with tinzaparin anti-Xa level only on Day 2, and this effect was lost when patients with CrCl >50 mL/min were excluded. Data from our cohort confirm the deliverability of therapeutic tinzaparin in patients with CrCl or CKD-EPI eGFR 20-50 mL/min. Bleeding and death outcomes were also comparable to other trials using tinzaparin in CA-VTE. For patients with renal insufficiency, tinzaparin represents an attractive alternative anticoagulant with once-daily administration in a range of potential indications.

An Evaluation of Time to Therapeutic Range of Intravenous Unfractionated Heparin After Transitioning From Direct Oral Factor Xa Inhibitors.

Purpose: Direct oral factor Xa inhibitors (Xa inhibitor) may falsely elevate anti-Xa assays, creating a challenge when patients transition from Xa inhibitors to intravenous unfractionated heparin (IV UFH). This study compared the time to therapeutic anti-Xa range in patients transitioning from Xa inhibitors to IV UFH to those not previously anticoagulated and initiated on IV UFH. Methods: This single-center, retrospective study included adults receiving IV UFH from August 2018 through August 2019. The study group received apixaban or rivaroxaban prior to the initiation of IV UFH, and the control group was not previously anticoagulated. The primary outcome was the time to reach therapeutic range. Secondary outcomes included the number of anti-Xa levels drawn to reach therapeutic range, incidence of treatment failure, and incidence of major bleeding episodes. Categorical and continuous data were analyzed with chi-square and Mann-Whitney U tests, respectively. Results: The time to reach therapeutic range was a median of 18.5 hours in the study group (IQR 14.9-26.9) compared to 7.3 hours (IQR 5.9-14.7) in the control group (P < .001). Two anti-Xa levels were drawn in the study group (IQR 1-4) compared to 1 (IQR 1-2) in the control group (P < .001). There was no difference in the incidence of treatment failures (P = .981) or major bleeding episodes (P = .972). Conclusions: In patients transitioning from Xa inhibitors to IV UFH, the time to therapeutic range was longer and required additional laboratory tests compared to those not previously anticoagulated. Further research is needed to examine the incidence of treatment failures or major bleeding episodes.