Utility of Anti-Xa Monitoring in Children Receiving Enoxaparin for Therapeutic Anticoagulation (original) (raw)
Related papers
Evaluation of a novel point-of-care enoxaparin monitor with central laboratory anti-Xa levels
Thrombosis Research, 2003
Background: Measurement of enoxaparin's anticoagulant activity has been limited to specialized coagulation laboratories and has been impractical for areas needing rapid results, such as during coronary angioplasty. A new point-of-care device, RapidpointR ENOXR, was recently developed to measure clotting times with enoxaparin use. Objectives: To correlate ENOX times with anti-Xa levels among patients receiving enoxaparin. Methods: A total of 166 patients receiving enoxaparin for the prevention of deep venous thrombosis or as treatment during acute coronary syndromes or angioplasty were prospectively studied. Citrated and non-citrated whole-blood (CWB and NCWB) samples were obtained at baseline and peak enoxaparin activity. ENOX times were measured with whole-blood, and the StachromR anti-Xa assay was performed on the plasma from the remainder of the samples. The Pearson correlation coefficient was used to assess the relationship between these two assays. Results: There was a strong linear correlation between the ENOX times and the anti-Xa activities for both CWB (r = 0.89, p < 0.001) and NCWB (r = 0.82, p < 0.001) when considering all 332 samples (baseline and peak). When baseline samples were excluded, the correlation remained strong for CWB ENOX times and anti-Xa levels (r = 0.84, p < 0.001), but was only moderate for NCWB (r = 0.73, p < 0.001). A CWB ENOX time of V 160 s corresponded to anti-Xa level of V 0.5 IU/ml in 95% (188/197) of patients. A CWB ENOX time z 200 s corresponded to anti-Xa levels z 0.8 IU/ml in 96% (93/96) of patients. Conclusions: RapidpointR ENOXR times correlate strongly to anti-Xa activities measured by the StachromR Heparin Assays for citrated whole-blood samples. This novel test can be used for rapid bedside measurements of enoxaparin anticoagulant activity. D
Dosing and monitoring of enoxaparin (Low molecular weight heparin) therapy in children
British Journal of Haematology, 2010
Low molecular weight heparins (LMWHs) are commonly used in paediatric tertiary institutions for primary prophylaxis and treatment of thromboembolic events. This probably reflects the assumption that LMWHs have increased dose-response predictability compared to other anticoagulants, such as unfractionated heparin and warfarin.
An Assessment of Published Pediatric Dosage Guidelines for Enoxaparin
Journal of Pediatric Hematology/Oncology, 2004
Objective: To evaluate the ability of published dosage guidelines for enoxaparin to achieve therapeutic anticoagulation and to determine whether the routine monitoring of anti-Xa levels is still necessary at a tertiary care pediatric institution. Methods: Consecutive charts and laboratory records were reviewed for all patients receiving treatment doses of enoxaparin for thrombosis in the authors' institution over a 4-year period (1998-2002). Results: Sixty-six percent (25/38) of the anti-Xa levels were within the recommended therapeutic range (0.5-1.0 [± 10%] U/mL) after two doses. The success rates of achieving therapeutic levels were 1/6, 2/3, 6/9, 10/11, and 6/9, for patients 2 months or younger, more than 2 months to 1 year, more than 1 year to 6 years, more than 6 years to 12 years, and more than 12 years of age, respectively. Patients with cardiac or renal disease were more likely to achieve high anti-Xa levels. Thirty-seven percent of patients reported adverse effects. The most common effects were injection site-related bruising and minor bleeding. One patient experienced a major bleed that was not lifethreatening. Conclusions: Most patients achieved therapeutic anticoagulation when dosed according to the published guidelines. Children with cardiac conditions or renal insufficiency or those younger than 2 months were more likely to require dosage adjustments to achieve the therapeutic range. Routine monitoring of anti-Xa levels is still necessary in these patient populations, particularly when the early establishment of therapeutic anticoagulation may be critical. Enoxaparin appears to be well tolerated in the authors' patient population.
Journal of the American College of Surgeons, 2019
Background: Previous studies have evaluated dose/weight ratios in order to define best practices for obtaining therapeutic anti-Xa assays for enoxaparin venous thromboembolism (VTE) prophylaxis. These studies have not examined relationships between dosing, patient characteristics, and therapeutic assays. This study examines factors associated with therapeutic assays and enoxaparin prophylaxis. Study Design: This is a retrospective review of patients admitted to a Level 1 Trauma Center between March 2016 and June 2018. Prophylaxis was managed according to the trauma service's enoxaparin VTE prophylaxis protocol which targets anti-Xa concentrations of 0.2-0.5IU/mL. Assays were divided into sub-therapeutic, therapeutic, and super-therapeutic groups to determine factors associated with therapeutic concentrations. Results: Overall, 623 patients (634 total anti-Xa assays) were identified during the study period. Patients with sub-therapeutic(n=35) and therapeutic(n=536) assays did not differ. Significant differences were identified between patients with therapeutic and super-therapeutic assays(n=63). Receiver operating characteristic curve analysis was used to determine that the optimal cutoff for the dose/weight ratio was 0.4mg/kg/dose(AUC=0.78,95%CI 0.73-0.84, p<0,001) differentiating therapeutic and super-therapeutic assays. Logistic regression revealed male gender, doses of 0.31-0.4mg/kg, and CrCl>90mL/min were independently associated with therapeutic assays. The combined effect of these three variables revealed that therapeutic assays were 13.76 times more likely to occur(OR13.76, 3.43-56.96, p<0.001). Conclusions: These data demonstrate that a dose of 0.4mg/kg predicts a therapeutic anti-Xa level. When regimens of 0.31-0.4mg/kg/dose are administered in males with a CrCl>90mL/min therapeutic results are 13.76 times more likely, suggesting that monitoring with anti-Xa assays may be unnecessary in this subgroup. Further prospective study of these findings is warranted.
British Journal of Clinical Pharmacology, 2005
AimRecent studies have suggested that intravenous (i.v.) enoxaparin could be used as antithrombotic therapy in patients ongoing percutaneous coronary intervention (PCI). However, anti-Xa pharmacokinetics following different i.v. dosing regimens is not clearly established.Recent studies have suggested that intravenous (i.v.) enoxaparin could be used as antithrombotic therapy in patients ongoing percutaneous coronary intervention (PCI). However, anti-Xa pharmacokinetics following different i.v. dosing regimens is not clearly established.MethodsA population pharmacokinetic analysis was developed using anti-Xa activities measured in 546 patients who received a single 0.5 mg kg−1 i.v. dose of enoxaparin immediately before PCI. Effects of higher doses (0.75 mg kg−1 and 1 mg kg−1) and/or additional bolus after the initial administration were similarly simulated.A population pharmacokinetic analysis was developed using anti-Xa activities measured in 546 patients who received a single 0.5 mg kg−1 i.v. dose of enoxaparin immediately before PCI. Effects of higher doses (0.75 mg kg−1 and 1 mg kg−1) and/or additional bolus after the initial administration were similarly simulated.ResultsEnoxaparin anti-Xa time profiles were best described by a one-compartment model with zero-order kinetics. Mean population parameters (intersubject variability, %) were CL 1.2 l h−1 (33), V 2.9 l (30) and zero-order input 0.25 h (24). With a single bolus of 0.5 mg kg−1, the totality of the patients reached an effective anticoagulation level (anti-Xa >0.5 IU ml−1) and only 2.5% reached levels above 1.5 IU ml−1. Simulations showed that greater doses (0.75 mg kg−1 and 1 mg kg−1) prolonged the duration of anticoagulation (3.4 and 4.1 h, respectively) compared with the 0.5 mg kg−1 bolus (2.7 h) and markedly increased the proportion (48% and 79%, respectively) of patients with anti-Xa levels >1.5 IU ml−1. For delayed and/or prolonged procedures, patients could be administered a second bolus of half the initial dose in a time interval between 90 min to 2 h after in order to maintain similar anticoagulation profile levels.Enoxaparin anti-Xa time profiles were best described by a one-compartment model with zero-order kinetics. Mean population parameters (intersubject variability, %) were CL 1.2 l h−1 (33), V 2.9 l (30) and zero-order input 0.25 h (24). With a single bolus of 0.5 mg kg−1, the totality of the patients reached an effective anticoagulation level (anti-Xa >0.5 IU ml−1) and only 2.5% reached levels above 1.5 IU ml−1. Simulations showed that greater doses (0.75 mg kg−1 and 1 mg kg−1) prolonged the duration of anticoagulation (3.4 and 4.1 h, respectively) compared with the 0.5 mg kg−1 bolus (2.7 h) and markedly increased the proportion (48% and 79%, respectively) of patients with anti-Xa levels >1.5 IU ml−1. For delayed and/or prolonged procedures, patients could be administered a second bolus of half the initial dose in a time interval between 90 min to 2 h after in order to maintain similar anticoagulation profile levels.ConclusionsA single 0.5 mg kg−1 i.v. dose of enoxaparin reached anticoagulation levels adequately and should be safer compared with greater doses for anticoagulation in patients undergoing an elective PCI. An additional second bolus could be proposed in patients with delayed or prolonged procedures.A single 0.5 mg kg−1 i.v. dose of enoxaparin reached anticoagulation levels adequately and should be safer compared with greater doses for anticoagulation in patients undergoing an elective PCI. An additional second bolus could be proposed in patients with delayed or prolonged procedures.
Enoxaparin for thrombosis in neonates: preliminary
Paediatrics Today, 2013
Objectives -To investigate the dose of enoxaparin required in neonates to achieve target therapeutic ranges of anti factor Xa 48 hours after starting therapy, and compare this dose to recommended guideline dosages for neonates. Methods -We retrospectively reviewed 19 records of newborns who received enoxaparin at different doses for the treatment of thrombosis and evaluated how many among them reached the target anti-factor Xa level after 48 hours. Results -Only 1/5 neonates (20%) treated with 150 UI/kg twice a day, but 100% (6/6) of those treated with 175 UI/kg twice a day reached therapeutic levels of anti-factor Xa at 48 hours. Of the 8 neonates treated with lower starting doses none reached the therapeutic range after 48 hours and these required the highest number of dose changes. Conclusions -Our results reinforce the need to increase in neonates the dosage of enoxaparin suggested in published guidelines, in order to shorten the time-delay in achieving a therapeutic level of anti-factor Xa, and also reducing the number of blood tests necessary for dosing anti-factor Xa.
Background: Enoxaparin is one of the LMWH that has been used for long time in the treatment of acute pulmonary embolism. In this study, we will monitor anticoagulant therapy by anti-Xa assay and correlate its level to the efficacy and safety of enoxaparin in the treatment of pulmonary embolism. Methods: The study was conducted on 42 patients in ICU diagnosed to have pulmonary embolism by CT pulmonary angiography and treated by subcutaneous enoxaparin 1 mg/kg every 12 hours. Anticoagulant therapy was followed by anti-Xa assay done 4 hours after the third dose of subcutaneous enoxaparin and the results were correlated to the clinical outcome of the patients as regards complications (recurrent pulmonary embolism, bleeding, low platelet count and death). Results: According to anti-Xa assay, we divided the patients into three groups. Group I with anti-Xa level < 0.5 IU/mL, group II with anti-Xa level ≥ 0.5 and < 1.2 IU/mL and group III with anti-Xa level ≥ 1.2 IU/mL. 9 patients were in group I, 22 patients were in group II and 11 patients were in group III. There was no significant difference between the three groups as regards age, sex, BMI and underlying risk factors for pulmonary embolism. Serum creatinine level and pulmonary artery pressure were significantly higher in group I than in group II and III. The incidence of recurrent pulmonary embolism was significantly higher in group I than in group II and III with 7 out of 9 patients in group I had recurrent pulmonary embolism compared with only 4 out of 22 and 1 out of 9 in group II and III respectively. The mortality rate was significantly higher in group I than in group II and III with 3 recorded death cases in group I compared with zero recorded cases in group II and III. There was no significant difference between the three groups as regards thrombocytopenia and major bleeding complications. Conclusion: Anti-Xa assay is a good and reliable test for monitoring the efficacy of LMWH therapy using enoxaparin for patients with pulmonary embolism as regards recurrence and mortality rates of pulmonary embolism but it will not monitor safety of enoxaparin therapy as regards incidence of thrombocytopenia and bleeding complications. The study was registered on www.clinicaltrials.gov, Registration ID: NCT02977013. Registered November 27, 2016.
Cardiology in the Young, 2010
Background: Thromboembolic events are a serious complication occurring in critically ill children admitted to the cardiac intensive care unit. Although enoxaparin is one of the current anticoagulants of choice, dosages in children are extrapolated from adult guidelines. Recent data suggest that this population may need a higher dose than what is currently recommended to achieve target anti-factor Xa levels. The purpose of this study was to evaluate whether children less than 2 years old admitted to the cardiac intensive care unit require a higher enoxaparin dose than that currently recommended to achieve target anti-factor Xa levels. Methods: Retrospective chart review including patients who received enoxaparin for the treatment or prophylaxis of venous thrombosis between January, 2005 and October, 2007. Patients were classified as younger and older as well as prophylactic and therapeutic on the basis of age and enoxaparin dose, respectively. Younger patients were those 2 month old or less and older patients were those older than 2 months of age. Results: A total of 31 patients were identified; 13 (42%) were 2 months or younger and 25 (81%) were postoperative patients. Ten (32%) received prophylactic and 21 (68%) received therapeutic enoxaparin doses. To achieve optimal anti-factor Xa levels, enoxaparin dose was increased in all groups and reached statistical significance in all patients except those older than 2 months who received prophylactic enoxaparin. An average of 2.8 dosage adjustments was needed. No bleeding complications were reported. Conclusions: Young children, infants, and neonates admitted to the cardiac intensive care unit required a significantly higher enoxaparin dose than that currently recommended to achieve target anti-factor Xa levels.
Critical Care Medicine, 2021
OBJECTIVES: We explored the age-dependent heterogeneity in the efficacy of prophylaxis with enoxaparin against central venous catheter-associated deep venous thrombosis in critically ill children. DESIGN: Post hoc analysis of a Bayesian phase 2b randomized clinical trial. SETTING: Seven PICUs. PATIENTS: Children less than 18 years old with newly inserted central venous catheter. INTERVENTIONS: Enoxaparin started less than 24 hours after insertion of central venous catheter and adjusted to anti-Xa level of 0.2–0.5 international units/mL versus usual care. MEASUREMENTS AND MAIN RESULTS: Of 51 children randomized, 24 were infants less than 1 year old. Risk ratios of central venous catheter-associated deep venous thrombosis with prophylaxis with enoxaparin were 0.98 (95% credible interval, 0.37–2.44) in infants and 0.24 (95% credible interval, 0.04–0.82) in older children greater than or equal to 1 year old. Infants and older children achieved anti-Xa level greater than or equal to 0.2 ...